The Identification of Two Arabinosyltransferases from Tomato Reveals Functional Equivalency of Xyloglucan Side Chain Substituents1[W][OPEN

PubMed Central

Schultink, Alex; Cheng, Kun; Park, Yong Bum; Cosgrove, Daniel J.; Pauly, Markus

2013-01-01

Xyloglucan (XyG) is the dominant hemicellulose present in the primary cell walls of dicotyledonous plants. Unlike Arabidopsis (Arabidopsis thaliana) XyG, which contains galactosyl and fucosyl substituents, tomato (Solanum lycopersicum) XyG contains arabinofuranosyl residues. To investigate the biological function of these differing substituents, we used a functional complementation approach. Candidate glycosyltransferases were identified from tomato by using comparative genomics with known XyG galactosyltransferase genes from Arabidopsis. These candidate genes were expressed in an Arabidopsis mutant lacking XyG galactosylation, and two of them resulted in the production of arabinosylated XyG, a structure not previously found in this plant species. These genes may therefore encode XyG arabinofuranosyltransferases. Moreover, the addition of arabinofuranosyl residues to the XyG of this Arabidopsis mutant rescued a growth and cell wall biomechanics phenotype, demonstrating that the function of XyG in plant growth, development, and mechanics has considerable flexibility in terms of the specific residues in the side chains. These experiments also highlight the potential of reengineering the sugar substituents on plant wall polysaccharides without compromising growth or viability. PMID:23893172

Biological proliferation of cesium-137 through the detrital food chain in a forest ecosystem in Japan

PubMed Central

Murakami, Masashi; Ohte, Nobuhito; Suzuki, Takahiro; Ishii, Nobuyoshi; Igarashi, Yoshiaki; Tanoi, Keitaro

2014-01-01

Radionuclides, including 137Cs, were released from the disabled Fukushima Daiichi Nuclear Power Plant and had been deposited broadly over forested areas of north-eastern Honshu Island, Japan. In the forest, 137Cs was highly concentrated on leaf litters deposited in autumn 2010, before the accident. Monitoring of the distribution of 137Cs among functional groups clearly showed the role of the detrital food chain as the primary channel of 137Cs transfer to consumer organisms. Although many studies have reported the bioaccumulation (or dilution) of radioactive materials through trophic interactions, the present results highlight the importance of examining multiple possible pathways (e.g., grazing vs. detrital chains) in the proliferation of 137Cs through food webs. These results provide important insight into the future distribution and transfer of 137Cs within forest ecosystems. PMID:24398571

Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

PubMed Central

Mullaney, Brendan; Ashrafi, Kaveh

2010-01-01

Summary Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a long-chain acyl-CoA synthase, causes enhanced intestinal lipid uptake, de novo fat synthesis, and accumulation of enlarged, neutral lipid rich intestinal depots. Here, we show that ACS-3 functions in seam cells, epidermal cells anatomically distinct from sites of fat uptake and storage, and that acs-3 mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3 derived long chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans. PMID:20889131

Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains.

PubMed

Guédon, Yann; d'Aubenton-Carafa, Yves; Thermes, Claude

2006-03-01

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davoudi, Mina; Kallijärvi, Jukka; Marjavaara, Sanna

2014-04-18

Highlights: • Reversible chemical inhibition of complex III in wild type mouse. • Myxothiazol causes decreased complex III activity in mouse liver. • The model is useful for therapeutic trials to improve mitochondrial function. - Abstract: Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIIImore » inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.« less

Amylopectin molecular structure in relation to physicochemical properties of quinoa starch.

PubMed

Li, Guantian; Zhu, Fan

2017-05-15

Structure-function relationships of starch components remain a subject of research interest. Quinoa starch has very small granules (∼2μm) with unique properties. In this study, nine quinoa starches varied greatly in composition, structure, and physicochemical properties were selected for the analysis of structure-function relationships. Pearson correlation analysis revealed that the properties related to gelatinization such as swelling power, water solubility index, crystallinity, pasting, and thermal properties are much affected by the amylopectin chain profile and amylose content. The parameters of gel texture and amylose leaching are much related to amylopectin internal structure. Other properties such as enzyme susceptibility and particle size distribution are also strongly correlated with starch composition and amylopectin structure. Interesting findings indicate the importance of amylopectin internal structure and individual unit chain profile in determining the physicochemical properties of starch. This work highlights some relationships among composition, amylopectin structure and physicochemical properties of quinoa starch. Copyright © 2017 Elsevier Ltd. All rights reserved.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun

Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complexmore » III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.« less

Recent Progress in Producing Lignin-Based Carbon Fibers for Functional Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul, Ryan; Burwell, Deanna; Dai, Xuliang

Lignin, a biopolymer, has been investigated as a renewable and low-cost carbon fiber precursor since the 1960s. Although successful lab-scale production of lignin-based carbon fibers has been reported, there are currently not any commercial producers. This paper will highlight some of the known challenges with converting lignin-based precursors into carbon fiber, and the reported methods for purifying and modifying lignin to improve it as a precursor. Several of the challenges with lignin are related to its diversity in chemical structure and purity, depending on its biomass source (e.g. hardwood, softwood, grasses) and extraction method (e.g. organosolv, kraft). In order tomore » make progress in this field, GrafTech and Oak Ridge National Laboratory are collaborating to develop lignin-based carbon fiber technology and to demonstrate it in functional applications, as part of a cooperative agreement with the DOE Advanced Manufacturing Office. The progress made to date with producing lignin-based carbon fiber for functional applications, as well as developing and qualifying a supply chain and value proposition, are also highlighted.« less

Pulse propagation in granular chains

NASA Astrophysics Data System (ADS)

Rosas, Alexandre; Lindenberg, Katja

2018-03-01

In this comprehensive review we present, discuss, and compare a number of theoretical approaches to the propagation of impulses in granular chains found in the literature, emphasizing the strengths and weaknesses of each. Experimental and numerical results are compared, and common features of the dynamics of pulse propagation for distinct chain setups are highlighted.

Recent Developments in the Synthesis of Biomacromolecules and their Conjugates by Single Electron Transfer-Living Radical Polymerization.

PubMed

Lligadas, Gerard; Grama, Silvia; Percec, Virgil

2017-04-10

Single electron transfer-living radical polymerization (SET-LRP) represents a robust and versatile tool for the synthesis of vinyl polymers with well-defined topology and chain end functionality. The crucial step in SET-LRP is the disproportionation of the Cu(I)X generated by activation with Cu(0) wire, powder, or nascent Cu(0) generated in situ into nascent, extremely reactive Cu(0) atoms and nanoparticles and Cu(II)X 2 . Nascent Cu(0) activates the initiator and dormant chains via a homogeneous or heterogeneous outer-sphere single-electron transfer mechanism (SET-LRP). SET-LRP provides an ultrafast polymerization of a plethora of monomers (e.g., (meth)-acrylates, (meth)-acrylamides, styrene, and vinyl chloride) including hydrophobic and water insoluble to hydrophilic and water soluble. Some advantageous features of SET-LRP are (i) the use of Cu(0) wire or powder as readily available catalysts under mild reaction conditions, (ii) their excellent control over molecular weight evolution and distribution as well as polymer chain ends, (iii) their high functional group tolerance allowing the polymerization of commercial-grade monomers, and (iv) the limited purification required for the resulting polymers. In this Perspective, we highlight the recent advancements of SET-LRP in the synthesis of biomacromolecules and of their conjugates.

Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina

2013-02-15

Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sitesmore » (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity.« less

Computational mining for hypothetical patterns of amino acid side chains in protein data bank (PDB)

NASA Astrophysics Data System (ADS)

Ghani, Nur Syatila Ab; Firdaus-Raih, Mohd

2018-04-01

The three-dimensional structure of a protein can provide insights regarding its function. Functional relationship between proteins can be inferred from fold and sequence similarities. In certain cases, sequence or fold comparison fails to conclude homology between proteins with similar mechanism. Since the structure is more conserved than the sequence, a constellation of functional residues can be similarly arranged among proteins of similar mechanism. Local structural similarity searches are able to detect such constellation of amino acids among distinct proteins, which can be useful to annotate proteins of unknown function. Detection of such patterns of amino acids on a large scale can increase the repertoire of important 3D motifs since available known 3D motifs currently, could not compensate the ever-increasing numbers of uncharacterized proteins to be annotated. Here, a computational platform for an automated detection of 3D motifs is described. A fuzzy-pattern searching algorithm derived from IMagine an Amino Acid 3D Arrangement search EnGINE (IMAAAGINE) was implemented to develop an automated method for searching of hypothetical patterns of amino acid side chains in Protein Data Bank (PDB), without the need for prior knowledge on related sequence or structure of pattern of interest. We present an example of the searches, which is the detection of a hypothetical pattern derived from known structural motif of C2H2 structural pattern from zinc fingers. The conservation of particular patterns of amino acid side chains in unrelated proteins is highlighted. This approach can act as a complementary method for available structure- and sequence-based platforms and may contribute in improving functional association between proteins.

Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid Esters.

PubMed

Koh, Amanda; Todd, Katherine; Sherbourne, Ezekiel; Gross, Richard A

2017-06-13

Surfactants are ubiquitous constituents of commercial and biological systems that function based on complex structure-dependent interactions. Sophorolipid (SL) n-alkyl esters (SL-esters) comprise a group of modified naturally derived glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a function of SL-ester chain length was studied. Surface tensions as low as 31.2 mN/m and critical micelle concentrations (CMCs) as low as 1.1 μM were attained for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n-butyl (SL-BE, 1-3 μM). This behavior of SL-esters with increasing hydrophobic tail length is unlike other known surfactants. Diffusion-ordered spectroscopy (DOSY) and T 1 relaxation NMR experiments indicate this behavior is due to a change in intramolecular interactions, which impedes the self-assembly of SL-esters with chain lengths above SL-BE. This hypothesis is supported by micellar thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters exhibit an even more unusual trend in that CMC increases from 1.75 to 815 μM for SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies, performed to reveal the macroscopic implications of SL-ester micellar behavior, show that the observed instability in foams formed using SL-esters are due to coalescence, which highlights the importance of understanding intermicellar interactions. This work reveals that SL-esters are an important new family of green high-performing surfactants with unique structure-property relationships that can be tuned to optimize micellar characteristics.

Methods in Enzymology: “Flexible backbone sampling methods to model and design protein alternative conformations”

PubMed Central

Ollikainen, Noah; Smith, Colin A.; Fraser, James S.; Kortemme, Tanja

2013-01-01

Sampling alternative conformations is key to understanding how proteins work and engineering them for new functions. However, accurately characterizing and modeling protein conformational ensembles remains experimentally and computationally challenging. These challenges must be met before protein conformational heterogeneity can be exploited in protein engineering and design. Here, as a stepping stone, we describe methods to detect alternative conformations in proteins and strategies to model these near-native conformational changes based on backrub-type Monte Carlo moves in Rosetta. We illustrate how Rosetta simulations that apply backrub moves improve modeling of point mutant side chain conformations, native side chain conformational heterogeneity, functional conformational changes, tolerated sequence space, protein interaction specificity, and amino acid co-variation across protein-protein interfaces. We include relevant Rosetta command lines and RosettaScripts to encourage the application of these types of simulations to other systems. Our work highlights that critical scoring and sampling improvements will be necessary to approximate conformational landscapes. Challenges for the future development of these methods include modeling conformational changes that propagate away from designed mutation sites and modulating backbone flexibility to predictively design functionally important conformational heterogeneity. PMID:23422426

Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

PubMed

Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

2010-02-23

The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

Nonequilibrium steady state in open quantum systems: Influence action, stochastic equation and power balance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsiang, J.-T., E-mail: cosmology@gmail.com; Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan; Hu, B.L.

2015-11-15

The existence and uniqueness of a steady state for nonequilibrium systems (NESS) is a fundamental subject and a main theme of research in statistical mechanics for decades. For Gaussian systems, such as a chain of classical harmonic oscillators connected at each end to a heat bath, and for classical anharmonic oscillators under specified conditions, definitive answers exist in the form of proven theorems. Answering this question for quantum many-body systems poses a challenge for the present. In this work we address this issue by deriving the stochastic equations for the reduced system with self-consistent backaction from the two baths, calculatingmore » the energy flow from one bath to the chain to the other bath, and exhibiting a power balance relation in the total (chain + baths) system which testifies to the existence of a NESS in this system at late times. Its insensitivity to the initial conditions of the chain corroborates to its uniqueness. The functional method we adopt here entails the use of the influence functional, the coarse-grained and stochastic effective actions, from which one can derive the stochastic equations and calculate the average values of physical variables in open quantum systems. This involves both taking the expectation values of quantum operators of the system and the distributional averages of stochastic variables stemming from the coarse-grained environment. This method though formal in appearance is compact and complete. It can also easily accommodate perturbative techniques and diagrammatic methods from field theory. Taken all together it provides a solid platform for carrying out systematic investigations into the nonequilibrium dynamics of open quantum systems and quantum thermodynamics. -- Highlights: •Nonequilibrium steady state (NESS) for interacting quantum many-body systems. •Derivation of stochastic equations for quantum oscillator chain with two heat baths. •Explicit calculation of the energy flow from one bath to the chain to the other bath. •Power balance relation shows the existence of NESS insensitive to initial conditions. •Functional method as a viable platform for issues in quantum thermodynamics.« less

Membrane composition and dynamics: a target of bioactive virgin olive oil constituents.

PubMed

Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Jaramillo, Sara; Varela, Lourdes M; Ortega-Gomez, Almudena; Abia, Rocio; Muriana, Francisco J G

2014-06-01

The endogenous synthesis of lipids, which requires suitable dietary raw materials, is critical for the formation of membrane bilayers. In eukaryotic cells, phospholipids are the predominant membrane lipids and consist of hydrophobic acyl chains attached to a hydrophilic head group. The relative balance between saturated, monounsaturated, and polyunsaturated acyl chains is required for the organization and normal function of membranes. Virgin olive oil is the richest natural dietary source of the monounsaturated lipid oleic acid and is one of the key components of the healthy Mediterranean diet. Virgin olive oil also contains a unique constellation of many other lipophilic and amphipathic constituents whose health benefits are still being discovered. The focus of this review is the latest evidence regarding the impact of oleic acid and the minor constituents of virgin olive oil on the arrangement and behavior of lipid bilayers. We highlight the relevance of these interactions to the potential use of virgin olive oil in preserving the functional properties of membranes to maintain health and in modulating membrane functions that can be altered in several pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural symmetry breaking of silicon containing polymers and their relation with electrical conductivity and Raman active vibrations

NASA Astrophysics Data System (ADS)

Cabrera, Alejandro; González, Carmen; Tagle, Luis; Terraza, Claudio; Volkmann, Ulrich; Barriga, Andrés; Ramos, Esteban; Pavez, Maximiliano

2011-03-01

The incorporation of silicon into the polymeric main chain or side groups can provide an enhancement in chemical, physical and mechanical properties. We report an efficient method for the synthesis of polymers containing silicon in the main chain, from the polycondensation reactions of four optically active carboxylic diacid. The solubility of the polymers, the molecular weight, the glass transition and the thermal stability were studied by standard techniques. Raman spectroscopy was used to probe the conformation of stretching modes as function of the temperature. The conductivity measurements indicated that the alignment of the molecules is a crucial parameter for electrical performance. When the polymers were exposed to iodine, charge transfer increased their mobility and decreased their optical band gaps. These novel properties highlight the possibility to generate alternative active opto-electronics polymers.

Single-Chain Folding of Synthetic Polymers: A Critical Update.

PubMed

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and Application of Functionalized Protein Binders in Multicellular Organisms.

PubMed

Bieli, D; Alborelli, I; Harmansa, S; Matsuda, S; Caussinus, E; Affolter, M

2016-01-01

Protein-protein interactions are crucial for almost all biological processes. Studying such interactions in their native environment is critical but not easy to perform. Recently developed genetically encoded protein binders were shown to function inside living cells. These molecules offer a new, direct way to assess protein function, distribution and dynamics in vivo. A widely used protein binder scaffold are the so-called nanobodies, which are derived from the variable domain of camelid heavy-chain antibodies. Another commonly used scaffold, the DARPins, is based on Ankyrin repeats. In this review, we highlight how these binders can be functionalized in order to study proteins in vivo during the development of multicellular organisms. It is to be anticipated that many more applications for such synthetic protein binders will be developed in the near future. Copyright © 2016 Elsevier Inc. All rights reserved.

Inference of R 0 and Transmission Heterogeneity from the Size Distribution of Stuttering Chains

PubMed Central

Blumberg, Seth; Lloyd-Smith, James O.

2013-01-01

For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer , but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, ) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in is detectable. In addition, by allowing for superspreading events, inference of shifts the threshold above which a transmission chain should be considered anomalously large for a given value of (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results. PMID:23658504

Versatile Synthesis of Amino Acid Functional Polymers without Protection Group Chemistry.

PubMed

Brisson, Emma R L; Xiao, Zeyun; Franks, George V; Connal, Luke A

2017-01-09

The copolymerization of N-isopropylacrylamide (NiPAm) with aldehyde functional monomers facilitates postpolymerization functionalization with amino acids via reductive amination, negating the need for protecting groups. In reductive amination, the imine formed from the condensation reaction between an amine and an aldehyde is reduced to an amine. In this work, we categorize amino acids into four classes based on the functionality of their side chains (acidic, polar neutral, neutral, and basic) and use their amine groups in condensation reactions with aldehyde functional polymers. The dynamic nature of the imine as well as the versatility of reductive amination to functionalize a polymer with a range of amino acids is highlighted. In this manner, amino acid functional polymers are synthesized without the use of protecting groups with high yields, demonstrating the high functional group tolerance of carbonyl condensation chemistry and the subsequent reduction of the imine. Prior to the reduction of the imine bond, transimination reactions are used to demonstrate dynamic polymers that shuffle from a glycine- to a histidine-functional polymer.

Facile ionothermal synthesis of microporous and mesoporous carbons from task specific ionic liquids.

PubMed

Lee, Je Seung; Wang, Xiqing; Luo, Huimin; Baker, Gary A; Dai, Sheng

2009-04-08

An expedient, template-free, high-yield, and solventless route to nitrogen-rich micro- and mesoporous carbons is reported based on direct, atmospheric-pressure carbonization of task-specific ionic liquids bearing one or more nitrile side chains. The resulting textural properties (pore regime, surface area) are highly dependent upon the structural motifs of the ions comprising the corresponding parent ionic liquid, and uniform carbon films are routinely deposited with this novel methodology, highlighting excited new opportunities in the development of advanced functional carbon composites.

Isomer-sensitive deboronation in reductive aminations of aryl boronic acids

DOE PAGES

Jones, Brad Howard; Wheeler, David R.; Wheeler, Jill S.; ...

2015-09-05

Deboronation is observed during the reductive amination of formylphenylboronic acid (FPBA) to the amine termini and side chains of peptides. This deboronation is sensitive to the isomerism of the boronic acid (BA), with ortho-FPBA yielding complete deboronation in the preparation of an N-terminally-modified dipeptide. The observed behavior is also clearly mediated by the chemical identity of the amine substrate. These results reveal a previously undocumented subtlety of BA functionalization and highlight the importance of thorough spectroscopic characterization in the preparation of peptide and small molecule BAs.

Quasi one-dimensional band dispersion and surface metallization in long-range ordered polymeric wires

DOE PAGES

Vasseur, Guillaume; Fagot-Revurat, Yannick; Sicot, Muriel; ...

2016-01-04

We study the electronic structure of an ordered array of poly(para-phenylene) chains produced by surface-catalyzed dehalogenative polymerization of 1,4-dibromobenzene on copper (110). The quantization of unoccupied molecular states is measured as a function of oligomer length by scanning tunnelling spectroscopy, with Fermi level crossings observed for chains longer than ten phenyl rings. Angle-resolved photoelectron spectroscopy reveals a quasi-one-dimensional valence band as well as a direct gap of 1.15 eV, as the conduction band is partially filled through adsorption on the surface. Tight-binding modelling and ab initio density functional theory calculations lead to a full description of the organic band-structure, includingmore » the k-dispersion, the gap size and electron charge transfer mechanisms, highlighting a strong substrate-molecule interaction that drives the system into a metallic behaviour. In summary, we have fully characterized the band structure of a carbon-based conducting wire. This model system may be considered as a fingerprint of -conjugation of surface organic frameworks.« less

Brominated flame retardant: environmental and exposed individuals' health impact.

PubMed

Dufour, Patrice; Charlier, Corinne

2017-04-01

Since Antiquity, men have used chemicals to protect their goods against fire. Effective and easy to use, brominated flame retardants are used since decades massively in plastic industry. Such like other organohalogenated compounds, brominated flame retardants are very persistent in the environment and able to accumulate along the food chain. Many authors highlight their presence in the environment, in many animal species and in the human serum. Worryingly, man is exposed as soon as the pregnancy and then by the breastfeeding. This exposition may have consequence on our health. Many studies (in vitro, in vivo or epidemiologic) highlight brominated flame retardant negative effects on the endocrine system, mainly on the thyroid function but also on the reproduction, the neurodevelopment in the children and on the metabolism with increasing diabetes risk. If authorities and some big enterprises are aware about the problematic, new studies are needed to confirm previous results, elucidate endocrine disrupting mechanisms and highlight hypothetical synergies with other pollutants such like PCBs.

Non-invasive vibrational SFG spectroscopy reveals that bacterial adhesion can alter the conformation of grafted "brush" chains on SAM.

PubMed

Bulard, Emilie; Guo, Ziang; Zheng, Wanquan; Dubost, Henri; Fontaine-Aupart, Marie-Pierre; Bellon-Fontaine, Marie-Noëlle; Herry, Jean-Marie; Briandet, Romain; Bourguignon, Bernard

2011-04-19

Understanding bacterial adhesion on a surface is a crucial step to design new materials with improved properties or to control biofilm formation and eradication. Sum Frequency Generation (SFG) vibrational spectroscopy has been employed to study in situ the conformational response of a self-assembled monolayer (SAM) of octadecanethiol (ODT) on a gold film to the adhesion of hydrophilic and hydrophobic ovococcoid model bacteria. The present work highlights vibrational SFG spectroscopy as a powerful and unique non-invasive biophysical technique to probe and control bacteria interaction with ordered surfaces. Indeed, the SFG vibrational spectral changes reveal different ODT SAM conformations in air and upon exposure to aqueous solution or bacterial adhesion. Furthermore, this effect depends on the bacterial cell surface properties. The SFG spectral modeling demonstrates that hydrophobic bacteria flatten the ODT SAM alkyl chain terminal part, whereas the hydrophilic ones raise this ODT SAM terminal part. Microorganism-induced alteration of grafted chains can thus affect the desired interfacial functionality, a result that should be considered for the design of new reactive materials. © 2011 American Chemical Society

The Physiology of Protein S-acylation

PubMed Central

Chamberlain, Luke H.; Shipston, Michael J.

2015-01-01

Protein S-acylation, the only fully reversible posttranslational lipid modification of proteins, is emerging as a ubiquitous mechanism to control the properties and function of a diverse array of proteins and consequently physiological processes. S-acylation results from the enzymatic addition of long-chain lipids, most typically palmitate, onto intracellular cysteine residues of soluble and transmembrane proteins via a labile thioester linkage. Addition of lipid results in increases in protein hydrophobicity that can impact on protein structure, assembly, maturation, trafficking, and function. The recent explosion in global S-acylation (palmitoyl) proteomic profiling as a result of improved biochemical tools to assay S-acylation, in conjunction with the recent identification of enzymes that control protein S-acylation and de-acylation, has opened a new vista into the physiological function of S-acylation. This review introduces key features of S-acylation and tools to interrogate this process, and highlights the eclectic array of proteins regulated including membrane receptors, ion channels and transporters, enzymes and kinases, signaling adapters and chaperones, cell adhesion, and structural proteins. We highlight recent findings correlating disruption of S-acylation to pathophysiology and disease and discuss some of the major challenges and opportunities in this rapidly expanding field. PMID:25834228

Working memory in children assessed with serial chaining and Simon tasks.

PubMed

Parrish, Audrey E; Perdue, Bonnie M; Kelly, Andrew J; Beran, Michael J

2018-06-06

In the serial chaining task, participants are required to produce a sequence of responses to stimuli in the correct order, and sometimes must determine the sequence at trial outset if stimuli are masked after the first response is made. Similarly, the Simon memory span task presents a participant with a sequence of colors, and the participant must recreate the sequence after the full series is shown. In efforts to directly link the comparative literature on sequential planning behavior and working memory span with the developmental literature, we presented preschool children with the serial chaining task using masked Arabic numerals (N = 44) and the Simon memory span task (N = 65). Older children outperformed younger children in each task, sequencing a longer string of numbers in the serial chaining task and remembering a greater number of items in the Simon task. Controlling for the role of age, there was a significant positive relationship between task scores. These results highlight the emergence of working memory skills that might underlie planning capacities in children using a task developed for nonhuman animals, and the results indicate that improvement in general executive functions could be measured using either or both of these tasks among human children and nonhuman species. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normalmore » glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

IL-21: an executor of B cell fate.

PubMed

Konforte, Danijela; Simard, Nathalie; Paige, Christopher J

2009-02-15

IL-21 is a type I cytokine that shares the common receptor gamma-chain with IL-2, IL-4, IL-7, IL-9, and IL-15. B cells are one of the lymphoid cell types whose development and function are regulated by IL-21. Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, IL-21 can induce proliferation, differentiation into Ig-producing plasma cells, or apoptosis in both mice and humans. Alone and in combination with Th cell-derived cytokines IL-21 can regulate class switch recombination to IgG, IgA, or IgE isotypes, indicating its important role in shaping the effector function of B cells. This review highlights the role of IL-21 in B cell development, function, and disease and provides some perspectives on the future studies in this area.

On the formation of suspended noble-metal monatomic chains

NASA Astrophysics Data System (ADS)

Hasmy, A.; Rincón, L.; Hernández, R.; Mujica, V.; Márquez, M.; González, C.

2008-09-01

We present a tight-binding molecular-dynamics investigation of the geometrical and the electronic structure of suspended monatomic noble-metal chains. We show that linear monatomic chains are formed at temperatures equal to or smaller than 500 K for Au, 200 K for Ag, and 4 K for Cu and that they are stable for at least 10 ns. We also evidence that such stability is associated with the persisting sd orbital hybridization along the chains. The study highlights fundamental limitations of conductance measurement experiments to detect these chains in the breaking process of nanowires.

Chimeric relaxin peptides highlight the role of the A-chain in the function of H2 relaxin.

PubMed

Hossain, Mohammed Akhter; Wade, John D; Bathgate, Ross A D

2012-05-01

Human gene-2 (H2) relaxin is a member of the insulin-relaxin peptide superfamily. Because of the potential clinical applications of H2 relaxin, there is a need for novel analogs that have improved biological activity and receptor specificity. In this respect, we have chemically assembled chimeric peptides consisting of the B-chain of H2 relaxin in combination with A-chains from other insulin/relaxin family members. The peptides were prepared using solid phase peptide synthesis together with regioselective disulfide bond formation and characterized by RP-HPLC, MALDI-TOF MS and amino acid analysis. Their in vitro activity was assessed in RXFP1 or RXFP2 expressing cells. Replacement of the H2 relaxin A-chain resulted in parallel losses of binding affinity and activity on RXFP1. Not surprisingly H1A-H2B demonstrated the highest activity as the H1 A-chain shares high homology with H2 relaxin whereas INSLA-H2B, which shows low homology, had very poor activity. Importantly A-chain replacements had a dramatic effect on RXFP2 activity similar to previous results demonstrating different modes of activation of A-chain variants on RXFP1 and RXFP2. H3A-H2B is particularly interesting as it displays moderate activity at RXFP1 but poor activity at RXFP2 indicating that it may be a template for specific RXFP1 agonist development. Our study confirms that the activity of H2 relaxin at both RXFP1 and RXFP2 relies on interactions with both the B- and A-chains, and also provide new biochemical insights into the mechanism of relaxin action that the A-chain needs to be in native or near-native form for strong RXFP1 or RXFP2 agonist activity. Copyright © 2012 Elsevier Inc. All rights reserved.

Coupled-cluster sum-frequency generation nonlinear susceptibilities of methyl (CH3) and methylene (CH2) groups.

PubMed

Tetsassi Feugmo, Conrard Giresse; Liégeois, Vincent; Champagne, Benoît

2017-11-15

The first vibrational sum frequency generation (SFG) spectra based on molecular properties calculated at the coupled cluster singles and doubles (CCSD) level of approximation have been simulated for interfacial model alkyl chains, providing benchmark data for comparisons with approximate methods, including density functional theory (DFT). The approach proceeds in three steps. In the first two steps, the molecular spectral properties are determined: the vibrational normal modes and frequencies and then the derivatives of the dipole moment and of the polarizability with respect to the normal coordinates. These derivatives are evaluated with a numerical differentiation approach, of which the accuracy was monitored using Romberg's procedure. Then, in the last step, a three-layer model is employed to evaluate the macroscopic second-order nonlinear optical responses and thereby the simulated SFG spectra of the alkyl interface. Results emphasize the following facts: (i) the dipole and polarizability derivatives calculated at the DFT level with the B3LYP exchange-correlation functional can differ, with respect to CCSD, by as much as ±10 to 20% and ±20 to 50% for the CH 3 and CH 2 vibrations, respectively; (ii) these differences are enhanced when considering the SFG intensities as well as their variations as a function of the experimental configuration (ppp versus ssp) and as a function of the tilt and rotation angles, defining the orientation of the alkyl chain at the interface; (iii) these differences originate from both the vibrational normal coordinates and the Cartesian derivatives of the dipole moment and polarizability; (iv) freezing the successive fragments of the alkyl chain strongly modifies the SFG spectrum and enables highlighting the delocalization effects between the terminal CH 3 group and its neighboring CH 2 units; and finally (v) going from the free chain to the free methyl model, and further to C 3v constraints on leads to large variations of two ratios that are frequently used to probe the molecular orientation at the interface, the (r + r)/r + ratio for both antisymmetric and symmetric CH 3 vibrations and the I ppp /I ssp ratio.

Perhaps More Consideration of Pavlovian–Operant Interaction May Improve the Clinical Efficacy of Behaviorally Based Drug Treatment Programs

PubMed Central

Troisi, Joseph R.

2014-01-01

Drug abuse remains costly. Drug-related cues can evoke cue-reactivity and craving, contributing to relapse. The Pavlovian extinction-based cue-exposure therapy (CET) has not been very successful in treating drug abuse. A functional operant analysis of complex rituals involved in CET is outlined and reinterpreted as an operant heterogeneous chain maintained by observing responses, conditioned reinforcers, and discriminative stimuli. It is further noted that operant functions are not predicated on Pavlovian processes but can be influenced by them in contributing to relapse; several empirical studies from the animal and human literature highlight this view. Cue-reactivity evoked by Pavlovian processes is conceptualized as an operant establishing/motivating operation. CET may be more effective in incorporating an operant-based approach that takes into account the complexity of Pavlovian–operant interaction. Extinction of the operant chain coupled with the shaping of alternative behaviors is proposed as an integrated therapy. It is proposed that operant-based drug abuse treatments (contingency management, voucher programs, and the therapeutic work environment) might consider incorporating cue-reactivity, as establishing/motivating operations, to increase long-term success—a hybrid approach based on Pavlovian–operant interaction. PMID:25346551

Perhaps More Consideration of Pavlovian-Operant Interaction May Improve the Clinical Efficacy of Behaviorally Based Drug Treatment Programs.

PubMed

Troisi, Joseph R

2013-01-01

Drug abuse remains costly. Drug-related cues can evoke cue-reactivity and craving, contributing to relapse. The Pavlovian extinction-based cue-exposure therapy (CET) has not been very successful in treating drug abuse. A functional operant analysis of complex rituals involved in CET is outlined and reinterpreted as an operant heterogeneous chain maintained by observing responses, conditioned reinforcers, and discriminative stimuli. It is further noted that operant functions are not predicated on Pavlovian processes but can be influenced by them in contributing to relapse; several empirical studies from the animal and human literature highlight this view. Cue-reactivity evoked by Pavlovian processes is conceptualized as an operant establishing/motivating operation. CET may be more effective in incorporating an operant-based approach that takes into account the complexity of Pavlovian-operant interaction. Extinction of the operant chain coupled with the shaping of alternative behaviors is proposed as an integrated therapy. It is proposed that operant-based drug abuse treatments (contingency management, voucher programs, and the therapeutic work environment) might consider incorporating cue-reactivity, as establishing/motivating operations, to increase long-term success-a hybrid approach based on Pavlovian-operant interaction.

Combinatorics of aliphatic amino acids

NASA Astrophysics Data System (ADS)

Grützmann, Konrad; Böcker, Sebastian; Schuster, Stefan

2011-01-01

This study combines biology and mathematics, showing that a relatively simple question from molecular biology can lead to complicated mathematics. The question is how to calculate the number of theoretically possible aliphatic amino acids as a function of the number of carbon atoms in the side chain. The presented calculation is based on earlier results from theoretical chemistry concerning alkyl compounds. Mathematical properties of this number series are highlighted. We discuss which of the theoretically possible structures really occur in living organisms, such as leucine and isoleucine with a chain length of four. This is done both for a strict definition of aliphatic amino acids only involving carbon and hydrogen atoms in their side chain and for a less strict definition allowing sulphur, nitrogen and oxygen atoms. While the main focus is on proteinogenic amino acids, we also give several examples of non-proteinogenic aliphatic amino acids, playing a role, for instance, in signalling. The results are in agreement with a general phenomenon found in biology: Usually, only a small number of molecules are chosen as building blocks to assemble an inconceivable number of different macromolecules as proteins. Thus, natural biological complexity arises from the multifarious combination of building blocks.

Can the scaling behavior of electric conductivity be used to probe the self-organizational changes in solution with respect to the ionic liquid structure? The case of [C8MIM][NTf2].

PubMed

Paluch, Marian; Wojnarowska, Zaneta; Goodrich, Peter; Jacquemin, Johan; Pionteck, Jürgen; Hensel-Bielowka, Stella

2015-08-28

Electrical conductivity of the supercooled ionic liquid [C8MIM][NTf2], determined as a function of temperature and pressure, highlights strong differences in its ionic transport behavior between low and high temperature regions. To date, the crossover effect which is very well known for low molecular van der Waals liquids has been rarely described for classical ionic liquids. This finding highlights that the thermal fluctuations could be dominant mechanisms driving the dramatic slowing down of ion motions near Tg. An alternative way to analyze separately low and high temperature dc-conductivity data using a density scaling approach was then proposed. Based on which a common value of the scaling exponent γ = 2.4 was obtained, indicating that the applied density scaling is insensitive to the crossover effect. By comparing the scaling exponent γ reported herein along with literature data for other ionic liquids, it appears that γ decreases by increasing the alkyl chain length on the 1-alkyl-3-methylimidazolium-based ionic liquids. This observation may be related to changes in the interaction between ions in solution driven by an increase in the van der Waals type interaction by increasing the alkyl chain length on the cation. This effect may be related to changes in the ionic liquid nanostructural organization with the alkyl chain length on the cation as previously reported in the literature based on molecular dynamic simulations. In other words, the calculated scaling exponent γ may be then used as a key parameter to probe the interaction and/or self-organizational changes in solution with respect to the ionic liquid structure.

Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation

PubMed Central

Shaikh, Saame Raza; Fessler, Michael B.

2016-01-01

Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection. PMID:27286794

Synthesis and biomedical applications of functional poly(α-hydroxy acids) via ring-opening polymerization of O-carboxyanhydrides.

PubMed

Yin, Qian; Yin, Lichen; Wang, Hua; Cheng, Jianjun

2015-07-21

Poly(α-hydroxy acids) (PAHAs) are a class of biodegradable and biocompatible polymers that are widely used in numerous applications. One drawback of these conventional polymers, however, is their lack of side-chain functionalities, which makes it difficult to conjugate active moieties to PAHA or to fine-tune the physical and chemical properties of PAHA-derived materials through side-chain modifications. Thus, extensive efforts have been devoted to the development of methodology that allows facile preparation of PAHAs with controlled molecular weights and a variety of functionalities for widespread utilities. However, it is highly challenging to introduce functional groups into conventional PAHAs derived from ring-opening polymerization (ROP) of lactides and glycolides to yield functional PAHAs with favorable properties, such as tunable hydrophilicity/hydrophobicity, facile postpolymerization modification, and well-defined physicochemical properties. Amino acids are excellent resources for functional polymers because of their low cost, availability, and structural as well as stereochemical diversity. Nevertheless, the synthesis of functional PAHAs using amino acids as building blocks has been rarely reported because of the difficulty of preparing large-scale monomers and poor yields during the synthesis. The synthesis of functionalized PAHAs from O-carboxyanhydrides (OCAs), a class of five-membered cyclic anhydrides derived from amino acids, has proven to be one of the most promising strategies and has thus attracted tremendous interest recently. In this Account, we highlight the recent progress in our group on the synthesis of functional PAHAs via ROP of OCAs and their self-assembly and biomedical applications. New synthetic methodologies that allow the facile preparation of PAHAs with controlled molecular weights and various functionalities through ROP of OCAs are reviewed and evaluated. The in vivo stability, side-chain functionalities, and/or trigger responsiveness of several functional PAHAs are evaluated. Their biomedical applications in drug and gene delivery are also discussed. The ready availability of starting materials from renewable resources and the facile postmodification strategies such as azide-alkyne cycloaddition and the thiol-yne "click" reaction have enabled the production of a multitude of PAHAs with controlled molecular weights, narrow polydispersity, high terminal group fidelities, and structural diversities that are amenable for self-assembly and bioapplications. We anticipate that this new generation of PAHAs and their self-assembled nanosystems as biomaterials will open up exciting new opportunities and have widespread utilities for biological applications.

A quantitative metric to identify critical elements within seafood supply networks.

PubMed

Plagányi, Éva E; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

A Quantitative Metric to Identify Critical Elements within Seafood Supply Networks

PubMed Central

Plagányi, Éva E.; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J.; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H.; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical. PMID:24633147

Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains.

PubMed

Harper, Stephen; Gratton, Hayley E; Cornaciu, Irina; Oberer, Monika; Scott, David J; Emsley, Jonas; Dreveny, Ingrid

2014-05-13

The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

Revisiting the metabolism and physiological functions of caprylic acid (C8:0) with special focus on ghrelin octanoylation.

PubMed

Lemarié, Fanny; Beauchamp, Erwan; Legrand, Philippe; Rioux, Vincent

2016-01-01

Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural sources of dietary C8:0 but higher intakes of this fatty acid can be provided with MCT (Medium-Chain Triglycerides) oil that consists in 75% of C8:0. MCFAs have physical and metabolic properties that are distinct from those of long-chain saturated fatty acids (LCFAs ≥ 12 carbons). Beneficial physiological effects of dietary C8:0 have been studied for a long time and MCT oil has been used as a special energy source for patients suffering from pancreatic insufficiency, impaired lymphatic chylomicron transport and fat malabsorption. More recently, caprylic acid was also shown to acylate ghrelin, the only known peptide hormone with an orexigenic effect. Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an emerging and specific role in modulating physiological functions themselves regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl-CoA co-substrates necessary for the acyl modification of ghrelin. This review tries to highlight the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. The subsequent aim of this review is to demonstrate the relevance of carrying out further studies to better understand the physiological functions of this particular fatty acid. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Systems metabolic engineering design: Fatty acid production as an emerging case study

PubMed Central

Tee, Ting Wei; Chowdhury, Anupam; Maranas, Costas D; Shanks, Jacqueline V

2014-01-01

Increasing demand for petroleum has stimulated industry to develop sustainable production of chemicals and biofuels using microbial cell factories. Fatty acids of chain lengths from C6 to C16 are propitious intermediates for the catalytic synthesis of industrial chemicals and diesel-like biofuels. The abundance of genetic information available for Escherichia coli and specifically, fatty acid metabolism in E. coli, supports this bacterium as a promising host for engineering a biocatalyst for the microbial production of fatty acids. Recent successes rooted in different features of systems metabolic engineering in the strain design of high-yielding medium chain fatty acid producing E. coli strains provide an emerging case study of design methods for effective strain design. Classical metabolic engineering and synthetic biology approaches enabled different and distinct design paths towards a high-yielding strain. Here we highlight a rational strain design process in systems biology, an integrated computational and experimental approach for carboxylic acid production, as an alternative method. Additional challenges inherent in achieving an optimal strain for commercialization of medium chain-length fatty acids will likely require a collection of strategies from systems metabolic engineering. Not only will the continued advancement in systems metabolic engineering result in these highly productive strains more quickly, this knowledge will extend more rapidly the carboxylic acid platform to the microbial production of carboxylic acids with alternate chain-lengths and functionalities. PMID:24481660

Mono-, di- and trimethylated homologues of isoprenoid tetraether lipid cores in archaea and environmental samples: mass spectrometric identification and significance.

PubMed

Knappy, Chris; Barillà, Daniela; Chong, James; Hodgson, Dominic; Morgan, Hugh; Suleman, Muhammad; Tan, Christine; Yao, Peng; Keely, Brendan

2015-12-01

Higher homologues of widely reported C(86) isoprenoid diglycerol tetraether lipid cores, containing 0-6 cyclopentyl rings, have been identified in (hyper)thermophilic archaea, representing up to 21% of total tetraether lipids in the cells. Liquid chromatography-tandem mass spectrometry confirms that the additional carbon atoms in the C(87-88) homologues are located in the etherified chains. Structures identified include dialkyl and monoalkyl ('H-shaped') tetraethers containing C(40-42) or C(81-82) hydrocarbons, respectively, many representing novel compounds. Gas chromatography-mass spectrometric analysis of hydrocarbons released from the lipid cores by ether cleavage suggests that the C(40) chains are biphytanes and the C(41) chains 13-methylbiphytanes. Multiple isomers, having different chain combinations, were recognised among the dialkyl lipids. Methylated tetraethers are produced by Methanothermobacter thermautotrophicus in varying proportions depending on growth conditions, suggesting that methylation may be an adaptive mechanism to regulate cellular function. The detection of methylated lipids in Pyrobaculum sp. AQ1.S2 and Sulfolobus acidocaldarius represents the first reported occurrences in Crenarchaeota. Soils and aquatic sediments from geographically distinct mesotemperate environments that were screened for homologues contained monomethylated tetraethers, with di- and trimethylated structures being detected occasionally. The structural diversity and range of occurrences of the C(87-89) tetraethers highlight their potential as complementary biomarkers for archaea in natural environments. Copyright © 2015 John Wiley & Sons, Ltd.

Systems metabolic engineering design: fatty acid production as an emerging case study.

PubMed

Tee, Ting Wei; Chowdhury, Anupam; Maranas, Costas D; Shanks, Jacqueline V

2014-05-01

Increasing demand for petroleum has stimulated industry to develop sustainable production of chemicals and biofuels using microbial cell factories. Fatty acids of chain lengths from C6 to C16 are propitious intermediates for the catalytic synthesis of industrial chemicals and diesel-like biofuels. The abundance of genetic information available for Escherichia coli and specifically, fatty acid metabolism in E. coli, supports this bacterium as a promising host for engineering a biocatalyst for the microbial production of fatty acids. Recent successes rooted in different features of systems metabolic engineering in the strain design of high-yielding medium chain fatty acid producing E. coli strains provide an emerging case study of design methods for effective strain design. Classical metabolic engineering and synthetic biology approaches enabled different and distinct design paths towards a high-yielding strain. Here we highlight a rational strain design process in systems biology, an integrated computational and experimental approach for carboxylic acid production, as an alternative method. Additional challenges inherent in achieving an optimal strain for commercialization of medium chain-length fatty acids will likely require a collection of strategies from systems metabolic engineering. Not only will the continued advancement in systems metabolic engineering result in these highly productive strains more quickly, this knowledge will extend more rapidly the carboxylic acid platform to the microbial production of carboxylic acids with alternate chain-lengths and functionalities. © 2014 Wiley Periodicals, Inc.

Structural and Functional Studies of a Pyran Synthase Domain from a trans-Acyltransferase Assembly Line.

PubMed

Wagner, Drew T; Zhang, Zhicheng; Meoded, Roy A; Cepeda, Alexis J; Piel, Jörn; Keatinge-Clay, Adrian T

2018-04-20

trans-Acyltransferase assembly lines possess enzymatic domains often not observed in their better characterized cis-acyltransferase counterparts. Within this repertoire of largely unexplored biosynthetic machinery is a class of enzymes called the pyran synthases that catalyze the formation of five- and six-membered cyclic ethers from diverse polyketide chains. The 1.55 Å resolution crystal structure of a pyran synthase domain excised from the ninth module of the sorangicin assembly line highlights the similarity of this enzyme to the ubiquitous dehydratase domain and provides insight into the mechanism of ring formation. Functional assays of point mutants reveal the central importance of the active site histidine that is shared with the dehydratases as well as the supporting role of a neighboring semiconserved asparagine.

Recent advances in plant-herbivore interactions

PubMed Central

Burkepile, Deron E.; Parker, John D.

2017-01-01

Plant-herbivore interactions shape community dynamics across marine, freshwater, and terrestrial habitats. From amphipods to elephants and from algae to trees, plant-herbivore relationships are the crucial link generating animal biomass (and human societies) from mere sunlight. These interactions are, thus, pivotal to understanding the ecology and evolution of virtually any ecosystem. Here, we briefly highlight recent advances in four areas of plant-herbivore interactions: (1) plant defense theory, (2) herbivore diversity and ecosystem function, (3) predation risk aversion and herbivory, and (4) how a changing climate impacts plant-herbivore interactions. Recent advances in plant defense theory, for example, highlight how plant life history and defense traits affect and are affected by multiple drivers, including enemy pressure, resource availability, and the local plant neighborhood, resulting in trait-mediated feedback loops linking trophic interactions with ecosystem nutrient dynamics. Similarly, although the positive effect of consumer diversity on ecosystem function has long been recognized, recent advances using DNA barcoding to elucidate diet, and Global Positioning System/remote sensing to determine habitat selection and impact, have shown that herbivore communities are probably even more functionally diverse than currently realized. Moreover, although most diversity-function studies continue to emphasize plant diversity, herbivore diversity may have even stronger impacts on ecosystem multifunctionality. Recent studies also highlight the role of risk in plant-herbivore interactions, and risk-driven trophic cascades have emerged as landscape-scale patterns in a variety of ecosystems. Perhaps not surprisingly, many plant-herbivore interactions are currently being altered by climate change, which affects plant growth rates and resource allocation, expression of chemical defenses, plant phenology, and herbivore metabolism and behavior. Finally, we conclude by noting that although the field is advancing rapidly, the world is changing even more rapidly, challenging our ability to manage these pivotal links in the food chain. PMID:28232868

Insights into the post-transcriptional regulation of the mitochondrial electron transport chain.

PubMed

Sirey, Tamara M; Ponting, Chris P

2016-10-15

The regulation of the mitochondrial electron transport chain is central to the control of cellular homeostasis. There are significant gaps in our understanding of how the expression of the mitochondrial and nuclear genome-encoded components of the electron transport chain are co-ordinated, and how the assembly of the protein complexes that constitute the electron transport chain are regulated. Furthermore, the role post-transcriptional gene regulation may play in modulating these processes needs to be clarified. This review summarizes the current knowledge regarding the post-transcriptional gene regulation of the electron transport chain and highlights how noncoding RNAs may contribute significantly both to complex electron transport chain regulatory networks and to mitochondrial dysfunction. © 2016 The Author(s).

The Epistemological Chain: Practical Applications in Sports

ERIC Educational Resources Information Center

Grecic, David; Collins, Dave

2013-01-01

This article highlights the role of personal epistemology in decision-making and proposes the construct of an epistemological chain (EC) to support this process in the domain of sports coaching. First, the EC is outlined using examples from education and other parallel disciplines. What it looks like to sports coaches is then described, and its…

One-norm geometric quantum discord and critical point estimation in the XY spin chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Chang-Cheng; Wang, Yao; Guo, Jin-Liang, E-mail: guojinliang80@163.com

2016-11-15

In contrast with entanglement and quantum discord (QD), we investigate the thermal quantum correlation in terms of Schatten one-norm geometric quantum discord (GQD) in the XY spin chain, and analyze their capabilities in detecting the critical point of quantum phase transition. We show that the one-norm GQD can reveal more properties about quantum correlation between two spins, especially for the long-range quantum correlation at finite temperature. Under the influences of site distance, anisotropy and temperature, one-norm GQD and its first derivative make it possible to detect the critical point efficiently for a general XY spin chain. - Highlights: • Comparingmore » with entanglement and QD, one-norm GQD is more robust versus the temperature. • One-norm GQD is more efficient in characterization of long-range quantum correlation between two distant qubits. • One-norm GQD performs well in highlighting the critical point of QPT at zero or low finite temperature. • One-norm GQD has a number of advantages over QD in detecting the critical point of the spin chain.« less

Deconstructing Quinoline-Class Antimalarials to Identify Fundamental Physicochemical Properties of Beta-Hematin Crystal Growth Inhibitors.

PubMed

Olafson, Katy N; Nguyen, Tam Q; Vekilov, Peter G; Rimer, Jeffrey D

2017-10-04

A versatile approach to control crystallization involves the use of modifiers, which are additives that interact with crystal surfaces and alter their growth rates. Elucidating a modifier's binding specificity to anisotropic crystal surfaces is a ubiquitous challenge that is critical to their design. In this study, we select hematin, a byproduct of malaria parasites, as a model system to examine the complementarity of modifiers (i.e., antimalarial drugs) to β-hematin crystal surfaces. We divide two antimalarials, chloroquine and amodiaquine, into segments consisting of a quinoline base, common to both drugs, and side chains that differentiate their modes of action. Using a combination of scanning probe microscopy, bulk crystallization, and analytical techniques, we show that the base and side chain work synergistically to reduce the rate of hematin crystallization. In contrast to general observations that modifiers retain their function upon segmentation, we show that the constituents do not act as modifiers. A systematic study of quinoline isomers and analogues shows how subtle rearrangement and removal of functional moieties can create effective constituents from previously ineffective modifiers, along with tuning their inhibitory modes of action. These findings highlight the importance of specific functional moieties in drug compounds, leading to an improved understanding of modifier-crystal interactions that could prove to be applicable to the design of new antimalarials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sustainable value creation through new industrial supply chains in apparel and fashion

NASA Astrophysics Data System (ADS)

Pal, R.; Sandberg, E.

2017-10-01

This paper explores the inter-organizational value creation, in apparel supply chain context, through circularity and digitalization for sustainability, by gathering evidences from vivid research experiences. It can be highlighted that inter-organizational value creation in both circular- and digital- apparel supply chains largely builds upon a variety of collaborative initiatives, and among a range of included members. Knowledge co-evolvement and business co-development, end-to-end integration and information transfer, and open networks are crucial to such collaborations - making development of new supply chain structures a meta-capability of apparel firms in the changing industrial landscape.

Teaching Young Adults with Intellectual and Developmental Disabilities Community-Based Navigation Skills to Take Public Transportation.

PubMed

Price, Richard; Marsh, Abbie J; Fisher, Marisa H

2018-03-01

Facilitating the use of public transportation enhances opportunities for independent living and competitive, community-based employment for individuals with intellectual and developmental disabilities (IDD). Four young adults with IDD were taught through total-task chaining to use the Google Maps application, a self-prompting, visual navigation system, to take the bus to locations around a college campus and the community. Three of four participants learned to use Google Maps to independently navigate public transportation. Google Maps may be helpful in supporting independent travel, highlighting the importance of future research in teaching navigation skills. Learning to independently use public transportation increases access to autonomous activities, such as opportunities to work and to attend postsecondary education programs on large college campuses.Individuals with IDD can be taught through chaining procedures to use the Google Maps application to navigate public transportation.Mobile map applications are an effective and functional modern tool that can be used to teach community navigation.

Effect of Terminal Modification on the Molecular Assembly and Mechanical Properties of Protein-Based Block Copolymers.

PubMed

Jacobsen, Matthew M; Tokareva, Olena S; Ebrahimi, Davoud; Huang, Wenwen; Ling, Shengjie; Dinjaski, Nina; Li, David; Simon, Marc; Staii, Cristian; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

2017-09-01

Accurate prediction and validation of the assembly of bioinspired peptide sequences into fibers with defined mechanical characteristics would aid significantly in designing and creating materials with desired properties. This process may also be utilized to provide insight into how the molecular architecture of many natural protein fibers is assembled. In this work, computational modeling and experimentation are used in tandem to determine how peptide terminal modification affects a fiber-forming core domain. Modeling shows that increased terminal molecular weight and hydrophilicity improve peptide chain alignment under shearing conditions and promote consolidation of semicrystalline domains. Mechanical analysis shows acute improvements to strength and elasticity, but significantly reduced extensibility and overall toughness. These results highlight an important entropic function that terminal domains of fiber-forming peptides exhibit as chain alignment promoters, which ultimately has notable consequences on the mechanical behavior of the final fiber products. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Disruptions in valine degradation affect seed development and germination in Arabidopsis.

PubMed

Gipson, Andrew B; Morton, Kyla J; Rhee, Rachel J; Simo, Szabolcs; Clayton, Jack A; Perrett, Morgan E; Binkley, Christiana G; Jensen, Erika L; Oakes, Dana L; Rouhier, Matthew F; Rouhier, Kerry A

2017-06-01

We have functionally characterized the role of two putative mitochondrial enzymes in valine degradation using insertional mutants. Prior to this study, the relationship between branched-chain amino acid degradation (named for leucine, valine and isoleucine) and seed development was limited to leucine catabolism. Using a reverse genetics approach, we show that disruptions in the mitochondrial valine degradation pathway affect seed development and germination in Arabidopsis thaliana. A null mutant of 3-hydroxyisobutyryl-CoA hydrolase (CHY4, At4g31810) resulted in an embryo lethal phenotype, while a null mutant of methylmalonate semialdehyde dehydrogenase (MMSD, At2g14170) resulted in seeds with wrinkled coats, decreased storage reserves, elevated valine and leucine, and reduced germination rates. These data highlight the unique contributions CHY4 and MMSD make to the overall growth and viability of plants. It also increases our knowledge of the role branched-chain amino acid catabolism plays in seed development and amino acid homeostasis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Nanoscale amphiphilic macromolecules with variable lipophilicity and stereochemistry modulate inhibition of oxidized low-density lipoprotein uptake.

PubMed

Poree, Dawanne E; Zablocki, Kyle; Faig, Allison; Moghe, Prabhas V; Uhrich, Kathryn E

2013-08-12

Amphiphilic macromolecules (AMs) based on carbohydrate domains functionalized with poly(ethylene glycol) can inhibit the uptake of oxidized low density lipoprotein (oxLDL) and counteract foam cell formation, a key characteristic of early atherogenesis. To investigate the influence of lipophilicity and stereochemistry on the AMs' physicochemical and biological properties, mucic acid-based AMs bearing four aliphatic chains (2a) and tartaric acid-based AMs bearing two (2b and 2l) and four aliphatic chains (2g and 2k) were synthesized and evaluated. Solution aggregation studies suggested that both the number of hydrophobic arms and the length of the hydrophobic domain impact AM micelle sizes, whereas stereochemistry impacts micelle stability. 2l, the meso analogue of 2b, elicited the highest reported oxLDL uptake inhibition values (89%), highlighting the crucial effect of stereochemistry on biological properties. This study suggests that stereochemistry plays a critical role in modulating oxLDL uptake and must be considered when designing biomaterials for potential cardiovascular therapies.

Aspirin increases mitochondrial fatty acid oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse themore » mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.« less

Enzymatically Crosslinked Emulsion Gels Using Star-Polymer Stabilizers.

PubMed

Ma, Kai; An, Zesheng

2016-10-01

A novel type of emulsion gel based on star-polymer-stabilized emulsions is highlighted, which contains discrete hydrophobic oil and hydrophilic aqueous solution domains. Well-defined phenol-functionalized core-crosslinked star polymers are synthesized via reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization and are used as stabilizers for oil-in-water emulsions. Horseradish-peroxidase-catalyzed polymerization of the phenol moieties in the presence of H 2 O 2 enables rapid formation of crosslinked emulsion gels under mild conditions. The crosslinked emulsion gels exhibit enhanced mechanical strength, as well as widely tunable composition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering microbial fatty acid metabolism for biofuels and biochemicals.

PubMed

Marella, Eko Roy; Holkenbrink, Carina; Siewers, Verena; Borodina, Irina

2018-04-01

Traditional oleochemical industry chemically processes animal fats and plant oils to produce detergents, lubricants, biodiesel, plastics, coatings, and other products. Biotechnology offers an alternative process, where the same oleochemicals can be produced from abundant biomass feedstocks using microbial catalysis. This review summarizes the recent advances in the engineering of microbial metabolism for production of fatty acid-derived products. We highlight the efforts in engineering the central carbon metabolism, redox metabolism, controlling the chain length of the products, and obtaining metabolites with different functionalities. The prospects of commercializing microbial oleochemicals are also discussed. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Correlation functions of main-chain polymer nematics constrained by tensorial and vectorial conservation laws

NASA Astrophysics Data System (ADS)

Svenšek, Daniel; Podgornik, Rudolf

2015-09-01

We present and analyze correlation functions of a main-chain polymer nematic in a continuum worm-like chain description for two types of constraints formalized by the tensorial and vectorial conservation laws, both originating in the microscopic chain integrity, i.e., the connectivity of the polymer chains. In particular, our aim is to identify the features of the correlation functions that are most susceptible to the differences between the two constraints. Besides the density and director autocorrelations in both the tensorial and vectorial cases, we calculate also the density-director correlation functions, the latter being a direct signature of the presence of a specific constraint. Its amplitude is connected to the strength of the constraint and is zero if none of the constraints are present, i.e., for a standard non-polymeric nematic. Generally, the correlation functions with the constraints differ substantially from the correlation functions in the non-polymeric case, if the constraints are strong which in practice requires long chains. Moreover, for the tensorial conservation law to be well distinguishable from the vectorial one, the chain persistence length should be much smaller than the total length of the chain, so that hairpins (chain backfolding) are numerous and the polar order is small.

Study of China green supply chain management policies and standard

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxin; Huang, Jin; Lin, Ling

2017-11-01

With the highlight of the environment issues, manufacturing industry needs to be environmentally managed with integrated methods in system aspect. Green supply chain management, integrating the environment aspect into each step of the implement of supply chain management, is the key measure to improve the efficiency of environmental management and to remit the pollution. It also helps to make best use and configuration of the resources and has been attracting much attention from our government, enterprises and academia in recent years. This paper introduced the definition and content of green supply chain management, concluded the research progress of green supply chain management by domestic scholars, stated the characteristic and achievement of the implement of green supply chain management in China as well as analyzed the current existing problems and suggestions in the future.

Traceability and Risk Analysis Strategies for Addressing Counterfeit Electronics in Supply Chains for Complex Systems.

PubMed

DiMase, Daniel; Collier, Zachary A; Carlson, Jinae; Gray, Robin B; Linkov, Igor

2016-10-01

Within the microelectronics industry, there is a growing concern regarding the introduction of counterfeit electronic parts into the supply chain. Even though this problem is widespread, there have been limited attempts to implement risk-based approaches for testing and supply chain management. Supply chain risk management tends to focus on the highly visible disruptions of the supply chain instead of the covert entrance of counterfeits; thus counterfeit risk is difficult to mitigate. This article provides an overview of the complexities of the electronics supply chain, and highlights some gaps in risk assessment practices. In particular, this article calls for enhanced traceability capabilities to track and trace parts at risk through various stages of the supply chain. Placing the focus on risk-informed decision making through the following strategies is needed, including prioritization of high-risk parts, moving beyond certificates of conformance, incentivizing best supply chain management practices, adoption of industry standards, and design and management for supply chain resilience. © 2016 Society for Risk Analysis.

Functional Agents to Biologically Control Deoxynivalenol Contamination in Cereal Grains

PubMed Central

Tian, Ye; Tan, Yanglan; Liu, Na; Liao, Yucai; Sun, Changpo; Wang, Shuangxia; Wu, Aibo

2016-01-01

Mycotoxins, as microbial secondary metabolites, frequently contaminate cereal grains and pose a serious threat to human and animal health around the globe. Deoxynivalenol (DON), a commonly detected Fusarium mycotoxin, has drawn utmost attention due to high exposure levels and contamination frequency in the food chain. Biological control is emerging as a promising technology for the management of DON contamination. Functional biological control agents (BCAs), which include antagonistic microbes, natural fungicides derived from plants and detoxification enzymes, can be used to control DON contamination at different stages of grain production. In this review, studies regarding different biological agents for DON control in recent years are summarized for the first time. Furthermore, this article highlights the significance of BCAs for controlling DON contamination, as well as the need for more practical and efficient BCAs concerning food safety. PMID:27064760

Missing data exploration: highlighting graphical presentation of missing pattern.

PubMed

Zhang, Zhongheng

2015-12-01

Functions shipped with R base can fulfill many tasks of missing data handling. However, because the data volume of electronic medical record (EMR) system is always very large, more sophisticated methods may be helpful in data management. The article focuses on missing data handling by using advanced techniques. There are three types of missing data, that is, missing completely at random (MCAR), missing at random (MAR) and not missing at random (NMAR). This classification system depends on how missing values are generated. Two packages, Multivariate Imputation by Chained Equations (MICE) and Visualization and Imputation of Missing Values (VIM), provide sophisticated functions to explore missing data pattern. In particular, the VIM package is especially helpful in visual inspection of missing data. Finally, correlation analysis provides information on the dependence of missing data on other variables. Such information is useful in subsequent imputations.

TiO2 nanorods/PMMA copolymer-based nanocomposites: highly homogeneous linear and nonlinear optical material

NASA Astrophysics Data System (ADS)

Sciancalepore, C.; Cassano, T.; Curri, M. L.; Mecerreyes, D.; Valentini, A.; Agostiano, A.; Tommasi, R.; Striccoli, M.

2008-05-01

Original nanocomposites have been obtained by direct incorporation of pre-synthesized oleic acid capped TiO2 nanorods into properly functionalized poly(methyl methacrylate) copolymers, carrying carboxylic acid groups on the repeating polymer unit. The presence of carboxylic groups on the alkyl chain of the host functionalized copolymer allows an highly homogeneous dispersion of the nanorods in the organic matrix. The prepared TiO2/PMMA-co-MA nanocomposites show high optical transparency in the visible region, even at high TiO2 nanorod content, and tunable linear refractive index depending on the nanoparticle concentration. Finally measurements of nonlinear optical properties of TiO2 polymer nanocomposites demonstrate a negligible two-photon absorption and a negative value of nonlinear refractive index, highlighting the potential of the nanocomposite for efficient optical devices operating in the visible region.

Residues with similar hexagon neighborhoods share similar side-chain conformations.

PubMed

Li, Shuai Cheng; Bu, Dongbo; Li, Ming

2012-01-01

We present in this study a new approach to code protein side-chain conformations into hexagon substructures. Classical side-chain packing methods consist of two steps: first, side-chain conformations, known as rotamers, are extracted from known protein structures as candidates for each residue; second, a searching method along with an energy function is used to resolve conflicts among residues and to optimize the combinations of side chain conformations for all residues. These methods benefit from the fact that the number of possible side-chain conformations is limited, and the rotamer candidates are readily extracted; however, these methods also suffer from the inaccuracy of energy functions. Inspired by threading and Ab Initio approaches to protein structure prediction, we propose to use hexagon substructures to implicitly capture subtle issues of energy functions. Our initial results indicate that even without guidance from an energy function, hexagon structures alone can capture side-chain conformations at an accuracy of 83.8 percent, higher than 82.6 percent by the state-of-art side-chain packing methods.

On the Interfacial Properties of Polymers/Functionalized Single-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Ansari, R.; Rouhi, S.; Ajori, S.

2016-06-01

Molecular dynamics (MD) simulations is used to study the adsorption of polyethylene (PE) and poly(ethylene oxide) (PEO) on the functionalized single-walled carbon nanotubes (SWCNTs). The effects of functionalization factor weight percent on the interaction energies of polymer chains with nanotubes are studied. Besides, the influences of different functionalization factors on the SWCNT/polymer interactions are investigated. It is shown that for both types of polymer chains, the largest interaction energies associates with the random O functionalized nanotubes. Besides, increasing temperature results in increasing the nanotube/polymer interaction energy. Considering the final shapes of adsorbed polymer chains on the SWCNTs, it is observed that the adsorbed conformations of PE chains are more contracted than those of PEO chains.

General base-general acid catalysis by terpenoid cyclases.

PubMed

Pemberton, Travis A; Christianson, David W

2016-07-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.

General Base-General Acid Catalysis by Terpenoid Cyclases§

PubMed Central

Pemberton, Travis A.; Christianson, David W.

2016-01-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains. PMID:27072285

BCAA Metabolism and NH3 Homeostasis.

PubMed

Conway, M E; Hutson, S M

2016-01-01

The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur. Efficient regulation of these pathways is mediated through the redox environment and phosphorylation in response to dietary and hormonal stimuli. The wide distribution of these proteins allows for effective BCAA utilisation. We discuss how BCAT, BCKDC, and glutamate dehydrogenase operate in supramolecular complexes, allowing for efficient channelling of substrates. The role of BCAAs in brain metabolism is highlighted in rodent and human brain, where differential expression of BCATm indicates differences in nitrogen metabolism between species. Finally, we introduce a new role for BCAT, where a change in function is triggered by oxidation of its redox-active switch. Our understanding of how BCAA metabolism and nitrogen transfer is regulated is important as many studies now point to BCAA metabolic dysregulation in metabolic and neurodegenerative conditions.

Myosin light chains: Teaching old dogs new tricks

PubMed Central

Heissler, Sarah M; Sellers, James R

2014-01-01

The myosin holoenzyme is a multimeric protein complex consisting of heavy chains and light chains. Myosin light chains are calmodulin family members which are crucially involved in the mechanoenzymatic function of the myosin holoenzyme. This review examines the diversity of light chains within the myosin superfamily, discusses interactions between the light chain and the myosin heavy chain as well as regulatory and structural functions of the light chain as a subunit of the myosin holoenzyme. It covers aspects of the myosin light chain in the localization of the myosin holoenzyme, protein-protein interactions and light chain binding to non-myosin binding partners. Finally, this review challenges the dogma that myosin regulatory and essential light chain exclusively associate with conventional myosin heavy chains while unconventional myosin heavy chains usually associate with calmodulin. PMID:26155737

Nitric Oxide and Mitochondrial Function in Neurological Diseases.

PubMed

Ghasemi, Mehdi; Mayasi, Yunis; Hannoun, Anas; Eslami, Seyed Majid; Carandang, Raphael

2018-04-15

Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. Moreover, excess NO or the formation of reactive NO species (RNS), e.g., peroxynitrite (ONOO - ), impairs mitochondrial functioning and this, in conjunction with nuclear events, eventually affects neuronal cell metabolism and survival, contributing to the pathogenesis of several neurodegenerative diseases. In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC); (ii) ONOO - -mediated alteration in mitochondrial permeability transition; (iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex; (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial ONOO - -induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys)function can provide new insights into the treatment of neurodegenerative diseases. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Barriers affecting successful technology enablement of supply chain: An Indian perspective

NASA Astrophysics Data System (ADS)

Arora, R.; Haleem, A.; Farooquie, J. A.

2018-03-01

In order to compete, organizations need to focus on improving supply chain and technology acts as a major enabler. Technology enablement of supply chain has not always been successful and has been examined by many researchers. The purpose of this paper is to do a systematic literature review of technology enabled supply chain from a strategic viewpoint. The literature is examined from two perspectives. Firstly, it studies the growing interest in technology-enabled supply chain in India. Secondly, it studies barriers affecting technology enablement of supply chain. The literature review identifies that technology enabled supply chain helps in improving performance via effective decision making, monitoring entire supply chain, faster reaction to customer service problems, etc. The research has emphasized the importance of 12 barriers affecting technology enablement. This research will help as a guide for practitioners in order to successfully implement technology and fills the gap in existing literature by highlighting and consolidating the significant research work done in past.

Environmental footprints in the meat chain

NASA Astrophysics Data System (ADS)

Đekić, I.; Tomašević, I.

2017-09-01

The objective of this paper was to present environmental performance of the meat chain and highlight main environmental footprints. The meat sector is recognized as one of the leading polluting sectors in the food industry. The meat chain was analyzed from a five-link perspective introducing the following actors: farm(er)s, slaughterhouses, meat processors, customers and consumers. Meat production needs natural resources (water and energy) resulting in waste and waste water discharge. As an outcome it has a high influence on climate change in respect to global warming, acidification and eutrophication potentials and ozone depletion substances.

Controlled chain polymerisation and chemical soldering for single-molecule electronics.

PubMed

Okawa, Yuji; Akai-Kasaya, Megumi; Kuwahara, Yuji; Mandal, Swapan K; Aono, Masakazu

2012-05-21

Single functional molecules offer great potential for the development of novel nanoelectronic devices with capabilities beyond today's silicon-based devices. To realise single-molecule electronics, the development of a viable method for connecting functional molecules to each other using single conductive polymer chains is required. The method of initiating chain polymerisation using the tip of a scanning tunnelling microscope (STM) is very useful for fabricating single conductive polymer chains at designated positions and thereby wiring single molecules. In this feature article, developments in the controlled chain polymerisation of diacetylene compounds and the properties of polydiacetylene chains are summarised. Recent studies of "chemical soldering", a technique enabling the covalent connection of single polydiacetylene chains to single functional molecules, are also introduced. This represents a key step in advancing the development of single-molecule electronics.

Decomposition of conditional probability for high-order symbolic Markov chains.

PubMed

Melnik, S S; Usatenko, O V

2017-07-01

The main goal of this paper is to develop an estimate for the conditional probability function of random stationary ergodic symbolic sequences with elements belonging to a finite alphabet. We elaborate on a decomposition procedure for the conditional probability function of sequences considered to be high-order Markov chains. We represent the conditional probability function as the sum of multilinear memory function monomials of different orders (from zero up to the chain order). This allows us to introduce a family of Markov chain models and to construct artificial sequences via a method of successive iterations, taking into account at each step increasingly high correlations among random elements. At weak correlations, the memory functions are uniquely expressed in terms of the high-order symbolic correlation functions. The proposed method fills the gap between two approaches, namely the likelihood estimation and the additive Markov chains. The obtained results may have applications for sequential approximation of artificial neural network training.

Decomposition of conditional probability for high-order symbolic Markov chains

NASA Astrophysics Data System (ADS)

Melnik, S. S.; Usatenko, O. V.

2017-07-01

The main goal of this paper is to develop an estimate for the conditional probability function of random stationary ergodic symbolic sequences with elements belonging to a finite alphabet. We elaborate on a decomposition procedure for the conditional probability function of sequences considered to be high-order Markov chains. We represent the conditional probability function as the sum of multilinear memory function monomials of different orders (from zero up to the chain order). This allows us to introduce a family of Markov chain models and to construct artificial sequences via a method of successive iterations, taking into account at each step increasingly high correlations among random elements. At weak correlations, the memory functions are uniquely expressed in terms of the high-order symbolic correlation functions. The proposed method fills the gap between two approaches, namely the likelihood estimation and the additive Markov chains. The obtained results may have applications for sequential approximation of artificial neural network training.

Orthogonal Polynomials Associated with Complementary Chain Sequences

NASA Astrophysics Data System (ADS)

Behera, Kiran Kumar; Sri Ranga, A.; Swaminathan, A.

2016-07-01

Using the minimal parameter sequence of a given chain sequence, we introduce the concept of complementary chain sequences, which we view as perturbations of chain sequences. Using the relation between these complementary chain sequences and the corresponding Verblunsky coefficients, the para-orthogonal polynomials and the associated Szegő polynomials are analyzed. Two illustrations, one involving Gaussian hypergeometric functions and the other involving Carathéodory functions are also provided. A connection between these two illustrations by means of complementary chain sequences is also observed.

Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melton, Elaina M.; Center for Cardiovascular Sciences, Albany Medical College, Albany, NY; Cerny, Ronald L.

Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4,more » for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The trafficking of exogenous C16:0 and C22:6 into PA was significant where there was 6.9- and 5.3-fold increased incorporation, respectively, over the control; C18:3 and C20:4 also trended to increase in the PA pool while there were no changes for C18:1 and C18:2. The trafficking of C18:3 into PC and PI trended higher and approached significance. In the case of C20:4, expression of FATP2 resulted in increases in all four classes of phospholipid, indicating little selectivity. In the case of C22:6, there were significant increases of this exogenous fatty acids being trafficking into PC and PI. Collectively, these data support the conclusion that FATP2 has a dual function in the pathways linking the transport and activation of exogenous fatty acids. We discuss the differential roles of FATP2 and its role in both fatty acid transport and fatty acid activation in the context of lipid homeostasis.« less

Integrating Evolutionary and Functional Tests of Adaptive Hypotheses: A Case Study of Altitudinal Differentiation in Hemoglobin Function in an Andean Sparrow, Zonotrichia capensis

PubMed Central

Cheviron, Zachary A.; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Eddy, Douglas K.; Jones, Jennifer; Carling, Matthew D.; Witt, Christopher C.; Moriyama, Hideaki; Weber, Roy E.; Fago, Angela; Storz, Jay F.

2014-01-01

In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the αA-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the αD-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative αA-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling. PMID:25135942

Thermoswitchable Janus Gold Nanoparticles with Stimuli-Responsive Hydrophilic Polymer Brushes.

PubMed

Niu, Xiaoqin; Ran, Fen; Chen, Limei; Lu, Gabriella Jia-En; Hu, Peiguang; Deming, Christopher P; Peng, Yi; Rojas-Andrade, Mauricio D; Chen, Shaowei

2016-05-03

Well-defined thermoswitchable Janus gold nanoparticles with stimuli-responsive hydrophilic polymer brushes were fabricated by combining ligand exchange reactions and the Langmuir technique. Stimuli-responsive polydi(ethylene glycol) methyl ether methacrylate was prepared by addition-fragmentation chain-transfer polymerization. The polymer brushes were then anchored onto the nanoparticle surface by interfacial ligand exchange reactions with hexanethiolate-protected gold nanoparticles, leading to the formation of a hydrophilic (polymer) hemisphere and a hydrophobic (hexanethiolate) one. The resulting Janus nanoparticles showed temperature-switchable wettability, hydrophobicity at high temperatures, and hydrophilicity at low temperatures, due to thermally induced conformational transition of the polymer ligands. The results further highlight the importance of interfacial engineering in the deliberate functionalization of nanoparticle materials.

DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes

PubMed Central

Kleiner, Ralph E.; Brudno, Yevgeny; Birnbaum, Michael E.; Liu, David R.

2009-01-01

The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that the polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence-specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry, but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step towards the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities. PMID:18341334

Assessing cold chain status in a metro city of India: an intervention study.

PubMed

Mallik, S; Mandal, P K; Chatterjee, C; Ghosh, P; Manna, N; Chakrabarty, D; Bagchi, S N; Dasgupta, S

2011-03-01

Cold chain maintenance is an essential activity to maintain the potency of vaccines and to prevent adverse events following immunization. One baseline study highlighted the unsatisfactory cold chain status in city of Kolkata in India. To assess the changes which occurred in the cold chain status after the intervention undertaken to improve the status and also to assess the awareness of the cold chain handlers regarding cold chain maintenance. Intervention consisted of reorganization of cold chain points and training of health manpower in Kolkata Municipal area regarding immunization and cold chain following the guidelines as laid by Govt of India. Reevaluation of cold chain status was done at 20 institutions selected by stratified systematic random sampling after the intervention. The results were compared with baseline survey. Significant improvement had been observed in correct placing of cold chain equipment, maintenance of stock security, orderly placing of ice packs, diluents and vaccines inside the equipment, temperature recording and maintenance. But awareness and skill of cold chain handlers regarding basics of cold chain maintenance was not satisfactory. The success of intervention included significant improvement of cold chain status including creation of a designated cold chain handler. The gaps lay in non-availability of non-electrical cold chain equipment and separate cold chain room, policy makers should stress. Cold chain handlers need reorientation training regarding heat & cold sensitive vaccines, preventive maintenance and correct contingency plan.

Peptide-Based Molecular Hydrogels as Supramolecular Protein Mimics.

PubMed

Singh, Nishant; Kumar, Mohit; Miravet, Juan F; Ulijn, Rein V; Escuder, Beatriu

2017-01-23

This Minireview concerns recent advances in the design, synthesis, and application of low molecular-weight peptidic hydrogelators. The sequence-specific combinations of amino acid side chain functionalities combined with hydrogen bonding of amide backbones and hydrophobic (aromatic) capping groups give these peptidic molecules the intrinsic tendency to self-assemble. The most prevalent designs include N-capped amino acid residues, bolamphiphilic peptides, and amphipathic peptides. Factors such as hydrophobic effects, the Hofmeister effect, and tunable ionization influence their aggregation properties. The self-assembly of simple bio-inspired building blocks into higher organized structures allows comparisons to be drawn with proteins and their complex functionalities, providing preliminary insights into complex biological functions and also enabling their application in a wide range of fields including catalysis, biomedical applications, and mimicry of natural dissipative systems. The Minireview is concluded by a short summary and outlook, highlighting the advances and steps required to bridge the gaps in the understanding of such systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Positive association of vitamin D receptor gene variations with multiple sclerosis in South East Iranian population.

PubMed

Narooie-Nejad, Mehrnaz; Moossavi, Maryam; Torkamanzehi, Adam; Moghtaderi, Ali

2015-01-01

Among the factors postulated to play a role in MS susceptibility, the role of vitamin D is outstanding. Since the function of vitamin D receptor (VDR) represents the effect of vitamin D on the body and genetic variations in VDR gene may affect its function, we aim to highlight the association of two VDR gene polymorphisms with MS susceptibility. In current study, we recruited 113 MS patients and 122 healthy controls. TaqI (rs731236) and ApaI (rs7975232) genetic variations in these two groups were evaluated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All genotype and allele frequencies in both variations showed association with the disease status. However, to find the definite connection between genetic variations in VDR gene and MS disease in a population of South East of Iran, more researches on gene structure and its function with regard to patients' conditions are required.

Human ferritin for tumor detection and therapy.

PubMed

Fan, Kelong; Gao, Lizeng; Yan, Xiyun

2013-01-01

Ferritin, a major iron storage protein found in most living organisms, is composed of a 24-subunit protein cage with a hollow interior cavity. Serum ferritin serves as a critical marker to detect total body iron status. However, recent research reveals a number of novel functions of ferritin besides iron storage; for example, a ferritin receptor, transferrin receptor 1 (TfR1), has been identified and serum ferritin levels are found to be elevated in tumors. A particular new finding is that magnetoferritin nanoparticles, biomimetically synthesized using H-chain ferritin to form a 24-subunit cage with an iron oxide core, possess intrinsic dual functionality, the protein shell specifically targeting tumors and the iron oxide core catalyzing peroxidase substrates to produce a color reaction allowing visualization of tumor tissues. Here we attempt to summarize current research on ferritin, particularly newly identified functions related to tumors, in order to address current challenges and highlight future directions. Copyright © 2013 Wiley Periodicals, Inc.

Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

PubMed

Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang

2010-10-06

Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.

Supply chain optimization: a practitioner's perspective on the next logistics breakthrough.

PubMed

Schlegel, G L

2000-08-01

The objective of this paper is to profile a practitioner's perspective on supply chain optimization and highlight the critical elements of this potential new logistics breakthrough idea. The introduction will briefly describe the existing distribution network, and business environment. This will include operational statistics, manufacturing software, and hardware configurations. The first segment will cover the critical success factors or foundations elements that are prerequisites for success. The second segment will give you a glimpse of a "working game plan" for successful migration to supply chain optimization. The final segment will briefly profile "bottom-line" benefits to be derived from the use of supply chain optimization as a strategy, tactical tool, and competitive advantage.

Polymerase Chain Reaction in the Diagnosis of Visceral Leishmaniasis Recurrence in the Setting of Negative Splenic Smears

PubMed Central

Hasnain, Golam; Basher, Ariful; Nath, Proggananda; Ghosh, Prakash; Hossain, Faria; Hossain, Shakhawat; Mondal, Dinesh

2016-01-01

This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence. PMID:26556834

Cultivating a disease management partnership: a value-chain model.

PubMed

Murray, Carolyn F; Monroe, Wendy; Stalder, Sharon A

2003-01-01

Disease management (DM) is one of the health care industry's more innovative value-chain models, whereby multiple relationships are created to bring complex and time-sensitive services to market. The very nature of comprehensive, seamless DM provided through an outsourced arrangement necessitates a level of cooperation, trust, and synergy that may be lacking from more traditional vendor-customer relationships. This discussion highlights the experience of one health plan and its vendor partner and their approach to the development and delivery of an outsourced heart failure (HF) DM program. The program design and rollout are discussed within principles adapted from the theoretical framework of a value-chain model. Within the value-chain model, added value is created by the convergence and synergistic integration of the partners' discrete strengths. Although each partner brings unique attributes to the relationship, those attributes are significantly enhanced by the value-chain model, thus allowing each party to bring the added value of the relationship to their respective customers. This partnership increases innovation, leverages critical capabilities, and improves market responsiveness. Implementing a comprehensive, outsourced DM program is no small task. DM programs incorporate a broad array of services affecting nearly every department in a health plan's organization. When true seamless integration between multiple organizations with multiple stakeholders is the objective, implementation and ongoing operations can become even more complex. To effectively address the complexities presented by an HF DM program, the parties in this case moved beyond a typical purchaser-vendor relationship to one that is more closely akin to a strategic partnership. This discussion highlights the development of this partnership from the perspective of both organizations, as revealed through contracting and implementation activities. It is intended to provide insight into the program development and rollout processes that one health plan and its partner have adopted to advance a DM model that integrates appropriately within the local environment. This discussion also highlights how an organizational culture can shift from an emphasis on cost, growth, and control to an emphasis on quality, innovation, and service within a value-chain model.

Missing data exploration: highlighting graphical presentation of missing pattern

PubMed Central

2015-01-01

Functions shipped with R base can fulfill many tasks of missing data handling. However, because the data volume of electronic medical record (EMR) system is always very large, more sophisticated methods may be helpful in data management. The article focuses on missing data handling by using advanced techniques. There are three types of missing data, that is, missing completely at random (MCAR), missing at random (MAR) and not missing at random (NMAR). This classification system depends on how missing values are generated. Two packages, Multivariate Imputation by Chained Equations (MICE) and Visualization and Imputation of Missing Values (VIM), provide sophisticated functions to explore missing data pattern. In particular, the VIM package is especially helpful in visual inspection of missing data. Finally, correlation analysis provides information on the dependence of missing data on other variables. Such information is useful in subsequent imputations. PMID:26807411

Rapid fabrication of hierarchically structured supramolecular nanocomposite thin films in one minute

DOEpatents

Xu, Ting; Kao, Joseph

2016-11-08

Functional nanocomposites containing nanoparticles of different chemical compositions may exhibit new properties to meet demands for advanced technology. It is imperative to simultaneously achieve hierarchical structural control and to develop rapid, scalable fabrication to minimize degradation of nanoparticle properties and for compatibility with nanomanufacturing. The assembly kinetics of supramolecular nanocomposite in thin films is governed by the energetic cost arising from defects, the chain mobility, and the activation energy for inter-domain diffusion. By optimizing only one parameter, the solvent fraction in the film, the assembly kinetics can be precisely tailored to produce hierarchically structured thin films of supramolecular nanocomposites in approximately one minute. Moreover, the strong wavelength dependent optical anisotropy in the nanocomposite highlights their potential applications for light manipulation and information transmission. The present invention opens a new avenue in designing manufacture-friendly continuous processing for the fabrication of functional nanocomposite thin films.

Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

PubMed

Armstrong, Jo; Dass, Crispin R

2018-01-01

The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain. As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin. Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

PubMed Central

Bow, Eric W.; Rimoldi, John M.

2016-01-01

The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

The interacting effects of temperature and food chain length on trophic abundance and ecosystem function.

PubMed

Beveridge, Oliver S; Humphries, Stuart; Petchey, Owen L

2010-05-01

1. While much is known about the independent effects of trophic structure and temperature on density and ecosystem processes, less is known about the interaction(s) between the two. 2. We manipulated the temperature of laboratory-based bacteria-protist communities that contained communities with one, two, or three trophic levels, and recorded species' densities and bacterial decomposition. 3. Temperature, food chain length and their interaction produced significant responses in microbial density and bacterial decomposition. Prey and resource density expressed different patterns of temperature dependency during different phases of population dynamics. The addition of a predator altered the temperature-density relationship of prey, from a unimodal trend to a negative one. Bacterial decomposition was greatest in the presence of consumers at higher temperatures. 4. These results are qualitatively consistent with a recent model of direct and indirect temperature effects on resource-consumer population dynamics. Results highlight and reinforce the importance of indirect effects of temperature mediated through trophic interactions. Understanding and predicting the consequences of environmental change will require that indirect effects, trophic structure, and individual species' tolerances be incorporated into theory and models.

Integration of vaccine supply chains with other health commodity supply chains: a framework for decision making.

PubMed

Yadav, Prashant; Lydon, Patrick; Oswald, Julianna; Dicko, Modibo; Zaffran, Michel

2014-11-28

One of the primary objectives of National Immunization Programs is to strengthen and optimize immunization supply chains so that vaccines are delivered to the end recipients effectively, efficiently and sustainably. As a result of larger investments in global health and a wider portfolio of vaccines, global agencies are recognizing the need for vaccine supply chains to operate at their most optimal levels. Integration with other supply chains is often presented as a strategy to improve efficiency. However, it remains unclear if the proposed benefits from integration of vaccine supply chains with other supply chains will outweigh the costs. This paper provides a framework for deciding where such integration offers the most significant benefits. It also cautions about the pitfalls of integration as a one size fits all strategy. It also highlights the need for systematic collection of cost and efficiency data in order to understand the value of integration and other such initiatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFβ1 antibody

PubMed Central

Honey, Denise M.; Best, Annie; Qiu, Huawei

2018-01-01

ABSTRACT Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering. Therefore, we designed insertion mutants in the elbow region and screened for binding and potency. Our results indicated that increasing the elbow region linker length in each chain successfully restored the isoform-specific and high affinity binding of CAT192 to TGFβ1. The crystal structure of the high binding affinity mutant displays large conformational rearrangements of the variable domains compared to the wild-type antigen-binding fragment (Fab) and the low binding affinity mutants. Insertion of two glycines in both the heavy and light chain elbow regions provided sufficient flexibility for the variable domains to extend further apart than the wild-type Fab, and allow the CDR3s to make additional interactions not seen in the wild-type Fab structure. These interactions coupled with the dramatic conformational changes provide a possible explanation of how the scFv and elbow-engineered Fabs bind TGFβ1 with high affinity. This study demonstrates the benefits of re-examining both structure and function when converting scFv to IgG molecules, and highlights the potential of structure-based engineering to produce fully functional antibodies. PMID:29333938

Discontinuous functional for linear-response time-dependent density-functional theory: The exact-exchange kernel and approximate forms

NASA Astrophysics Data System (ADS)

Hellgren, Maria; Gross, E. K. U.

2013-11-01

We present a detailed study of the exact-exchange (EXX) kernel of time-dependent density-functional theory with an emphasis on its discontinuity at integer particle numbers. It was recently found that this exact property leads to sharp peaks and step features in the kernel that diverge in the dissociation limit of diatomic systems [Hellgren and Gross, Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.85.022514 85, 022514 (2012)]. To further analyze the discontinuity of the kernel, we here make use of two different approximations to the EXX kernel: the Petersilka Gossmann Gross (PGG) approximation and a common energy denominator approximation (CEDA). It is demonstrated that whereas the PGG approximation neglects the discontinuity, the CEDA includes it explicitly. By studying model molecular systems it is shown that the so-called field-counteracting effect in the density-functional description of molecular chains can be viewed in terms of the discontinuity of the static kernel. The role of the frequency dependence is also investigated, highlighting its importance for long-range charge-transfer excitations as well as inner-shell excitations.

Taxes and Bribes in Uganda.

PubMed

Jagger, Pamela; Shively, Gerald

Using data from 433 firms operating along Uganda's charcoal and timber supply chains we investigate patterns of bribe payment and tax collection between supply chain actors and government officials responsible for collecting taxes and fees. We examine the factors associated with the presence and magnitude of bribe and tax payments using a series of bivariate probit and Tobit regression models. We find empirical support for a number of hypotheses related to payments, highlighting the role of queuing, capital-at-risk, favouritism, networks, and role in the supply chain. We also find that taxes crowd-in bribery in the charcoal market.

Current Barriers to Large-scale Interoperability of Traceability Technology in the Seafood Sector.

PubMed

Hardt, Marah J; Flett, Keith; Howell, Colleen J

2017-08-01

Interoperability is a critical component of full-chain digital traceability, but is almost nonexistent in the seafood industry. Using both quantitative and qualitative methodology, this study explores the barriers impeding progress toward large-scale interoperability among digital traceability systems in the seafood sector from the perspectives of seafood companies, technology vendors, and supply chains as a whole. We highlight lessons from recent research and field work focused on implementing traceability across full supply chains and make some recommendations for next steps in terms of overcoming challenges and scaling current efforts. © 2017 Institute of Food Technologists®.

Insights from Hydrogen Refueling Station Manufacturing Competitiveness Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayyas, Ahmad

2015-12-18

In work for the Clean Energy Manufacturing Analysis Center (CEMAC), NREL is currently collaborating with Great Lakes Wind Network in conducting a comprehensive hydrogen refueling stations manufacturing competitiveness and supply chain analyses. In this project, CEMAC will be looking at several metrics that will facilitate understanding of the interactions between and within the HRS supply chain, such metrics include innovation potential, intellectual properties, learning curves, related industries and clustering, existing supply chains, ease of doing business, and regulations and safety. This presentation to Fuel Cell Seminar and Energy Exposition 2015 highlights initial findings from CEMAC's analysis.

Taxes and Bribes in Uganda

PubMed Central

Jagger, Pamela; Shively, Gerald

2016-01-01

Using data from 433 firms operating along Uganda’s charcoal and timber supply chains we investigate patterns of bribe payment and tax collection between supply chain actors and government officials responsible for collecting taxes and fees. We examine the factors associated with the presence and magnitude of bribe and tax payments using a series of bivariate probit and Tobit regression models. We find empirical support for a number of hypotheses related to payments, highlighting the role of queuing, capital-at-risk, favouritism, networks, and role in the supply chain. We also find that taxes crowd-in bribery in the charcoal market. PMID:27274568

Entanglement dynamics in critical random quantum Ising chain with perturbations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yichen, E-mail: ychuang@caltech.edu

We simulate the entanglement dynamics in a critical random quantum Ising chain with generic perturbations using the time-evolving block decimation algorithm. Starting from a product state, we observe super-logarithmic growth of entanglement entropy with time. The numerical result is consistent with the analytical prediction of Vosk and Altman using a real-space renormalization group technique. - Highlights: • We study the dynamical quantum phase transition between many-body localized phases. • We simulate the dynamics of a very long random spin chain with matrix product states. • We observe numerically super-logarithmic growth of entanglement entropy with time.

Analytical expression for the correlation function of a hard sphere chain fluid

NASA Astrophysics Data System (ADS)

Chang, Jaeeon; Kim, Hwayong

A closed form expression is given for the correlation function of flexible hard sphere chain fluid. A set of integral equations obtained from Wertheim's multidensity Ornstein-Zernike integral equation theory with the polymer Percus-Yevick ideal chain approximation is considered. Applying the Laplace transformation method to the integral equations and then solving the resulting equations algebraically, the Laplace transforms of individual correlation functions are obtained. By inverse Laplace transformation the inter- and intramolecular radial distribution functions (RDFs) are obtained in closed forms up to 3D(D is segment diameter). These analytical expressions for the RDFs would be useful in developing the perturbation theory of chain fluids.

Genome complexity in the coelacanth is reflected in its adaptive immune system

USGS Publications Warehouse

Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.

2014-01-01

We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

Development of double chain phosphatidylcholine functionalized polymeric monoliths for immobilized artificial membrane chromatography.

PubMed

Wang, Qiqin; Peng, Kun; Chen, Weijia; Cao, Zhen; Zhu, Peijie; Zhao, Yumei; Wang, Yuqiang; Zhou, Haibo; Jiang, Zhengjin

2017-01-06

This study described a simple synthetic methodology for preparing biomembrane mimicking monolithic column. The suggested approach not only simplifies the preparation procedure but also improves the stability of double chain phosphatidylcholine (PC) functionalized monolithic column. The physicochemical properties of the optimized monolithic column were characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and nano-LC. Satisfactory column permeability, efficiency, stability and reproducibility were obtained on this double chain PC functionalized monolithic column. It is worth noting that the resulting polymeric monolith exhibits great potential as a useful alternative of commercial immobilized artificial membrane (IAM) columns for in vitro predication of drug-membrane interactions. Furthermore, the comparative study of both double chain and single chain PC functionalized monoliths indicates that the presence or absence of glycerol backbone and the number of acyl chains are not decisive for the predictive ability of IAM monoliths on drug-membrane interactions. This novel PC functionalized monolithic column also exhibited good selectivity for a protein mixture and a set of pharmaceutical compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Uncovering the fruit bat bushmeat commodity chain and the true extent of fruit bat hunting in Ghana, West Africa

PubMed Central

Kamins, A.O.; Restif, O.; Ntiamoa-Baidu, Y.; Suu-Ire, R.; Hayman, D.T.S.; Cunningham, A.A.; Wood, J.L.N.; Rowcliffe, J.M.

2011-01-01

Harvesting, consumption and trade of bushmeat are important causes of both biodiversity loss and potential zoonotic disease emergence. In order to identify possible ways to mitigate these threats, it is essential to improve our understanding of the mechanisms by which bushmeat gets from the site of capture to the consumer’s table. In this paper we highlight the previously unrecognized scale of hunting of the African straw-colored fruit bat, Eidolon helvum, a species which is important in both ecological and public health contexts, and describe the commodity chain in southern Ghana for its trade. Based on interviews with 551 Ghanaians, including bat hunters, vendors and consumers, we estimate that a minimum of 128,000 E. helvum bats are sold each year through a commodity chain stretching up to 400 km and involving multiple vendors. Unlike the general bushmeat trade in Ghana, where animals are sold in both specialized bushmeat markets and in restaurants, E. helvum is sold primarily in marketplaces; many bats are also kept by hunters for personal consumption. The offtake estimated in this paper raises serious conservation concerns, while the commodity chain identified in this study may offer possible points for management intervention. The separation of the E. helvum commodity chain from that of other bushmeat highlights the need for species-specific research in this area, particularly for bats, whose status as bushmeat is largely unknown. PMID:22514356

Uncovering the fruit bat bushmeat commodity chain and the true extent of fruit bat hunting in Ghana, West Africa.

PubMed

Kamins, A O; Restif, O; Ntiamoa-Baidu, Y; Suu-Ire, R; Hayman, D T S; Cunningham, A A; Wood, J L N; Rowcliffe, J M

2011-12-01

Harvesting, consumption and trade of bushmeat are important causes of both biodiversity loss and potential zoonotic disease emergence. In order to identify possible ways to mitigate these threats, it is essential to improve our understanding of the mechanisms by which bushmeat gets from the site of capture to the consumer's table. In this paper we highlight the previously unrecognized scale of hunting of the African straw-colored fruit bat, Eidolon helvum, a species which is important in both ecological and public health contexts, and describe the commodity chain in southern Ghana for its trade. Based on interviews with 551 Ghanaians, including bat hunters, vendors and consumers, we estimate that a minimum of 128,000 E. helvum bats are sold each year through a commodity chain stretching up to 400 km and involving multiple vendors. Unlike the general bushmeat trade in Ghana, where animals are sold in both specialized bushmeat markets and in restaurants, E. helvum is sold primarily in marketplaces; many bats are also kept by hunters for personal consumption. The offtake estimated in this paper raises serious conservation concerns, while the commodity chain identified in this study may offer possible points for management intervention. The separation of the E. helvum commodity chain from that of other bushmeat highlights the need for species-specific research in this area, particularly for bats, whose status as bushmeat is largely unknown.

The Buccaneer software for automated model building. 1. Tracing protein chains.

PubMed

Cowtan, Kevin

2006-09-01

A new technique for the automated tracing of protein chains in experimental electron-density maps is described. The technique relies on the repeated application of an oriented electron-density likelihood target function to identify likely C(alpha) positions. This function is applied both in the location of a few promising ;seed' positions in the map and to grow those initial C(alpha) positions into extended chain fragments. Techniques for assembling the chain fragments into an initial chain trace are discussed.

Environmental and Economic Implications of Distributed Additive Manufacturing: The Case of Injection Mold Tooling: Environmental Implications of Additive Manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Runze; Riddle, Matthew E.; Graziano, Diane

Additive manufacturing (AM) holds great potentials in enabling superior engineering functionality, streamlining supply chains, and reducing life cycle impacts compared to conventional manufacturing (CM). This study estimates the net changes in supply-chain lead time, life cycle primary energy consumption, greenhouse gas (GHG) emissions, and life cycle costs (LCC) associated with AM technologies for the case of injection molding, to shed light on the environmental and economic advantages of a shift from international or onshore CM to AM in the United States. A systems modeling framework is developed, with integrations of lead-time analysis, life cycle inventory analysis, LCC model, and scenariosmore » considering design differences, supply-chain options, productions, maintenance, and AM technological developments. AM yields a reduction potential of 3% to 5% primary energy, 4% to 7% GHG emissions, 12% to 60% lead time, and 15% to 35% cost over 1 million cycles of the injection molding production depending on the AM technology advancement in future. The economic advantages indicate the significant role of AM technology in raising global manufacturing competitiveness of local producers, while the relatively small environmental benefits highlight the necessity of considering trade-offs and balance techniques between environmental and economic performances when AM is adopted in the tooling industry. The results also help pinpoint the technological innovations in AM that could lead to broader benefits in future.« less

Environmental and Economic Implications of Distributed Additive Manufacturing: The Case of Injection Mold Tooling: Environmental Implications of Additive Manufacturing

DOE PAGES

Huang, Runze; Riddle, Matthew E.; Graziano, Diane; ...

2017-08-26

Additive manufacturing (AM) holds great potentials in enabling superior engineering functionality, streamlining supply chains, and reducing life cycle impacts compared to conventional manufacturing (CM). This study estimates the net changes in supply-chain lead time, life cycle primary energy consumption, greenhouse gas (GHG) emissions, and life cycle costs (LCC) associated with AM technologies for the case of injection molding, to shed light on the environmental and economic advantages of a shift from international or onshore CM to AM in the United States. A systems modeling framework is developed, with integrations of lead-time analysis, life cycle inventory analysis, LCC model, and scenariosmore » considering design differences, supply-chain options, productions, maintenance, and AM technological developments. AM yields a reduction potential of 3% to 5% primary energy, 4% to 7% GHG emissions, 12% to 60% lead time, and 15% to 35% cost over 1 million cycles of the injection molding production depending on the AM technology advancement in future. The economic advantages indicate the significant role of AM technology in raising global manufacturing competitiveness of local producers, while the relatively small environmental benefits highlight the necessity of considering trade-offs and balance techniques between environmental and economic performances when AM is adopted in the tooling industry. The results also help pinpoint the technological innovations in AM that could lead to broader benefits in future.« less

Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

PubMed Central

Henegar, Corneliu; Tordjman, Joan; Achard, Vincent; Lacasa, Danièle; Cremer, Isabelle; Guerre-Millo, Michèle; Poitou, Christine; Basdevant, Arnaud; Stich, Vladimir; Viguerie, Nathalie; Langin, Dominique; Bedossa, Pierre; Zucker, Jean-Daniel; Clement, Karine

2008-01-01

Background Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. Results Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components. Conclusion This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity. PMID:18208606

Is DNA a metal, semiconductor or insulator? A theoretical approach

NASA Astrophysics Data System (ADS)

Rey-Gonzalez, Rafael; Fonseca-Romero, Karen; Plazas, Carlos; Grupo de Óptica e Información Cuántica Team

Over the last years, scientific interest for designing and making low dimensional electronic devices with traditional or novel materials has been increased. These experimental and theoretical researches in electronic properties at molecular scale are looking for developing efficient devices able to carry out tasks which are currently done by silicon transistors and devices. Among the new materials DNA strands are highlighted, but the experimental results have been contradictories pointing to behaviors as conductor, semiconductor or insulator. To contribute to the understanding of the origin of the disparity of the measurements, we perform a numerical calculation of the electrical conductance of DNA segments, modeled as 1D disordered finite chains. The system is described into a Tight binding model with nearest neighbor interactions and a s orbital per site. Hydration effects are included as random variations of self-energies. The electronic current as a function of applied bias is calculated using Launder formalism, where the transmission probability is determined into the transfer matrix formalism. We find a conductor-to-semiconductor-to-insulator transition as a function of the three effects taken into account: chain size, intrinsic disorder, and hydration We thank Fundación para la Promoción de la Investigación y la Tecnología, Colombia, and Dirección de Investigación de Bogotá, Universidad Nacional de Colombia, for partial financial support.

Recent data concerning heparanase: focus on fibrosis, inflammation and cancer.

PubMed

Secchi, Maria Francesca; Masola, Valentina; Zaza, Gianluigi; Lupo, Antonio; Gambaro, Giovanni; Onisto, Maurizio

2015-12-01

Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-β. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.

Cross-sectional examination of metabolites and metabolic phenotypes in uremia.

PubMed

Kalim, Sahir; Clish, Clary B; Deferio, Joseph J; Ortiz, Guillermo; Moffet, Alexander S; Gerszten, Robert E; Thadhani, Ravi; Rhee, Eugene P

2015-07-07

Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown. In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure. Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan's significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity. In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population.

Understanding the policy environment for immunization supply chains: Lessons learned from landscape analyses in Uganda and Senegal.

PubMed

Luzze, Henry; Badiane, Ousseynou; Mamadou Ndiaye, El Hadji; Ndiaye, Annette Seck; Atuhaire, Brian; Atuhebwe, Phionah; Guinot, Phillippe; Fry Sosne, Erin; Gueye, Abdoulaye

2017-04-19

As immunization programs around the world undergo rapid change and expansion, supply chain and logistics systems have become strained, making it increasingly challenging for national public health systems to provide reliable, safe, and efficient access to vaccines. Governments and immunization partners have been aware of this problem for several years, and in 2010, the World Health Organization (WHO) launched the Effective Vaccine Management (EVM) process to help countries identify shortcomings in their immunization supply chains and develop plans for systematic improvement. EVM improvement plans now exist in all Gavi-eligible countries plus many middle- and upper-income countries; however, implementation has been slow and in many cases fraught with financial, managerial, structural, and political roadblocks. Recognizing that significant change of any kind requires a supportive policy environment and strong leadership, PATH began working in Uganda and Senegal to landscape the policy environment around immunization and identify relevant policies, administrative and technical roles and responsibilities, and other issues that may be affecting the supply chain for immunization. The policy landscape assessments included a desk review and a series of structured, in-depth interviews with key international, national, and local stakeholders. The findings highlighted a number of critical issues and challenges in both countries that may be preventing supply chains from functioning optimally. These challenges include a need for better coordination and planning between immunization programs and supply chain managers; the need for sufficient, timely and reliable financing for all aspects of immunization programs; the need for high-level managers trained in immunization supply chain management; and an urgent need for better, more timely data for decision-making. Overcoming these challenges will require the involvement of high-level political actors-including ministers of health and finance, parliamentarians, and other officials who have the ability to approve and influence policy, personnel, and structural changes; ensure work plans are backed with adequate resources for implementation; and hold program managers accountable for achieving agreed indicators. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of topological phases of dimerized Kitaev chain via edge correlation functions

NASA Astrophysics Data System (ADS)

Wang, Yucheng; Miao, Jian-Jian; Jin, Hui-Ke; Chen, Shu

2017-11-01

We study analytically topological properties of a noninteracting modified dimerized Kitaev chain and an exactly solvable interacting dimerized Kitaev chain under open boundary conditions by analyzing two introduced edge correlation functions. The interacting dimerized Kitaev chain at the symmetry point Δ =t and the chemical potential μ =0 can be exactly solved by applying two Jordan-Wigner transformations and a spin rotation, which permits us to calculate the edge correlation functions analytically. We demonstrate that the two edge correlation functions can be used to characterize the trivial, Su-Schrieffer-Heeger-like topological and topological superconductor phases of both the noninteracting and interacting systems and give their phase diagrams.

PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns.

PubMed

Thomas, James A; Deaton, Rebecca A; Hastings, Nicole E; Shang, Yueting; Moehle, Christopher W; Eriksson, Ulf; Topouzis, Stavros; Wamhoff, Brian R; Blackman, Brett R; Owens, Gary K

2009-02-01

Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF alphaalpha-, alphabeta-, and betabeta-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM alpha-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM alpha-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF beta-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE(-/-)) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.

Polymerase Chain Reaction in the Diagnosis of Visceral Leishmaniasis Recurrence in the Setting of Negative Splenic Smears.

PubMed

Hasnain, Golam; Basher, Ariful; Nath, Proggananda; Ghosh, Prakash; Hossain, Faria; Hossain, Shakhawat; Mondal, Dinesh

2016-01-01

This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence. © The American Society of Tropical Medicine and Hygiene.

Multiplex ligation-dependent probe amplification analysis on capillary electrophoresis instruments for a rapid gene copy number study.

PubMed

Jankowski, Stéphane; Currie-Fraser, Erica; Xu, Licen; Coffa, Jordy

2008-09-01

Annotated DNA samples that had been previously analyzed were tested using multiplex ligation-dependent probe amplification (MLPA) assays containing probes targeting BRCA1, BRCA2, and MMR (MLH1/MSH2 genes) and the 9p21 chromosomal region. MLPA polymerase chain reaction products were separated on a capillary electrophoresis platform, and the data were analyzed using GeneMapper v4.0 software (Applied Biosystems, Foster City, CA). After signal normalization, loci regions that had undergone deletions or duplications were identified using the GeneMapper Report Manager and verified using the DyeScale functionality. The results highlight an easy-to-use, optimal sample preparation and analysis workflow that can be used for both small- and large-scale studies.

Complex pectin metabolism by gut bacteria reveals novel catalytic functions

PubMed Central

Baslé, Arnaud; Gray, Joseph; Venditto, Immacolata; Briggs, Jonathon; Zhang, Xiaoyang; Labourel, Aurore; Terrapon, Nicolas; Buffetto, Fanny; Nepogodiev, Sergey; Xiao, Yao; Field, Robert A.; Zhu, Yanping; O’Neil, Malcolm A.; Urbanowicz, Breeana R.; York, William S.; Davies, Gideon J.; Abbott, D. Wade; Ralet, Marie-Christine; Martens, Eric C.; Henrissat, Bernard; Gilbert, Harry J.

2017-01-01

Carbohydrate polymers drive microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron utilizes the most structurally complex glycan known; the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but one of its 21 distinct glycosidic linkages. We show that rhamnogalacturonan-II side-chain and backbone deconstruction are coordinated, to overcome steric constraints, and that degradation reveals previously undiscovered enzyme families and novel catalytic activities. The degradome informs revision of the current structural model of RG-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycans in the human diet. PMID:28329766

Molecular dynamics investigation of the physisorption and interfacial characteristics of NBR chains on carbon nanotubes with different characteristics

NASA Astrophysics Data System (ADS)

Li, Kun; Gu, Boqin

2017-07-01

The present study investigates the physisorption and interfacial interactions between multiwalled carbon nanotubes (MWNTs) with different characteristics, including different numbers of walls and different functional groups, and acrylonitrile-butadiene rubber (NBR) polymer chains based on molecular dynamics simulations performed using modeled MWNT/NBR compound systems. The effects of the initial orientation of NBR chains and their relative distances to nanotubes, number of nanotube layers, and the surface functional groups of nanotubes on nanotube/polymer interactions are examined. Analysis is conducted according to the final configuration obtained in conjunction with the binding energy (Eb), radius of gyration (Rg) and end-to-end distance (h). The results show that the final conformations of NBR chains adsorbed on MWNT surfaces is associated with the initial relative angle of the NBR chains and their distance from the nanotubes. For non-functionalized MWNTs, Eb is almost directly proportional to Rg under equivalent parameters. Moreover, it is observed that functional groups hinder the wrapping of NBR chains on the MWNT surfaces. This indicates that functional groups do not always benefit the macro-mechanical properties of the composites. Moreover, the type of the major interaction force has been dramatically changed into electrostatic force from vdW force because of functionalization.

Disconnection: the user voice within the wound dressing supply chain.

PubMed

Campling, Natasha; Grocott, Patricia; Cowley, Sarah

2008-03-01

This study examined the user voice in England's National Health Service (NHS) wound dressing supply chain. The impetus for this work came from involvement in a collaboration between industry and clinicians, entitled Woundcare Research for Appropriate Products. Experiences from that study highlighted the notable absence of research about the impact of the supply chain on the users of dressings. Interview data are presented following an outline of the grounded theory method used. These data were obtained from key stakeholders (n = 41) within the wound dressing supply chain such as nurses, manufacturers, distributors, professional organizations, government organizations and user groups. The consequences of supply disconnection revealed haphazard supply, unmet user needs and lack of information transfer between player groups. These consequences explain the lack of user voice in the supply chain and have far-reaching implications for nursing management, through purchasing decisions and nurses' management of wound care.

B2B collaboration method through trust values for e-supply chain integrator: a case study of Malaysian construction industry

NASA Astrophysics Data System (ADS)

Ab. Aziz, Norshakirah; Ahmad, Rohiza; Dhanapal Durai, Dominic

2011-12-01

Limited trust, cooperation and communication have been identified as some of the issues that hinder collaboration among business partners. These one also true in the acceptance of e-supply chain integrator among organizations that involve in the same industry. On top of that, the huge number of components in supply chain industry also makes it impossible to include entire supply chain components in the integrator. Hence, this study intends to propose a method for identifying "trusted" collaborators for inclusion into an e-supply chain integrator. For the purpose of constructing and validating the method, the Malaysian construction industry is chosen as the case study due to its size and importance to the economy. This paper puts forward the background of the research, some relevant literatures which lead to trust values elements formulation, data collection from Malaysian Construction Supply Chain and a glimpse of the proposed method for trusted partner selection. Future work is also presented to highlight the next step of this research.

Acylphloroglucinol Biosynthesis in Strawberry Fruit1

PubMed Central

Song, Chuankui; Ring, Ludwig; Hoffmann, Thomas; Huang, Fong-Chin; Slovin, Janet; Schwab, Wilfried

2015-01-01

Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry (Fragaria × ananassa), we discovered four acylphloroglucinol (APG)-glucosides as native Fragaria spp. fruit metabolites whose levels were differently regulated in the transgenic fruits. The biosynthesis of the APG aglycones was investigated by examination of the enzymatic properties of three recombinant Fragaria vesca chalcone synthase (FvCHS) proteins. CHS is involved in anthocyanin biosynthesis during ripening. The F. vesca enzymes readily catalyzed the condensation of two intermediates in branched-chain amino acid metabolism, isovaleryl-Coenzyme A (CoA) and isobutyryl-CoA, with three molecules of malonyl-CoA to form phlorisovalerophenone and phlorisobutyrophenone, respectively, and formed naringenin chalcone when 4-coumaroyl-CoA was used as starter molecule. Isovaleryl-CoA was the preferred starter substrate of FvCHS2-1. Suppression of CHS activity in both transient and stable CHS-silenced fruit resulted in a substantial decrease of APG glucosides and anthocyanins and enhanced levels of volatiles derived from branched-chain amino acids. The proposed APG pathway was confirmed by feeding isotopically labeled amino acids. Thus, Fragaria spp. plants have the capacity to synthesize pharmaceutically important APGs using dual functional CHS/(phloriso)valerophenone synthases that are expressed during fruit ripening. Duplication and adaptive evolution of CHS is the most probable scenario and might be generally applicable to other plants. The results highlight that important promiscuous gene function may be missed when annotation relies solely on in silico analysis. PMID:26169681

Acylphloroglucinol Biosynthesis in Strawberry Fruit.

PubMed

Song, Chuankui; Ring, Ludwig; Hoffmann, Thomas; Huang, Fong-Chin; Slovin, Janet; Schwab, Wilfried

2015-11-01

Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry (Fragaria × ananassa), we discovered four acylphloroglucinol (APG)-glucosides as native Fragaria spp. fruit metabolites whose levels were differently regulated in the transgenic fruits. The biosynthesis of the APG aglycones was investigated by examination of the enzymatic properties of three recombinant Fragaria vesca chalcone synthase (FvCHS) proteins. CHS is involved in anthocyanin biosynthesis during ripening. The F. vesca enzymes readily catalyzed the condensation of two intermediates in branched-chain amino acid metabolism, isovaleryl-Coenzyme A (CoA) and isobutyryl-CoA, with three molecules of malonyl-CoA to form phlorisovalerophenone and phlorisobutyrophenone, respectively, and formed naringenin chalcone when 4-coumaroyl-CoA was used as starter molecule. Isovaleryl-CoA was the preferred starter substrate of FvCHS2-1. Suppression of CHS activity in both transient and stable CHS-silenced fruit resulted in a substantial decrease of APG glucosides and anthocyanins and enhanced levels of volatiles derived from branched-chain amino acids. The proposed APG pathway was confirmed by feeding isotopically labeled amino acids. Thus, Fragaria spp. plants have the capacity to synthesize pharmaceutically important APGs using dual functional CHS/(phloriso)valerophenone synthases that are expressed during fruit ripening. Duplication and adaptive evolution of CHS is the most probable scenario and might be generally applicable to other plants. The results highlight that important promiscuous gene function may be missed when annotation relies solely on in silico analysis. © 2015 American Society of Plant Biologists. All Rights Reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina

The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidencesmore » a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell lipidome.« less

The commercial performance of cellulosic ethanol supply-chains in Europe

PubMed Central

Slade, Raphael; Bauen, Ausilio; Shah, Nilay

2009-01-01

Background The production of fuel-grade ethanol from lignocellulosic biomass resources has the potential to increase biofuel production capacity whilst minimising the negative environmental impacts. These benefits will only be realised if lignocellulosic ethanol production can compete on price with conventional fossil fuels and if it can be produced commercially at scale. This paper focuses on lignocellulosic ethanol production in Europe. The hypothesis is that the eventual cost of production will be determined not only by the performance of the conversion process but by the performance of the entire supply-chain from feedstock production to consumption. To test this, a model for supply-chain cost comparison is developed, the components of representative ethanol supply-chains are described, the factors that are most important in determining the cost and profitability of ethanol production are identified, and a detailed sensitivity analysis is conducted. Results The most important cost determinants are the cost of feedstocks, primarily determined by location and existing markets, and the value obtained for ethanol, primarily determined by the oil price and policy incentives. Both of these factors are highly uncertain. The best performing chains (ethanol produced from softwood and sold as a low percentage blend with gasoline) could ultimately be cost competitive with gasoline without requiring subsidy, but production from straw would generally be less competitive. Conclusion Supply-chain design will play a critical role in determining commercial viability. The importance of feedstock supply highlights the need for location-specific assessments of feedstock availability and price. Similarly, the role of subsidies and policy incentives in creating and sustaining the ethanol market highlights the importance of political engagement and the need to include political risks in investment appraisal. For the supply-chains described here, and with the cost and market parameters selected, selling ethanol as a low percentage blend with gasoline will maximise ethanol revenues and minimise the need for subsidies. It follows, therefore, that the market for low percentage blends should be saturated before markets for high percentage blends. PMID:19192294

Further Evaluations of Functional Communication Training and Chained Schedules of Reinforcement to Treat Multiple Functions of Challenging Behavior

ERIC Educational Resources Information Center

Falcomata, Terry S.; Muething, Colin S.; Gainey, Summer; Hoffman, Katherine; Fragale, Christina

2013-01-01

We evaluated functional communication training (FCT) combined with a chained schedule of reinforcement procedure for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism. Following functional analyses that suggested that challenging behavior served multiple functions for both participants,…

pysimm: A Python Package for Simulation of Molecular Systems

NASA Astrophysics Data System (ADS)

Fortunato, Michael; Colina, Coray

pysimm, short for python simulation interface for molecular modeling, is a python package designed to facilitate the structure generation and simulation of molecular systems through convenient and programmatic access to object-oriented representations of molecular system data. This poster presents core features of pysimm and design philosophies that highlight a generalized methodology for incorporation of third-party software packages through API interfaces. The integration with the LAMMPS simulation package is explained to demonstrate this methodology. pysimm began as a back-end python library that powered a cloud-based application on nanohub.org for amorphous polymer simulation. The extension from a specific application library to general purpose simulation interface is explained. Additionally, this poster highlights the rapid development of new applications to construct polymer chains capable of controlling chain morphology such as molecular weight distribution and monomer composition.

Estimating Supply-Chain Burdens in Support of Acquisition Decisions

DTIC Science & Technology

2013-03-20

Çì~íÉ=pÅÜççä= Abstract Acquisition decisions drive supply-chain requirements that incur financial costs and other critical impacts. To account ...their rates are fully burdened with respect to the cost of transport assets and any force protection, if necessary. However, DoD accounting systems and...Board (DSB) report (2008) highlighted the failure of DoD management processes to properly account for the enterprise- wide costs of fuel. Before 2009

Investigation of the adsorption of polymer chains on amine-functionalized double-walled carbon nanotubes.

PubMed

Ansari, R; Ajori, S; Rouhi, S

2015-12-01

Molecular dynamics (MD) simulations were used to study the adsorption of different polymer chains on functionalized double-walled carbon nanotubes (DWCNTs). The nanotubes were functionalized with two different amines: NH2 (a small amine) and CH2-NH2 (a large amine). Considering three different polymer chains, all with the same number of atoms, the effect of polymer type on the polymer-nanotube interaction was studied. In general, it was found that covalent functionalization considerably improved the polymer-DWCNT interaction. By comparing the results obtained with different polymer chains, it was observed that, unlike polyethylene and polyketone, poly(styrene sulfonate) only weakly interacts with the functionalized DWCNTs. Accordingly, the smallest radius of gyration was obtained with adsorbed poly(styrene sulfonate). It was also observed that the DWCNTs functionalized with the large amine presented more stable interactions with polyketone and poly(styrene sulfonate) than with polyethylene, whereas the DWCNTs functionalized with the small amine showed better interfacial noncovalent bonding with polyethylene.

Langmuir-Blodgett Films of Aromatic Schiff’s Bases Functionalized in the Side Chains of Polymethacrylate

DTIC Science & Technology

1991-05-03

Report No. 21 - Latigmuir-Blodgett Films of Aromatic Schiffs Bases , K Fuctionalized in the Side Chains of Polymethacrylate by T. Takahashi, P. Miller...aromatic Schiff’s bases functionalized in the side chains of Polymethacrylate T. Takahashi**, P. Miller*, Y. M. Chen*, L. Samuelson***, D. Galotti, B...has been investigated for polymers in which nonlinear optical (NLO) moieties are attachcd i, the side chain of polymethacrylate (PMA) backbone. Polymer

Path-integral theory of an axially confined worm-like chain

NASA Astrophysics Data System (ADS)

Smith, D. A.

2001-06-01

A path-integral formulation is developed for the thermodynamic properties of a worm-like chain moving on a surface and laterally confined by a harmonic potential. The free energy of the chain is calculated as a function of its length and boundary conditions at each end. Distribution functions for chain displacements can be constructed by utilizing the Markov property as a function of displacement φ(s) and its derivative dφ(s)/ds along the path. These quantities are also calculated in the presence of pinning sites which impose fixed positive or negative displacements, foreshadowing their application to a model for the regulation of striated muscle.

The Homotopic Probability Distribution and the Partition Function for the Entangled System Around a Ribbon Segment Chain

NASA Astrophysics Data System (ADS)

Qian, Shang-Wu; Gu, Zhi-Yu

2001-12-01

Using the Feynman's path integral with topological constraints arising from the presence of one singular line, we find the homotopic probability distribution P_L^n for the winding number n and the partition function P_L of the entangled system around a ribbon segment chain. We find that when the width of the ribbon segment chain 2a increases,the partition function exponentially decreases, whereas the free energy increases an amount, which is proportional to the square of the width. When the width tends to zero we obtain the same results as those of a single chain with one singular point.

Anomalous I-V curve for mono-atomic carbon chains

NASA Astrophysics Data System (ADS)

Song, Bo; Sanvito, Stefano; Fang, Haiping

2010-10-01

The electronic transport properties of mono-atomic carbon chains were studied theoretically using a combination of density functional theory and the non-equilibrium Green's functions method. The I-V curves for the chains composed of an even number of atoms and attached to gold electrodes through sulfur exhibit two plateaus where the current becomes bias independent. In contrast, when the number of carbon atoms in the chain is odd, the electric current simply increases monotonically with bias. This peculiar behavior is attributed to dimerization of the chains, directly resulting from their one-dimensional nature. The finding is expected to be helpful in designing molecular devices, such as carbon-chain-based transistors and sensors, for nanoscale and biological applications.

Majorana bound states in the finite-length chain

NASA Astrophysics Data System (ADS)

Zvyagin, A. A.

2015-08-01

Recent experiments investigating edge states in ferromagnetic atomic chains on superconducting substrate are analyzed. In particular, finite size effects are considered. It is shown how the energy of the Majorana bound state depends on the length of the chain, as well as on the parameters of the model. Oscillations of the energy of the bound edge state in the chain as a function of the length of the chain, and as a function of the applied voltage (or the chemical potential) are studied. In particular, it has been shown that oscillations can exist only for some values of the effective potential.

Greenhouse Gas and Ammonia Emissions from Different Stages of Liquid Manure Management Chains: Abatement Options and Emission Interactions.

PubMed

Mohankumar Sajeev, Erangu Purath; Winiwarter, Wilfried; Amon, Barbara

2018-01-01

Farm livestock manure is an important source of ammonia and greenhouse gases. Concerns over the environmental impact of emissions from manure management have resulted in research efforts focusing on emission abatement. However, questions regarding the successful abatement of manure-related emissions remain. This study uses a meta-analytical approach comprising 89 peer-reviewed studies to quantify emission reduction potentials of abatement options for liquid manure management chains from cattle and pigs. Analyses of emission reductions highlight the importance of accounting for interactions between emissions. Only three out of the eight abatement options considered (frequent removal of manure, anaerobic digesters, and manure acidification) reduced ammonia (3-60%), nitrous oxide (21-55%), and methane (29-74%) emissions simultaneously, whereas in all other cases, tradeoffs were identified. The results demonstrate that a shift from single-stage emission abatement options towards a whole-chain perspective is vital in reducing overall emissions along the manure management chain. The study also identifies some key elements like proper clustering, reporting of influencing factors, and explicitly describing assumptions associated with abatement options that can reduce variability in emission reduction estimates. Prioritization of abatement options according to their functioning can help to determine low-risk emission reduction options, specifically options that alter manure characteristics (e.g., reduced protein diets, anaerobic digestion, or slurry acidification). These insights supported by comprehensive emission measurement studies can help improve the effectiveness of emission abatement and harmonize strategies aimed at reducing air pollution and climate change simultaneously. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

PubMed

Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

2017-10-01

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

PubMed

Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

2013-11-26

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

The yeast Saccharomyces cerevisiae- the main character in beer brewing.

PubMed

Lodolo, Elizabeth J; Kock, Johan L F; Axcell, Barry C; Brooks, Martin

2008-11-01

Historically, mankind and yeast developed a relationship that led to the discovery of fermented beverages. Numerous inventions have led to improved technologies and capabilities to optimize fermentation technology on an industrial scale. The role of brewing yeast in the beer-making process is reviewed and its importance as the main character is highlighted. On considering the various outcomes of functions in a brewery, it has been found that these functions are focused on supporting the supply of yeast requirements for fermentation and ultimately to maintain the integrity of the product. The functions/processes include: nutrient supply to the yeast (raw material supply for brewhouse wort production); utilities (supply of water, heat and cooling); quality assurance practices (hygiene practices, microbiological integrity measures and other specifications); plant automation (vessels, pipes, pumps, valves, sensors, stirrers and centrifuges); filtration and packaging (product preservation until consumption); distribution (consumer supply); and marketing (consumer awareness). Considering this value chain of beer production and the 'bottle neck' during production, the spotlight falls on fermentation, the age-old process where yeast transforms wort into beer.

Mechanism and evidence of nonsense suppression therapy for genetic eye disorders.

PubMed

Richardson, Rose; Smart, Matthew; Tracey-White, Dhani; Webster, Andrew R; Moosajee, Mariya

2017-02-01

Between 5 and 70% of genetic disease is caused by in-frame nonsense mutations, which introduce a premature termination codon (PTC) within the disease-causing gene. Consequently, during translation, non-functional or gain-of-function truncated proteins of pathological significance, are formed. Approximately 50% of all inherited retinal disorders have been associated with PTCs, highlighting the importance of novel pharmacological or gene correction therapies in ocular disease. Pharmacological nonsense suppression of PTCs could delineate a therapeutic strategy that treats the mutation in a gene- and disease-independent manner. This approach aims to suppress the fidelity of the ribosome during protein synthesis so that a near-cognate aminoacyl-tRNA, which shares two of the three nucleotides of the PTC, can be inserted into the peptide chain, allowing translation to continue, and a full-length functional protein to be produced. Here we discuss the mechanisms and evidence of nonsense suppression agents, including the small molecule drug ataluren (or PTC124) and next generation 'designer' aminoglycosides, for the treatment of genetic eye disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biological functions of iduronic acid in chondroitin/dermatan sulfate

PubMed Central

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-01-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler–Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. PMID:23441919

Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr; CHRU Montpellier, 34295 Montpellier; Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques

2012-03-01

The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complexmore » I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.« less

A Polymeric Fastener can Easily Functionalize Liposome Surfaces with Gadolinium for Enhanced Magnetic Resonance Imaging

PubMed Central

Smith, Cartney E.; Shkumatov, Artem; Withers, Sarah G.; Glockner, James F.; Misra, Sanjay; Roy, Edward J.; Wong, Chun-Ho; Zimmerman, Steven C.; Kong, Hyunjoon

2013-01-01

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization, and therefore has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication. PMID:24083377

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

PubMed Central

Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

2014-01-01

ABSTRACT The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCE Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota. Small-molecule inducers of the lytic cycle are desired for oncolytic therapy. Inhibition of viral reactivation, alternatively, may prove useful in cancer treatment. Overall, our findings contribute to the understanding of pathways that control the latent-to-lytic switch and identify naturally occurring molecules that may regulate this process. PMID:24807711

Linking Biological Responses of Terrestrial N Eutrophication to the Final Ecosystem Goods and Services Classification System

NASA Astrophysics Data System (ADS)

Bell, M. D.; Clark, C.; Blett, T.

2015-12-01

The response of a biological indicator to N deposition can indicate that an ecosystem has surpassed a critical load and is at risk of significant change. The importance of this exceedance is often difficult to digest by policy makers and public audiences if the change is not linked to a familiar ecosystem endpoint. A workshop was held to bring together scientists, resource managers, and policy makers with expertise in ecosystem functioning, critical loads, and economics in an effort to identify the ecosystem services impacted by air pollution. This was completed within the framework of the Final Ecosystem Goods and Services (FEGS) Classification System to produce a product that identified distinct interactions between society and the effects of nitrogen pollution. From each change in a biological indicator, we created multiple ecological production functions to identify the cascading effects of the change to a measureable ecosystem service that a user interacts with either by enjoying, consuming, or appreciating the good or service, or using it as an input in the human economy. This FEGS metric was then linked to a beneficiary group that interacts with the service. Chains detailing the links from the biological indicator to the beneficiary group were created for aquatic and terrestrial acidification and eutrophication at the workshop, and here we present a subset of the workshop results by highlighting for 9 different ecosystems affected by terrestrial eutrophication. A total of 213 chains that linked to 37 unique FEGS metrics and impacted 15 beneficiary groups were identified based on nitrogen deposition mediated changes to biological indicators. The chains within each ecosystem were combined in flow charts to show the complex, overlapping relationships among biological indicators, ecosystem services, and beneficiary groups. Strength of relationship values were calculated for each chain based on support for the link in the scientific literature. We produced the complex diagrams to provide details to scientists and experts, identify research gaps, and understand the complexity of critical load exceedances. We then simplified the flow charts into stories that could produce an emotional connection and resonate with a general audience. These stories are important steps to breach the gaps between science and policy.

Adsorption of poly(ethylene succinate) chain onto graphene nanosheets: A molecular simulation.

PubMed

Kelich, Payam; Asadinezhad, Ahmad

2016-09-01

Understanding the interaction between single polymer chain and graphene nanosheets at local and global length scales is essential for it underlies the mesoscopic properties of polymer nanocomposites. A computational attempt was then performed using atomistic molecular dynamics simulation to gain physical insights into behavior of a model aliphatic polyester, poly(ethylene succinate), single chain near graphene nanosheets, where the effects of the polymer chain length, graphene functionalization, and temperature on conformational properties of the polymer were studied comparatively. Graphene functionalization was carried out through extending the parameters set of an all-atom force field. The results showed a significant conformational transition of the polymer chain from three-dimensional statistical coil, in initial state, to two-dimensional fold, in final state, during adsorption on graphene. The conformational order, overall shape, end-to-end separation statistics, and mobility of the polymer chain were found to be influenced by the graphene functionalization, temperature, and polymer chain length. Furthermore, the polymer chain dynamics mode during adsorption on graphene was observed to transit from normal diffusive to slow subdiffusive mode. The findings from this computational study could shed light on the physics of the early stages of aliphatic polyester chain organization induced by graphene. Copyright © 2016 Elsevier Inc. All rights reserved.

Understanding transferable supply chain lessons and practices to a "high-tech" industry using guidelines from a primary sector industry: a case study in the food industry supply chain.

PubMed

Coronado Mondragon, Adrian E; Coronado Mondragon, Christian E; Coronado, Etienne S

2015-01-01

Flexibility and innovation at creating shapes, adapting processes, and modifying materials characterize composites materials, a "high-tech" industry. However, the absence of standard manufacturing processes and the selection of materials with defined properties hinder the configuration of the composites materials supply chain. An interesting alternative for a "high-tech" industry such as composite materials would be to review supply chain lessons and practices in "low-tech" industries such as food. The main motivation of this study is to identify lessons and practices that comprise innovations in the supply chain of a firm in a perceived "low-tech" industry that can be used to provide guidelines in the design of the supply chain of a "high-tech" industry, in this case composite materials. This work uses the case study/site visit with analogy methodology to collect data from a Spanish leading producer of fresh fruit juice which is sold in major European markets and makes use of a cold chain. The study highlights supply base management and visibility/traceability as two elements of the supply chain in a "low-tech" industry that can provide guidelines that can be used in the configuration of the supply chain of the composite materials industry.

Molecular structure of starches from maize mutants deficient in starch synthase III.

PubMed

Zhu, Fan; Bertoft, Eric; Källman, Anna; Myers, Alan M; Seetharaman, Koushik

2013-10-16

Molecular structures of starches from dull1 maize mutants deficient in starch synthase III (SSIII) with a common genetic background (W64A) were characterized and compared with the wild type. Amylose content with altered structure was higher in the nonwaxy mutants (25.4-30.2%) compared to the wild type maize (21.5%) as revealed by gel permeation chromatography. Superlong chains of the amylopectin component were found in all nonwaxy samples. Unit chain length distribution of amylopectins and their φ,β-limit dextrins (reflecting amylopectin internal structure) from dull1 mutants were also characterized by anion-exchange chromatography after debranching. Deficiency of SSIII led to an increased amount of short chains (DP ≤36 in amylopectin), whereas the content of long chains decreased from 8.4% to between 3.1 and 3.7% in both amylopectin and φ,β-limit dextrins. Moreover, both the external and internal chain lengths decreased, suggesting a difference in their cluster structures. Whereas the molar ratio of A:B-chains was similar in all samples (1.1-1.2), some ratios of chain categories were affected by the absence of SSIII, notably the ratio of "fingerprint" A-chains to "clustered" A-chains. This study highlighted the relationship between SSIII and the internal molecular structure of maize starch.

Mapping the ecosystem service delivery chain: Capacity, flow, and demand pertaining to aesthetic experiences in mountain landscapes.

PubMed

Egarter Vigl, Lukas; Depellegrin, Daniel; Pereira, Paulo; de Groot, Rudolf; Tappeiner, Ulrike

2017-01-01

Accounting for the spatial connectivity between the provision of ecosystem services (ES) and their beneficiaries (supply-benefit chain) is fundamental to understanding ecosystem functioning and its management. However, the interrelationships of the specific chain links within ecosystems and the actual benefits that flow from natural landscapes to surrounding land have rarely been analyzed. We present a spatially explicit model for the analysis of one cultural ecosystem service (aesthetic experience), which integrates the complete ecosystem service delivery chain for Puez-Geisler Nature Park (Italy): (1) The potential service stock (ES capacity) relies on an expert-based land use ranking matrix, (2) the actual supply (ES flow) is based on visibility properties of observation points along recreational routes, (3) the beneficiaries of the service (ES demand) are derived from socioeconomic data as a measure of the visitation rate to the recreation location, and (4) the supply-demand relationship (ES budget) addresses the spatially explicit oversupply and undersupply of ES. The results indicate that potential ES stocks are substantially higher in core and buffer zones of protected areas than in surrounding land owing to the specific landscape composition. ES flow maps reveal service delivery to 80% of the total area studied, with the highest actual service supply to locations with long and open vistas. ES beneficiary analyses show the highest demand for aesthetic experiences in all-season tourist destinations like Val Badia and Val Gardena, where both recreational amenity and overnight stays are equally high. ES budget maps identify ES hot and cold spots in terms of ES delivery, and they highlight ES undersupply in nature protection buffer zones although they are characterized by highest ES capacity. We show how decision/policy makers can use the presented methodology to plan landscape protection measures and develop specific regulation strategies for visitors based on the ES delivery chain concept. Copyright © 2016 Elsevier B.V. All rights reserved.

Copolymer Synthesis and Characterization by Post-Polymerization Modification

NASA Astrophysics Data System (ADS)

Galvin, Casey James

This PhD thesis examines the physical behavior of surface-grafted polymer assemblies (SGPAs) derived from post-polymerization modification (PPM) reactions in aqueous and vapor enriched environments, and offers an alternative method of creating SGPAs using a PPM approach. SGPAs comprise typically polymer chains grafted covalently to solid substrates. These assemblies show promise in a number of applications and technologies due to the stability imparted by the covalent graft and ability to modify interfacial properties and stability. SGPAs also offer a set of rich physics to explore in fundamental investigations as a result of confining macromolecules to a solid substrate. PPM reactions (also called polymer analogous reactions) apply small molecule organic chemistry reactions to the repeat units of polymer chains in order to generate new chemistries. By applying a PPM strategy to SGPAs, a wide variety of functional groups can be introduced into a small number of well-studied and well-behaved model polymer systems. This approach offers the advantage of holding constant other properties of the SGPA (e.g., molecular weight, MW, and grafting density, sigma) to isolate the effect of chemistry on physical behavior. Using a combination of PPM and fabrication methods that facilitate the formation of SPGAs with position-dependent gradual variation of sigma on flat impenetrable substrate, the influence of polymer chemistry and sigma is examined on the stability of weak polyelectrolyte brushes in aqueous environments at different pH levels. Degrafting of polymer chains in SGPAs exhibits a complex dependence on side chain chemistry, sigma, pH and the charge fraction (alpha) within the brush. Results of these experiments support a proposed mechanism of degrafting, wherein extension of the grafted chains away from the substrate generates tension along the polymer backbone, which activates the grafting chemistry for hydrolysis. The implications of these findings are important in developing technologies that use SGPAs in aqueous environments, and point to a need for potential alternative grafting chemistries. The behavior of SGPAs in vapor environments remains an underexplored phenomenon. By changing systematically the chemistry of SGPAs derived from a parent sample, the influence of side chain functional groups on the swelling of weak and strong polyelectrolyte brushes in the presence of water, methanol and ethanol vapors is explored. The extent of swelling and solvent uptake depends strongly on the chemistry in the polymer side chain and of the solvent. Despite bearing a permanent electrostatic charge in the side chain, the strong polyelectrolyte brushes exhibit no behavior typical of polyelectrolytes in water due to no dissociation of the counterion. Of particular interest is the behavior in humid environments of an SGPA bearing a zwitterionic group in its side chain, which results in exposure of electrostatic charges without counterions. Using substrates bearing the aforementioned sigma gradient of polymeric grafts, evidence of inter- and intramolecular complex formation is presented. Finally, a method of developing SGPAs by polymerizing bulk polymer chains through surface-grafted monomers (SGMs) is described. The SGMs are incorporated onto a solid substrate using the same PPM reaction employed in the degrafting and vapor swelling experiments, highlighting the versatility of PPM. The thickness of these SGPAs is correlated to the bulk polymer chains MW, suggesting this technique can be used in existing industrial bulk polymerization processes.

Perfluoroalkyl acids: recent research highlights

EPA Science Inventory

Perfluorinated compounds are organic chemicals in which all hydrogen molecules of the carbon-chain are substituted by fluorine molecules. Generally, there are two types of perfluorinated compounds, the perfluoroalkanes that are primarily used clinically for oxygenation and respir...

Production, Purification and Characterisation of a Potential Fibrinolytic Protease from Endophytic Xylaria curta by Solid Substrate Fermentation.

PubMed

Meshram, Vineet; Saxena, Sanjai; Paul, Karan; Gupta, Mahiti; Kapoor, Neha

2017-04-01

The present investigation highlights the optimal conditions for production of a non-toxic, bi-functional fibrinolytic enzyme xylarinase produced by endophytic fungus Xylaria curta by solid substrate fermentation using rice chaff medium. The purified enzyme is a monomeric protein with a molecular mass of ∼33 kDa. The enzyme exhibits cleavage of Aα and Bβ chains of fibrin(ogen) and has no effect on γ chain. The optimal fibrinolytic activity of the enzyme was observed at 35 °C and pH 8. The fibrinolytic activity was enhanced in the presence of Ca 2+ , whereas it was completely inhibited in the presence of Fe 2+ and Zn 2+ ions and inhibitors like EDTA and EGTA suggesting it to be a metalloprotease. The K m and V max of the enzyme for azocasein were 326 μM and 0.13 μM min -1 . The N-terminal sequence of the enzyme (SNGPLPGGVVWAG) was same when compared to xylarinase isolated from culture broth of X. curta. Thus, xylarinase could be exploited as a potent clot busting enzyme which could be produced on large scale using solid substrate fermentation.

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

Mass spectrometry techniques for studying the ubiquitin system.

PubMed

Heap, Rachel E; Gant, Megan S; Lamoliatte, Frederic; Peltier, Julien; Trost, Matthias

2017-10-15

Post-translational control of proteins through covalent attachment of ubiquitin plays important roles in all eukaryotic cell functions. The ubiquitin system in humans consists of 2 E1, 35 E2 and >600 E3 ubiquitin ligases as well as hundreds of deubiquitylases, which reverse ubiquitin attachment. Moreover, there are hundreds of proteins with ubiquitin-binding domains that bind one of the eight possible polyubiquitin chains. Dysfunction of the ubiquitin system is associated with many diseases such as cancer, autoimmunity and neurodegeneration, demonstrating the importance of ubiquitylation. Therefore, enzymes of the ubiquitin system are considered highly attractive drug targets. In recent years, mass spectrometry (MS)-based techniques have become increasingly important in the deciphering of the ubiquitin system. This short review addresses the state-of-the-art MS techniques for the identification of ubiquitylated proteins and their ubiquitylation sites. We also discuss the identification and quantitation of ubiquitin chain topologies and highlight how the activity of enzymes in the ubiquitin pathway can be measured. Finally, we present current MS tools that can be used for drug discovery in the ubiquitin space. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Network structure and concentration fluctuations in a series of elemental, binary, and tertiary liquids and glasses.

PubMed

Soper, Alan K

2010-10-13

Liquids and glasses continue to produce a lively debate about the nature of the disordered structure in these materials, and whether it is driven by longer range concentration or density fluctuations. One factor often lacking in these studies is an overview of a wide range of structures from which common features of and differences between materials can be identified. Here I examine the structure of a wide range of chain and network, elemental, binary and tertiary liquids and glasses, using available x-ray and neutron diffraction data and combining them with empirical potential structure refinement. Calculation of the Bhatia-Thornton number-number and concentration-concentration structure factors and distribution functions highlights common structural motifs that run through many of the series. It is found that the greatest structural overlap occurs where the nearest-neighbour and second-neighbour coordination numbers are similar for different materials. As these coordination numbers increase, so the structures undergo a sequence of characteristic changes involving increasingly bent bond angle distributions and increased packing fractions. In these regards liquid and amorphous phosphorus appear to be in a structural class of their own, combining both chain-like and network-like characteristics.

Synthesis and characterization of ester and amide derivatives of titanium(IV) carboxymethylphosphonate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melánová, Klára, E-mail: klara.melanova@upce.cz; Beneš, Ludvík; Trchová, Miroslava

2013-06-15

A set of layered ester and amide derivatives of titanium(IV) carboxymethylphosphonate was prepared by solvothermal treatment of amorphous titanium(IV) carboxymethylphosphonate with corresponding 1-alkanols, 1,ω-alkanediols, 1-aminoalkanes, 1,ω-diaminoalkanes and 1,ω-amino alcohols and characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetric analysis. Whereas alkyl chains with one functional group form bilayers tilted to the layers, 1,ω-diaminoalkanes and most of 1,ω-alkanediols form bridges connecting the adjacent layers. In the case of amino alcohols, the alkyl chains form bilayer and either hydroxyl or amino group is used for bonding. This simple method for the synthesis of ester and amide derivatives does not require preparationmore » of acid chloride derivative as a precursor or pre-intercalation with alkylamines and can be used also for the preparation of ester and amide derivatives of titanium carboxyethylphosphonate and zirconium carboxymethylphosphonate. - Graphical abstract: Ester and amide derivatives of layered titanium carboxymethylphosphonate were prepared by solvothermal treatment of amorphous solid with alkanol or alkylamine. - Highlights: • Ester and amide derivatives of titanium carboxymethylphosphonate. • Solvothermal treatment of amorphous solid with alkanol or alkylamine. • Ester and amide formation confirmed by IR spectroscopy.« less

Kinetic chain contributions to elbow function and dysfunction in sports.

PubMed

Ben Kibler, W; Sciascia, Aaron

2004-10-01

The elbow functions in throwing and other athletic activities as a link in the kinetic chain of force development, regulation, and transfer. Efficient function, with maximal performance and minimal injury risk, requires optimum activation of all the link in the kinetic chain. Injury is often associated with alterations in force production or regulation capabilities in links that may be distant to the site of injury. Evaluation of injured athletes should include screening examinations for these areas, and treatment and conditioning should also include these areas.

Retinoic acid signaling pathways in development and diseases.

PubMed

Das, Bhaskar C; Thapa, Pritam; Karki, Radha; Das, Sasmita; Mahapatra, Sweta; Liu, Ting-Chun; Torregroza, Ingrid; Wallace, Darren P; Kambhampati, Suman; Van Veldhuizen, Peter; Verma, Amit; Ray, Swapan K; Evans, Todd

2014-01-15

Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon Nanotubes.

PubMed

Hart, Martin; White, Edward R; Chen, Ji; McGilvery, Catriona M; Pickard, Chris J; Michaelides, Angelos; Sella, Andrea; Shaffer, Milo S P; Salzmann, Christoph G

2017-07-03

Elemental phosphorus displays an impressive number of allotropes with highly diverse chemical and physical properties. White phosphorus has now been filled into single-wall carbon nanotubes (SWCNTs) from the liquid and thereby stabilized against the highly exothermic reaction with atmospheric oxygen. The encapsulated tetraphosphorus molecules were visualized with transmission electron microscopy, but found to convert readily into chain structures inside the SWCNT "nanoreactors". The energies of the possible chain structures were determined computationally, highlighting a delicate balance between the extent of polymerization and the SWCNT diameter. Experimentally, a single-stranded zig-zag chain of phosphorus atoms was observed, which is the lowest energy structure at small confinement diameters. These one-dimensional chains provide a glimpse into the very first steps of the transformation from white to red phosphorus. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

PubMed

Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

2016-01-01

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

PubMed

Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

2016-04-01

As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

Integrating evolutionary and functional tests of adaptive hypotheses: a case study of altitudinal differentiation in hemoglobin function in an Andean Sparrow, Zonotrichia capensis.

PubMed

Cheviron, Zachary A; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Eddy, Douglas K; Jones, Jennifer; Carling, Matthew D; Witt, Christopher C; Moriyama, Hideaki; Weber, Roy E; Fago, Angela; Storz, Jay F

2014-11-01

In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the α(A)-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the α(D)-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative α(A)-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins.

PubMed

Feige, Matthias J; Gräwert, Melissa A; Marcinowski, Moritz; Hennig, Janosch; Behnke, Julia; Ausländer, David; Herold, Eva M; Peschek, Jirka; Castro, Caitlin D; Flajnik, Martin; Hendershot, Linda M; Sattler, Michael; Groll, Michael; Buchner, Johannes

2014-06-03

Sharks and other cartilaginous fish are the phylogenetically oldest living organisms that rely on antibodies as part of their adaptive immune system. They produce the immunoglobulin new antigen receptor (IgNAR), a homodimeric heavy chain-only antibody, as a major part of their humoral adaptive immune response. Here, we report the atomic resolution structure of the IgNAR constant domains and a structural model of this heavy chain-only antibody. We find that despite low sequence conservation, the basic Ig fold of modern antibodies is already present in the evolutionary ancient shark IgNAR domains, highlighting key structural determinants of the ubiquitous Ig fold. In contrast, structural differences between human and shark antibody domains explain the high stability of several IgNAR domains and allowed us to engineer human antibodies for increased stability and secretion efficiency. We identified two constant domains, C1 and C3, that act as dimerization modules within IgNAR. Together with the individual domain structures and small-angle X-ray scattering, this allowed us to develop a structural model of the complete IgNAR molecule. Its constant region exhibits an elongated shape with flexibility and a characteristic kink in the middle. Despite the lack of a canonical hinge region, the variable domains are spaced appropriately wide for binding to multiple antigens. Thus, the shark IgNAR domains already display the well-known Ig fold, but apart from that, this heavy chain-only antibody employs unique ways for dimerization and positioning of functional modules.

Cloning and expression of recombinant, functional ricin B chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, M.S.; Russell, D.W.; Uhr, J.W.

1987-08-01

The cDNA encoding the B chain of the plant toxin ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with (/sup 35/S)methionine and (/sup 35/S)-cysteine and demonstrating the secretion of a protein with a M/sub r/ of 30,000-32,000 that was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B-chain antibody and the amount of recombinant B chain secreted by the COS-M6 cells was determined by a radioimmunoassay. Virtually all of the recombinant B chain formed active ricinmore » when mixed with native A chain; it could also bind to the galactose-containing glycoprotein asialofetuin as effectively as native B chain.These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function« less

Mitochondria and α-Synuclein: Friends or Foes in the Pathogenesis of Parkinson's Disease?

PubMed

Faustini, Gaia; Bono, Federica; Valerio, Alessandra; Pizzi, Marina; Spano, PierFranco; Bellucci, Arianna

2017-12-08

Parkinson's disease (PD) is a movement disorder characterized by dopaminergic nigrostriatal neuron degeneration and the formation of Lewy bodies (LB), pathological inclusions containing fibrils that are mainly composed of α-synuclein. Dopaminergic neurons, for their intrinsic characteristics, have a high energy demand that relies on the efficiency of the mitochondria respiratory chain. Dysregulations of mitochondria, deriving from alterations of complex I protein or oxidative DNA damage, change the trafficking, size and morphology of these organelles. Of note, these mitochondrial bioenergetics defects have been related to PD. A series of experimental evidence supports that α-synuclein physiological action is relevant for mitochondrial homeostasis, while its pathological aggregation can negatively impinge on mitochondrial function. It thus appears that imbalances in the equilibrium between the reciprocal modulatory action of mitochondria and α-synuclein can contribute to PD onset by inducing neuronal impairment. This review will try to highlight the role of physiological and pathological α-synuclein in the modulation of mitochondrial functions.

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

PubMed Central

ElZarrad, M. Khair; Mukhopadhyay, Partha; Mohan, Nishant; Hao, Enkui; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Pacher, Pal; Wu, Wen Jin

2013-01-01

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. PMID:24255707

Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

PubMed Central

Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël; Lankar, Danielle; Piolot, Tristan; Adelstein, Robert S.; Zhang, Yingfan; Sixt, Michael; Jacobelli, Jordan; Bénichou, Olivier; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-Maria

2015-01-01

The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. PMID:26109323

Cohesiveness tunes assembly and morphology of FG nucleoporin domain meshworks – Implications for nuclear pore permeability

PubMed Central

Eisele, Nico B.; Labokha, Aksana A.; Frey, Steffen; Görlich, Dirk; Richter, Ralf P.

2013-01-01

Nuclear pore complexes control the exchange of macromolecules between the cytoplasm and the nucleus. A selective permeability barrier that arises from a supramolecular assembly of intrinsically unfolded nucleoporin domains rich in phenylalanine-glycine dipeptides (FG domains) fills the nuclear pore. There is increasing evidence that selective transport requires cohesive FG domain interactions. To understand the functional roles of cohesive interactions, we studied monolayers of end-grafted FG domains as a bottom-up nanoscale model system of the permeability barrier. Based on detailed physicochemical analysis of the model films and comparison of the data with polymer theory, we propose that cohesiveness is tuned to promote rapid assembly of the permeability barrier and to generate a stable and compact pore-filling meshwork with a small mesh size. Our results highlight the functional importance of weak interactions, typically a few kBT per chain, and contribute important information to understand the mechanism of size-selective transport. PMID:24138862

Lipid Cell Biology: A Focus on Lipids in Cell Division.

PubMed

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Differences in the Triacylglycerol and Fatty Acid Compositions of Human Colostrum and Mature Milk.

PubMed

Zhao, Pu; Zhang, Shuwen; Liu, Lu; Pang, Xiaoyang; Yang, Yang; Lu, Jing; Lv, Jiaping

2018-05-02

Human colostrum is important for immune system development and plays a protective role for infants. However, the comprehensive exploration of lipids, which account for 3-5% of milk, and their biological functions in human colostrum was limited. In present study, the triacylglycerol (TAG) and fatty acid (FA) compositions of human colostrum and mature milk were analyzed and compared. Variations were observed in both the TAG and FA compositions. The concentrations of 18:1/18:1/16:0 TAG, high-molecular-weight and unsaturated TAGs were significantly higher in colostrum, whereas mature milk contained more low/medium-molecular-weight TAGs and medium-chain FAs. Furthermore, there were also specific TAGs in both colostrum and mature milk. Our data highlighted targets for further investigation to elucidate the biological function of lipids in colostrum milk. In addition, the comprehensive analysis of TAGs in Chinese colostrum might help in designing infant formula for Chinese babies, especially the preterm ones.

Comprehensive metabolic characterization of serum osteocalcin action in a large non-diabetic sample.

PubMed

Entenmann, Lukas; Pietzner, Maik; Artati, Anna; Hannemann, Anke; Henning, Ann-Kristin; Kastenmüller, Gabi; Völzke, Henry; Nauck, Matthias; Adamski, Jerzy; Wallaschofski, Henri; Friedrich, Nele

2017-01-01

Recent research suggested a metabolic implication of osteocalcin (OCN) in e.g. insulin sensitivity or steroid production. We used an untargeted metabolomics approach by analyzing plasma and urine samples of 931 participants using mass spectrometry to reveal further metabolic actions of OCN. Several detected relations between OCN and metabolites were strongly linked to renal function, however, a number of associations remained significant after adjustment for renal function. Intermediates of proline catabolism were associated with OCN reflecting the implication in bone metabolism. The association to kynurenine points towards a pro-inflammatory state with increasing OCN. Inverse relations with intermediates of branch-chained amino acid metabolism suggest a link to energy metabolism. Finally, urinary surrogate markers of smoking highlight its adverse effect on OCN metabolism. In conclusion, the present study provides a read-out of metabolic actions of OCN. However, most of the associations were weak arguing for a limited role of OCN in whole-body metabolism.

Cognitive Development of Applying the Chain Rule through Three Worlds of Mathematics

ERIC Educational Resources Information Center

Kabael, Tangul Uygur

2010-01-01

The derivative of a composite function, taken with the chain rule is one of the important notions in calculus. This paper describes a study conducted in Turkey that shows that the chain rule was given with the formula in function notation and/or the Leibniz notation without relating these formulas to life-related problem situations in the…

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics

NASA Astrophysics Data System (ADS)

Mansbach, Rachael A.; Ferguson, Andrew L.

2015-03-01

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics.

PubMed

Mansbach, Rachael A; Ferguson, Andrew L

2015-03-14

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Phase transitions, optical and electronic properties of the layered perovskite hybrid [NH3(CH2)2COOH ]2CdCl4 of Y-aminobutyric acid (GABA)

NASA Astrophysics Data System (ADS)

AlShammari, Mohammed B.; Kaiba, A.; Guionneau, P.; Geesi, Mohammed H.; Aljohani, Talal; Riadi, Yassine

2018-06-01

A new organic-inorganic hybrid with the formula (NH3C3H6CO2H)2CdCl4 has been crystallized and investigated by X-ray diffraction. Structural investigations highlight a first-order reversible structural phase transition occurring within the range (290-370 K) between a chiral (phase II) and non-centrosymmetric (Phase I) crystal packing. This strong structural reorganization is the result of conformational changes in the organic chains accompanied by a decrease in octahedral distortion. The accurate crystallographic analysis illustrates the crucial role of organic moieties. The experimental energy gap value (3.65 eV) is in good agreement with the theoretical value obtained by density functional theory.

Multiplex Ligation-Dependent Probe Amplification Analysis on Capillary Electrophoresis Instruments for a Rapid Gene Copy Number Study

PubMed Central

Jankowski, Stéphane; Currie-Fraser, Erica; Xu, Licen; Coffa, Jordy

2008-01-01

Annotated DNA samples that had been previously analyzed were tested using multiplex ligation-dependent probe amplification (MLPA) assays containing probes targeting BRCA1, BRCA2, and MMR (MLH1/MSH2 genes) and the 9p21 chromosomal region. MLPA polymerase chain reaction products were separated on a capillary electrophoresis platform, and the data were analyzed using GeneMapper v4.0 software (Applied Biosystems, Foster City, CA). After signal normalization, loci regions that had undergone deletions or duplications were identified using the GeneMapper Report Manager and verified using the DyeScale functionality. The results highlight an easy-to-use, optimal sample preparation and analysis workflow that can be used for both small- and large-scale studies. PMID:19137113

A review on chitosan centred scaffolds and their applications in tissue engineering.

PubMed

Ahmed, Shakeel; Annu; Sheikh, Javed; Ali, Akbar

2018-05-03

The diversity and availability of biopolymer and increased clinical demand for safe scaffolds lead to an increased interest in fabricating scaffolds in order to achieve fruitful progress in tissue engineering. Due to biocompatibility, biodegradability, inherent antimicrobial character, chitosan has drawn ample consideration in recent years. Chitosan is a biopolymer obtained by de-acetylation of chitin extracted from shells of crustaceans and fungi. Due to the presence of reactive functionality in the molecular chain chitosan can be modified either chemically or physically to fabricate the tailor-made scaffolds having desired properties for tissue engineering centered applications. In this review chitosan, its properties and role either virgin, chemically or physically modified, 2D or 3D scaffolds for tissue engineering application have been highlighted. Copyright © 2017. Published by Elsevier B.V.

Atomistic simulations of aromatic polyurea and polyamide for capacitive energy storage

NASA Astrophysics Data System (ADS)

Dong, Rui; Ranjan, V.; Buongiorno Nardelli, Marco; Bernholc, J.

2015-07-01

Materials for capacitive energy storage with high energy density and low loss are desired in many fields. We investigate several polymers with urea and amide functional groups using density functional theory and classical molecular dynamics simulations. For aromatic polyurea (APU) and para-aramid (PA), we find several nearly energetically degenerate ordered structures, while meta-aromatic polyurea (mAPU) tends to be rotationally disordered along the polymer chains. Simulated annealing of APU and PA structures results in the formation of hydrogen-bonded sheets, highlighting the importance of dipole-dipole interactions. In contrast, hydrogen bonding does not play a significant role in mAPU, hence the propensity to disorder. We find that the disordered structures with misaligned chains have significantly larger dielectric constants, due to significant increase in the free volume, which leads to easier reorientation of dipolar groups in the presence of an electric field. Large segment motion is still not allowed below the glass transition temperature, which explains the experimentally observed very low loss at high field and elevated temperature. However, the degree of disorder needs to be controlled, because highly entangled structures diminish the free dipoles and decrease permittivity. Among the considered materials, mAPU is the most promising dielectric for capacitive energy storage, but the concept of increasing permittivity while maintaining low loss through disorder-induced free volume increase is generally applicable and provides an alternative pathway for the design of high-performance dielectrics for capacitive energy storage.

A transcriptional serenAID: the role of noncoding RNAs in class switch recombination

PubMed Central

Yewdell, William T.; Chaudhuri, Jayanta

2017-01-01

Abstract During an immune response, activated B cells may undergo class switch recombination (CSR), a molecular rearrangement that allows B cells to switch from expressing IgM and IgD to a secondary antibody heavy chain isotype such as IgG, IgA or IgE. Secondary antibody isotypes provide the adaptive immune system with distinct effector functions to optimally combat various pathogens. CSR occurs between repetitive DNA elements within the immunoglobulin heavy chain (Igh) locus, termed switch (S) regions and requires the DNA-modifying enzyme activation-induced cytidine deaminase (AID). AID-mediated DNA deamination within S regions initiates the formation of DNA double-strand breaks, which serve as biochemical beacons for downstream DNA repair pathways that coordinate the ligation of DNA breaks. Myriad factors contribute to optimal AID targeting; however, many of these factors also localize to genomic regions outside of the Igh locus. Thus, a current challenge is to explain the specific targeting of AID to the Igh locus. Recent studies have implicated noncoding RNAs in CSR, suggesting a provocative mechanism that incorporates Igh-specific factors to enable precise AID targeting. Here, we chronologically recount the rich history of noncoding RNAs functioning in CSR to provide a comprehensive context for recent and future discoveries. We present a model for the RNA-guided targeting of AID that attempts to integrate historical and recent findings, and highlight potential caveats. Lastly, we discuss testable hypotheses ripe for current experimentation, and explore promising ideas for future investigations. PMID:28535205

Linear and nonlinear dynamics of isospectral granular chains

NASA Astrophysics Data System (ADS)

Chaunsali, R.; Xu, H.; Yang, J.; Kevrekidis, P. G.

2017-04-01

We study the dynamics of isospectral granular chains that are highly tunable due to the nonlinear Hertz contact law interaction between the granular particles. The system dynamics can thus be tuned easily from being linear to strongly nonlinear by adjusting the initial compression applied to the chain. In particular, we introduce both discrete and continuous spectral transformation schemes to generate a family of granular chains that are isospectral in their linear limit. Inspired by the principle of supersymmetry in quantum systems, we also introduce a methodology to add or remove certain eigenfrequencies, and we demonstrate numerically that the corresponding physical system can be constructed in the setting of one-dimensional granular crystals. In the linear regime, we highlight the similarities in the elastic wave transmission characteristics of such isospectral systems, and emphasize that the presented mathematical framework allows one to suitably tailor the wave transmission through a general class of granular chains, both ordered and disordered. Moreover, we show how the dynamic response of these structures deviates from its linear limit as we introduce Hertzian nonlinearity in the chain and how nonlinearity breaks the notion of linear isospectrality.

Electron transport chains in organohalide-respiring bacteria and bioremediation implications.

PubMed

Wang, Shanquan; Qiu, Lan; Liu, Xiaowei; Xu, Guofang; Siegert, Michael; Lu, Qihong; Juneau, Philippe; Yu, Ling; Liang, Dawei; He, Zhili; Qiu, Rongliang

In situ remediation employing organohalide-respiring bacteria represents a promising solution for cleanup of persistent organohalide pollutants. The organohalide-respiring bacteria conserve energy by utilizing H 2 or organic compounds as electron donors and organohalides as electron acceptors. Reductive dehalogenase (RDase), a terminal reductase of the electron transport chain in organohalide-respiring bacteria, is the key enzyme that catalyzes halogen removal. Accumulating experimental evidence thus far suggests that there are distinct models for respiratory electron transfer in organohalide-respirers of different lineages, e.g., Dehalococcoides, Dehalobacter, Desulfitobacterium and Sulfurospirillum. In this review, to connect the knowledge in organohalide-respiratory electron transport chains to bioremediation applications, we first comprehensively review molecular components and their organization, together with energetics of the organohalide-respiratory electron transport chains, as well as recent elucidation of intramolecular electron shuttling and halogen elimination mechanisms of RDases. We then highlight the implications of organohalide-respiratory electron transport chains in stimulated bioremediation. In addition, major challenges and further developments toward understanding the organohalide-respiratory electron transport chains and their bioremediation applications are identified and discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Exploring Alkyl Chains in Benzobisthiazole-Naphthobisthiadiazole Polymers: Impact on Solar-Cell Performance, Crystalline Structures, and Optoelectronics.

PubMed

Al-Naamani, Eman; Gopal, Anesh; Ide, Marina; Osaka, Itaru; Saeki, Akinori

2017-11-01

The shapes and lengths of the alkyl chains of conjugated polymers greatly affect the efficiencies of organic photovoltaic devices. This often results in a trade-off between solubility and self-organizing behavior; however, each material has specific optimal chains. Here we report on the effect of alkyl side chains on the film morphologies, crystallinities, and optoelectronic properties of new benzobisthiazole-naphthobisthiadiazole (PBBT-NTz) polymers. The power conversion efficiencies (PCEs) of linear-branched and all-branched polymers range from 2.5% to 6.6%; the variations in these PCEs are investigated by atomic force microscopy, two-dimensional X-ray diffraction (2D-GIXRD), and transient photoconductivity techniques. The best-performing linear-branched polymer, bearing dodecyl and decyltetradecyl chains (C12-DT), exhibits nanometer-scale fibers along with the highest crystallinity, comprising predominant edge-on and partial face-on orientations. This morphology leads to the highest photoconductivity and the longest carrier lifetime. These results highlight the importance of long alkyl chains for inducing intermolecular stacking, which is in contrast to observations made for analogous previously reported polymers.

CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy.

PubMed

Mosqueira, Diogo; Mannhardt, Ingra; Bhagwan, Jamie R; Lis-Slimak, Katarzyna; Katili, Puspita; Scott, Elizabeth; Hassan, Mustafa; Prondzynski, Maksymilian; Harmer, Stephen C; Tinker, Andrew; Smith, James G W; Carrier, Lucie; Williams, Philip M; Gaffney, Daniel; Eschenhagen, Thomas; Hansen, Arne; Denning, Chris

2018-05-08

Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated to hPSC-CMs for high-throughput, non-subjective molecular and functional assessment using 12 approaches in 2D monolayers and/or 3D engineered heart tissues. Although immature, edited hPSC-CMs exhibited the main hallmarks of HCM (hypertrophy, multi-nucleation, hypertrophic marker expression, sarcomeric disarray). Functional evaluation supported the energy depletion model due to higher metabolic respiration activity, accompanied by abnormalities in calcium handling, arrhythmias, and contraction force. Partial phenotypic rescue was achieved with ranolazine but not omecamtiv mecarbil, while RNAseq highlighted potentially novel molecular targets. Our holistic and comprehensive approach showed that energy depletion affected core cardiomyocyte functionality. The engineered R453C-βMHC-mutation triggered compensatory responses in hPSC-CMs, causing increased ATP production and αMHC to energy-efficient βMHC switching. We showed that pharmacological rescue of arrhythmias was possible, while MHY7: MYH6 and mutant: wild-type MYH7 ratios may be diagnostic, and previously undescribed lncRNAs and gene modifiers are suggestive of new mechanisms.

Higher-order automatic differentiation of mathematical functions

NASA Astrophysics Data System (ADS)

Charpentier, Isabelle; Dal Cappello, Claude

2015-04-01

Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

Model systems for single molecule polymer dynamics

PubMed Central

Latinwo, Folarin

2012-01-01

Double stranded DNA (dsDNA) has long served as a model system for single molecule polymer dynamics. However, dsDNA is a semiflexible polymer, and the structural rigidity of the DNA double helix gives rise to local molecular properties and chain dynamics that differ from flexible chains, including synthetic organic polymers. Recently, we developed single stranded DNA (ssDNA) as a new model system for single molecule studies of flexible polymer chains. In this work, we discuss model polymer systems in the context of “ideal” and “real” chain behavior considering thermal blobs, tension blobs, hydrodynamic drag and force–extension relations. In addition, we present monomer aspect ratio as a key parameter describing chain conformation and dynamics, and we derive dynamical scaling relations in terms of this molecular-level parameter. We show that asymmetric Kuhn segments can suppress monomer–monomer interactions, thereby altering global chain dynamics. Finally, we discuss ssDNA in the context of a new model system for single molecule polymer dynamics. Overall, we anticipate that future single polymer studies of flexible chains will reveal new insight into the dynamic behavior of “real” polymers, which will highlight the importance of molecular individualism and the prevalence of non-linear phenomena. PMID:22956980

Perceptual and Neural Olfactory Similarity in Honeybees

PubMed Central

Sandoz, Jean-Christophe

2005-01-01

The question of whether or not neural activity patterns recorded in the olfactory centres of the brain correspond to olfactory perceptual measures remains unanswered. To address this question, we studied olfaction in honeybees Apis mellifera using the olfactory conditioning of the proboscis extension response. We conditioned bees to odours and tested generalisation responses to different odours. Sixteen odours were used, which varied both in their functional group (primary and secondary alcohols, aldehydes and ketones) and in their carbon-chain length (from six to nine carbons).The results obtained by presentation of a total of 16 × 16 odour pairs show that (i) all odorants presented could be learned, although acquisition was lower for short-chain ketones; (ii) generalisation varied depending both on the functional group and the carbon-chain length of odours trained; higher generalisation was found between long-chain than between short-chain molecules and between groups such as primary and secondary alcohols; (iii) for some odour pairs, cross-generalisation between odorants was asymmetric; (iv) a putative olfactory space could be defined for the honeybee with functional group and carbon-chain length as inner dimensions; (v) perceptual distances in such a space correlate well with physiological distances determined from optophysiological recordings of antennal lobe activity. We conclude that functional group and carbon-chain length are inner dimensions of the honeybee olfactory space and that neural activity in the antennal lobe reflects the perceptual quality of odours. PMID:15736975

Improved packing of protein side chains with parallel ant colonies.

PubMed

Quan, Lijun; Lü, Qiang; Li, Haiou; Xia, Xiaoyan; Wu, Hongjie

2014-01-01

The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms.

Sampling rare fluctuations of discrete-time Markov chains

NASA Astrophysics Data System (ADS)

Whitelam, Stephen

2018-03-01

We describe a simple method that can be used to sample the rare fluctuations of discrete-time Markov chains. We focus on the case of Markov chains with well-defined steady-state measures, and derive expressions for the large-deviation rate functions (and upper bounds on such functions) for dynamical quantities extensive in the length of the Markov chain. We illustrate the method using a series of simple examples, and use it to study the fluctuations of a lattice-based model of active matter that can undergo motility-induced phase separation.

Sampling rare fluctuations of discrete-time Markov chains.

PubMed

Whitelam, Stephen

2018-03-01

We describe a simple method that can be used to sample the rare fluctuations of discrete-time Markov chains. We focus on the case of Markov chains with well-defined steady-state measures, and derive expressions for the large-deviation rate functions (and upper bounds on such functions) for dynamical quantities extensive in the length of the Markov chain. We illustrate the method using a series of simple examples, and use it to study the fluctuations of a lattice-based model of active matter that can undergo motility-induced phase separation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com; Choudhury, Mahua; Janssen, Rachel C.

Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known aboutmore » its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.« less

Structure and dynamics of water inside endohedrally functionalized carbon nanotubes.

PubMed

Paul, Sanjib; Abi, T G; Taraphder, Srabani

2014-05-14

We have carried out classical molecular dynamics simulations on the formation of extended water chains inside single-walled carbon nanotubes (SWCNTs) in water in the presence of selected functional groups covalently attached to the inner wall of the tube. Analogues of polar amino acid sidechains have been chosen to carry out the endohedral functionalization of SWCNTs. Our results show a spontaneous and asymmetric filling of the nanotube with dynamical water chains in all the cases studied. The presence of Asp- and Glu-like sidechains is found to result in the formation of well-ordered water chains across the tube having the maximum number of water molecules being retained within the core with the largest residence times. The presence of methyl or methylene groups along the suspended chain is observed to disrupt the formation of water chains with higher length and/or longer residence times. The importance of hydrogen bonding in forming these water chains is assessed in terms of the relaxations of different hydrogen bond correlation functions. For a given dimension of the hydrophobic nanopore, we thus obtain a scale comparing the ability of carboxylic, alcohol, and imidazole groups in controlling the structure and dynamics of water in it. Our results also suggest that SWCNTs of varying lengths, endohedrally functionalized with Asp- and Glu-like sidechains, may be used as design templates in CNT-based water storage devices.

Solution Hybrid Selection Capture for the Recovery of Functional Full-Length Eukaryotic cDNAs From Complex Environmental Samples

PubMed Central

Bragalini, Claudia; Ribière, Céline; Parisot, Nicolas; Vallon, Laurent; Prudent, Elsa; Peyretaillade, Eric; Girlanda, Mariangela; Peyret, Pierre; Marmeisse, Roland; Luis, Patricia

2014-01-01

Eukaryotic microbial communities play key functional roles in soil biology and potentially represent a rich source of natural products including biocatalysts. Culture-independent molecular methods are powerful tools to isolate functional genes from uncultured microorganisms. However, none of the methods used in environmental genomics allow for a rapid isolation of numerous functional genes from eukaryotic microbial communities. We developed an original adaptation of the solution hybrid selection (SHS) for an efficient recovery of functional complementary DNAs (cDNAs) synthesized from soil-extracted polyadenylated mRNAs. This protocol was tested on the Glycoside Hydrolase 11 gene family encoding endo-xylanases for which we designed 35 explorative 31-mers capture probes. SHS was implemented on four soil eukaryotic cDNA pools. After two successive rounds of capture, >90% of the resulting cDNAs were GH11 sequences, of which 70% (38 among 53 sequenced genes) were full length. Between 1.5 and 25% of the cloned captured sequences were expressed in Saccharomyces cerevisiae. Sequencing of polymerase chain reaction-amplified GH11 gene fragments from the captured sequences highlighted hundreds of phylogenetically diverse sequences that were not yet described, in public databases. This protocol offers the possibility of performing exhaustive exploration of eukaryotic gene families within microbial communities thriving in any type of environment. PMID:25281543

Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

PubMed Central

Liu, Li; Goldberg, Ira J.

2015-01-01

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

DOE PAGES

Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; ...

1990-01-01

Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .t has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

Ferritin light-chain subunits: key elements for the electron transfer across the protein cage.

PubMed

Carmona, Unai; Li, Le; Zhang, Lianbing; Knez, Mato

2014-12-18

The first specific functionality of the light-chain (L-chain) subunit of the universal iron storage protein ferritin was identified. The electrons released during iron-oxidation were transported across the ferritin cage specifically through the L-chains and the inverted electron transport through the L-chains also accelerated the demineralization of ferritin.

Understanding Transferable Supply Chain Lessons and Practices to a “High-Tech” Industry Using Guidelines from a Primary Sector Industry: A Case Study in the Food Industry Supply Chain

PubMed Central

Coronado Mondragon, Adrian E.; Coronado, Etienne S.

2015-01-01

Flexibility and innovation at creating shapes, adapting processes, and modifying materials characterize composites materials, a “high-tech” industry. However, the absence of standard manufacturing processes and the selection of materials with defined properties hinder the configuration of the composites materials supply chain. An interesting alternative for a “high-tech” industry such as composite materials would be to review supply chain lessons and practices in “low-tech” industries such as food. The main motivation of this study is to identify lessons and practices that comprise innovations in the supply chain of a firm in a perceived “low-tech” industry that can be used to provide guidelines in the design of the supply chain of a “high-tech” industry, in this case composite materials. This work uses the case study/site visit with analogy methodology to collect data from a Spanish leading producer of fresh fruit juice which is sold in major European markets and makes use of a cold chain. The study highlights supply base management and visibility/traceability as two elements of the supply chain in a “low-tech” industry that can provide guidelines that can be used in the configuration of the supply chain of the composite materials industry. PMID:25821848

Modeling traceability information and functionality requirement in export-oriented tilapia chain.

PubMed

Zhang, Xiaoshuan; Feng, Jianying; Xu, Mark; Hu, Jinyou

2011-05-01

Tilapia has been named as the 'food fish of the 21st century' and has become the most important farmed fish. China is the world leader in tilapia production and export. Identifying information and functional requirements is critical in developing an efficient traceability system because traceability has become a fundamental prerequisite for exporting aquaculture products. This paper examines the export-oriented tilapia chains and information flow in the chains, and identifies the key actors, information requirements and information-capturing points. Unified Modeling Language (UML) technology is adopted to describe the information and functionality requirement for chain traceability. The barriers of traceability system adoption are also identified. The results show that the traceability data consist of four categories that must be recorded by each link in the chain. The functionality requirement is classified into four categories from the fundamental information record to decisive quality control; the top three barriers to the traceability system adoption are: high costs of implementing the system, lack of experienced and professional staff; and low level of government involvement and support. Copyright © 2011 Society of Chemical Industry.

Characterization of beta-turn and Asx-turns mimicry in a model peptide: stabilization via C--H . . . O interaction.

PubMed

Thakur, A K; Kishore, R

2006-04-15

The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins. Copyright 2006 Wiley Periodicals, Inc.

Overcoming double-step CO2 adsorption and minimizing water co-adsorption in bulky diamine-appended variants of Mg2(dobpdc).

PubMed

Milner, Phillip J; Martell, Jeffrey D; Siegelman, Rebecca L; Gygi, David; Weston, Simon C; Long, Jeffrey R

2018-01-07

Alkyldiamine-functionalized variants of the metal-organic framework Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary , secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behavior likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2 (dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2 (dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2 (pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para -carboxylate), which, in contrast to Mg 2 (dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2 (pc-dobpdc) with large diamines such as N -( n -heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.

Overcoming double-step CO 2 adsorption and minimizing water co-adsorption in bulky diamine-appended variants of Mg 2(dobpdc)

DOE PAGES

Milner, Phillip J.; Martell, Jeffrey D.; Siegelman, Rebecca L.; ...

2017-10-26

Alkyldiamine-functionalized variants of the metal–organic framework Mg 2(dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary,secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behaviormore » likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2(dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2(dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2(pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para-carboxylate), which, in contrast to Mg 2(dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2(pc-dobpdc) with large diamines such as N-(n-heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milner, Phillip J.; Martell, Jeffrey D.; Siegelman, Rebecca L.

Alkyldiamine-functionalized variants of the metal–organic framework Mg 2(dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are promising for CO 2 capture applications owing to their unique step-shaped CO 2 adsorption profiles resulting from the cooperative formation of ammonium carbamate chains. Primary,secondary (1°,2°) alkylethylenediamine-appended variants are of particular interest because of their low CO 2 step pressures (≤1 mbar at 40 °C), minimal adsorption/desorption hysteresis, and high thermal stability. Herein, we demonstrate that further increasing the size of the alkyl group on the secondary amine affords enhanced stability against diamine volatilization, but also leads to surprising two-step CO 2 adsorption/desorption profiles. This two-step behaviormore » likely results from steric interactions between ammonium carbamate chains induced by the asymmetrical hexagonal pores of Mg 2(dobpdc) and leads to decreased CO 2 working capacities and increased water co-adsorption under humid conditions. To minimize these unfavorable steric interactions, we targeted diamine-appended variants of the isoreticularly expanded framework Mg 2(dotpdc) (dotpdc 4- = 4,4''-dioxido-[1,1':4',1''-terphenyl]-3,3''-dicarboxylate), reported here for the first time, and the previously reported isomeric framework Mg-IRMOF-74-II or Mg 2(pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate, pc = para-carboxylate), which, in contrast to Mg 2(dobpdc), possesses uniformally hexagonal pores. By minimizing the steric interactions between ammonium carbamate chains, these frameworks enable a single CO 2 adsorption/desorption step in all cases, as well as decreased water co-adsorption and increased stability to diamine loss. Functionalization of Mg 2(pc-dobpdc) with large diamines such as N-(n-heptyl)ethylenediamine results in optimal adsorption behavior, highlighting the advantage of tuning both the pore shape and the diamine size for the development of new adsorbents for carbon capture applications.« less

Molecular Strategies for Morphology Control in Semiconducting Polymers for Optoelectronics.

PubMed

Rahmanudin, Aiman; Sivula, Kevin

2017-06-28

Solution-processable semiconducting polymers have been explored over the last decades for their potential applications in inexpensively fabricated transistors, diodes and photovoltaic cells. However, a remaining challenge in the field is to control the solid-state self-assembly of polymer chains in thin films devices, as the aspects of (semi)crystallinity, grain boundaries, and chain entanglement can drastically affect intra-and inter-molecular charge transport/transfer and thus device performance. In this short review we examine how the aspects of molecular weight and chain rigidity affect solid-state self-assembly and highlight molecular engineering strategies to tune thin film morphology. Side chain engineering, flexibly linking conjugation segments, and block co-polymer strategies are specifically discussed with respect to their effect on field effect charge carrier mobility in transistors and power conversion efficiency in solar cells. Example systems are taken from recent literature including work from our laboratories to illustrate the potential of molecular engineering semiconducting polymers.

Diffusion of chains in a periodic potential

NASA Astrophysics Data System (ADS)

Terranova, G. R.; Mártin, H. O.; Aldao, C. M.

2017-09-01

We studied the diffusion of 1D rigid chains in a square wave potential of period T. We considered chains of type A (composed of N particles A) and chains of type A-B (composed of N/2 particles A and N/2 particles B). The square wave potential represents domains, a lamellar structure observed for block copolymers, in which the repulsive δ energy between each A particle (B particle) of the chain and B particles (A particles) of the medium where the chains diffuse. From Monte Carlo simulations and analytical results it is found that the normalized diffusivity D, for N\\ll T , presents a universal behavior as a function of X  =  Nδ for chains of type A and X  =  (Nδ  -  lnT 2) for chains of type A-B, with and exponential decay for large values of X. For fixed values of δ and T, D is a periodic function of N with period T and 2T for chains of type A and type A-B, respectively.

Functional Communication Training and Chained Schedules of Reinforcement to Treat Challenging Behavior Maintained by Terminations of Activity Interruptions

ERIC Educational Resources Information Center

Falcomata, Terry S.; Roane, Henry S.; Muething, Colin S.; Stephenson, Kasey M.; Ing, Anna D.

2012-01-01

In this article, the authors evaluated functional communication training (FCT) and a chained schedule of reinforcement for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism, respectively. Following a functional analysis with undifferentiated results, the authors demonstrated that…

Theoretical and Experimental Studies of Functionalized Carbon Nanotubes for Improved Thermal Conductivity

NASA Astrophysics Data System (ADS)

Kerr, Alexander; Burt, Timothy; Mullen, Kieran; Glatzhofer, Daniel; Houck, Matthew; Huang, Paul

The use of carbon nanotubes (CNTs) to improve the thermal conductivity of composite materials is thwarted by their large thermal boundary resistance. We study how to overcome this Kapitza resistance by functionalizing CNTs with mixed molecular chains. Certain configurations of chains improve the transmission of thermal vibrations through our systems by decreasing phonon mismatch between the CNTs and their surrounding matrix. Through the calculation of vibrational normal modes and Green's functions, we develop a variety of computational metrics to compare the thermal conductivity (κ) of our systems. We show how different configurations of attached chains affect the samples' κ values by varying chain identity, chain length, number of chains, and heat driver behavior. We vary the parameters to maximize κ. To validate and optimize these metrics, we perform molecular dynamics simulations for comparison. We also present experimental results of composites enhanced with CNTs and make comparisons to the theory. We observe that some composites are thermally improved with the inclusion of CNTs, while others are scarcely changed, in agreement with theoretical models. This work was supported by NSF Grant DMR-1310407.

Long-range Kitaev chains via planar Josephson junctions

NASA Astrophysics Data System (ADS)

Liu, Dillon T.; Shabani, Javad; Mitra, Aditi

2018-06-01

We show how a recently proposed solid-state Majorana platform comprising a planar Josephson junction proximitized to a 2D electron gas (2DEG) with Rashba spin-orbit coupling and Zeeman field can be viewed as an effectively one-dimensional (1D) Kitaev chain with long-range pairing and hopping terms. We highlight how the couplings of the 1D system may be tuned by changing experimentally realistic parameters. We also show that the mapping is robust to disorder by computing the Clifford pseudospectrum index in real space for the long-range Kitaev chain across several topological phases. This mapping opens up the possibility of using current experimental setups to explore 1D topological superconductors with nonstandard and tunable couplings.

DOS cones along atomic chains

NASA Astrophysics Data System (ADS)

Kwapiński, Tomasz

2017-03-01

The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin-orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears.

Influence of alkyl chain length compatibility on microemulsion structure and solubilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, V.K.; O'Connell, J.P.; Shah, D.O.

1980-06-01

The water solubilization capacity of water/oil microemulsions is studied as a function of alkyl chain length of oil (C/sub 8/ to C/sub 16/), surfactant (C/sub 14/ and C/sub 18/ fatty acid soaps), and alcohol (C/sub 4/ to C/sub 7/). Sodium stearate and sodium myristate were used as surfactants. For n-butanol microemulsions the maximum amount of water solubilized in the microemulsion decreased continuously with increasing oil chain length; for n-heptanol it increased continuously. For n-pentanol and n-hexanol systems, water solubilization reached a maximum when the oil chain length plus alcohol chain length was equal to that of the surfactant. The electricmore » resistance and dielectric constant of the microemulsions also are measured as a function of alkyl chain length of the oil. 48 references.« less

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

PubMed

Tsurudome, M; Ito, Y

2000-01-01

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

On the semi-classical limit of scalar products of the XXZ spin chain

NASA Astrophysics Data System (ADS)

Jiang, Yunfeng; Brunekreef, Joren

2017-03-01

We study the scalar products between Bethe states in the XXZ spin chain with anisotropy |Δ| > 1 in the semi-classical limit where the length of the spin chain and the number of magnons tend to infinity with their ratio kept finite and fixed. Our method is a natural yet non-trivial generalization of similar methods developed for the XXX spin chain. The final result can be written in a compact form as a contour integral in terms of Faddeev's quantum dilogarithm function, which in the isotropic limit reduces to the classical dilogarithm function.

Linking Supply Chain Governance and Biosecurity in the Context of HPAI Control in Western Java: A Value Chain Perspective

PubMed Central

Indrawan, Dikky; Rich, Karl M.; van Horne, Peter; Daryanto, Arief; Hogeveen, Henk

2018-01-01

Despite extensive efforts to control the highly pathogenic avian influenza (HPAI), it remains endemic in Western Java, Indonesia. To understand the limited effectiveness of HPAI control measures, it is important to map the complex structure of the poultry sector. The governance of the poultry value chain in particular, could play a pivotal role, yet there is limited information on the different chain governance structures and their impacts on HPAI control. This article uses value chain analysis (VCA), focusing on an in-depth assessment of governance structures as well as transaction cost economics and quantitative estimates of the market power of different chain actors, to establish a theoretical framework to examine biosecurity and HPAI control in the Western Java poultry chain. During the research, semi-structured interviews were conducted with key value-chain stakeholders, and the economic performance of identified actors was estimated. Results indicated the co-existence of four different poultry value chains in West Java: the integrator chain, the semi-automated slaughterhouse chain, the controlled slaughter-point chain, and the private slaughter-point chain. The integrator chain was characterized by the highest levels of coordination and a tight, hierarchical governance. In contrast, the other three types of value chains were less coordinated. The market power of the different actors within the four value chains also differed. In more integrated chains, slaughterhouses held considerable market power, while in more informal value chains, market power was in the hands of traders. The economic effects of HPAI and biosecurity measures also varied for the identified actors in the different value chains. Implementation of biosecurity and HPAI control measures was strongly related to the governance structure of the chain, with interactions between different chains and governance structures accentuating the risk of HPAI. Our findings highlight that a proper understanding of the chain governance structure is vital to improve the effectiveness of HPAI control measures, by making the interventions more specific and fit-for-purpose given the incentive structures present in different chains. PMID:29770325

Linking Supply Chain Governance and Biosecurity in the Context of HPAI Control in Western Java: A Value Chain Perspective.

PubMed

Indrawan, Dikky; Rich, Karl M; van Horne, Peter; Daryanto, Arief; Hogeveen, Henk

2018-01-01

Despite extensive efforts to control the highly pathogenic avian influenza (HPAI), it remains endemic in Western Java, Indonesia. To understand the limited effectiveness of HPAI control measures, it is important to map the complex structure of the poultry sector. The governance of the poultry value chain in particular, could play a pivotal role, yet there is limited information on the different chain governance structures and their impacts on HPAI control. This article uses value chain analysis (VCA), focusing on an in-depth assessment of governance structures as well as transaction cost economics and quantitative estimates of the market power of different chain actors, to establish a theoretical framework to examine biosecurity and HPAI control in the Western Java poultry chain. During the research, semi-structured interviews were conducted with key value-chain stakeholders, and the economic performance of identified actors was estimated. Results indicated the co-existence of four different poultry value chains in West Java: the integrator chain, the semi-automated slaughterhouse chain, the controlled slaughter-point chain, and the private slaughter-point chain. The integrator chain was characterized by the highest levels of coordination and a tight, hierarchical governance. In contrast, the other three types of value chains were less coordinated. The market power of the different actors within the four value chains also differed. In more integrated chains, slaughterhouses held considerable market power, while in more informal value chains, market power was in the hands of traders. The economic effects of HPAI and biosecurity measures also varied for the identified actors in the different value chains. Implementation of biosecurity and HPAI control measures was strongly related to the governance structure of the chain, with interactions between different chains and governance structures accentuating the risk of HPAI. Our findings highlight that a proper understanding of the chain governance structure is vital to improve the effectiveness of HPAI control measures, by making the interventions more specific and fit-for-purpose given the incentive structures present in different chains.

Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes.

PubMed

Kotenko, S V; Izotova, L S; Mirochnitchenko, O V; Esterova, E; Dickensheets, H; Donnelly, R P; Pestka, S

2001-01-26

Interleukin-10 (IL-10)-related T cell-derived inducible factor (IL-TIF; provisionally designated IL-22) is a cytokine with limited homology to IL-10. We report here the identification of a functional IL-TIF receptor complex that consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the second chain of the IL-10 receptor complex. Expression of the CRF2-9 chain in monkey COS cells renders them sensitive to IL-TIF. However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex. The CRF2-9 chain (or the IL-TIF-R1 chain) is responsible for Stat recruitment. Substitution of the CRF2-9 intracellular domain with the IFN-gammaR1 intracellular domain changes the pattern of IL-TIF-induced Stat activation. The CRF2-9 gene is expressed in normal liver and kidney, suggesting a possible role for IL-TIF in regulating gene expression in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of binding IL-TIF independently and can be cross-linked to the radiolabeled IL-TIF. However, binding of IL-TIF to the receptor complex is greater than binding to either receptor chain alone. Sharing of the common IL-10R2 chain between the IL-10 and IL-TIF receptor complexes is the first such case for receptor complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the shared use of the gamma common chain (gamma(c)) by several cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15.

λ Light Chain Bias Associated With Enhanced Binding and Function of Anti-HIV Env Glycoprotein Antibodies

PubMed Central

Sajadi, Mohammad M.; Farshidpour, Maham; Brown, Eric P.; Ouyang, Xin; Seaman, Michael S.; Pazgier, Marzena; Ackerman, Margaret E.; Robinson, Harriet; Tomaras, Georgia; Parsons, Matthew S.; Charurat, Manhattan; DeVico, Anthony L.; Redfield, Robert R.; Lewis, George K.

2016-01-01

The humoral response to human immunodeficiency virus (HIV) remains incompletely understood. In this report, we describe biased λ light chain use during the HIV Env glycoprotein (Env) response in HIV infection and vaccination. We examined HIV Env binding (and neutralization) in the context of light chain use in subjects with acute HIV infection, chronic HIV infection, and among HIV vaccinees. In all populations tested, there was a λ chain bias for HIV Env binding antibodies, compared with other HIV antigens (such as p24) or tetanus toxoid. In subjects with chronic HIV infection, a λ bias was noted for neutralization, with λ antibodies accounting for up to 90% of all neutralization activity observed. This is the first report of antibody function in a human infection being tied to light chain use. In HIV infection, antibodies expressing λ light chains tended to have longer CDRL3s, increased light chain contact with HIV Env, and less hypermutation in the heavy chain, compared with antibodies using the κ light chain. These data also support an evolutionary model for the understanding the various κ to λ light chain ratios observed across species and suggest that the λ light chain bias against HIV provides the host an advantage in developing a more efficient humoral response. PMID:26347575

Polymer composites containing nanotubes

NASA Technical Reports Server (NTRS)

Bley, Richard A. (Inventor)

2008-01-01

The present invention relates to polymer composite materials containing carbon nanotubes, particularly to those containing singled-walled nanotubes. The invention provides a polymer composite comprising one or more base polymers, one or more functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers and carbon nanotubes. The invention also relates to functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers, particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having side chain functionalization, and more particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having olefin side chains and alkyl epoxy side chains. The invention further relates to methods of making polymer composites comprising carbon nanotubes.

Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders.

PubMed

Capello, Daniela; Cerri, Michaela; Muti, Giuliana; Lucioni, Marco; Oreste, Pierluigi; Gloghini, Annunziata; Berra, Eva; Deambrogi, Clara; Franceschetti, Silvia; Rossi, Davide; Alabiso, Oscar; Morra, Enrica; Rambaldi, Alessandro; Carbone, Antonino; Paulli, Marco; Gaidano, Gianluca

2006-12-01

Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n=10; diffuse large B-cell lymphoma, n=35; and Burkitt/Burkitt-like lymphoma, n=5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations.

Visualizing the Chain Rule (for Functions over R and C) and More

ERIC Educational Resources Information Center

Kreminski, Rick

2009-01-01

A visual approach to understanding the chain rule and related derivative formulae, for functions from R to R and from C to C, is presented. This apparently novel approach has been successfully used with several audiences: students first studying calculus, students with some background in linear algebra, students beginning study of functions of a…

End-Functionalized Palladium SCS Pincer Polymers via Controlled Radical Polymerizations.

PubMed

Lye, Diane S; Cohen, Aaron E; Wong, Madeleine Z; Weck, Marcus

2017-07-01

A direct and facile route toward semitelechelic polymers, end-functionalized with palladated sulfur-carbon-sulfur pincer (Pd II -pincer) complexes is reported that avoids any post-polymerization step. Key to our methodology is the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization with functionalized chain-transfer agents. This strategy yields Pd end-group-functionalized materials with monomodal molar mass dispersities (Đ) of 1.18-1.44. The RAFT polymerization is investigated using a Pd II -pincer chain-transfer agent for three classes of monomers: styrene, tert-butyl acrylate, and N-isopropylacrylamide. The ensuing Pd II -pincer end-functionalized polymers are analyzed using 1 H NMR spectroscopy, gel-permeation chromatography, and elemental analysis. The RAFT polymerization methodology provides a direct pathway for the fabrication of Pd II -pincer functionalized polymers with complete end-group functionalization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly efficient recovery of functional single-chain Fv fragments from inclusion bodies overexpressed in Escherichia coli by controlled introduction of oxidizing reagent--application to a human single-chain Fv fragment.

PubMed

Tsumoto, K; Shinoki, K; Kondo, H; Uchikawa, M; Juji, T; Kumagai, I

1998-10-01

An improved and efficient refolding system for a single-chain antibody fragment (scFv) from inclusion bodies expressed in Escherichia coli was developed. Stepwise removal of denaturing reagent and controlled addition of oxidizing reagent were found to be the most effective conditions to achieve for almost complete recovery of functional monomeric scFv from inclusion bodies. Adding L-arginine to the refolding solution also increased the yield of refolded functional scFv. The single-chain Fv fragments of both a mouse anti-lysozyme monoclonal antibody, HyHEL10, and a human monoclonal antibody against the D antigen of the Rh blood group, D10, in solubilized inclusion bodies could be refolded under these conditions with yields of up to 95%. The refolding procedures developed in this study will contribute to providing a stable supply of large amounts of human single-chain Fv fragments.

Developing a model for agile supply: an empirical study from Iranian pharmaceutical supply chain.

PubMed

Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

2013-01-01

Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API.

Developing a Model for Agile Supply: an Empirical Study from Iranian Pharmaceutical Supply Chain

PubMed Central

Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

2013-01-01

Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API. PMID:24250689

Ab initio treatment of fully open-shell medium-mass nuclei with the IM-SRG

NASA Astrophysics Data System (ADS)

Stroberg, Ragnar; Calci, Angelo; Holt, Jason; Navratil, Petr; Bogner, Scott; Hergert, Heiko; Roth, Robert; Schwenk, Achim

2016-09-01

The in-medium similarity renormalization group (IM-SRG) is a recently-developed theoretical many-body framework which - like the coupled cluster and the self-consistent Green's function approaches - allows for the treatment of medium-mass nuclei using interactions fit at the few-body level. I will give a brief overview of how the IM-SRG may be used to decouple a shell-model type valence space. I will then describe a recent development for the approximate treatment of residual 3N forces in the valence space which extends the reach of IM-SRG to essentially all medium-mass nuclei, and I will present some selected results spanning isotopic chains from beryllium (Z=4) to nickel (Z=28). Finally, I will discuss the consistent treatment of transition operators, highlighting the potential for future applications in electroweak physics.

Disinfectant susceptibility of different Salmonella serotypes isolated from chicken and egg production chains.

PubMed

Long, M; Lai, H; Deng, W; Zhou, K; Li, B; Liu, S; Fan, L; Wang, H; Zou, L

2016-09-01

The study aimed to serotype the Salmonella isolates recovered from chicken and egg production chains, and to investigate the disinfectant resistance phenotypes and genotypes of these isolates. The Salmonella isolates were serotyped, and the minimal inhibitory concentrations (MICs) of disinfectants were determined. Results showed that the Salmonella isolates recovered from both chains were diverse, and the serotypes in each part of the production chain and between the two production chains were significantly different. In the chicken production chain, 19 different serotypes were recovered, while only five serotypes were found in the egg production chain. The isolates showed a high susceptibility to didecyldimethylammonium bromide (DDAB) but a low susceptibility to benzalkonium chloride (BC), benzalkonium bromide (BAB) and chlorhexidine (CHX). Salmonella Enteritidis and Salmonella Typhimurium were more resistant to BC and BAB. The qacEΔ1 and qacF resistance genes were detected in 26·7 and 7·7% of the isolates respectively. The qacEΔ1 gene was frequently found in Salmonella Derby and Salm. Enteritidis (P < 0·05). Our findings indicated that Salmonella was commonly present in both chains, and could serve as a critical vector in spreading disinfectant resistance associated with different serotypes. This study first demonstrated disinfectant resistance phenotypes and genotypes of serotyped Salmonella. The study highlights the need for monitoring the disinfectant resistance varied in different Salmonella serotypes. © 2016 The Society for Applied Microbiology.

Improved packing of protein side chains with parallel ant colonies

PubMed Central

2014-01-01

Introduction The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. Methods We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. Results We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. Conclusions This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms. PMID:25474164

Optimising the laboratory supply chain: The key to effective laboratory services

PubMed Central

Williams, Jason; Smith, Peter; Kuritsky, Joel

2014-01-01

Background The Supply Chain Management System (SCMS) is a contract managed under the Partnership for Supply Chain Management (PFSCM) consortium by the United States Agency for International Development (USAID). SCMS procures commodities for programmes supported by the US President’s Emergency Plan for AIDS Relief (PEPFAR). From 2005 to mid-2012, PEPFAR, through SCMS, spent approximately $384 million on non-pharmaceutical commodities. Of this, an estimated $90m was used to purchase flow cytometry technology, largely for flow cytometry platforms and reagents. Objectives The purpose of this paper is to highlight the cost differences between low, medium and high utilisation rates of common CD4 testing instruments that have been procured though PEPFAR funding. Method A scale of costs per test as a function of test volume through the machine was calculated for the two most common CD4 testing machines used in HIV programmes: Becton Dickinson (BD) FACSCount™ and BD FACSCalibur™. Instrument utilisation data collected at the facility level in three selected countries were then used to calculate the onsite cost-per-test experienced in each country. Results Cost analyses indicated that a target of at least 40% utilisation for FACSCount™ and 15% utilisation for FACSCalibur™, respectively, closely approach maximal per-test cost efficiency. The average utilisation rate for CD4 testing instruments varies widely by country, level of laboratory and partner (0% − 68%). Conclusion Our analysis indicates that, because cost-per-test is related inversely to sample throughput, the underutilisation of flow cytometry machines is resulting in an increase in average cost-per-test for many instruments. PMID:29043175

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids*

PubMed Central

Yagita, Yuichi; Shinohara, Kyoko; Abe, Yuichi; Nakagawa, Keiko; Al-Owain, Mohammed; Alkuraya, Fowzan S.; Fujiki, Yukio

2017-01-01

Acyl-CoA binding domain-containing 5 (ACBD5) is a peroxisomal protein that carries an acyl-CoA binding domain (ACBD) at its N-terminal region. The recent identification of a mutation in the ACBD5 gene in patients with a syndromic form of retinal dystrophy highlights the physiological importance of ACBD5 in humans. However, the underlying pathogenic mechanisms and the precise function of ACBD5 remain unclear. We herein report that ACBD5 is a peroxisomal tail-anchored membrane protein exposing its ACBD to the cytosol. Using patient-derived fibroblasts and ACBD5 knock-out HeLa cells generated via genome editing, we demonstrate that ACBD5 deficiency causes a moderate but significant defect in peroxisomal β-oxidation of very-long-chain fatty acids (VLCFAs) and elevates the level of cellular phospholipids containing VLCFAs without affecting peroxisome biogenesis, including the import of membrane and matrix proteins. Both the N-terminal ACBD and peroxisomal localization of ACBD5 are prerequisite for efficient VLCFA β-oxidation in peroxisomes. Furthermore, ACBD5 preferentially binds very-long-chain fatty acyl-CoAs (VLC-CoAs). Together, these results suggest a direct role of ACBD5 in peroxisomal VLCFA β-oxidation. Based on our findings, we propose that ACBD5 captures VLC-CoAs on the cytosolic side of the peroxisomal membrane so that the transport of VLC-CoAs into peroxisomes and subsequent β-oxidation thereof can proceed efficiently. Our study reclassifies ACBD5-related phenotype as a novel peroxisomal disorder. PMID:27899449

Site-Specific N-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

NASA Astrophysics Data System (ADS)

Moh, Edward S. X.; Lin, Chi-Hung; Thaysen-Andersen, Morten; Packer, Nicolle H.

2016-07-01

Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.

PubMed

Powell, Christopher A; Kopajtich, Robert; D'Souza, Aaron R; Rorbach, Joanna; Kremer, Laura S; Husain, Ralf A; Dallabona, Cristina; Donnini, Claudia; Alston, Charlotte L; Griffin, Helen; Pyle, Angela; Chinnery, Patrick F; Strom, Tim M; Meitinger, Thomas; Rodenburg, Richard J; Schottmann, Gudrun; Schuelke, Markus; Romain, Nadine; Haller, Ronald G; Ferrero, Ileana; Haack, Tobias B; Taylor, Robert W; Prokisch, Holger; Minczuk, Michal

2015-08-06

Deficiencies in respiratory-chain complexes lead to a variety of clinical phenotypes resulting from inadequate energy production by the mitochondrial oxidative phosphorylation system. Defective expression of mtDNA-encoded genes, caused by mutations in either the mitochondrial or nuclear genome, represents a rapidly growing group of human disorders. By whole-exome sequencing, we identified two unrelated individuals carrying compound heterozygous variants in TRMT5 (tRNA methyltransferase 5). TRMT5 encodes a mitochondrial protein with strong homology to members of the class I-like methyltransferase superfamily. Both affected individuals presented with lactic acidosis and evidence of multiple mitochondrial respiratory-chain-complex deficiencies in skeletal muscle, although the clinical presentation of the two affected subjects was remarkably different; one presented in childhood with failure to thrive and hypertrophic cardiomyopathy, and the other was an adult with a life-long history of exercise intolerance. Mutations in TRMT5 were associated with the hypomodification of a guanosine residue at position 37 (G37) of mitochondrial tRNA; this hypomodification was particularly prominent in skeletal muscle. Deficiency of the G37 modification was also detected in human cells subjected to TRMT5 RNAi. The pathogenicity of the detected variants was further confirmed in a heterologous yeast model and by the rescue of the molecular phenotype after re-expression of wild-type TRMT5 cDNA in cells derived from the affected individuals. Our study highlights the importance of post-transcriptional modification of mitochondrial tRNAs for faithful mitochondrial function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Geometry and combinatorics of Julia sets of real quadratic maps

NASA Astrophysics Data System (ADS)

Barnsley, M. F.; Geronimo, J. S.; Harrington, A. N.

1984-10-01

For real λ a correspondence is made between the Julia set B λ for z→( z- λ)2, in the hyperbolic case, and the set of λ-chains λ±√(λ±√(λ±..., with the aid of Cremer's theorem. It is shown how a number of features of Bλ can be understood in terms of λ-chains. The structure of B λ is determined by certain equivalence classes of λ-chains, fixed by orders of visitation of certain real cycles; and the bifurcation history of a given cycle can be conveniently computed via the combinatorics of λ-chains. The functional equations obeyed by attractive cycles are investigated, and their relation to λ-chains is given. The first cascade of period-doubling bifurcations is described from the point of view of the associated Julia sets and λ-chains. Certain "Julia sets" associated with the Feigenbaum function and some theorems of Lanford are discussed.

Quantum conductance oscillation in linear monatomic silicon chains

NASA Astrophysics Data System (ADS)

Liu, Fu-Ti; Cheng, Yan; Yang, Fu-Bin; Chen, Xiang-Rong

2014-02-01

The conductance of linear silicon atomic chains with n=1-8 atoms sandwiched between Au electrodes is investigated by using the density functional theory combined with non-equilibrium Green's function. The results show that the conductance oscillates with a period of two atoms as the number of atoms in the chain is varied. We optimize the geometric structure of nanoscale junctions in different distances, and obtain that the average bond-length of silicon atoms in each chain at equilibrium positions is 2.15±0.03 Å. The oscillation of average Si-Si bond-length can explain the conductance oscillation from the geometric structure of atomic chains. We calculate the transmission spectrum of the chains in the equilibrium positions, and explain the conductance oscillation from the electronic structure. The transport channel is mainly contributed by px and py orbital electrons of silicon atoms. The even-odd oscillation is robust under external voltage up to 1.2 V.

Evidence-based rehabilitation of athletes with glenohumeral instability.

PubMed

Cools, Ann M; Borms, Dorien; Castelein, Birgit; Vanderstukken, Fran; Johansson, Fredrik R

2016-02-01

To give an overview of current knowledge and guidelines with respect to evidence-based rehabilitation of athletes with glenohumeral instability. This narrative review combines scientific evidence with clinical guidelines based on the current literature to highlight the different components of the rehabilitation of glenohumeral instability. Depending on the specific characteristics of the instability pattern, the severity, recurrence, and direction, the therapeutic approach may be adapted to the needs and demands of the athlete. In general, attention should go to (1) restoration of rotator cuff strength and inter-muscular balance, focusing on the eccentric capacity of the external rotators, (2) normalization of rotational range of motion with special attention to the internal rotation ROM, (3) optimization of the flexibility and muscle performance of the scapular muscles, and (4) gradually increasing the functional sport-specific load on the shoulder girdle. The functional kinetic chain should be implemented throughout all stages of the rehabilitation program. Return to play should be based on subjective assessment as well as objective measurements of ROM, strength, and function. This paper summarizes evidence-based guidelines for treatment of glenohumeral instability. These guidelines may assist the clinician in the prevention and rehabilitation of the overhead athlete. Expert opinion, Level V.

Hybrid fusions show that inter-monomer electron transfer robustly supports cytochrome bc{sub 1} function in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekiert, Robert; Czapla, Monika; Sarewicz, Marcin

2014-08-22

Highlights: • We used hybrid fusion bc{sub 1} complex to test inter-monomer electron transfer in vivo. • Cross-inactivated complexes were able to sustain photoheterotrophic growth. • Inter-monomer electron transfer supports catalytic cycle in vivo. • bc{sub 1} dimer is functional even when cytochrome b subunits come from different species. - Abstract: Electronic connection between Q{sub o} and Q{sub i} quinone catalytic sites of dimeric cytochrome bc{sub 1} is a central feature of the energy-conserving Q cycle. While both the intra- and inter-monomer electron transfers were shown to connect the sites in the enzyme, mechanistic and physiological significance of the lattermore » remains unclear. Here, using a series of mutated hybrid cytochrome bc{sub 1}-like complexes, we show that inter-monomer electron transfer robustly sustains the function of the enzyme in vivo, even when the two subunits in a dimer come from different species. This indicates that minimal requirement for bioenergetic efficiency is to provide a chain of cofactors for uncompromised electron flux between the catalytic sites, while the details of protein scaffold are secondary.« less

Reprogramming cellular events by poly(ADP-ribose)-binding proteins

PubMed Central

Pic, Émilie; Ethier, Chantal; Dawson, Ted M.; Dawson, Valina L.; Masson, Jean-Yves; Poirier, Guy G.; Gagné, Jean-Philippe

2013-01-01

Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions. PMID:23268355

Biological functions of iduronic acid in chondroitin/dermatan sulfate.

PubMed

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

2013-05-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS.

Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters

PubMed Central

Andreoletti, Pierre; Raas, Quentin; Gondcaille, Catherine; Cherkaoui-Malki, Mustapha; Trompier, Doriane; Savary, Stéphane

2017-01-01

The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins. The lack of a clear consensus on the secondary and tertiary structure of the TMDs weakens any structure-function hypothesis based on the very diverse ABCD1 mutations found in X-ALD patients. Therefore, we first reinvestigated thoroughly the structure-function data available and performed refined alignments of ABCD protein sequences. Based on the 2.85  Å resolution crystal structure of the mitochondrial ABC transporter ABCB10, here we propose a structural model of peroxisomal ABCD proteins that specifies the position of the transmembrane and coupling helices, and highlight functional motifs and putative important amino acid residues. PMID:28737695

Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut-Off Hemodialysis

PubMed Central

Hutchison, Colin A.; Bradwell, Arthur R.; Cook, Mark; Basnayake, Kolitha; Basu, Supratik; Harding, Stephen; Hattersley, John; Evans, Neil D.; Chappel, Mike J.; Sampson, Paul; Foggensteiner, Lukas; Adu, Dwomoa; Cockwell, Paul

2009-01-01

Background and objectives: Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. Design, setting, participants, & measurements: An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. Results: There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). Conclusion: In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function. PMID:19339414

Structure and thermodynamics of liquid alkali metals in variational modified hypernetted-chain theory

NASA Astrophysics Data System (ADS)

Chen, H. C.; Lai, S. K.

1992-03-01

The role of the Percus-Yevick hard-sphere bridge function in the modified hypernetted-chain integral equation is examined within the context of Lado's criterion [F. Lado, S. M. Foiles, and N. W. Ashcroft, Phys. Rev. A 28, 2374 (1983)]. It is found that the commonly used Lado's criterion, which takes advantage of the analytical simplicity of the Percus-Yevick hard-sphere bridge function, is inadequate for determining an accurate static pair-correlation function. Following Rosenfeld [Y. Rosenfeld, Phys. Rev. A 29, 2877 (1984)], we reconsider Lado's criterion in the so-called variational modified hypernetted-chain theory. The main idea is to construct a free-energy functional satisfying the virial-energy thermodynamic self-consistency. It turns out that the widely used Gibbs-Bogoliubov inequality is equivalent to this integral approach of Lado's criterion. Detailed comparison between the presently obtained structural and thermodynamic quantities for liquid alkali metals and those calculated also in the modified hypernetted-chain theory but with the one-component-plasma reference system leads us to a better understanding of the universality property of the bridge function.

Structural propensities and entropy effects in peptide helix-coil transitions

NASA Astrophysics Data System (ADS)

Chemmama, Ilan E.; Pelea, Adam Colt; Bhandari, Yuba R.; Chapagain, Prem P.; Gerstman, Bernard S.

2012-09-01

The helix-coil transition in peptides is a critical structural transition leading to functioning proteins. Peptide chains have a large number of possible configurations that must be accounted for in statistical mechanical investigations. Using hydrogen bond and local helix propensity interaction terms, we develop a method for obtaining and incorporating the degeneracy factor that allows the exact calculation of the partition function for a peptide as a function of chain length. The partition function is used in calculations for engineered peptide chains of various lengths that allow comparison with a variety of different types of experimentally measured quantities, such as fraction of helicity as a function of both temperature and chain length, heat capacity, and denaturation studies. When experimental sensitivity in helicity measurements is properly accounted for in the calculations, the calculated curves fit well with the experimental curves. We determine values of interaction energies for comparison with known biochemical interactions, as well as quantify the difference in the number of configurations available to an amino acid in a random coil configuration compared to a helical configuration.

Role of internal motions and molecular geometry on the NMR relaxation of hydrocarbons

NASA Astrophysics Data System (ADS)

Singer, P. M.; Asthagiri, D.; Chen, Z.; Valiya Parambathu, A.; Hirasaki, G. J.; Chapman, W. G.

2018-04-01

The role of internal motions and molecular geometry on 1H NMR relaxation rates in liquid-state hydrocarbons is investigated using MD (molecular dynamics) simulations of the autocorrelation functions for intramolecular and intermolecular 1H-1H dipole-dipole interactions. The effects of molecular geometry and internal motions on the functional form of the autocorrelation functions are studied by comparing symmetric molecules such as neopentane and benzene to corresponding straight-chain alkanes n-pentane and n-hexane, respectively. Comparison of rigid versus flexible molecules shows that internal motions cause the intramolecular and intermolecular correlation-times to get significantly shorter, and the corresponding relaxation rates to get significantly smaller, especially for longer-chain n-alkanes. Site-by-site simulations of 1H's across the chains indicate significant variations in correlation times and relaxation rates across the molecule, and comparison with measurements reveals insights into cross-relaxation effects. Furthermore, the simulations reveal new insights into the relative strength of intramolecular versus intermolecular relaxation as a function of internal motions, as a function of molecular geometry, and on a site-by-site basis across the chain.

Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis

PubMed Central

Fan, Jun-Bao; Arimoto, Kei-lchiro; Motamedchaboki, Khatereh; Yan, Ming; Wolf, Dieter A.; Zhang, Dong-Er

2015-01-01

As a ubiquitin-like modifier, ISG15 is conjugated to many cellular proteins in a process termed protein ISGylation. However, the crosstalk between protein ISGylation and the ubiquitin proteasome system is not fully understood. Here, we report that cellular ubiquitin is a substrate of ISG15 and Lys 29 on ubiquitin is the major ISG15 acceptor site. Using a model substrate, we demonstrate that ISG15 can modify ubiquitin, which is immobilized on its substrate, to form ISG15-ubiquitin mixed chains. Furthermore, our results indicate that ISG15-ubiquitin mixed chains do not serve as degradation signals for a ubiquitin fusion degradation substrate. Accordingly, an ISG15-ubiquitin fusion protein, which mimics an ISG15-ubiquitin mixed chain, negatively regulates cellular turnover of ubiquitylated proteins. In addition, ISG15-ubiquitin mixed chains, which are detectable on endogenously ubiquitylated proteins, dampen cellular turnover of these proteins. Thus, our studies unveil an unanticipated interplay between two protein modification systems and highlight its role in coordinating protein homeostasis. PMID:26226047

Bias-dependent oscillatory electron transport of monatomic sulfur chains

NASA Astrophysics Data System (ADS)

Yu, Jing-Xin; Cheng, Yan; Sanvito, Stefano; Chen, Xiang-Rong

2012-03-01

The bias-dependent oscillatory electron transport of monatomic sulfur chains sandwiched between gold electrodes is investigated with density functional theory and non-equilibrium Green's function method. At zero bias, in contrast to the typical odd-even oscillations observed in most metallic chains, we find that the conductance oscillates with a period of four atoms. However, as the bias voltage is increased the current displays a two-atom periodicity. This emerges gradually, first for the longer chains and then, at voltages larger than 0.7 V, for lengths. The oscillatory behaviors are analyzed by the density of states and the energy-dependent and bias-dependent transmission coefficients.

Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

PubMed Central

Rizzo, William B.

2014-01-01

Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

Dynamic covalent polymers

PubMed Central

García, Fátima

2016-01-01

ABSTRACT This Highlight presents an overview of the rapidly growing field of dynamic covalent polymers. This class of polymers combines intrinsic reversibility with the robustness of covalent bonds, thus enabling formation of mechanically stable, polymer‐based materials that are responsive to external stimuli. It will be discussed how the inherent dynamic nature of the dynamic covalent bonds on the molecular level can be translated to the macroscopic level of the polymer, giving access to a range of applications, such as stimuli‐responsive or self‐healing materials. A primary distinction will be made based on the type of dynamic covalent bond employed, while a secondary distinction will be based on the consideration whether the dynamic covalent bond is used in the main chain of the polymer or whether it is used to allow side chain modification of the polymer. Emphasis will be on the chemistry of the dynamic covalent bonds present in the polymer, in particular in relation to how the specific (dynamic) features of the bond impart functionality to the polymer material, and to the conditions under which this dynamic behavior is manifested. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3551–3577. PMID:27917019

DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Zirong; Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL 32610; Jin, Guorong

2012-06-08

Highlights: Black-Right-Pointing-Pointer CDA-II inhibits myogenic differentiation in a dose-dependent manner. Black-Right-Pointing-Pointer CDA-II repressed expression of muscle transcription factors and structural proteins. Black-Right-Pointing-Pointer CDA-II inhibited proliferation and migration of C2C12 myoblasts. -- Abstract: CDA-II (cell differentiation agent II), isolated from healthy human urine, is a DNA methyltransferase inhibitor. Previous studies indicated that CDA-II played important roles in the regulation of cell growth and certain differentiation processes. However, it has not been determined whether CDA-II affects skeletal myogenesis. In this study, we investigated effects of CDA-II treatment on skeletal muscle progenitor cell differentiation, migration and proliferation. We found that CDA-II blocked differentiationmore » of murine myoblasts C2C12 in a dose-dependent manner. CDA-II repressed expression of muscle transcription factors, such as Myogenin and Mef2c, and structural proteins, such as myosin heavy chain (Myh3), light chain (Mylpf) and MCK. Moreover, CDA-II inhibited C1C12 cell migration and proliferation. Thus, our data provide the first evidence that CDA-II inhibits growth and differentiation of muscle progenitor cells, suggesting that the use of CDA-II might affect skeletal muscle functions.« less

Testing Geometrical Discrimination within an Enzyme Active Site: Constrained Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

PubMed Central

Sigala, Paul A.; Kraut, Daniel A.; Caaveiro, Jose M. M.; Pybus, Brandon; Ruben, Eliza A.; Ringe, Dagmar; Petsko, Gregory A.; Herschlag, Daniel

2009-01-01

Enzymes are classically proposed to accelerate reactions by binding substrates within active site environments that are structurally preorganized to optimize binding interactions with reaction transition states rather than ground states. This is a remarkably formidable task considering the limited 0.1 – 1 Å scale of most substrate rearrangements. The flexibility of active site functional groups along the coordinate of substrate rearrangement, the distance scale on which enzymes can distinguish structural rearrangement, and the energetic significance of discrimination on that scale remain open questions that are fundamental to a basic physical understanding of enzyme active sites and catalysis. We bring together high resolution X-ray crystallography, 1H and 19F NMR spectroscopy, quantum mechanical calculations, and transition state analog binding measurements to test the distance scale on which non-covalent forces can constrain side chain and ligand relaxation or translation along a specific coordinate and the energetic consequences of such geometric constraints within the active site of bacterial ketosteroid isomerase (KSI). Our results strongly suggest that packing and binding interactions within the KSI active site can constrain local side chain reorientation and prevent hydrogen bond shortening by 0.1 Å or less. Further, this constraint has substantial energetic effects on ligand binding and stabilization of negative charge within the oxyanion hole. These results provide evidence that subtle geometric effects, indistinguishable in most X-ray crystallographic structures, can have significant energetic consequences and highlight the importance of using synergistic experimental approaches to dissect enzyme function. PMID:18808119

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Jian; Zhang, Lin; Dai, Weiqi

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and alsomore » prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.« less

Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism.

PubMed

Streich, Frederick C; Ronchi, Virginia P; Connick, J Patrick; Haas, Arthur L

2013-03-22

Ligation of polyubiquitin chains to proteins is a fundamental post-translational modification, often resulting in targeted degradation of conjugated proteins. Attachment of polyubiquitin chains requires the activities of an E1 activating enzyme, an E2 carrier protein, and an E3 ligase. The mechanism by which polyubiquitin chains are formed remains largely speculative, especially for RING-based ligases. The tripartite motif (TRIM) superfamily of ligases functions in many cellular processes including innate immunity, cellular localization, development and differentiation, signaling, and cancer progression. The present results show that TRIM ligases catalyze polyubiquitin chain formation in the absence of substrate, the rates of which can be used as a functional readout of enzyme function. Initial rate studies under biochemically defined conditions show that TRIM32 and TRIM25 are specific for the Ubc5 family of E2-conjugating proteins and, along with TRIM5α, exhibit cooperative kinetics with respect to Ubc5 concentration, with submicromolar [S]0.5 and Hill coefficients of 3-5, suggesting they possess multiple binding sites for their cognate E2-ubiquitin thioester. Mutation studies reveal a second, non-canonical binding site encompassing the C-terminal Ubc5α-helix. Polyubiquitin chain formation requires TRIM subunit oligomerization through the conserved coiled-coil domain, but can be partially replaced by fusing the catalytic domain to GST to promote dimerization. Other results suggest that TRIM32 assembles polyubiquitin chains as a Ubc5-linked thioester intermediate. These results represent the first detailed mechanistic study of TRIM ligase activity and provide a functional context for oligomerization observed in the superfamily.

Statistical model of a flexible inextensible polymer chain: The effect of kinetic energy.

PubMed

Pergamenshchik, V M; Vozniak, A B

2017-01-01

Because of the holonomic constraints, the kinetic energy contribution in the partition function of an inextensible polymer chain is difficult to find, and it has been systematically ignored. We present the first thermodynamic calculation incorporating the kinetic energy of an inextensible polymer chain with the bending energy. To explore the effect of the translation-rotation degrees of freedom, we propose and solve a statistical model of a fully flexible chain of N+1 linked beads which, in the limit of smooth bending, is equivalent to the well-known wormlike chain model. The partition function with the kinetic and bending energies and correlations between orientations of any pair of links and velocities of any pair of beads are found. This solution is precise in the limits of small and large rigidity-to-temperature ratio b/T. The last exact solution is essential as even very "harmless" approximation results in loss of the important effects when the chain is very rigid. For very high b/T, the orientations of different links become fully correlated. Nevertheless, the chain does not go over into a hard rod even in the limit b/T→∞: While the velocity correlation length diverges, the correlations themselves remain weak and tend to the value ∝T/(N+1). The N dependence of the partition function is essentially determined by the kinetic energy contribution. We demonstrate that to obtain the correct energy and entropy in a constrained system, the T derivative of the partition function has to be applied before integration over the constraint-setting variable.

Statistical model of a flexible inextensible polymer chain: The effect of kinetic energy

NASA Astrophysics Data System (ADS)

Pergamenshchik, V. M.; Vozniak, A. B.

2017-01-01

Because of the holonomic constraints, the kinetic energy contribution in the partition function of an inextensible polymer chain is difficult to find, and it has been systematically ignored. We present the first thermodynamic calculation incorporating the kinetic energy of an inextensible polymer chain with the bending energy. To explore the effect of the translation-rotation degrees of freedom, we propose and solve a statistical model of a fully flexible chain of N +1 linked beads which, in the limit of smooth bending, is equivalent to the well-known wormlike chain model. The partition function with the kinetic and bending energies and correlations between orientations of any pair of links and velocities of any pair of beads are found. This solution is precise in the limits of small and large rigidity-to-temperature ratio b /T . The last exact solution is essential as even very "harmless" approximation results in loss of the important effects when the chain is very rigid. For very high b /T , the orientations of different links become fully correlated. Nevertheless, the chain does not go over into a hard rod even in the limit b /T →∞ : While the velocity correlation length diverges, the correlations themselves remain weak and tend to the value ∝T /(N +1 ). The N dependence of the partition function is essentially determined by the kinetic energy contribution. We demonstrate that to obtain the correct energy and entropy in a constrained system, the T derivative of the partition function has to be applied before integration over the constraint-setting variable.

The distribution of genome shared identical by descent for a pair of full sibs by means of the continuous time Markov chain

NASA Astrophysics Data System (ADS)

Julie, Hongki; Pasaribu, Udjianna S.; Pancoro, Adi

2015-12-01

This paper will allow Markov Chain's application in genome shared identical by descent by two individual at full sibs model. The full sibs model was a continuous time Markov Chain with three state. In the full sibs model, we look for the cumulative distribution function of the number of sub segment which have 2 IBD haplotypes from a segment of the chromosome which the length is t Morgan and the cumulative distribution function of the number of sub segment which have at least 1 IBD haplotypes from a segment of the chromosome which the length is t Morgan. This cumulative distribution function will be developed by the moment generating function.

Efficient sampling of reversible cross-linking polymers: Self-assembly of single-chain polymeric nanoparticles

NASA Astrophysics Data System (ADS)

Oyarzún, Bernardo; Mognetti, Bortolo Matteo

2018-03-01

We present a new simulation technique to study systems of polymers functionalized by reactive sites that bind/unbind forming reversible linkages. Functionalized polymers feature self-assembly and responsive properties that are unmatched by the systems lacking selective interactions. The scales at which the functional properties of these materials emerge are difficult to model, especially in the reversible regime where such properties result from many binding/unbinding events. This difficulty is related to large entropic barriers associated with the formation of intra-molecular loops. In this work, we present a simulation scheme that sidesteps configurational costs by dedicated Monte Carlo moves capable of binding/unbinding reactive sites in a single step. Cross-linking reactions are implemented by trial moves that reconstruct chain sections attempting, at the same time, a dimerization reaction between pairs of reactive sites. The model is parametrized by the reaction equilibrium constant of the reactive species free in solution. This quantity can be obtained by means of experiments or atomistic/quantum simulations. We use the proposed methodology to study the self-assembly of single-chain polymeric nanoparticles, starting from flexible precursors carrying regularly or randomly distributed reactive sites. We focus on understanding differences in the morphology of chain nanoparticles when linkages are reversible as compared to the well-studied case of irreversible reactions. Intriguingly, we find that the size of regularly functionalized chains, in good solvent conditions, is non-monotonous as a function of the degree of functionalization. We clarify how this result follows from excluded volume interactions and is peculiar of reversible linkages and regular functionalizations.

Developing a Comprehensive Approach Could Help DOD Better Manage National Security Risks in the Supply Chain

DTIC Science & Technology

2016-02-01

functionality in weapon system components. Many steps in the rare earths supply chain, such as mining , are conducted in China, a situation that may pose...functionality in weapon systems components.1 Many steps in the rare earths supply chain, such as mining and refining the ore, are primarily conducted outside...are difficult and costly to mine and process. Rare earth elements are Page 5 GAO-16-161 Rare Earth Materials often classified as either

Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

PubMed

Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

2012-04-01

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Chemistry, Creativity, Collaboration, and C60: An Interview with Harold W. Kroto

NASA Astrophysics Data System (ADS)

Cardellini, Liberato

2005-05-01

This interview offers a sketch of the story of Harold Kroto’s scientific life, highlighting his research activities and discoveries. Illustrative examples include Kroto's study of electronic spectra of molecules, the synthesis of phosphoalkenes and phosphoalkynes, the study of long carbon chain molecules in the lab, and the search for long carbon chain molecules in the interstellar medium while at Rice University that led to the serendipitous discovery of fullerene. Kroto defends and stresses the importance of fundamental research and the role of scientists in society; he also suggests a way to foster children's interest in science.

AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress

PubMed Central

Sriskanthadevan, Shrivani; Jeyaraju, Danny V.; Chung, Timothy E.; Prabha, Swayam; Xu, Wei; Skrtic, Marko; Jhas, Bozhena; Hurren, Rose; Gronda, Marcela; Wang, Xiaoming; Jitkova, Yulia; Sukhai, Mahadeo A.; Lin, Feng-Hsu; Maclean, Neil; Laister, Rob; Goard, Carolyn A.; Mullen, Peter J.; Xie, Stephanie; Penn, Linda Z.; Rogers, Ian M.; Dick, John E.; Minden, Mark D.

2015-01-01

Mitochondrial respiration is a crucial component of cellular metabolism that can become dysregulated in cancer. Compared with normal hematopoietic cells, acute myeloid leukemia (AML) cells and patient samples have higher mitochondrial mass, without a concomitant increase in respiratory chain complex activity. Hence these cells have a lower spare reserve capacity in the respiratory chain and are more susceptible to oxidative stress. We therefore tested the effects of increasing the electron flux through the respiratory chain as a strategy to induce oxidative stress and cell death preferentially in AML cells. Treatment with the fatty acid palmitate induced oxidative stress and cell death in AML cells, and it suppressed tumor burden in leukemic cell lines and primary patient sample xenografts in the absence of overt toxicity to normal cells and organs. These data highlight a unique metabolic vulnerability in AML, and identify a new therapeutic strategy that targets abnormal oxidative metabolism in this malignancy. PMID:25631767

Circular economy practices among Chinese manufacturers varying in environmental-oriented supply chain cooperation and the performance implications.

PubMed

Zhu, Qinghua; Geng, Yong; Lai, Kee-hung

2010-06-01

The rapidly growing industrial activities in emerging economies such as China have been causing resource depletion and pollution problems. This reality requires China to adopt an integrated management approach to resolve the conflict between industrial development and environmental protection, and the concept of circular economy (CE) serves this purpose. In this paper, we examine if different types of manufacturing enterprises on environmental-oriented supply chain cooperation (ESCC) exist. We also determine if the Chinese manufacturer types varying in ESCC differ in their implementation of the CE practices towards achieving the CE-targeted goals on improving both environmental and economic performance. Our cluster analytic results with multivariate analysis of variance (MANOVA) among the four identified types of Chinese manufacturers varying in environmental-oriented supply chain cooperation highlight the importance to intensify the cooperation with upstream and downstream supply chain partners for a CE initiative to succeed. (c) 2010 Elsevier Ltd. All rights reserved.

Decision support for green supply chain operations by integrating dynamic simulation and LCA indicators: diaper case study.

PubMed

Adhitya, Arief; Halim, Iskandar; Srinivasan, Rajagopalan

2011-12-01

As the issue of environmental sustainability is becoming an important business factor, companies are now looking for decision support tools to assess the fuller picture of the environmental impacts associated with their manufacturing operations and supply chain (SC) activities. Lifecycle assessment (LCA) is widely used to measure the environmental consequences assignable to a product. However, it is usually limited to a high-level snapshot of the environmental implications over the product value chain without consideration of the dynamics arising from the multitiered structure and the interactions along the SC. This paper proposes a framework for green supply chain management by integrating a SC dynamic simulation and LCA indicators to evaluate both the economic and environmental impacts of various SC decisions such as inventories, distribution network configuration, and ordering policy. The advantages of this framework are demonstrated through an industrially motivated case study involving diaper production. Three distinct scenarios are evaluated to highlight how the proposed approach enables integrated decision support for green SC design and operation.

Linear and nonlinear susceptibilities from diffusion quantum Monte Carlo: application to periodic hydrogen chains.

PubMed

Umari, P; Marzari, Nicola

2009-09-07

We calculate the linear and nonlinear susceptibilities of periodic longitudinal chains of hydrogen dimers with different bond-length alternations using a diffusion quantum Monte Carlo approach. These quantities are derived from the changes in electronic polarization as a function of applied finite electric field--an approach we recently introduced and made possible by the use of a Berry-phase, many-body electric-enthalpy functional. Calculated susceptibilities and hypersusceptibilities are found to be in excellent agreement with the best estimates available from quantum chemistry--usually extrapolations to the infinite-chain limit of calculations for chains of finite length. It is found that while exchange effects dominate the proper description of the susceptibilities, second hypersusceptibilities are greatly affected by electronic correlations. We also assess how different approximations to the nodal surface of the many-body wave function affect the accuracy of the calculated susceptibilities.

Density functional theory for polymeric systems in 2D.

PubMed

Słyk, Edyta; Roth, Roland; Bryk, Paweł

2016-06-22

We propose density functional theory for polymeric fluids in two dimensions. The approach is based on Wertheim's first order thermodynamic perturbation theory (TPT) and closely follows density functional theory for polymers proposed by Yu and Wu (2002 J. Chem. Phys. 117 2368). As a simple application we evaluate the density profiles of tangent hard-disk polymers at hard walls. The theoretical predictions are compared against the results of the Monte Carlo simulations. We find that for short chain lengths the theoretical density profiles are in an excellent agreement with the Monte Carlo data. The agreement is less satisfactory for longer chains. The performance of the theory can be improved by recasting the approach using the self-consistent field theory formalism. When the self-avoiding chain statistics is used, the theory yields a marked improvement in the low density limit. Further improvements for long chains could be reached by going beyond the first order of TPT.

Executives "Plug in" to Electronic Commerce

ERIC Educational Resources Information Center

Education & Training, 2002

2002-01-01

Describes a programme, developed by FT Knowledge and the Wharton School of the University of Pennsylvania, USA, to guide managers through the opportunities and threats presented by electronic commerce. Focuses on areas such as marketing, electronic retailing, pricing, product design, supply chain management and communication. Highlights how the…

Systems chemistry: All in a spin

NASA Astrophysics Data System (ADS)

Clark, Lucy; Lightfoot, Philip

2016-05-01

A fundamental challenge in systems chemistry is to engineer the emergence of complex behaviour. The collective structures of metal cyanide chains have now been interpreted in the same manner as the myriad of magnetic phases displayed by frustrated spin systems, highlighting a symbiotic approach between systems chemistry and magnetism.

Guidelines for Selecting a Construction Approach for Education Building Programs.

ERIC Educational Resources Information Center

Barton Malow Co., Southfield, MI.

This book discusses the advantages and disadvantages of the two most common construction planning methods utilized for educational facilities: general contracting and construction management. Diagrams are provided that illustrate the chain of command and communication within each approach, and highlight considerations that every school district…

Effect of Molecular Flexibility upon Ice Adhesion Shear Strength

NASA Technical Reports Server (NTRS)

Smith, Joseph G.; Wohl, Christopher J.; Kreeger, Richard E.; Palacios, Jose; Knuth, Taylor; Hadley, Kevin

2016-01-01

Ice formation on aircraft surfaces effects aircraft performance by increasing weight and drag leading to loss of lift. Current active alleviation strategies involve pneumatic boots, heated surfaces, and usage of glycol based de-icing fluids. Mitigation or reduction of in-flight icing by means of a passive approach may enable retention of aircraft capabilities, i.e., no reduction in lift, while reducing the aircraft weight and mechanical complexity. Under a NASA Aeronautics Research Institute Seedling activity, the effect of end group functionality and chain length upon ice adhesion shear strength (IASS) was evaluated with the results indicating that chemical functionality and chain length (i.e. molecular flexibility) affected IASS. Based on experimental and modeling results, diamine monomers incorporating molecular flexibility as either a side chain or in between diamine functionalities were prepared, incorporated into epoxy resins that were subsequently used to fabricate coatings on aluminum substrates, and tested in a simulated icing environment. The IASS was found to be lower when molecular flexibility was incorporated in the polymer chain as opposed to a side chain.

The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages.

PubMed

Padala, Prasanth; Soudah, Nadine; Giladi, Moshe; Haitin, Yoni; Isupov, Michail N; Wiener, Reuven

2017-12-08

The ability of ubiquitin to function in a wide range of cellular processes is ascribed to its capacity to cause a diverse spectrum of modifications. While a target protein can be modified with monoubiquitin, it can also be modified with ubiquitin chains. The latter include seven types of homotypic chains as well as mixed ubiquitin chains. In a mixed chain, not all the isopeptide bonds are restricted to a specific lysine of ubiquitin, resulting in a chain possessing more than one type of linkage. While structural characterization of homotypic chains has been well elucidated, less is known about mixed chains. Here we present the crystal structure of a mixed tri-ubiquitin chain at 3.1-Å resolution. In the structure, the proximal ubiquitin is connected to the middle ubiquitin via K48 and these two ubiquitins adopt a compact structure as observed in K48 di-ubiquitin. The middle ubiquitin links to the distal ubiquitin via its K63 and these ubiquitins adopt two conformations, suggesting a flexible structure. Using small-angle X-ray scattering, we unexpectedly found differences between the conformational ensembles of the above tri-ubiquitin chains and chains possessing the same linkages but in the reverse order. In addition, cleavage of the K48 linkage by DUB is faster if this linkage is at the distal end. Taken together, our results suggest that in mixed chains, not only the type of the linkages but also their sequence determine the structural and functional properties of the chain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Density Functional Study of Stacking Structures and Electronic Behaviors of AnE-PV Copolymer.

PubMed

Dong, Chuan-Ding; Beenken, Wichard J D

2016-10-10

In this work, we report an in-depth investigation on the π-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the π-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport.

Energetics and electronic structures of chemically decorated C60 chains

NASA Astrophysics Data System (ADS)

Furutani, Sho; Okada, Susumu

2018-06-01

We studied the energetics and electronic structures of one-dimensional molecular chains of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) using the density functional theory (DFT). Our DFT calculations show that the binding energies of PCBM range from 90 to 300 meV, depending on not only the intermolecular spacing but also the intermolecular arrangements owing to the interaction between functional groups and C60. The electronic structure of PCBM chains are also sensitive to the mutual arrangements of PCBM in their chain structure. The calculated effective masses of the conduction band range from 0.58 to 634.97m e, giving rise to anisotropic transport properties in their condensed phase.

From Puffins to Plankton: A DNA-Based Analysis of a Seabird Food Chain in the Northern Gulf of Maine

PubMed Central

Bowser, A. Kirsten; Diamond, Antony W.; Addison, Jason A.

2013-01-01

The predator-prey interactions within food chains are used to both characterize and understand ecosystems. Conventional methods of constructing food chains from visual identification of prey in predator diet can suffer from poor taxonomic resolution, misidentification, and bias against small or completely digestible prey. Next-generation sequencing (NGS) technology has become a powerful tool for diet reconstruction through barcoding of DNA in stomach content or fecal samples. Here we use multi-locus (16S and CO1) next-generation sequencing of DNA barcodes on the feces of Atlantic puffin (Fratercula arctica) chicks (n=65) and adults (n=64) and the stomach contents of their main prey, Atlantic herring (Clupea harengus, n=44) to investigate a previously studied food chain. We compared conventional and molecular-derived chick diet, tested the similarity between the diets of puffin adults and chicks, and determined whether herring prey can be detected in puffin diet samples. There was high variability in the coverage of prey groups between 16S and CO1 markers. We identified more unique prey with our 16S compared to CO1 barcoding markers (51 and 39 taxa respectively) with only 12 taxa identified by both genes. We found no significant difference between the 16S-identified diets of puffin adults (n=17) and chicks (n=41). Our molecular method is more taxonomically resolved and detected chick prey at higher frequencies than conventional field observations. Many likely planktonic prey of herring were detected in feces from puffin adults and chicks, highlighting the impact secondary consumption may have on the interpretation of molecular dietary analysis. This study represents the first simultaneous molecular investigation into the diet of multiple components of a food chain and highlights the utility of a multi-locus approach to diet reconstruction that is broadly applicable to food web analysis. PMID:24358258

Clathrin Heavy Chain Is Important for Viability, Oviposition, Embryogenesis and, Possibly, Systemic RNAi Response in the Predatory Mite Metaseiulus occidentalis

PubMed Central

Wu, Ke; Hoy, Marjorie A.

2014-01-01

Clathrin heavy chain has been shown to be important for viability, embryogenesis, and RNA interference (RNAi) in arthropods such as Drosophila melanogaster. However, the functional roles of clathrin heavy chain in chelicerate arthropods, such as the predatory mite Metaseiulus occidentalis, remain unknown. We previously showed that dsRNA ingestion, followed by feeding on spider mites, induced systemic and robust RNAi in M. occidentalis females. In the current study, we performed a loss-of-function analysis of the clathrin heavy chain gene in M. occidentalis using RNAi. We showed that ingestion of clathrin heavy chain dsRNA by M. occidentalis females resulted in gene knockdown and reduced longevity. In addition, clathrin heavy chain dsRNA treatment almost completely abolished oviposition by M. occidentalis females and the few eggs produced did not hatch. Finally, we demonstrated that clathrin heavy chain gene knockdown in M. occidentalis females significantly reduced a subsequent RNAi response induced by ingestion of cathepsin L dsRNA. The last finding suggests that clathrin heavy chain may be involved in systemic RNAi responses mediated by orally delivered dsRNAs in M. occidentalis. PMID:25329675

Site-directed mutagenesis of the regulatory light-chain Ca2+/Mg2+ binding site and its role in hybrid myosins

NASA Astrophysics Data System (ADS)

Reinach, Fernando C.; Nagai, Kiyoshi; Kendrick-Jones, John

1986-07-01

The regulatory light chains, small polypeptides located on the myosin head, regulate the interaction of myosin with actin in response to either Ca2+ or phosphorylation. The demonstration that the regulatory light chains on scallop myosin can be replaced by light chains from other myosins has allowed us to compare the functional capabilities of different light chains1, but has not enabled us to probe the role of features, such as the Ca2+/Mg2+ binding site, that are common to all of them. Here, we describe the use of site-directed mutagenesis to study the function of that site. We synthesized the chicken skeletal myosin light chain in Escherichia coli and constructed mutants with substitutions within the Ca2+/Mg2+ binding site. When the aspartate residues at the first and sixth Ca2+ coordination positions are replaced by uncharged alanines, the light chains have a reduced Ca2+ binding capacity but still bind to scallop myosin with high affinity. Unlike the wild-type skeletal light chain which inhibits myosin interaction with actin, the mutants activate it. Thus, an intact Ca2+/Mg2+ binding site in the N-terminal region of the light chain is essential for regulating the interaction of myosin with actin.

The Agr quorum-sensing system regulates fibronectin binding but not hemolysis in the absence of a functional electron transport chain.

PubMed

Pader, Vera; James, Ellen H; Painter, Kimberley L; Wigneshweraraj, Sivaramesh; Edwards, Andrew M

2014-10-01

Staphylococcus aureus is responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain of S. aureus genetically (hemB and menD) or chemically, using 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in both hemB mutant strains and S. aureus grown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression in hemB mutant strains or S. aureus grown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells.

PubMed

Shi, Xiarong; Burkart, Alison; Nicoloro, Sarah M; Czech, Michael P; Straubhaar, Juerg; Corvera, Silvia

2008-11-07

Adipocyte function is crucial for the control of whole body energy homeostasis. Pathway analysis of differentiating 3T3-L1 adipocytes reveals that major metabolic pathways induced during differentiation involve mitochondrial function. However, it is not clear why differentiated white adipocytes require enhanced respiratory chain activity relative to pre-adipocytes. To address this question, we used small interference RNA to interfere with the induction of the transcription factor Tfam, which is highly induced between days 2 and 4 of differentiation and is crucial for replication of mitochondrial DNA. Interference with Tfam resulted in cells with decreased respiratory chain capacity, reflected by decreased basal oxygen consumption, and decreased mitochondrial ATP synthesis, but no difference in many other adipocyte functions or expression levels of adipose-specific genes. However, insulin-stimulated GLUT4 translocation to the cell surface and subsequent glucose transport are impaired in Tfam knockdown cells. Paradoxically, insulin-stimulated Akt phosphorylation is significantly enhanced in these cells. These studies reveal independent links between mitochondrial function, insulin signaling, and glucose transport, in which impaired respiratory chain activity enhances insulin signaling to Akt phosphorylation, but impairs GLUT4 translocation. These results indicate that mitochondrial respiratory chain dysfunction in adipocytes can cause impaired insulin responsiveness of GLUT4 translocation by a mechanism downstream of the Akt protein kinase.

The Agr Quorum-Sensing System Regulates Fibronectin Binding but Not Hemolysis in the Absence of a Functional Electron Transport Chain

PubMed Central

Pader, Vera; James, Ellen H.; Painter, Kimberley L.; Wigneshweraraj, Sivaramesh

2014-01-01

Staphylococcus aureus is responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain of S. aureus genetically (hemB and menD) or chemically, using 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in both hemB mutant strains and S. aureus grown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression in hemB mutant strains or S. aureus grown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain. PMID:25092909

Measuring the environmental sustainability performance of global supply chains: A multi-regional input-output analysis for carbon, sulphur oxide and water footprints.

PubMed

Acquaye, Adolf; Feng, Kuishuang; Oppon, Eunice; Salhi, Said; Ibn-Mohammed, Taofeeq; Genovese, Andrea; Hubacek, Klaus

2017-02-01

Measuring the performance of environmentally sustainable supply chains instead of chain constitute has become a challenge despite the convergence of the underlining principles of sustainable supply chain management. This challenge is exacerbated by the fact that supply chains are inherently dynamic and complex and also because multiple measures can be used to characterize performances. By identifying some of the critical issues in the literature regarding performance measurements, this paper contributes to the existing body of literature by adopting an environmental performance measurement approach for economic sectors. It uses economic sectors and evaluates them on a sectoral level in specific countries as well as part of the Global Value Chain based on the established multi-regional input-output (MRIO) modeling framework. The MRIO model has been used to calculate direct and indirect (that is supply chain or upstream) environmental effects such as CO 2 , SO 2 , biodiversity, water consumption and pollution to name just a few of the applications. In this paper we use MRIO analysis to calculate emissions and resource consumption intensities and footprints, direct and indirect impacts, and net emission flows between countries. These are exemplified by using carbon emissions, sulphur oxide emissions and water use in two highly polluting industries; Electricity production and Chemical industry in 33 countries, including the EU-27, Brazil, India and China, the USA, Canada and Japan from 1995 to 2009. Some of the highlights include: On average, direct carbon emissions in the electricity sector across all 27 member states of the EU was estimated to be 1368 million tons and indirect carbon emissions to be 470.7 million tons per year representing 25.6% of the EU-27 total carbon emissions related to this sector. It was also observed that from 2004, sulphur oxide emissions intensities in electricity production in India and China have remained relatively constant at about 62.8 gSO x /, respectively, $ and 84.4 gSO x /$ although being higher than in other countries. In terms of water use, the high water use intensity in China (1040.27 L/$) and India (961.63 L/$), which are among the highest in the sector in the electricity sector is exacerbated by both countries being ranked as High Water Stress Risk countries. The paper also highlights many advantages of the MRIO approach including: a 15-year time series study (which provides a measurement of environmental performance of key industries and an opportunity to assess technical and technological change during the investigated time period), a supply chain approach that provides a consistent methodological framework and accounts for all upstream supply chain environmental impacts throughout entire global supply chains. The paper also discusses the implications of the study to environmental sustainability performance measurement in terms of the level of analysis from a value chain hierarchy perspective, methodological issues, performance indicators, environmental exchanges and policy relevance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Initiation and strain compatibility of connected extension twins in AZ31 magnesium alloy at high temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiao, E-mail: liuxiao0105@163.com

2016-12-15

Uniaxial compression tests were carried out at 350 °C and a strain rate of 0.3 s{sup −1} on as-extruded AZ31 magnesium alloy samples. At a true strain of − 0.1, extension twin pairs in a grain and twin chains across adjacent grains were detected. The orientation of selected twins and their host grains were determined by electron backscattered diffraction (EBSD) techniques. The Schmid factors (SFs), accommodation strains and geometric compatibility factors (m{sup ′}) were calculated. Analysis of the data indicated that the formation of twin pair and twin chain was related to the SF and m{sup ′}. Regarding to twinmore » chain across adjacent grains, accommodation strain was also involved. The selection of twin variants in twin chain was generally determined by m{sup ′}. When the twins required the operation of pyramidal slip or twinning in adjacent grain, the corresponding connected twins with a relative high m{sup ′} were selected in this adjacent grain. - Highlights: •The formation of paired twins is studied during high temperature deformation. •The initiation of twinning in twin pair and twin chain obeys the Schmid law. •The twin variants' selection in twin chain is related to the geometric compatibility factor. •The accommodation strain plays an important role on the formation of twin chain.« less

Collapse transitions in thermosensitive multi-block copolymers: A Monte Carlo study

NASA Astrophysics Data System (ADS)

Rissanou, Anastassia N.; Tzeli, Despoina S.; Anastasiadis, Spiros H.; Bitsanis, Ioannis A.

2014-05-01

Monte Carlo simulations are performed on a simple cubic lattice to investigate the behavior of a single linear multiblock copolymer chain of various lengths N. The chain of type (AnBn)m consists of alternating A and B blocks, where A are solvophilic and B are solvophobic and N = 2nm. The conformations are classified in five cases of globule formation by the solvophobic blocks of the chain. The dependence of globule characteristics on the molecular weight and on the number of blocks, which participate in their formation, is examined. The focus is on relative high molecular weight blocks (i.e., N in the range of 500-5000 units) and very differing energetic conditions for the two blocks (very good—almost athermal solvent for A and bad solvent for B). A rich phase behavior is observed as a result of the alternating architecture of the multiblock copolymer chain. We trust that thermodynamic equilibrium has been reached for chains of N up to 2000 units; however, for longer chains kinetic entrapments are observed. The comparison among equivalent globules consisting of different number of B-blocks shows that the more the solvophobic blocks constituting the globule the bigger its radius of gyration and the looser its structure. Comparisons between globules formed by the solvophobic blocks of the multiblock copolymer chain and their homopolymer analogs highlight the important role of the solvophilic A-blocks.

Serum-free light-chain assay: clinical utility and limitations.

PubMed

Bhole, Malini V; Sadler, Ross; Ramasamy, Karthik

2014-09-01

In the last decade, the introduction of the serum-free light-chain (sFLC) assay has been an important advance in the diagnosis and management of plasma cell dyscrasias, particularly monoclonal light-chain diseases. The immunoassay was developed to detect free light chains in serum by using anti-FLC antibodies which specifically recognised epitopes on light chains that were 'hidden' in intact immunoglobulins. Since its introduction in 2001, there have been several publications in the English language literature discussing the clinical utility as well as analytical limitations of the sFLC assay. These studies have highlighted both positive and negative aspects of the assay particularly with regard to its sensitivity and specificity and the technical challenges that can affect its performance. The contribution and significance of the sFLC assay in the management of light-chain myeloma, primary amyloid light-chain (AL) amyloidosis and non-secretory myeloma are well recognised and will be addressed in this review. The aim of this article is to also review the published literature with a view to providing a clear understanding of its utility and limitations in the diagnosis, prognosis and monitoring of plasma dyscrasias including intact immunoglobulin multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). The increasing interest in using this assay in other haematological conditions will also be briefly discussed. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Functional modulation of a protein folding landscape via side-chain distortion

PubMed Central

Kelch, Brian A.; Salimi, Neema L.; Agard, David A.

2012-01-01

Ultrahigh-resolution (< 1.0 Å) structures have revealed unprecedented and unexpected details of molecular geometry, such as the deformation of aromatic rings from planarity. However, the functional utility of such energetically costly strain is unknown. The 0.83 Å structure of α-lytic protease (αLP) indicated that residues surrounding a conserved Phe side-chain dictate a rotamer which results in a ∼6° distortion along the side-chain, estimated to cost 4 kcal/mol. By contrast, in the closely related protease Streptomyces griseus Protease B (SGPB), the equivalent Phe adopts a different rotamer and is undistorted. Here, we report that the αLP Phe side-chain distortion is both functional and conserved in proteases with large pro regions. Sequence analysis of the αLP serine protease family reveals a bifurcation separating those sequences expected to induce distortion and those that would not, which correlates with the extent of kinetic stability. Structural and folding kinetics analyses of family members suggest that distortion of this side-chain plays a role in increasing kinetic stability within the αLP family members that use a large Pro region. Additionally, structural and kinetic folding studies of mutants demonstrate that strain alters the folding free energy landscape by destabilizing the transition state (TS) relative to the native state (N). Although side-chain distortion comes at a cost of foldability, it suppresses the rate of unfolding, thereby enhancing kinetic stability and increasing protein longevity under harsh extracellular conditions. This ability of a structural distortion to enhance function is unlikely to be unique to αLP family members and may be relevant in other proteins exhibiting side-chain distortions. PMID:22635267

Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced colitis in mice due to increased intestinal permeability.

PubMed

Kim, Ye-Ryung; Volpert, Giora; Shin, Kyong-Oh; Kim, So-Yeon; Shin, Sun-Hye; Lee, Younghay; Sung, Sun Hee; Lee, Yong-Moon; Ahn, Jung-Hyuck; Pewzner-Jung, Yael; Park, Woo-Jae; Futerman, Anthony H; Park, Joo-Won

2017-12-01

Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates. Using mixed bone-marrow chimeric mice, we showed that the host environment is primarily responsible for intestinal barrier dysfunction and increased intestinal permeability. In the colon of CerS2 null mice, the expression of junctional adhesion molecule-A was markedly decreased and the phosphorylation of myosin light chain 2 was increased. In vitro experiments using Caco-2 cells also confirmed an important role of CerS2 in maintaining epithelial barrier function; CerS2-knockdown via CRISPR-Cas9 technology impaired barrier function. In vivo myriocin administration, which normalized long-chain bases and C16-ceramides of the colon of CerS2 null mice, increased intestinal permeability as measured by serum FITC-dextran levels, indicating that altered SLs including deficiency of very-long-chain ceramides are critical for epithelial barrier function. In conclusion, deficiency of CerS2 influences intestinal barrier function and the severity of experimental colitis and may represent a potential mechanism for inflammatory bowel disease pathogenesis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Probing the Differential Tissue Distribution and Bioaccumulation Behavior of Per- and Polyfluoroalkyl Substances of Varying Chain-Lengths, Isomeric Structures and Functional Groups in Crucian Carp.

PubMed

Shi, Yali; Vestergren, Robin; Nost, Therese Haugdahl; Zhou, Zhen; Cai, Yaqi

2018-04-17

Understanding the bioaccumulation mechanisms of per- and polyfluoroalkyl substances (PFASs) across different chain-lengths, isomers and functional groups represents a monumental scientific challenge with implications for chemical regulation. Here, we investigate how the differential tissue distribution and bioaccumulation behavior of 25 PFASs in crucian carp from two field sites impacted by point sources can provide information about the processes governing uptake, distribution and elimination of PFASs. Median tissue/blood ratios (TBRs) were consistently <1 for all PFASs and tissues except bile which displayed a distinct distribution pattern and enrichment of several perfluoroalkyl sulfonic acids. Transformation of concentration data into relative body burdens (RBBs) demonstrated that blood, gonads, and muscle together accounted for >90% of the amount of PFASs in the organism. Principal component analyses of TBRs and RBBs showed that the functional group was a relatively more important predictor of internal distribution than chain-length for PFASs. Whole body bioaccumulation factors (BAFs) for short-chain PFASs deviated from the positive relationship with hydrophobicity observed for longer-chain homologues. Overall, our results suggest that TBR, RBB, and BAF patterns were most consistent with protein binding mechanisms although partitioning to phospholipids may contribute to the accumulation of long-chain PFASs in specific tissues.

DFT study of CdS-PVA film

NASA Astrophysics Data System (ADS)

Bala, Vaneeta; Tripathi, S. K.; Kumar, Ranjan

2015-02-01

Density functional theory has been applied to study cadmium sulphide-polyvinyl alcohol nanocomposite film. Structural models of two isotactic-polyvinyl alcohol (I-PVA) chains around one cadmium sulphide nanoparticle is considered in which each chain consists three monomer units of [-(CH2CH(OH))-]. All of the hydroxyl groups in I-PVA chains are directed to cadmium sulphide nanoparticle. Electronic and structural properties are investigated using ab-intio density functional code, SIESTA. Structural optimizations are done using local density approximations (LDA). The exchange correlation functional of LDA is parameterized by the Ceperley-Alder (CA) approach. The core electrons are represented by improved Troulier-Martins pseudopotentials. Densities of states clearly show the semiconducting nature of cadmium sulphide polyvinyl alcohol nanocomposite.

Characterization of Hydrophobic Interactions of Polymers with Water and Phospholipid Membranes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Drenscko, Mihaela

Polymers and lipid membranes are both essential soft materials. The structure and hydrophobicity/hydrophilicity of polymers, as well as the solvent they are embedded in, ultimately determines their size and shape. Understating the variation of shape of the polymer as well as its interactions with model biological membranes can assist in understanding the biocompatibility of the polymer itself. Computer simulations, in particular molecular dynamics, can aid in characterization of the interaction of polymers with solvent, as well as polymers with model membranes. In this thesis, molecular dynamics serve to describe polymer interactions with a solvent (water) and with a lipid membrane. To begin with, we characterize the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained molecular simulation. We next explore the scaling behavior of the collapsed globular shape at the minimum energy configuration, characterized by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behavior of the Solvent Accessible Surface Area (SASA) as a function of chain length, finding a similar exponent for both all-atomistic and coarse-grained simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths. Next, in order to investigate the molecular interactions between single hydrophobic polymer chains and lipids in biological membranes and at lipid membrane/solvent interface, we perform a series of molecular dynamics simulations of small membranes using all atomistic and coarse-grained methods. The molecular interaction between common polymer chains used in biomedical applications and the cell membrane is unknown. This interaction may affect the biocompatibility of the polymer chains. Molecular dynamics simulations offer an emerging tool to characterize the interaction between common degradable polymer chains used in biomedical applications, such as polycaprolactone, and model cell membranes. We systematically characterize with long-time all-atomistic molecular dynamics simulations the interaction between single polycaprolactone chains of varying chain lengths with a model phospholipid membrane. We find that the length of polymer chain greatly affects the nature of interaction with the membrane, as well as the membrane properties. Furthermore, we next utilize advanced sampling techniques in molecular dynamics to characterize the two-dimensional free energy surface for the interaction of varying polymer chain lengths (short, intermediate, and long) with model cell membranes. We find that the free energy minimum shifts from the membrane-water interface to the hydrophobic core of the phospholipid membrane as a function of chain length. These results can be used to design polymer chain lengths and chemistries to optimize their interaction with cell membranes at the molecular level.

The economic and poverty impacts of animal diseases in developing countries: new roles, new demands for economics and epidemiology.

PubMed

Rich, Karl M; Perry, Brian D

2011-09-01

Animal disease outbreaks pose significant threats to livestock sectors throughout the world, both from the standpoint of the economic impacts of the disease itself and the measures taken to mitigate the risk of disease introduction. These impacts are multidimensional and not always well understood, complicating effective policy response. In the developing world, livestock diseases have broader, more nuanced effects on markets, poverty, and livelihoods, given the diversity of uses of livestock and complexity of livestock value chains. In both settings, disease control strategies, particularly those informed by ex ante modeling platforms, often fail to recognize the constraints inherent among farmers, veterinary services, and other value chain actors. In short, context matters. Correspondingly, an important gap in the animal health economics literature is the explicit incorporation of behavior and incentives in impact analyses that highlight the interactions of disease with its socio-economic and institutional setting. In this paper, we examine new approaches and frameworks for the analysis of economic and poverty impacts of animal diseases. We propose greater utilization of "bottom-up" analyses, highlighting the strengths and weaknesses of value chain and information economics approaches in impact analyses and stressing the importance of improved integration between the epidemiology of disease and its relationships with economic behavior. Copyright © 2010 Elsevier B.V. All rights reserved.

U.S.-North American trade and freight transportation highlights : transborder freight data

DOT National Transportation Integrated Search

2005-06-01

In 2004, the value of U.S. merchandise trade with Canada and Mexico rose 13 percent over : the previous years total to an all-time high of $712 billion. Using chained 2000 dollars to adjust for inflation, this trade grew by 8 percent from 2003 to ...

A Functional Approach towards Understanding the Role of the Mitochondrial Respiratory Chain in an Endomycorrhizal Symbiosis

PubMed Central

Mercy, Louis; Lucic-Mercy, Eva; Nogales, Amaia; Poghosyan, Areg; Schneider, Carolin; Arnholdt-Schmitt, Birgit

2017-01-01

Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called “second green revolution” by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid – ABA and gibberellic acid – Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited in vitro spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, R. irregulare induced down-regulation of StAOX gene isoforms and up-regulation of genes involved in plant COX pathway. In all phosphorus (P) concentrations, blocking AOX or COX induced opposite mycorrhizal patterns in planta: KCN induced higher Arum-type arbuscule density, positive MGD but lower root colonization compared to SHAM, which favored Paris-type formation and negative MGD. Following our results and current state-of-the-art knowledge, we discuss metabolic functions linked to respiration that may occur within mycorrhizal behavior. We highlight potential connections between AOX pathways and fermentation, and we propose new research and mycorrhizal application perspectives. PMID:28424712

Barth syndrome: clinical observations and genetic linkage studies.

PubMed

Christodoulou, J; McInnes, R R; Jay, V; Wilson, G; Becker, L E; Lehotay, D C; Platt, B A; Bridge, P J; Robinson, B H; Clarke, J T

1994-04-15

Barth syndrome is an X-linked recessive condition characterized by skeletal myopathy, cardiomyopathy, proportionate short stature, and recurrent neutropenia, but with normal cognitive function. Some, but not all patients, exhibit carnitine deficiency and/or the presence of 3-methylglutaconic and ethylhydracylic acids in urine. Recently the mutation causing Barth syndrome was localised to the Xq28 region by linkage analysis. We report 6 cases of Barth syndrome from 4 families and highlight the fact that neuromuscular and cardiovascular symptoms and the severity of infections tend to improve with age, while short stature persists. Also previously unreported was myopathic facies and nasal quality to speech in our cases. The urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. We propose that they may be epiphenomena rather than indicators of the primary metabolic defect, and that the primary defect or defects in this disorder may lie in the mitochondrial electron transport chain.

Autonomous Integrated Receive System (AIRS) requirements definition. Volume 3: Performance and simulation

NASA Technical Reports Server (NTRS)

Chie, C. M.; Su, Y. T.; Lindsey, W. C.; Koukos, J.

1984-01-01

The autonomous and integrated aspects of the operation of the AIRS (Autonomous Integrated Receive System) are discussed from a system operation point of view. The advantages of AIRS compared to the existing SSA receive chain equipment are highlighted. The three modes of AIRS operation are addressed in detail. The configurations of the AIRS are defined as a function of the operating modes and the user signal characteristics. Each AIRS configuration selection is made up of three components: the hardware, the software algorithms and the parameters used by these algorithms. A comparison between AIRS and the wide dynamics demodulation (WDD) is provided. The organization of the AIRS analytical/simulation software is described. The modeling and analysis is for simulating the performance of the PN subsystem is documented. The frequence acquisition technique using a frequency-locked loop is also documented. Doppler compensation implementation is described. The technological aspects of employing CCD's for PN acquisition are addressed.

Silk Hydrogels of Tunable Structure and Viscoelastic Properties Using Different Chronological Orders of Genipin and Physical Cross-Linking.

PubMed

Elliott, Winston H; Bonani, Walter; Maniglio, Devid; Motta, Antonella; Tan, Wei; Migliaresi, Claudio

2015-06-10

Catering the hydrogel manufacturing process toward defined viscoelastic properties for intended biomedical use is important to hydrogel scaffolding function and cell differentiation. Silk fibroin hydrogels may undergo "physical" cross-linking through β-sheet crystallization during high pressure carbon dioxide treatment, or covalent "chemical" cross-linking by genipin. We demonstrate here that time-dependent mechanical properties are tunable in silk fibroin hydrogels by altering the chronological order of genipin cross-linking with β-sheet formation. Genipin cross-linking before β-sheet formation affects gelation mechanics through increased molecular weight, affecting gel morphology, and decreasing stiffness response. Alternately, genipin cross-linking after gelation anchored amorphous regions of the protein chain, and increasing stiffness. These differences are highlighted and validated through large amplitude oscillatory strain near physiologic levels, after incorporation of material characterization at molecular and micron length scales.

Application of Bottlebrush Block Copolymers as Photonic Crystals.

PubMed

Liberman-Martin, Allegra L; Chu, Crystal K; Grubbs, Robert H

2017-07-01

Brush block copolymers are a class of comb polymers that feature polymeric side chains densely grafted to a linear backbone. These polymers display interesting properties due to their dense functionality, low entanglement, and ability to rapidly self-assemble to highly ordered nanostructures. The ability to prepare brush polymers with precise structures has been enabled by advancements in controlled polymerization techniques. This Feature Article highlights the development of brush block copolymers as photonic crystals that can reflect visible to near-infrared wavelengths of light. Fabrication of these materials relies on polymer self-assembly processes to achieve nanoscale ordering, which allows for the rapid preparation of photonic crystals from common organic chemical feedstocks. The characteristic physical properties of brush block copolymers are discussed, along with methods for their preparation. Strategies to induce self-assembly at ambient temperatures and the use of blending techniques to tune photonic properties are emphasized. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Core/shell, protuberance-free multiwalled carbon nanotube/polyaniline nanocomposites via interfacial chemistry of aryl diazonium salts.

PubMed

Mekki, Ahmed; Samanta, Soumen; Singh, Ajay; Salmi, Zakaria; Mahmoud, Rachid; Chehimi, Mohamed M; Aswal, Dinesh K

2014-03-15

Highly uniform core-shell like multi-walled carbon nanotubes-polyaniline (MWCNT-PANI) nanocomposites were prepared in two steps (i) surface modification of MWCNTs with a 4-aminodiphenylamine group via in situ diazonium generation process; and (ii) polymerization of aniline onto surface modified MWCNTs. This functionalization helped to easily disperse the MWCNTs in acidic solutions; hence it is suitable for the chemical oxidative polymerization of aniline. It was found that MWCNT-PANI nano-composites with higher MWCNTs loading yield PANI chains with more quinoid units than the pure PANI, which results in significant improvement in the conductivity of the composites. This facile approach of synthesizing core-shell nanocomposites highlights the efficiency of the interfacial chemistry of aryl diazonium salts in generating conductive polymer/MWCNT nanocomposites with enhanced conductivity and high surface area. Copyright © 2013 Elsevier Inc. All rights reserved.

Concomitant prediction of function and fold at the domain level with GO-based profiles.

PubMed

Lopez, Daniel; Pazos, Florencio

2013-01-01

Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

Surface properties of functional polymer systems

NASA Astrophysics Data System (ADS)

Wong, Derek

Polymer surface modification typically involves blending with other polymers or chemical modification of the parent polymer. Such strategies inevitably result in polymer systems that are spatially and chemically heterogeneous, and which exhibit the phenomenon of surface segregation. This work investigates the effects of chain architecture on the surface segregation behavior of such functionally modified polymers using a series of end- and center-fluorinated poly(D,L-lactide). Surface segregation of the fluorinated functional groups was observed in both chain architectures via AMPS and water contact angle. Higher surface segregation was noted for functional groups located at the chain end as opposed to those in the middle of the chain. A self-consistent mean-field lattice theory was used to model the composition depth profiles of functional groups and excellent agreement was found between the model predictions and the experimental AMPS data in both chain architectures. Polymer properties are also in general dependent on both time and temperature, and exhibit a range of relaxation times in response to environmental stimuli. This behavior arises from the characteristic frequencies of molecular motions of the polymer chain and the interrelationship between time and temperature has been widely established for polymer bulk properties. There is evidence that surface properties also respond in a manner that is time and temperature dependent and that this dependence may not be the same as that observed for bulk properties. AMPS and water contact angle experiments were used to investigate the surface reorganization behavior of functional groups using a series of anionically synthesized end-fluorinated and end-carboxylated poly(styrene). It was found that both types of functional end-groups reorganized upon a change in the polarity of the surface environment in order to minimize the surface free energy. ADXPS and contact angle results suggest that the reorganization depth was confined to the top 2--3 nm of the surface. Contact angle results showed also that the reorganization process proceeded as a function of (time) 1/2, indicating that it is likely diffusion controlled. The magnitudes of the activation energies determined from the experimental data according to the Arhenius equation, suggest that the process is possibly correlated with known bulk beta and gamma relaxations in the polymer.

Construction and Development of CRM Technology and Industry Chain in China

NASA Astrophysics Data System (ADS)

Liu, Chunnian; Wang, Yonglong; Pan, Qin

CRM is any application or initiative designed to help an organization optimize interactions with customers, suppliers, or prospects via one or more touch points. CRM has been interpreted and used in different ways by researchers in the various disciplines and researchers have identified a variety of technologies related to CRM. This paper highlights the implementation from the technology level and contributes to some successful factors in CRM application. The development of CRM is not fully developed in China. There are many critical factors that determine the CRM market development. Construction and development of CRM industry chain in China is a valuable research field and the paper provided some suggestions and analyses on it. In future, it requires our joint efforts of many aspects from every walk of life to make sure that CRM industry chain can improve and maturate gradually.

Inelastic electron injection in a water chain

PubMed Central

Rizzi, Valerio; Todorov, Tchavdar N.; Kohanoff, Jorge J.

2017-01-01

Irradiation of biological matter triggers a cascade of secondary particles that interact with their surroundings, resulting in damage. Low-energy electrons are one of the main secondary species and electron-phonon interaction plays a fundamental role in their dynamics. We have developed a method to capture the electron-phonon inelastic energy exchange in real time and have used it to inject electrons into a simple system that models a biological environment, a water chain. We simulated both an incoming electron pulse and a steady stream of electrons and found that electrons with energies just outside bands of excited molecular states can enter the chain through phonon emission or absorption. Furthermore, this phonon-assisted dynamical behaviour shows great sensitivity to the vibrational temperature, highlighting a crucial controlling factor for the injection and propagation of electrons in water. PMID:28350013

The electrical and thermal transport properties of hybrid zigzag graphene-BN nanoribbons

NASA Astrophysics Data System (ADS)

Gao, Song; Lu, Wei; Zheng, Guo-Hui; Jia, Yalei; Ke, San-Huang

2017-06-01

The electron and phonon transport in hybrid graphene-BN zigzag nanoribbons are investigated by the nonequilibrium Green’s function method combined with density functional theory calculations. A 100% spin-polarized electron transport in a large energy window around the Fermi level is found and this behavior is independent of the ribbon width as long as there contain 3 zigzag carbon chains. The phonon transport calculations show that the ratio of C-chain number to BN-chain number will modify the thermal conductance of the hybrid nanoribbon in a complicated manner.

Using Kalman Filter Chemical Data Assimilation to Study Ozone Catalytic Loss Cycles in January 1992

NASA Technical Reports Server (NTRS)

Lary, David J.

2002-01-01

This paper presents for the first time a global study of the ozone catalytic destruction cycles operating in the stratosphere using a stratospheric analyses for January 1992. The chemical analyses were produced using a Kalman filter data assimilation system. Because a major component of the variability of trace gases is due to the atmospheric motions the analyses have been cast in a flow-tracking coordinate system that moves with the large scale flow pattern. Particular attention is paid to the kinetic aspects of these cycles such as the rate limiting step and chain length. Although it is an important kinetic parameter, the chain length of the various cycles is seldom considered when the various catalytic cycles are discussed. This survey highlights that in the low stratosphere the cycles involving HO2 and halogens (notably bromine) are particularly important. In approximate order of effectiveness the most important ozone loss cycles in the polar lower stratosphere are the BrO/ClO, HO2/BrO, and OH/HO2 cycles. The ClO/ClO cycle clearly delineates the regions of chlorine activation. The chain length of the HO2/ClO, OH/HO2, Br/BrO, and ClO/NO2, clearly delineate the vortex edge region. The chain length of the BrO/NO2 and Cl/NO2 cycles highlight the regions of chemical processing outside the vortex where streamers of chemically processed air are stripped-off and transported away from the vortex. This is also true in the very low stratosphere for the Cl/ClO and BrO/ClO cycles.

Critical Casimir effect in a polymer chain in supercritical solvents.

PubMed

Sumi, Tomonari; Imazaki, Nobuyuki; Sekino, Hideo

2009-03-01

Density fluctuation effects on the conformation of a polymer chain in a supercritical solvent were investigated by performing a multiscale simulation based on the density-functional theory. We found (a) a universal swelling of the polymer chain near the critical point, irrespective of whether the polymer chain is solvophilic or solvophobic, and (b) a characteristic collapse of the polymer chain having a strong solvophilicity at a temperature slightly higher than the critical point, where the isothermal compressibility becomes less than the ideal one.

Multidimensional competences of supply chain managers: an empirical study

NASA Astrophysics Data System (ADS)

Shou, Yongyi; Wang, Weijiao

2017-01-01

Supply chain manager competences have attracted increasing attention from both practitioners and scholars in recent years. This paper conducted an explorative study to understand the dimensionality of supply chain manager competences. Online job advertisements for supply chain managers were collected as secondary data, since these advertisements reflect employers' real job requirements. We adopted the multidimensional scaling (MDS) technique to process and analyse the data. Five dimensions of supply chain manager competences are identified: generic skills, functional skills, supply chain management (SCM) qualifications and leadership, SCM expertise, and industry-specific and senior management skills. Statistic tests indicate that supply chain manager competence saliences vary in different industries and regions.

An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells

NASA Astrophysics Data System (ADS)

Nilsson, Peter; Magnusson, Karin; Appelqvist, Hanna; Cieslar-Pobuda, Artur; Bäck, Marcus; Kågedal, Bertil; Jonasson, Jon; Los, Marek

2015-10-01

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

Thermal form factor approach to the ground-state correlation functions of the XXZ chain in the antiferromagnetic massive regime

NASA Astrophysics Data System (ADS)

Dugave, Maxime; Göhmann, Frank; Kozlowski, Karol K.; Suzuki, Junji

2016-09-01

We use the form factors of the quantum transfer matrix in the zero-temperature limit in order to study the two-point ground-state correlation functions of the XXZ chain in the antiferromagnetic massive regime. We obtain novel form factor series representations of the correlation functions which differ from those derived either from the q-vertex-operator approach or from the algebraic Bethe Ansatz approach to the usual transfer matrix. We advocate that our novel representations are numerically more efficient and allow for a straightforward calculation of the large-distance asymptotic behaviour of the two-point functions. Keeping control over the temperature corrections to the two-point functions we see that these are of order {T}∞ in the whole antiferromagnetic massive regime. The isotropic limit of our result yields a novel form factor series representation for the two-point correlation functions of the XXX chain at zero magnetic field. Dedicated to the memory of Petr Petrovich Kulish.

Sequence determination of synthesized chondroitin sulfate dodecasaccharides.

PubMed

Shioiri, Tatsumasa; Tsuchimoto, Jun; Watanabe, Hideto; Sugiura, Nobuo

2016-06-01

Chondroitin sulfate (CS) is a linear acidic polysaccharide composed of repeating disaccharide units of glucuronic acid and N-acetyl-d-galactosamine. The polysaccharide is modified with sulfate groups at different positions by a variety of sulfotransferases. CS chains exhibit various biological and pathological functions by interacting with cytokines and growth factors and regulating their signal transduction. The fine structure of the CS chain defines its specific biological roles. However, structural analysis of CS has been restricted to disaccharide analysis, hampering the understanding of the structure-function relationship of CS chains. Here, we chemo-enzymatically synthesized CS dodecasaccharides having various sulfate modifications using a bioreactor system of bacterial chondroitin polymerase mutants and various CS sulfotransferases. We developed a sequencing method for CS chains using the CS dodecasaccharides. The method consists of (i) labeling a reducing end with 2-aminopyridine (PA), (ii) partial digestion of CS with testicular hyaluronidase, followed by separation of PA-conjugated oligosaccharides with different chain lengths, (iii) limited digestion of these oligosaccharides with chondroitin lyase AC II into disaccharides, followed by labeling with 2-aminobenzamide, (iv) CS disaccharide analysis using a dual-fluorescence HPLC system (reversed-phase ion-pair and ion-exchange chromatography), and (v) estimation of the composition by calculating individual disaccharide ratios. This CS chain sequencing allows characterization of CS-modifying enzymes and provides a useful tool toward understanding the structure-function relationship of CS chains. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harstad, E. N.; Harlow, Francis Harvey,; Schreyer, H. L.

Our goal is to develop constitutive relations for the behavior of a solid polymer during high-strain-rate deformations. In contrast to the classic thermodynamic techniques for deriving stress-strain response in static (equilibrium) circumstances, we employ a statistical-mechanics approach, in which we evolve a probability distribution function (PDF) for the velocity fluctuations of the repeating units of the chain. We use a Langevin description for the dynamics of a single repeating unit and a Lioville equation to describe the variations of the PDF. Moments of the PDF give the conservation equations for a single polymer chain embedded in other similar chains. Tomore » extract single-chain analytical constitutive relations these equations have been solved for representative loading paths. By this process we discover that a measure of nonuniform chain link displacement serves this purpose very well. We then derive an evolution equation for the descriptor function, with the result being a history-dependent constitutive relation.« less

Very Long Chain Fatty Acids Are Functionally Involved in Necroptosis.

PubMed

Parisi, Laura R; Li, Nasi; Atilla-Gokcumen, G Ekin

2017-12-21

Necroptosis is a form of regulated cell death that is linked to various human diseases. Distinct membrane-related, thus lipid-dependent, alterations take place during necroptosis. However, little is known about the roles of specific lipids in this process. We used an untargeted LC-MS-based approach to reveal that distinct lipid species are regulated at the molecular level during necroptosis. We found that ceramides and very long chain fatty acids accumulate during this process. Intrigued by the specificity of very long chain fatty acid accumulation, we focused on characterizing their involvement during necroptosis. Biochemical characterizations suggested that activated fatty acid biosynthesis and elongation could be responsible for these accumulations. We further showed that inhibition of fatty acid biosynthesis and depletion of very long chain fatty acids prevented loss of plasma membrane integrity and cell death, strongly suggesting that very long chain fatty acids are functionally involved in necroptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanics and pathomechanics in the overhead athlete.

PubMed

Kibler, W Ben; Wilkes, Trevor; Sciascia, Aaron

2013-10-01

Optimal performance of the overhead throwing task requires precise mechanics that involve coordinated kinetic and kinematic chains to develop, transfer, and regulate the forces the body needs to withstand the inherent demands of the task and to allow optimal performance. These chains have been evaluated and the basic components, called nodes, have been identified. Impaired performance and/or injury, the DTS, is associated with alterations in the mechanics that are called pathomechanics. They can occur at multiple locations throughout the kinetic chain. They must be evaluated and treated as part of the overall problem. Observational analysis of the mechanics and pathomechanics using the node analysis method can be useful in highlighting areas of alteration that can be evaluated for anatomic injury or altered physiology. The comprehensive kinetic chain examination can evaluate sites of kinetic chain breakage, and a detailed shoulder examination can assess joint internal derangement of altered physiology that may contribute to the pathomechanics. Treatment of the DTS should be comprehensive, directed toward restoring physiology and mechanics and optimizing anatomy. This maximizes the body’s ability to develop normal mechanics to accomplish the overhead throwing task. Copyright © 2013 Elsevier Inc. All rights reserved.

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

PubMed Central

Daidone, Isabella; Neuweiler, Hannes; Doose, Sören; Sauer, Markus; Smith, Jeremy C.

2010-01-01

Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient β-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events. PMID:20098498

Supersymmetric quantum spin chains and classical integrable systems

NASA Astrophysics Data System (ADS)

Tsuboi, Zengo; Zabrodin, Anton; Zotov, Andrei

2015-05-01

For integrable inhomogeneous supersymmetric spin chains (generalized graded magnets) constructed employing Y( gl( N| M))-invariant R-matrices in finite-dimensional representations we introduce the master T-operator which is a sort of generating function for the family of commuting quantum transfer matrices. Any eigenvalue of the master T-operator is the tau-function of the classical mKP hierarchy. It is a polynomial in the spectral parameter which is identified with the 0-th time of the hierarchy. This implies a remarkable relation between the quantum supersymmetric spin chains and classical many-body integrable systems of particles of the Ruijsenaars-Schneider type. As an outcome, we obtain a system of algebraic equations for the spectrum of the spin chain Hamiltonians.

Aromatic anchor at an invariant hormone-receptor interface: Function of insulin residue B24 with application to protein design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandyarajan, Vijay; Smith, Brian J.; Phillips, Nelson B.

Crystallographic studies of insulin bound to fragments of the insulin receptor have recently defined the topography of the primary hormone-receptor interface. Here, we have investigated the role of Phe B24, an invariant aromatic anchor at this interface and site of a human mutation causing diabetes mellitus. An extensive set of B24 substitutions has been constructed and tested for effects on receptor binding. Although aromaticity has long been considered a key requirement at this position, Met B24 was found to confer essentially native affinity and bioactivity. Molecular modeling suggests that this linear side chain can serve as an alternative hydrophobic anchormore » at the hormone-receptor interface. These findings motivated further substitution of Phe B24 by cyclohexanylalanine (Cha), which contains a nonplanar aliphatic ring. Contrary to expectations, [Cha B24]insulin likewise exhibited high activity. Furthermore, its resistance to fibrillation and the rapid rate of hexamer disassembly, properties of potential therapeutic advantage, were enhanced. The crystal structure of the Cha B24 analog, determined as an R 6 zinc-stabilized hexamer at a resolution of 1.5 Å, closely resembles that of wild-type insulin. The nonplanar aliphatic ring exhibits two chair conformations with partial occupancies, each recapitulating the role of Phe B24 at the dimer interface. Together, these studies have defined structural requirements of an anchor residue within the B24-binding pocket of the insulin receptor; similar molecular principles are likely to pertain to insulin-related growth factors. Finally, our results highlight in particular the utility of nonaromatic side chains as probes of the B24 pocket and suggest that the nonstandard Cha side chain may have therapeutic utility.« less

Is benthic food web structure related to diversity of marine macrobenthic communities?

NASA Astrophysics Data System (ADS)

Sokołowski, A.; Wołowicz, M.; Asmus, H.; Asmus, R.; Carlier, A.; Gasiunaité, Z.; Grémare, A.; Hummel, H.; Lesutiené, J.; Razinkovas, A.; Renaud, P. E.; Richard, P.; Kędra, M.

2012-08-01

Numerical structure and the organisation of food webs within macrozoobenthic communities has been assessed in the European waters (Svalbard, Barents Sea, Baltic Sea, North Sea, Atlantic Ocean and the Mediterranean Sea) to address the interactions between biodiversity and ecosystem functioning. Abundance and classical species diversity indices (S, H', J) of macrofaunal communities were related to principal attributes of food webs (relative trophic level and food chain length, FCL) that were determined from carbon and nitrogen stable isotope values. Structure of marine macrobenthos varies substantially at a geographical scale; total abundance ranges from 63 ind. m-2 to 34,517 ind. m-2, species richness varies from 3 to 166 and the Shannon-Weaver diversity index from 0.26 to 3.26 while Pielou's evenness index is below 0.73. The major source of energy for macrobenthic communities is suspended particulate organic matter, consisting of phytoplankton and detrital particles, sediment particulate organic matter, and microphytobenthos in varying proportions. These food sources support the presence of suspension- and deposit-feeding communities, which dominate numerically on the sea floor. Benthic food webs include usually four to five trophic levels (FCL varies from 3.08 to 4.86). Most species are assigned to the second trophic level (primary consumers), fewer species are grouped in the third trophic level (secondary consumers), and benthic top predators are the least numerous. Most species cluster primarily at the lowest trophic level that is consistent with the typical organization of pyramidal food webs. Food chain length increases with biodiversity, highlighting a positive effect of more complex community structure on food web organisation. In more diverse benthic communities, energy is transferred through more trophic levels while species-poor communities sustain a shorter food chain.

Aromatic anchor at an invariant hormone-receptor interface: function of insulin residue B24 with application to protein design.

PubMed

Pandyarajan, Vijay; Smith, Brian J; Phillips, Nelson B; Whittaker, Linda; Cox, Gabriella P; Wickramasinghe, Nalinda; Menting, John G; Wan, Zhu-li; Whittaker, Jonathan; Ismail-Beigi, Faramarz; Lawrence, Michael C; Weiss, Michael A

2014-12-12

Crystallographic studies of insulin bound to fragments of the insulin receptor have recently defined the topography of the primary hormone-receptor interface. Here, we have investigated the role of Phe(B24), an invariant aromatic anchor at this interface and site of a human mutation causing diabetes mellitus. An extensive set of B24 substitutions has been constructed and tested for effects on receptor binding. Although aromaticity has long been considered a key requirement at this position, Met(B24) was found to confer essentially native affinity and bioactivity. Molecular modeling suggests that this linear side chain can serve as an alternative hydrophobic anchor at the hormone-receptor interface. These findings motivated further substitution of Phe(B24) by cyclohexanylalanine (Cha), which contains a nonplanar aliphatic ring. Contrary to expectations, [Cha(B24)]insulin likewise exhibited high activity. Furthermore, its resistance to fibrillation and the rapid rate of hexamer disassembly, properties of potential therapeutic advantage, were enhanced. The crystal structure of the Cha(B24) analog, determined as an R6 zinc-stabilized hexamer at a resolution of 1.5 Å, closely resembles that of wild-type insulin. The nonplanar aliphatic ring exhibits two chair conformations with partial occupancies, each recapitulating the role of Phe(B24) at the dimer interface. Together, these studies have defined structural requirements of an anchor residue within the B24-binding pocket of the insulin receptor; similar molecular principles are likely to pertain to insulin-related growth factors. Our results highlight in particular the utility of nonaromatic side chains as probes of the B24 pocket and suggest that the nonstandard Cha side chain may have therapeutic utility. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Aromatic anchor at an invariant hormone-receptor interface: Function of insulin residue B24 with application to protein design

DOE PAGES

Pandyarajan, Vijay; Smith, Brian J.; Phillips, Nelson B.; ...

2014-10-10

Crystallographic studies of insulin bound to fragments of the insulin receptor have recently defined the topography of the primary hormone-receptor interface. Here, we have investigated the role of Phe B24, an invariant aromatic anchor at this interface and site of a human mutation causing diabetes mellitus. An extensive set of B24 substitutions has been constructed and tested for effects on receptor binding. Although aromaticity has long been considered a key requirement at this position, Met B24 was found to confer essentially native affinity and bioactivity. Molecular modeling suggests that this linear side chain can serve as an alternative hydrophobic anchormore » at the hormone-receptor interface. These findings motivated further substitution of Phe B24 by cyclohexanylalanine (Cha), which contains a nonplanar aliphatic ring. Contrary to expectations, [Cha B24]insulin likewise exhibited high activity. Furthermore, its resistance to fibrillation and the rapid rate of hexamer disassembly, properties of potential therapeutic advantage, were enhanced. The crystal structure of the Cha B24 analog, determined as an R 6 zinc-stabilized hexamer at a resolution of 1.5 Å, closely resembles that of wild-type insulin. The nonplanar aliphatic ring exhibits two chair conformations with partial occupancies, each recapitulating the role of Phe B24 at the dimer interface. Together, these studies have defined structural requirements of an anchor residue within the B24-binding pocket of the insulin receptor; similar molecular principles are likely to pertain to insulin-related growth factors. Finally, our results highlight in particular the utility of nonaromatic side chains as probes of the B24 pocket and suggest that the nonstandard Cha side chain may have therapeutic utility.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guidarelli, Andrea; Fiorani, Mara; Carloni, Silvia

We herein report the results from a comparative study of arsenite toxicity in respiration-proficient (RP) and -deficient (RD) U937 cells. An initial characterization of these cells led to the demonstration that the respiration-deficient phenotype is not associated with apparent changes in mitochondrial mass and membrane potential. In addition, similar levels of superoxide (O{sub 2}{sup .-}) were generated by RP and RD cells in response to stimuli specifically triggering respiratory chain-independent mitochondrial mechanisms or extramitochondrial, NADPH-oxidase dependent, mechanisms. At the concentration of 2.5 μM, arsenite elicited selective formation of O{sub 2}{sup .-} in the respiratory chain of RP cells, with hardlymore » any contribution of the above mechanisms. Under these conditions, O{sub 2}{sup .-} triggered downstream events leading to endoplasmic reticulum (ER) stress, autophagy and apoptosis. RD cells challenged with similar levels of arsenite failed to generate O{sub 2}{sup .-} because of the lack of a functional respiratory chain and were therefore resistant to the toxic effects mediated by the metalloid. Their resistance, however, was lost after exposure to four fold greater concentrations of arsenite, coincidentally with the release of O{sub 2}{sup .-} mediated by NADPH oxidase. Interestingly, extramitochondrial O{sub 2}{sup .-} triggered the same downstream events and an identical mode of death previously observed in RP cells. Taken together, the results obtained in this study indicate that arsenite toxicity is strictly dependent on O{sub 2}{sup .-} availability that, regardless of whether generated in the mitochondrial or extramitochondrial compartments, triggers similar downstream events leading to ER stress, autophagy and apoptosis. - Highlights: • Mitochondrial superoxide mediates arsenite toxicity in respiration-proficient cells. • NADPH-derived superoxide mediates arsenite toxicity in respiration-deficient cells. • Arsenite causes apoptosis in respiration-proficient and -deficient cells. • Apoptosis is in both circumstances associated with ER stress and autophagy.« less

The Effect of Mechanical Stimulation on Mineralization in Differentiating Osteoblasts in Collagen-I Scaffolds

PubMed Central

Damaraju, Swathi; Matyas, John R.; Rancourt, Derrick E.

2014-01-01

Developing a viable and functional bone scaffold in vitro that is capable of surviving and bearing mechanical load in vivo requires an understanding of the cell biology of osteoprogenitor cells, particularly how they are influenced by mechanical stimulation during cell differentiation and maturation. In this study, mechanical load was applied using a modified FlexCell plate to impart confined compression to collagen-I scaffolds seeded with undifferentiated murine embryonic stem cells. The activity, presence, and expression of osteoblast-cadherin (OB-Cad) and connexin-43, as well as various pluripotent and osteogenic markers were examined at 5–30 days of differentiation as cells were stimulated to differentiate to osteoblasts with and without applied mechanical load. Fluorescence recovery after photobleaching, immunofluorescence, viability, von Kossa, and real-time polymerase chain reaction assessments revealed that mechanical prestimulation of this cell-seeded scaffold altered the expression of OB-Cad and connexin-43 and resulted in significant differences in the structure and organization of mineralization present in the collagen matrix. Specifically, cells in gels that were loaded for 40 h after 5 days of differentiation and then left to fully differentiate for 30 days produced a highly structured honeycomb-shaped mineralization in the matrix; an outcome that was previously shown to be indicative of late osteoblast/early osteocyte activity. This study highlights the potential of mechanical load to accelerate differentiation and enhance osteoblast communication and function during the differentiation process, and highlights a time point of cell differentiation within this scaffold to apply load in order to most effectively transduce a mechanical signal. PMID:24851936

Identification of the NC1 domain of {alpha}3 chain as critical for {alpha}3{alpha}4{alpha}5 type IV collagen network assembly.

PubMed

LeBleu, Valerie; Sund, Malin; Sugimoto, Hikaru; Birrane, Gabriel; Kanasaki, Keizo; Finan, Elizabeth; Miller, Caroline A; Gattone, Vincent H; McLaughlin, Heather; Shield, Charles F; Kalluri, Raghu

2010-12-31

The network organization of type IV collagen consisting of α3, α4, and α5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual α-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of α3NC1 domain while keeping the triple helical α3 chain intact by connecting it to the human α5NC1 domain. The absence of α3NC1 domain leads to the complete loss of the α4 chain. The α3 collagenous domain is incapable of incorporating the α5 chain, resulting in the impaired organization of the α3α4α5 chain-containing network. Although the α5 chain can assemble with the α1, α2, and α6 chains, such assembly is incapable of functionally replacing the α3α4α5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.

Spark Plasma Sintering for Nanostructured Smart Materials

DTIC Science & Technology

2009-03-02

polyester) with excess isocyanate to form a prepolymer , followed by the addition of a short chain diol that acts as a chain extender to link the... prepolymers together. Due to the thermodynamic imicisibility of segments of PU, phase separation into a flexible soft segment (long chain diol) and a...other reactions of the isocyanate groups with the other functional groups in the chain. [Hepburn, 1992] However, during the initial prepolymer

Irreversible Heavy Chain Transfer to Chondroitin*

PubMed Central

Lauer, Mark E.; Hascall, Vincent C.; Green, Dixy E.; DeAngelis, Paul L.; Calabro, Anthony

2014-01-01

We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture. PMID:25135638

Chain Dynamics in a Dilute Magnetorheological Fluid

NASA Technical Reports Server (NTRS)

Liu, Jing; Hagenbuchle, Martin

1996-01-01

The structure, formation, and dynamics of dilute, mono-dispersive ferrofluid emulsions in an external magnetic field have been investigated using dynamic light scattering techniques. In the absence of the magnetic field, the emulsion particles are randomly distributed and behave like hard spheres in Brownian motion. An applied magnetic field induces a magnetic dipole moment in each particle. Dipolar interactions between particles align them into chains where correlation functions show two decay processes. The short-time decay shows the motion of straight chains as a whole where the apparent chain length increases with the applied magnetic field and the particle volume fraction. Good scaling results are obtained showing that the apparent chain length grows with time following a power law with exponent of 0.6 and depends on the applied field, particle volume fraction, and diffusion constant of the particles. The long-time decay in the correlation function shows oscillation when the chains reach a certain length with time and stiffness with threshold field This result shows that chains not only fluctuate, but move in a periodic motion with a frequency of 364 Hz at lambda = 15. It may suggest the existence of phonons. This work is the first step in the understanding of the structure formation, especially chain coarsening mechanism, of magnetorheological (MR) fluids at higher volume fractions.

Collapse kinetics of vibrated granular chains

NASA Astrophysics Data System (ADS)

Jeng, Pei-Ren; Chen, Kuan Hua; Hwang, Gwo-jen; Lien, Chenhsin; To, Kiwing; Chou, Y. C.

2011-12-01

The kinetics of the collapse of the coil state into condensed states is studied with vibrated granular chain composed of N metal beads partially immersed in water. The radius of gyration of the chain, Rg is measured. For short chains (N < 140), disk-like condensed state is formed and Rg decreases with time such that the function ΔRg2 (≡ Rg2 - Rg2(∞)) = A e-t/τ, where the relaxation time τ follows a power-law dependence on the chain length N with an exponent γ = 1.9 ± 0.2. For the chains with length N ≥ 300, rod-like clusters are observed during the initial stage of collapse and Rg2 = Rg2(0) - Btβ, with β = 0.6 ± 0.1. In the coarsening stage, the exponential dependence of ΔRg2 on time still holds, however, the relaxation time τ fluctuates and has no simple dependence on N. Furthermore, the time dependence of the averaged radius of gyration of the individual clusters, Rg,cl can be described by the theory of Lifshitz and Slyozov. A peak in the structure function of long chains is observed in the initial stage of the collapse transition. The collapse transition in the bead chains is a first order phase transition. However, features of the spinodal decomposition are also observed.

Linear ubiquitin chains: enzymes, mechanisms and biology

PubMed Central

2017-01-01

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases. PMID:28446710

Linear ubiquitin chains: enzymes, mechanisms and biology.

PubMed

Rittinger, Katrin; Ikeda, Fumiyo

2017-04-01

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases. © 2017 The Authors.

Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly

DOE PAGES

Brown, Nicholas G.; Watson, Edmond R.; Weissmann, Florian; ...

2014-10-09

Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here in this paper we show that human APC’s RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms.more » During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation.« less

Overproduction of alpha chains provides a proton-insensitive component to the bluefish hemoglobin system.

PubMed

Bonaventura, Celia; Godette, Gerald; Stevens, Robert; Brenowitz, Michael; Henkens, Robert

2005-12-09

Expression of alpha and beta chains and their post-translational assembly into alpha(2)beta(2) tetramers is fundamental to the formation and function of most vertebrate hemoglobins. There is a strong evolutionary bias that favors expression of equal amounts of the two types of chains, because cooperativity, pH sensitivity, and anionic control of function occurs only for the alpha(2)beta(2) tetramers. Remarkably, an over-production of alpha chains, as in the pathological condition known as beta thalassemia in humans, is adaptive rather than pathological in the bluefish hemoglobin system. The thalassemia of the bluefish is a novel means of providing for oxygen uptake and delivery when low pH conditions incapacitate the highly pH-sensitive Root effect hemoglobins of the fish. Although fish often have pH-insensitive along with highly pH-sensitive hemoglobins, having pH-insensitive alpha chain monomers in circulation is an unusual structural variation. The role of bluefish alpha chains in oxygen transport is enabled by their remarkably lower oxygen affinity relative to human alpha chains. This is the first reported case of a thalassemic condition that is maintained in a species as an adaptive advantage.

When monoclonal antibodies are not monospecific: Hybridomas frequently express additional functional variable regions

PubMed Central

Bradbury, Andrew R. M.; Trinklein, Nathan D.; Wilkinson, Ian C.; Tandon, Atul K.; Anderson, Stephen; Bladen, Catherine L.; Jones, Brittany; Aldred, Shelley Force; Bestagno, Marco; Burrone, Oscar; Maynard, Jennifer; Ferrara, Fortunato; Görnemann, Janina; Glanville, Jacob; Wolf, Philipp; Frenzel, Andre; Wong, Julin; Koh, Xin Yu; Eng, Hui-Yan; Lane, David; Lefranc, Marie-Paule; Clark, Mike

2018-01-01

ABSTRACT Monoclonal antibodies are commonly assumed to be monospecific, but anecdotal studies have reported genetic diversity in antibody heavy chain and light chain genes found within individual hybridomas. As the prevalence of such diversity has never been explored, we analyzed 185 random hybridomas, in a large multicenter dataset. The hybridomas analyzed were not biased towards those with cloning difficulties or known to have additional chains. Of the hybridomas we evaluated, 126 (68.1%) contained no additional productive chains, while the remaining 59 (31.9%) contained one or more additional productive heavy or light chains. The expression of additional chains degraded properties of the antibodies, including specificity, binding signal and/or signal-to-noise ratio, as determined by enzyme-linked immunosorbent assay and immunohistochemistry. The most abundant mRNA transcripts found in a hybridoma cell line did not necessarily encode the antibody chains providing the correct specificity. Consequently, when cloning antibody genes, functional validation of all possible VH and VL combinations is required to identify those with the highest affinity and lowest cross-reactivity. These findings, reflecting the current state of hybridomas used in research, reiterate the importance of using sequence-defined recombinant antibodies for research or diagnostic use. PMID:29485921

Short-Chain PEG Mixed-Monolayer Protected Gold Clusters Increase Clearance and Red Blood Cell Counts

PubMed Central

Simpson, Carrie A.; Agrawal, Amanda C.; Balinski, Andrzej; Harkness, Kellen M.; Cliffel, David E.

2011-01-01

Monolayer-protected gold nanoparticles have great potential as novel building blocks for the design of new drugs and therapeutics based on the easy ability to multifunctionalize them for biological targeting and drug activity. In order to create nanoparticles that are biocompatible in vivo, poly-ethylene glycol functional groups have been added to many previous multifunctionalized particles to eliminate non-specific binding. Recently, monolayer-protected gold nanoparticles with mercaptoglycine functionalities were shown to elicit deleterious effects on the kidney in vivo that were eliminated by incorporating a long-chain, mercapto-undecyl-tetraethylene glycol, at very high loadings into a mixed monolayer. These long-chain PEGs induced an immune response to the particle presumably generating an anti-PEG antibody as seen in other long-chain PEG-ylated nanoparticles in vivo. In the present work, we explore the in vivo effects of high and low percent ratios of a shorter chain, mercapto-tetraethylene glycol, within the monolayer using simple place-exchange reactions. The shorter chain PEG MPCs were expected to have better water solubility due to elimination of the alkyl chain, no toxicity, and long-term circulation in vivo. Shorter chain lengths at lower concentrations should not trigger the immune system into creating an anti-PEG antibody. We found that a 10% molar exchange of this short chain PEG within the monolayer met three of the desired goals: high water solubility, no toxicity, and no immune response as measured by white blood cell counts, but none of the short chain PEG mixed monolayer compositions enabled the nanoparticles to have a long circulation time within the blood as compared to mercapto-undecyl-ethylene glycol, which had a residence time of 4 weeks. We also compared the effects of a hydroxyl versus a carboxylic acid terminal functional group on the end of the PEG thiol on both clearance and immune response. The results indicate that short-chain length PEGs, regardless of termini, increase clearance rates compared to the previous long-chain PEG studies while carboxylated-termini increase red blood cell counts at high loadings. Given these findings, short-chain, alcohol-terminated PEG, exchanged at 10% was identified as a potential nanoparticle for further in vivo applications requiring short circulation lifetimes with desired features of no toxicity, no immune response, and high water solubility. PMID:21473648

Use of polymerase chain reaction (PCR) in the diagnosis of congenital toxoplasmosis.

PubMed

Loveridge-Easther, Cam; Yardley, Anne-Marie; Breidenstein, Brenda

2018-06-01

Congenital toxoplasmosis (CT) is a parasitic disease that causes serious fetal and neonatal harm or death. In countries that do not have antenatal screening programs, the initiation of CT treatment relies on a postnatal diagnosis. Until recently, diagnosis was based on clinical signs and immunoglobulin seropositivity, which is fraught with difficulty. In these cases, diagnosis was often delayed or treatment, which carries risk, started empirically. We highlight the use of polymerase chain reaction to diagnose a case of congenital toxoplasmosis, allowing early treatment and justifying the treatment burden. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain.

PubMed

Logan, Clare V; Cossins, Judith; Rodríguez Cruz, Pedro M; Parry, David A; Maxwell, Susan; Martínez-Martínez, Pilar; Riepsaame, Joey; Abdelhamed, Zakia A; Lake, Alice V R; Moran, Maria; Robb, Stephanie; Chow, Gabriel; Sewry, Caroline; Hopkins, Philip M; Sheridan, Eamonn; Jayawant, Sandeep; Palace, Jacqueline; Johnson, Colin A; Beeson, David

2015-12-03

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs(∗)71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Structure-dependent binding and activation of perfluorinated compounds on human peroxisome proliferator-activated receptor γ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lianying; College of Life Science, Dezhou University, Dezhou 253023; Ren, Xiao-Min

2014-09-15

Perfluorinated compounds (PFCs) have been shown to disrupt lipid metabolism and even induce cancer in rodents through activation of peroxisome proliferator-activated receptors (PPARs). Lines of evidence showed that PPARα was activated by PFCs. However, the information on the binding interactions between PPARγ and PFCs and subsequent alteration of PPARγ activity is still limited and sometimes inconsistent. In the present study, in vitro binding of 16 PFCs to human PPARγ ligand binding domain (hPPARγ-LBD) and their activity on the receptor in cells were investigated. The results showed that the binding affinity was strongly dependent on their carbon number and functional group.more » For the eleven perfluorinated carboxylic acids (PFCAs), the binding affinity increased with their carbon number from 4 to 11, and then decreased slightly. The binding affinity of the three perfluorinated sulfonic acids (PFSAs) was stronger than their PFCA counterparts. No binding was detected for the two fluorotelomer alcohols (FTOHs). Circular dichroim spectroscopy showed that PFC binding induced distinctive structural change of the receptor. In dual luciferase reporter assays using transiently transfected Hep G2 cells, PFCs acted as hPPARγ agonists, and their potency correlated with their binding affinity with hPPARγ-LBD. Molecular docking showed that PFCs with different chain length bind with the receptor in different geometry, which may contribute to their differences in binding affinity and transcriptional activity. - Highlights: • Binding affinity between PFCs and PPARγ was evaluated for the first time. • The binding strength was dependent on fluorinated carbon chain and functional group. • PFC binding induced distinctive structural change of the receptor. • PFCs could act as hPPARγ agonists in Hep G2 cells.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, Grace H.; Rana, Ambar S. J. B.; Korkmaz, E. Nihal

Ubiquitin (Ub) chains regulate a wide range of biological processes, and Ub chain connectivity is a critical determinant of the many regulatory roles that this post-translational modification plays in cells. To understand how distinct Ub chains orchestrate different biochemical events, we and other investigators have developed enzymatic and non-enzymatic methods to synthesize Ub chains of well-defined length and connectivity. A number of chemical approaches have been used to generate Ub oligomers connected by non-native linkages; however, few studies have examined the extent to which non-native linkages recapitulate the structural and functional properties associated with native isopeptide bonds. Here, we comparemore » the structure and function of Ub dimers bearing native and non-native linkages. Using small-angle X-ray scattering (SAXS) analysis, we show that scattering profiles for the two types of dimers are similar. Moreover, using an experimental structural library and atomistic simulations to fit the experimental SAXS profiles, we find that the two types of Ub dimers can be matched to analogous structures. An important application of non-native Ub oligomers is to probe the activity and selectivity of deubiquitinases. Through steady-state kinetic analyses, we demonstrate that different families of deubiquitinases hydrolyze native and non-native isopeptide linkages with comparable efficiency and selectivity. Considering the significant challenges associated with building topologically diverse native Ub chains, our results illustrate that chains harboring non-native linkages can serve as surrogate substrates for explorations of Ub function.« less

One-pot synthesis of molecular bottle-brush functionalized single-walled carbon nanotubes with superior dispersibility in water.

PubMed

Deng, Yong; Hu, Qin; Yuan, Qiulin; Wu, Yan; Ling, Ying; Tang, Haoyu

2014-01-01

Molecular bottle-brush functionalized single-walled carbon nanotubes (SWCNTs) with superior dispersibility in water are prepared by a one-pot synthetic methodology. Elongating the main-chain and side-chain length of molecular bottle-brushes can further increase SWCNT dispersibility. They show significant enhancement of SWCNT dispersibility up to four times higher than those of linear molecular functionalized SWCNTs. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of well-defined bisbenzoin end-functionalized poly(ε-caprolactone) macrophotoinitiator by combination of ROP and click chemistry and its use in the synthesis of star copolymers by photoinduced free radical promoted cationic polymerization

PubMed Central

Uyar, Zafer; Degirmenci, Mustafa; Genli, Nasrettin; Yilmaz, Ayse

2017-01-01

Abstract A new well-defined bisbenzoin group end-functionalized poly(ε-caprolactone) macrophotoinitiator (PCL-(PI)2) was synthesized by combination of ring opening polymerization (ROP) and click chemistry. The ROP of ε-CL monomer in bulk at 110 °C, by means of a hydroxyl functional initiator namely, 3-cyclohexene-1-methanol in conjunction with stannous-2-ethylhexanoate, (Sn(Oct)2), yielded a well-defined PCL with a cyclohexene end-chain group (PCL-CH). The bromination and subsequent azidation of the cyclohexene end-chain group gave bisazido functionalized poly(ε-caprolactone) (PCL-(N3)2). Separately, an acetylene functionalized benzoin photoinitiator (PI-alkyne) was synthesized by using benzoin and propargyl bromide. Then the click reaction between PCL-(N3)2 and PI-alkyne was performed by Cu(I) catalysis. The spectroscopic studies revealed that poly(ε-caprolactone) with bisbenzoin photoactive functional group at the chain end (PCL-(PI)2) with controlled chain length and low-polydispersity was obtained. This PCL-(PI)2 macrophotoinitiator was used as a precursor in photoinduced free radical promoted cationic polymerization to synthesize an AB2-type miktoarm star copolymer consisting of poly(ε-caprolactone) (PCL, as A block) and poly(cyclohexene oxide) (PCHO, as B block), namely PCL(PCHO)2. PMID:29491778

Thioether-Bearing Hyperbranched Polyether Polyols with Methionine-Like Side-Chains: A Versatile Platform for Orthogonal Functionalization.

PubMed

Seiwert, Jan; Herzberger, Jana; Leibig, Daniel; Frey, Holger

2017-01-01

The synthesis of thioether-bearing hyperbranched polyether polyols based on an AB/AB 2 type copolymerization (cyclic latent monomers) is introduced. The polymers are prepared by anionic ring-opening multibranching copolymerization of glycidol and 2-(methylthio)ethyl glycidyl ether (MTEGE), which is conveniently accessible in a single etherification step. Slow monomer addition provides control over molecular weights. Moderate dispersities (Đ = 1.48-1.85) are obtained, given the hyperbranched structure. In situ 1 H NMR copolymerization kinetics reveal reactivity ratios of r G = 3.7 and r MTEGE = 0.27. Using slow monomer addition, copolymer composition can be systematically varied, allowing for the adjustment of the hydroxyl/thioether ratio, the degree of branching (DB = 0.36-0.48), thermal properties, and cloud point temperatures in aqueous solution in the range of 29-75 °C. Thioether oxidation to sulfoxides enables to tailor the copolymers' solubility profile. Use of these copolymers as a versatile, multifunctional platform for orthogonal modification is highlighted. The methyl sulfide groups can be selectively alkoxylated, using propylene oxide, allyl glycidyl ether, or furfuryl glycidyl ether, resulting in functional hyperbranched polyelectrolytes. Reaction of the alcohol groups with benzyl isocyanate demonstrates successful orthogonal functionalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy.

PubMed

Iebba, Valerio; Guerrieri, Francesca; Di Gregorio, Vincenza; Levrero, Massimo; Gagliardi, Antonella; Santangelo, Floriana; Sobolev, Anatoly P; Circi, Simone; Giannelli, Valerio; Mannina, Luisa; Schippa, Serena; Merli, Manuela

2018-05-29

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a 'functional dysbiosis' in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.

Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Compagnucci, Claudia; Barresi, Sabina; Petrini, Stefania

2015-04-03

Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify amore » new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.« less

A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in ApcMin/+ mice.

PubMed

Ni, Y; Wong, V H Y; Tai, W C S; Li, J; Wong, W Y; Lee, M M L; Fong, F L Y; El-Nezami, H; Panagiotou, G

2017-03-01

To investigate the in vivo effects of Lactobacillus rhamnosus GG (LGG) on intestinal polyp development and the interaction between this single-organism probiotic and the gut microbiota therein. The Apc Min/+ mouse model was used to study the potential preventive effect of LGG on intestinal polyposis, while shotgun metagenomic sequencing was employed to characterize both taxonomic and functional changes within the gut microbial community. We found that the progression of intestinal polyps in the control group altered the community functional profile remarkably despite small variation in the taxonomic diversity. In comparison, the consumption of LGG helped maintain the overall functional potential and taxonomic profile in the resident microbes, thereby leading to a 25% decrease of total polyp counts. Furthermore, we found that LGG enriched those microbes or microbial activities related to short-chain fatty acid production (e.g. Roseburia and Coprococcus), as well as suppressed the ones that can lead to inflammation (e.g. Bilophila wadsworthia). Our study using shotgun metagenomics highlights how single probiotic LGG may exert its beneficial effects and decrease polyp formation in mice by maintaining gut microbial functionality. This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human. © 2016 The Society for Applied Microbiology.

What We Don't Know.

ERIC Educational Resources Information Center

Hazen, Robert M.

1997-01-01

Highlights the unanswered questions of science. Summarizes current leading research that demonstrates that those questions are inherently limited in scope, and the chain of discovery and human curiosity that drives the quest for knowledge shows not the slightest sign of ending. Argues that we have yet to recognize and ask many of the most profound…

INTEGRATE: Driving Transformational Change - JISEA 2018 Annual Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

This report demonstrates 2017 highlights of the Joint Institute for Strategic Energy Analysis' (JISEA's) work. The Annual Report overviews JISEA's research and analysis accomplishments in natural gas and methane emissions; nuclear-renewable hybrid energy systems; the Clean Energy Manufacturing Analysis Center's work in global supply chains; the 21st Century Power Partnership; and more.

Charge and Spin Dynamics of the Hubbard Chains

NASA Technical Reports Server (NTRS)

Park, Youngho; Liang, Shoudan

1999-01-01

We calculate the local correlation functions of charge and spin for the one-chain and two-chain Hubbard model using density matrix renormalization group method and the recursion technique. Keeping only finite number of states we get good accuracy for the low energy excitations. We study the charge and spin gaps, bandwidths and weights of the spectra for various values of the on-site Coulomb interaction U and the electron filling. In the low energy part, the local correlation functions are different for the charge and spin. The bandwidths are proportional to t for the charge and J for the spin respectively.

A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

PubMed Central

D’Silva, Sheryl; Xiao, Xunjun; Lowe, Mark E.

2013-01-01

Type 2 diabetes mellitus is a multifactorial and polygenic disorder with increasing prevalence. Recently, a polymorphism in the gene encoding procolipase, a cysteine for arginine substitution at position 92, was associated with type 2 diabetes in two human populations. Because procolipase plays a critical role in dietary fat metabolism, polymorphisms that affect the function of procolipase could influence the development of type 2 diabetes. We hypothesized that the Arg92Cys polymorphism has functional consequences. To test our hypothesis, we expressed recombinant cysteine 92 (Cys92) procolipase in a yeast expression system and compared the function and stability of purified Cys92 with that of the more common arginine 92 (Arg92) procolipase. Cys92 fully restored the activity of bile-salt inhibited lipase with short- and medium-chain triglycerides but only had 50% of Arg92 function with long-chain triglycerides. After storage at 4°C, Cys92 lost the ability to restore pancreatic triglyceride lipase activity with medium- and long-chain triglycerides. The loss of function correlated with the inability of Cys92 to anchor lipase on an emulsion surface and oxidation of the cysteine. No detectable degradation or intramolecular disulfide formation occurred in Cys92 after storage. Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes. PMID:17715423

Critical role of γ4 chain in the expression of functional Vγ4Vδ1 T cell receptor of gastric tumour-infiltrating γδT lymphocytes.

PubMed

Jiang, Y; Tang, F; Li, Z; Cui, L; He, W

2012-01-01

Vγ4Vδ1 T cell receptor (TCRγ4δ1)-expressing γδT cells were the most dominant subset in gastric tumour-infiltrating γδT cells (γδTIL) we recently analyzed. To study the essential roles of γ and δ chains in assembly and function of TCRγ4δ1, we sequenced and constructed them into lentiviral vectors for the reconstitution of TCRγ4δ1 using different modalities of transduction. We were able to efficiently reconstitute TCRγ4δ1 with functional activities when both γ4 and δ1 chains are coexpressed in TCR-negative J.RT3-T3.5 cells. However, the expression of δ1 chain is greatly diminished when γ4 expression is absent, suggesting that the coexpressing γ4 is critical in maintaining the folding and stability of δ1 product. To functionally study the reconstituted TCRγ4δ1, we examined the cytolytic activity of TCRγ4δ1-reconstituted J.RT3-T3.5 cells and cytokine secretion and found the receptors are fully functional, but their functionality also requires the presence of γ4. Our results demonstrated that γ4 is critical for the stability of δ1 and the function of TCRγ4δ1. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Listeria monocytogenes cross-contamination of cheese: risk throughout the food supply chain.

PubMed

Sauders, B D; D'Amico, D J

2016-10-01

Listeria monocytogenes has been the most common microbial cause of cheese-related recalls in both the United States and Canada in recent years. Since L. monocytogenes is inactivated by pasteurization, the majority of these cases have been linked to environmental and cross-contamination of fresh-soft, soft-ripened, and semi-soft cheeses. Cross-contamination of foods with L. monocytogenes is a continuous risk throughout the food supply chain and presents unique challenges for subsequent illness and outbreak investigations. Reports on outbreaks of listeriosis attributed to cross-contamination downstream from primary processing help highlight the critical role of epidemiological investigation coupled with coordinated molecular subtyping and surveillance in the recognition and investigation of complex foodborne outbreaks. Despite their complexity, environmental sampling throughout the supply chain coupled with improved genotyping approaches and concomitant analysis of foodborne illness epidemiological exposure data are needed to help resolve these and similar cases more rapidly and with greater confidence.

The role of interactions along the flood process chain and implications for risk assessment

NASA Astrophysics Data System (ADS)

Vorogushyn, Sergiy; Apel, Heiko; Viet Nguyen, Dung; Guse, Björn; Kreibich, Heidi; Lüdtke, Stefan; Schröter, Kai; Merz, Bruno

2017-04-01

Floods with their manifold characteristics are shaped by various processes along the flood process chain - from triggering meteorological extremes through catchment and river network process down to impacts on societies. In flood risk systems numerous interactions and feedbacks along the process chain may occur which finally shape spatio-temporal flood patterns and determine the ultimate risk. In this talk, we review some important interactions in the atmosphere-catchment, river-dike-floodplain and vulnerability compartments of the flood risk system. We highlight the importance of spatial interactions for flood hazard and risk assessment. For instance, the role of spatial rainfall structure or wave superposition in river networks is elucidated with selected case studies. In conclusion, we show the limits of current methods in assessment of large-scale flooding and outline the approach to more comprehensive risk assessment based on our regional flood risk model (RFM) for Germany.

An assessment of the regional and national socio-economic impacts of the 2007 Rift Valley fever outbreak in Kenya.

PubMed

Rich, Karl M; Wanyoike, Francis

2010-08-01

Although Rift Valley fever (RVF) has significant impacts on human health and livestock production, it can also induce significant (and often overlooked) economic losses among various stakeholders in the marketing chain. This work assesses and quantifies the multi-dimensional socio-economic impacts of the 2007 RVF outbreak in Kenya based on a rapid assessment of livestock value chains in the northeast part of the country and a national macroeconomic analysis. Although study results show negative impacts among producers in terms of food insecurity and reductions in income, we also found significant losses among other downstream actors in the value chain, including livestock traders, slaughterhouses, casual laborers, and butchers, as well as other, non-agricultural sectors. The study highlights the need for greater sensitivity and analyses that address the multitude of economic losses resulting from an animal disease to better inform policy and decision making during animal health emergencies.

Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

PubMed

Zadeh-Tahmasebi, Melika; Duca, Frank A; Rasmussen, Brittany A; Bauer, Paige V; Côté, Clémence D; Filippi, Beatrice M; Lam, Tony K T

2016-04-15

Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates

DOE PAGES

Xia, Yan; Li, Ming; Charubin, Kamil; ...

2015-11-05

In this paper, we report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C 14, DMPC) in discoidal “bicelles” (0.156 h –1) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 × 10 –3 h –1). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C 14 DMPC to di-C 16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differentialmore » scanning calorimetry (DSC), and fluorescence correlation spectroscopy (FCS) are in good agreement. Finally, the present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes.« less

THz Local Oscillator Technology

NASA Technical Reports Server (NTRS)

Mehdi, Imran

2004-01-01

The last decade has seen a number of technological advancements that have now made it possible to implement fully solid state local oscillator chains up to 2 THz. These chains are composed of cascaded planar multiplier stages that are pumped with W-band high power sources. The high power W-band sources are achieved by power combining MMIC amplifiers and can provide in access of 150 mW with about 10% bandwidth. Planar diode technology has also enabled novel circuit topologies that can take advantage of the high input power and demonstrate significant efficiencies well into the THz range. Cascaded chains to 1.9 THz have now been demonstrated with enough output power to successfully pump hot-electron bolometer mixers in this frequency range. An overview of the current State-of-the-Art of the local oscillator technology will be presented along with highlighting future trends and challenges.

Magnetic field alignment of coil-coil diblock copolymers and blends via intrinsic chain anisotropy

NASA Astrophysics Data System (ADS)

Rokhlenko, Yekaterina; Majewski, Pawel; Larson, Steven; Yager, Kevin; Gopalan, Padma; Avgeropoulos, Apostolos; Chan, Edwin; Osuji, Chinedum

Magnetic fields can control alignment of self-assembled soft materials such as block copolymers provided there is a suitably large magnetic susceptibility anisotropy present in the system. Recent results have highlighted the existence of a non-trivial intrinsic anisotropy in coil-coil diblock copolymers, specifically in lamellar-forming PS-b-P4VP, which enables alignment at field strengths of a few tesla in systems lacking mesogenic components. Alignment is predicated on correlation in the orientation of end-end vectors implied by the localization of block junctions at the microdomain interface and is observed on cooling across the order-disorder transition in the presence of the field. For appropriate combinations of field strength and grain size, we can leverage intrinsic chain anisotropy to magnetically direct self-assembly of many non-mesogenic systems, including other coil-coil BCPs like PS-b-PDMS and PS-b-PMMA, blends of BCPs of disparate morphologies and MWs, and blends of BCPs with homopolymers. This is noteworthy as blends of PS-b-P4VP with PEO provide a route to form functional materials such as nanoporous films by dissolution of PEO, or aligned ion conduction materials. We survey these various systems using TEM and in-situ X-ray scattering to study the phase behavior and temperature-, time- and field- dependent dynamics of alignment.

The effect of charge mutations on the stability and aggregation of a human single chain Fv fragment.

PubMed

Austerberry, James I; Dajani, Rana; Panova, Stanislava; Roberts, Dorota; Golovanov, Alexander P; Pluen, Alain; van der Walle, Christopher F; Uddin, Shahid; Warwicker, Jim; Derrick, Jeremy P; Curtis, Robin

2017-06-01

The aggregation propensities for a series of single-chain variable fragment (scFv) mutant proteins containing supercharged sequences, salt bridges and lysine/arginine-enriched motifs were characterised as a function of pH and ionic strength to isolate the electrostatic contributions. Recent improvements in aggregation predictors rely on using knowledge of native-state protein-protein interactions. Consistent with previous findings, electrostatic contributions to native protein-protein interactions correlate with aggregate growth pathway and rates. However, strong reversible self-association observed for selected mutants under native conditions did not correlate with aggregate growth, indicating 'sticky' surfaces that are exposed in the native monomeric state are inaccessible when aggregates grow. We find that even though similar native-state protein-protein interactions occur for the arginine and lysine-enriched mutants, aggregation propensity is increased for the former and decreased for the latter, providing evidence that lysine suppresses interactions between partially folded states under these conditions. The supercharged mutants follow the behaviour observed for basic proteins under acidic conditions; where excess net charge decreases conformational stability and increases nucleation rates, but conversely reduces aggregate growth rates due to increased intermolecular electrostatic repulsion. The results highlight the limitations of using conformational stability and native-state protein-protein interactions as predictors for aggregation propensity and provide guidance on how to engineer stabilizing charged mutations. Copyright © 2017. Published by Elsevier B.V.

Separation mechanism of chiral impurities, ephedrine and pseudoephedrine, found in amphetamine-type substances using achiral modifiers in the gas phase.

PubMed

Holness, Howard K; Jamal, Adeel; Mebel, Alexander; Almirall, José R

2012-11-01

A new mechanism is proposed that describes the gas-phase separation of chiral molecules found in amphetamine-type substances (ATS) by the use of high-resolution ion mobility spectrometry (IMS). Straight-chain achiral alcohols of increasing carbon chain length, from methanol to n-octanol, are used as drift gas modifiers in IMS to highlight the mechanism proposed for gas-phase separations of these chiral molecules. The results suggest the possibility of using these achiral modifiers to separate the chiral molecules (R,S) and (S,R)-ephedrine and (S,S) and (R,R)-pseudoephedrine which contain an internal hydroxyl group at the first chiral center and an amino group at the other chiral center. Ionization was achieved with an electrospray source, the ions were introduced into an IMS with a resolving power of 80, and the resulting ion clusters were characterized with a coupled quadrupole mass spectrometer detector. A complementary computational study conducted at the density functional B3LYP/6-31g level of theory for the electronic structure of the analyte-modifier clusters was also performed, and showed either "bridged" or "independent" binding. The combined experimental and simulation data support the proposed mechanism for gas-phase chiral separations using achiral modifiers in the gas phase, thus enhancing the potential to conduct fast chiral separations with relative ease and efficiency.

Describing a Strongly Correlated Model System with Density Functional Theory.

PubMed

Kong, Jing; Proynov, Emil; Yu, Jianguo; Pachter, Ruth

2017-07-06

The linear chain of hydrogen atoms, a basic prototype for the transition from a metal to Mott insulator, is studied with a recent density functional theory model functional for nondynamic and strong correlation. The computed cohesive energy curve for the transition agrees well with accurate literature results. The variation of the electronic structure in this transition is characterized with a density functional descriptor that yields the atomic population of effectively localized electrons. These new methods are also applied to the study of the Peierls dimerization of the stretched even-spaced Mott insulator to a chain of H 2 molecules, a different insulator. The transitions among the two insulating states and the metallic state of the hydrogen chain system are depicted in a semiquantitative phase diagram. Overall, we demonstrate the capability of studying strongly correlated materials with a mean-field model at the fundamental level, in contrast to the general pessimistic view on such a feasibility.

The Effect of Surface Chemical Functionality Upon Ice Adhesion

NASA Technical Reports Server (NTRS)

Smith, Joseph G., Jr.; Wohl, Christopher J.; Doss, Jereme; Spence, Destiny; Kreeger, Richard E.; Palacios, Jose; Knuth, Taylor; Hadley, Kevin R.; McDougal, Nicholas D.

2015-01-01

In nature, anti-freeze proteins present in fish utilize specific organic functionalities to disrupt ice crystal formation and propagation. Based on these structures, surfaces with controlled chemical functionality and chain length were evaluated both experimentally and computationally to assess the effect of both parameters in mitigating ice formation. Linear aliphatic dimethylethoxysilanes terminated with methyl or hydroxyl groups were prepared, characterized, and used to coat aluminum. The effect upon icing using a microdroplet freezing apparatus and the Adverse Environment Rotor Test Stand found hydroxyl-terminated materials exhibited a greater propensity for ice formation and adhesion. Molecular dynamics simulations of a silica substrate bearing functionalized species of similar composition were brought into contact with a pre-equilibrated ice crystal. Several parameters including chain mobility were monitored to ascertain the size of a quasi-liquid layer. The studies suggested that chain mobility affected the interface between ice and the surface more than terminal group chemical composition.

Entropy of finite random binary sequences with weak long-range correlations.

PubMed

Melnik, S S; Usatenko, O V

2014-11-01

We study the N-step binary stationary ergodic Markov chain and analyze its differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain through the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses the two-point correlators instead of the block probability, it makes it possible to calculate the entropy of strings at much longer distances than using standard methods. A fluctuation contribution to the entropy due to finiteness of random chains is examined. This contribution can be of the same order as its regular part even at the relatively short lengths of subsequences. A self-similar structure of entropy with respect to the decimation transformations is revealed for some specific forms of the pair correlation function. Application of the theory to the DNA sequence of the R3 chromosome of Drosophila melanogaster is presented.

Entropy of finite random binary sequences with weak long-range correlations

NASA Astrophysics Data System (ADS)

Melnik, S. S.; Usatenko, O. V.

2014-11-01

We study the N -step binary stationary ergodic Markov chain and analyze its differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain through the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses the two-point correlators instead of the block probability, it makes it possible to calculate the entropy of strings at much longer distances than using standard methods. A fluctuation contribution to the entropy due to finiteness of random chains is examined. This contribution can be of the same order as its regular part even at the relatively short lengths of subsequences. A self-similar structure of entropy with respect to the decimation transformations is revealed for some specific forms of the pair correlation function. Application of the theory to the DNA sequence of the R3 chromosome of Drosophila melanogaster is presented.

Chain end distribution of block copolymer in two-dimensional microphase-separated structure studied by scanning near-field optical microscopy.

PubMed

Sekine, Ryojun; Aoki, Hiroyuki; Ito, Shinzaburo

2009-10-01

The chain end distribution of a block copolymer in a two-dimensional microphase-separated structure was studied by scanning near-field optical microscopy (SNOM). In the monolayer of poly(octadecyl methacrylate)-block-poly(isobutyl methacrylate) (PODMA-b-PiBMA), the free end of the PiBMA subchain was directly observed by SNOM, and the spatial distributions of the whole block and the chain end are examined and compared with the convolution of the point spread function of the microscope and distribution function of the model structures. It was found that the chain end distribution of the block copolymer confined in two dimensions has a peak near the domain center, being concentrated in the narrower region, as compared with three-dimensional systems.

Modification of Side Chains of Conjugated Molecules and Polymers for Charge Mobility Enhancement and Sensing Functionality.

PubMed

Liu, Zitong; Zhang, Guanxin; Zhang, Deqing

2018-06-19

Organic semiconductors have received increasing attentions in recent years because of their promising applications in various optoelectronic devices. The key performance metric for organic semiconductors is charge carrier mobility, which is governed by the electronic structures of conjugated backbones and intermolecular/interchain π-π interactions and packing in both microscopic and macroscopic levels. For this reason, more efforts have been paid to the design and synthesis of conjugated frameworks for organic semiconductors with high charge mobilities. However, recent studies manifest that appropriate modifications of side chains that are linked to conjugated frameworks can improve the intermolecular/interchain packing order and boost charge mobilities. In this Account, we discuss our research results in context of modification of side chains in organic semiconductors for charge mobility enhancement. These include the following: (i) The lengths of alkyl chains in sulfur-rich thiepin-fused heteroacences can dramatically influence the intermolecular arrangements and orbital overlaps, ushering in different hole mobilities. Inversely, the lamellar stacking modes of alkyl chains in naphthalene diimide (NDI) derivatives with tetrathiafulvalene (TTF) units are affected by the structures of conjugated cores. (ii) The steric hindrances owing to the bulky branching chains can be weakened by partial replacement of the branching alkyl chains with linear ones for diketopyrrolopyrrole (DPP)-based D (donor)-A (acceptor) conjugated polymers. Such modification of side chains makes the polymer backbones more planar and thus interchain packing order and charge mobilities are improved. The incorporation of hydrophilic tri(ethylene glycol) (TEG) chains into the polymers also leads to improved interchain packing order. In particular, the polymer in which TEG side chains are distributed uniformly exhibits relatively high charge mobility without thermal annealing. (iii) The incorporation of urea groups in the side chains induces the polymer chains to pack more orderly and form large domains because of the additional H-bonding among urea groups. Accordingly, thin film mobilities of the conjugated D-A polymers with side chains entailing urea groups are largely boosted in comparison with those of polymers of the same backbones with either branching alkyl chains or branching/linear alkyl chains. (iv) The torsions of branching alkyl chains in conjugated D-A polymers can be inhibited to some extent upon incorporation of tiny amount of NMe 4 I in the thin film. As a result, the polymer thin films with NMe 4 I exhibit improved crystallinity, and charge mobilities can be boosted by more than 20 times. (v) Side chains with functional groups in the conjugated polymers can endow the thin film field-effect transistors (FETs) with sensing functionality. FETs with the conjugated polymer with -COOH groups in the side chains show sensitive, selective, and fast responses toward ammonia and amines, while FETs with the ultrathin films of the polymer containing tetra(ethylene glycol) (TEEG) in the side chains can sense alcohol vapors (in particular ethanol vapor) sensitively and selectively with fast response.

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-01-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages. PMID:24992446

PolyUbiquitin chain linkage topology selects the functions from the underlying binding landscape.

PubMed

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-07-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

PubMed Central

Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

2016-01-01

Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy—combining sequential and modular concepts—enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain. PMID:27901024

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

PubMed

Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

2016-08-18

Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation.

PubMed

Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

2016-11-30

Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy-combining sequential and modular concepts-enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

Quality of service management framework for dynamic chaining of geographic information services

NASA Astrophysics Data System (ADS)

Onchaga, Richard

2006-06-01

Dynamic chaining of geographic information services (geo-services) is gaining popularity as a new paradigm for evolving flexible geo-information systems and for providing on-demand access to geo-information. In dynamic chaining, disparate geo-services are discovered and composed at run time to yield more elaborate functionality and create value-added geo-information. Common approaches to service chaining discover and compose disparate geo-services based on the functional capability of individual geo-services. The primary concern of common approaches is thus the emergent behavior of the resulting composite geo-service. However, as geo-services become mundane and take on a greater and more strategic role in mission critical processes, deliverable quality of service (QoS) becomes an important concern. QoS concerns operational characteristics of a service that determine its utility in an application context. To address pertinent QoS requirements, a new approach to service chaining becomes necessary. In this paper we propose a QoS-aware chaining approach in which geo-services are discovered, composed and executed considering both functional and QoS requirements. We prescribe a QoS management framework that defines fundamental principles, concepts and mechanisms which can be applied to evolve an effective distributed computing platform for QoS-aware chaining of geo-services - the so-called geo-service infrastructure. The paper also defines an extensible QoS model for services delivered by dynamic compositions of geo-services. The process of orthophoto generation is used to demonstrate the applicability of the prescribed framework to service-oriented geographic information processing.

Quantifying side-chain conformational variations in protein structure

PubMed Central

Miao, Zhichao; Cao, Yang

2016-01-01

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs. PMID:27845406

Quantifying side-chain conformational variations in protein structure

NASA Astrophysics Data System (ADS)

Miao, Zhichao; Cao, Yang

2016-11-01

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs.

Quantifying side-chain conformational variations in protein structure.

PubMed

Miao, Zhichao; Cao, Yang

2016-11-15

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs.

Surface water retardation around single-chain polymeric nanoparticles: critical for catalytic function?

PubMed

Stals, Patrick J M; Cheng, Chi-Yuan; van Beek, Lotte; Wauters, Annelies C; Palmans, Anja R A; Han, Songi; Meijer, E W

2016-03-01

A library of water-soluble dynamic single-chain polymeric nanoparticles (SCPN) was prepared using a controlled radical polymerisation technique followed by the introduction of functional groups, including probes at targeted positions. The combined tools of electron paramagnetic resonance (EPR) and Overhauser dynamic nuclear polarization (ODNP) reveal that these SCPNs have structural and surface hydration properties resembling that of enzymes.

A novel mutation in the FGB: c.1105C>T turns the codon for amino acid Bβ Q339 into a stop codon causing hypofibrinogenemia.

PubMed

Marchi, Rita; Brennan, Stephen; Meyer, Michael; Rojas, Héctor; Kanzler, Daniela; De Agrela, Marisela; Ruiz-Saez, Arlette

2013-03-01

Routine coagulation tests on a 14year-old male with frequent epistaxis showed a prolonged thrombin time together with diminished functional (162mg/dl) and gravimetric (122mg/dl) fibrinogen concentrations. His father showed similar aberrant results and sequencing of the three fibrinogen genes revealed a novel heterozygous nonsense mutation in the FGB gene c.1105C>T, which converts the codon for residue Bβ 339Q to stop, causing deletion of Bβ chain residues 339-461. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and RP-HPLC (reverse-phase high-pressure liquid chromatography) of purified fibrinogen showed only normal Aα, Bβ, and γ chains, indicating that molecules with the truncated 37,990Da β chain were not secreted into plasma. Functional analysis showed impaired fibrin polymerization, fibrin porosity, and elasticity compared to controls. By laser scanning confocal microscopy the patient's fibers were slightly thinner than normal. Electrospray ionization mass spectrometry (ESI MS) presented normal sialylation of the oligosaccharide chains, and liver function tests showed no evidence of liver dysfunction that might explain the functional abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PubMed

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Sutarni, Sri; Bawono, Rheza Gandi; Bayuangga, Halwan Fuad; Gofir, Abdul; Setyopranoto, Ismail

2017-12-29

Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = -0.232, p = 0.024). This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

KymoKnot: A web server and software package to identify and locate knots in trajectories of linear or circular polymers.

PubMed

Tubiana, Luca; Polles, Guido; Orlandini, Enzo; Micheletti, Cristian

2018-06-07

The KymoKnot software package and web server identifies and locates physical knots or proper knots in a series of polymer conformations. It is mainly intended as an analysis tool for trajectories of linear or circular polymers, but it can be used on single instances too, e.g. protein structures in PDB format. A key element of the software package is the so-called minimally interfering chain closure algorithm that is used to detect physical knots in open chains and to locate the knotted region in both open and closed chains. The web server offers a user-friendly graphical interface that identifies the knot type and highlights the knotted region on each frame of the trajectory, which the user can visualize interactively from various viewpoints. The dynamical evolution of the knotted region along the chain contour is presented as a kymograph. All data can be downloaded in text format. The KymoKnot package is licensed under the BSD 3-Clause licence. The server is publicly available at http://kymoknot.sissa.it/kymoknot/interactive.php .

Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

NASA Astrophysics Data System (ADS)

Pichierri, Fabio

2014-08-01

Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

Multitasking mesoporous nanomaterials for biorefinery applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandel, Kapil

2013-01-01

Mesoporous silica nanoparticles (MSNs) have attracted great interest for last two decades due to their unique and advantageous structural properties, such as high surface area, pore volume, stable mesostructure, tunable pore size and controllable particle morphology. The robust silica framework provides sites for organic modifications, making MSNs ideal platforms for adsorbents and supported organocatalysts. In addition, the pores of MSNs provide cavities/ channels for incorporation of metal and metal oxide nanoparticle catalysts. These supported metal nanoparticle catalysts benefit from confined local environments to enhance their activity and selectivity for various reactions. Biomass is considered as a sustainable feedstock with potentialmore » to replace diminishing fossil fuels for the production of biofuels. Among several strategies, one of the promising methods of biofuel production from biomass is to reduce the oxygen content of the feedstock in order to improve the energy density. This can be achieved by creating C-C bonds between biomass derived intermediates to increase the molecular weight of the final hydrocarbon molecules. In this context, pore size and organic functionality of MSNs are varied to obtain the ideal catalyst for a C-C bond forming reaction: the aldol condensation. The mechanistic aspects of this reaction in supported heterogeneous catalysts are explored. The modification of supported organocatalyst and the effect of solvent on the reaction are rationalized. The significance of two functional surfaces of MSNs is exploited by enzyme immobilization on the external surface and organo catalyst functionalization on the internal surface. Using this bifunctional catalyst, the tandem conversion of small chain alcohols into longer chain hydrocarbon molecules is demonstrated. The ability to incorporate metal and metal oxide nanoparticles in the pores and subsequent functionalization led to develop organic modified magnetic MSNs (OM-MSNs) for applications in microalgae biorefinery. Two different integrated biorefinery systems are highlighted. (i) OM-MSNs are used to harvest microalgae and selectively sequester free fatty acids (FFAs). (ii) OM-MSNs are shown to selectively sequester FFAs and convert them into diesel-range liquid hydrocarbon fuels. A similar MSN supported metal nanoparticle catalyst is demonstrated to transform FFAs into green diesel with even greater activity and selectivity. The incorporation of a different organic functional group into MSN provides a selective adsorbent for separation and purification of α-tocopherol from microalgae oil. The functional group with electron deficient aromatic rings demonstrated high sequestration capacity and selectivity of {alpha}-tocopherol.« less

A Facile Strategy for In Situ Core-Template-Functionalizing Siliceous Hollow Nanospheres for Guest Species Entrapment

PubMed Central

2009-01-01

The shell wall-functionalized siliceous hollow nanospheres (SHNs) with functional molecules represent an important class of nanocarriers for a rich range of potential applications. Herein, a self-templated approach has been developed for the synthesis of in situ functionalized SHNs, in which the biocompatible long-chain polycarboxylates (i.e., polyacrylate, polyaspartate, gelatin) provide the framework for silica precursor deposition by simply controlling chain conformation with divalent metal ions (i.e., Ca2+, Sr2+), without the intervention of any external templates. Metal ions play crucial roles in the formation of organic vesicle templates by modulating the long chains of polymers and preventing them from separation by washing process. We also show that, by in situ functionalizing the shell wall of SHNs, it is capable of entrapping nearly an eightfold quantity of vitamin Bc in comparison to the bare bulk silica nanospheres. These results confirm the feasibility of guest species entrapment in the functionalized shell wall, and SHNs are effective carriers of guest (bio-)molecules potentially for a variety of biomedical applications. By rationally choosing the functional (self-templating) molecules, this concept may represent a general strategy for the production of functionalized silica hollow structures. PMID:20596316

Assessing Chemical Transformation of Reactive, Interfacial Thin Films Made of End-Tethered Poly(2-vinyl-4,4-dimethyl azlactone) (PVDMA) Chains

DOE PAGES

Aden, Bethany; Kite, Camille M.; Hopkins, Benjamin W.; ...

2017-01-24

Designing thin films or surface scaffolds with an appropriate display of chemical functionality is useful for biomedical applications, sensing platforms, adhesives, and barrier coatings. Relationships between the structural characteristics of model thin films based on reactive poly(2-vinyl-4,4-dimethyl azlactone) (PVDMA) brushes and the amount and distribution of primary amines used to chemically functionalize these layers in situ are quantitatively detailed via neutron reflectometry and compared with results from ellipsometry. After functionalization, the PVDMA brush thickness increases as a result of the primary amines reacting with the azlactone rings. Both techniques show that the extent of functionalization by small-molecule amines depends onmore » the size of the amine, the grafting density of brush chains, and their molecular weight. However, constrained analysis of neutron reflectivity data predicated on that technique’s sensitivity to isotopic substitution and its ability to resolve structure at the nanoscale shows that the extent of functionalization is not accurately represented by the average extent of functionalization determined from ellipsometric thickness: reactive modification is not uniform, even in modestly dense brushes, except when the penetrant is small. In addition, there appears to be a loss of PVDMA chains during functionalization, attributed to chain scission resulting from additional stretching brought about by functionalization. In conclusion, these findings provide unprecedented insight into the alteration of surface properties by reactive modification and broadly support efforts to produce tailored surfaces in which properties such as friction, colloidal stability, adhesion, wettability, and biocompatibility can be modulated in situ by chemical modification.« less

Overlapping functions of the starch synthases SSII and SSIII in amylopectin biosynthesis in Arabidopsis

PubMed Central

Zhang, Xiaoli; Szydlowski, Nicolas; Delvallé, David; D'Hulst, Christophe; James, Martha G; Myers, Alan M

2008-01-01

Background The biochemical mechanisms that determine the molecular architecture of amylopectin are central in plant biology because they allow long-term storage of reduced carbon. Amylopectin structure imparts the ability to form semi-crystalline starch granules, which in turn provides its glucose storage function. The enzymatic steps of amylopectin biosynthesis resemble those of the soluble polymer glycogen, however, the reasons for amylopectin's architectural distinctions are not clearly understood. The multiplicity of starch biosynthetic enzymes conserved in plants likely is involved. For example, amylopectin chain elongation in plants involves five conserved classes of starch synthase (SS), whereas glycogen biosynthesis typically requires only one class of glycogen synthase. Results Null mutations were characterized in AtSS2, which codes for SSII, and mutant lines were compared to lines lacking SSIII and to an Atss2, Atss3 double mutant. Loss of SSII did not affect growth rate or starch quantity, but caused increased amylose/amylopectin ratio, increased total amylose, and deficiency in amylopectin chains with degree of polymerization (DP) 12 to DP28. In contrast, loss of both SSII and SSIII caused slower plant growth and dramatically reduced starch content. Extreme deficiency in DP12 to DP28 chains occurred in the double mutant, far more severe than the summed changes in SSII- or SSIII-deficient plants lacking only one of the two enzymes. Conclusion SSII and SSIII have partially redundant functions in determination of amylopectin structure, and these roles cannot be substituted by any other conserved SS, specifically SSI, GBSSI, or SSIV. Even though SSIII is not required for the normal abundance of glucan chains of DP12 to DP18, the enzyme clearly is capable of functioning in production such chains. The role of SSIII in producing these chains cannot be detected simply by analysis of an individual mutation. Competition between different SSs for binding to substrate could in part explain the specific distribution of glucan chains within amylopectin. PMID:18811962

A convenient strategy to functionalize carbon nanotubes with ascorbic acid and its effect on the physical and thermomechanical properties of poly(amide–imide) composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mallakpour, Shadpour, E-mail: mallak@cc.iut.ac.ir; Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan 84156-83111, I.R. Iran; Zadehnazari, Amin

Multi-walled carbon nanotubes (MWCNTs) were functionalized by ascorbic acid by a fast strategy under microwave irradiation to improve interfacial interactions and dispersion of CNTs in a poly(amide–imide) (PAI) matrix. This technique provides a rapid and economically viable route to produce covalently functionalized CNTs. The as-prepared, new type of functionalized CNTs were analyzed by several techniques. The thermal stabilities and mechanical interfacial properties of CNT/PAI composites were investigated using several techniques. The dispersion state of CNTs in the PAI matrix was observed by field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The mechanical interfacial property of the compositesmore » was significantly increased by the addition of ascorbic acid treated CNTs. The FE-SEM and TEM results showed that the separation and uniform dispersion of CNTs in the PAI matrix. The overview of these recent results is presented. -- Graphical abstract: Presentation of possible interactions of hydrogen bonding between the MWCNT-AS and the PAI chains. Highlights: • Surface functionalization of MWCNTs with ascorbic acid under microwave irradiation. • The MWCNT-AS/PAI composite films were fabricated by solution blending process. • Microstructure and MWCNT states in the composites were studied. • Thermal and mechanical properties of the composite films were evaluated. • Films of different contents of the MWCNTs-AS showed a superior tensile behavior.« less

End-functionalized ROMP polymers for Biomedical Applications

PubMed Central

Madkour, Ahmad E.; Koch, Amelie H. R.; Lienkamp, Karen; Tew, Gregory N.

2010-01-01

We present two novel allyl-based terminating agents that can be used to end-functionalize living polymer chains obtained by ring-opening metathesis polymerization (ROMP) using Grubbs’ third generation catalyst. Both terminating agents can be easily synthesized and yield ROMP polymers with stable, storable activated ester groups at the chain-end. These end-functionalized ROMP polymers are attractive building blocks for advanced polymeric materials, especially in the biomedical field. Dye-labeling and surface-coupling of antimicrobially active polymers using these end-groups were demonstrated. PMID:21499549

Orthogonal use of a human tRNA synthetase active site to achieve multi-functionality

PubMed Central

Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B.; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A.; Schimmel, Paul; Yang, Xiang-Lei

2011-01-01

Protein multi-functionality is an emerging explanation for the complexity of higher organisms. In this regard, while aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, some also act in pathways for inflammation, angiogenesis, and apoptosis. How multiple functions evolved and their relationship to the active site is not clear. Here structural modeling analysis, mutagenesis, and cell-based functional studies show that the potent angiostatic, natural fragment of human TrpRS associates via Trp side chains that protrude from the cognate cellular receptor VE-cadherin. Modeling indicates that (I prefer the way it was because the conclusion was reached not only by modeling, but more so by experimental studies.)VE-cadherin Trp side chains fit into the Trp-specific active site of the synthetase. Thus, specific side chains of the receptor mimic (?) amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multi-functionality of human tRNA synthetases and other proteins. PMID:20010843

Experimental and in silico modelling analyses of the gene expression pathway for recombinant antibody and by-product production in NS0 cell lines.

PubMed

Mead, Emma J; Chiverton, Lesley M; Spurgeon, Sarah K; Martin, Elaine B; Montague, Gary A; Smales, C Mark; von der Haar, Tobias

2012-01-01

Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often vary in the amounts of product produced and in the heterogeneity of the secreted products. The biological mechanisms of this variation are not fully defined. Here we have utilised experimental and modelling strategies to characterise and define the biology underpinning product heterogeneity in cell lines exhibiting varying antibody expression levels, and then experimentally validated these models. In undertaking these studies we applied and validated biochemical (rate-constant based) and engineering (nonlinear) models of antibody expression to experimental data from four NS0 cell lines with different IgG4 secretion rates. The models predict that export of the full antibody and its fragments are intrinsically linked, and cannot therefore be manipulated individually at the level of the secretory machinery. Instead, the models highlight strategies for the manipulation at the precursor species level to increase recombinant protein yields in both high and low producing cell lines. The models also highlight cell line specific limitations in the antibody expression pathway.

Pathophysiologic roles of the fibrinogen gamma chain.

PubMed

Farrell, David H

2004-05-01

Fibrinogen binds through its gamma chains to cell surface receptors, growth factors, and coagulation factors to perform its key roles in fibrin clot formation, platelet aggregation, and wound healing. However, these binding interactions can also contribute to pathophysiologic processes, including inflammation and thrombosis. This review summarizes the latest findings on the role of the fibrinogen gamma chain in these processes, and illustrates the potential for therapeutic intervention. Novel gamma chain epitopes that bind platelet integrin alpha IIbbeta3 and leukocyte integrin alphaMbeta2 have been characterized, leading to the revision of former dogma regarding the processes of platelet aggregation, clot retraction, inflammation, and thrombosis. A series of studies has shown that the gamma chain serves as a depot for fibroblast growth factor-2 (FGF-2), which is likely to play an important role in wound healing. Inhibition of gamma chain function with the monoclonal antibody 7E9 has been shown to interfere with multiple fibrinogen activities, including factor XIIIa crosslinking, platelet adhesion, and platelet-mediated clot retraction. The role of the enigmatic variant fibrinogen gamma chain has also become clearer. Studies have shown that gamma chain binding to thrombin and factor XIII results in clots that are mechanically stiffer and resistant to fibrinolysis, which may explain the association between gammaA/gamma' fibrinogen levels and cardiovascular disease. The identification of new interactions with gamma chains has revealed novel targets for the treatment of inflammation and thrombosis. In addition, several exciting studies have shown new functions for the variant gamma chain that may contribute to cardiovascular disease.

Surface Layer Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (SL-MALDI-ToF-MS) Analysis of Polymer Blend Surface Composition

NASA Astrophysics Data System (ADS)

Hill, Jacob A.

The composition of a polymer blend is generally different at the surface than in the bulk and the gradient in composition with depth has important implications for surface properties. The determination of the surface composition presents various challenges which continue to prompt the development of new techniques for quantifying the composition. Here the technique of surface layer matrix-assisted laser desorption ionization time-of-flight mass spectrometry (SL-MALDI-ToF-MS) has been further developed to address four specific questions of polymer blend surface behavior within the general category of surface composition determination. The first question is how chain length disparity affects surface segregation in the case that the disparity is quite small. While such segregation is known for blends containing low molecular weight additives or systems with large polydispersity, it has not been reported for anionically polymerized polymers that are viewed, in practice, as monodisperse. For 6 kDa polystyrene the number average molecular weight (Mn) at the surface is ca. 300 Da (5%) lower than that in the bulk and for 7 kDa polymethyl methacrylate the shift is ca. 500 Da. The second question is how chain-end functionalization effects not the location of chain ends at the surface, but rather the prevalence at the surface of any part of a chain having an end functionalization. A key issue of such an approach is understanding precisely where the functionalities ultimately reside and how this functionalization shifts the balance of forces that determine the distribution of chains with depth. The surface of a blend of 6 kDa polystyrene and 6 kDa polystyrene functionalized with hydroxymethyl ends is not only depleted of the higher energy end groups, but is depleted of any segments belonging to the functionalized chains. This is demonstrated using SL-MALDI-ToF-MS, which detects entire chains that have any repeat unit at the outer surface, and requires no labelling. This study was extended to the surfaces of blends of 6 kDa polystyrene and 6 kDa polystyrene functionalized with hydroxyethyl ends. Blends of all compositions less than 90 wt. % functionalized chains showed depletion. Finally, the challenge of determining lateral variations in the surface composition has been addressed with the development of SL-MALDI-ToF-MS imaging (SL-MALDI-ToF-MSI). Key to developing imaging capability was improving the lateral uniformity of the matrix deposition. This uniformity was achieved using solvent free sublimation of matrix and salt onto the sample's surface. The capabilities of SL-MALDI-ToF-MSI were demonstrated by imaging the absence of material due to masking during material deposition, mechanical scribing or solvent perturbation at the surface of low molecular weight poly(methyl methacrylate) and polystyrene thin films. SL-MALDI-ToF MSI was made possible through the first uniform, solvent free simultaneous sublimation of matrix and salt onto the material's surface.

Protein side chain conformation predictions with an MMGBSA energy function.

PubMed

Gaillard, Thomas; Panel, Nicolas; Simonson, Thomas

2016-06-01

The prediction of protein side chain conformations from backbone coordinates is an important task in structural biology, with applications in structure prediction and protein design. It is a difficult problem due to its combinatorial nature. We study the performance of an "MMGBSA" energy function, implemented in our protein design program Proteus, which combines molecular mechanics terms, a Generalized Born and Surface Area (GBSA) solvent model, with approximations that make the model pairwise additive. Proteus is not a competitor to specialized side chain prediction programs due to its cost, but it allows protein design applications, where side chain prediction is an important step and MMGBSA an effective energy model. We predict the side chain conformations for 18 proteins. The side chains are first predicted individually, with the rest of the protein in its crystallographic conformation. Next, all side chains are predicted together. The contributions of individual energy terms are evaluated and various parameterizations are compared. We find that the GB and SA terms, with an appropriate choice of the dielectric constant and surface energy coefficients, are beneficial for single side chain predictions. For the prediction of all side chains, however, errors due to the pairwise additive approximation overcome the improvement brought by these terms. We also show the crucial contribution of side chain minimization to alleviate the rigid rotamer approximation. Even without GB and SA terms, we obtain accuracies comparable to SCWRL4, a specialized side chain prediction program. In particular, we obtain a better RMSD than SCWRL4 for core residues (at a higher cost), despite our simpler rotamer library. Proteins 2016; 84:803-819. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Statistical properties of multi-theta polymer chains

NASA Astrophysics Data System (ADS)

Uehara, Erica; Deguchi, Tetsuo

2018-04-01

We study statistical properties of polymer chains with complex structures whose chemical connectivities are expressed by graphs. The multi-theta curve of m subchains with two branch points connected by them is one of the simplest graphs among those graphs having closed paths, i.e. loops. We denoted it by θm , and for m  =  2 it is given by a ring. We derive analytically the pair distribution function and the scattering function for the θm -shaped polymer chains consisting of m Gaussian random walks of n steps. Surprisingly, it is shown rigorously that the mean-square radius of gyration for the Gaussian θm -shaped polymer chain does not depend on the number m of subchains if each subchain has the same fixed number of steps. For m  =  3 we show the Kratky plot for the theta-shaped polymer chain consisting of hard cylindrical segments by the Monte-Carlo method including reflection at trivalent vertices.

Modular in situ-Functionalization Strategy: Multicomponent Polymerization via Palladium/Norbornene Cooperative Catalysis.

PubMed

Yoon, Ki-Young; Dong, Guangbin

2018-05-23

Herein, we report the palladium/norbornene cooperatively catalyzed polymerization, which simplifies synthesis of functional aromatic polymers, including conjugated polymers. Specifically, an A2B2C-type multicomponent polymerization is developed using ortho-amination/ipso-alkynylation reaction for preparing various amine-functionalized arylacetylene-containing polymers. Within a single catalytic cycle, the amine side-chains are site-selectively installed in situ via C-H activation during the polymerization process, which represents a major difference from conventional cross-coupling polymerizations. This in situ-functionalization strategy enables modular incorporation of functional side-chains from simple monomers, thereby conveniently affording a diverse range of functional polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ECERIFERUM2-LIKE proteins have unique biochemical and physiological functions in very-long-chain fatty acid elongation.

PubMed

Haslam, Tegan M; Haslam, Richard; Thoraval, Didier; Pascal, Stéphanie; Delude, Camille; Domergue, Frédéric; Fernández, Aurora Mañas; Beaudoin, Frédéric; Napier, Johnathan A; Kunst, Ljerka; Joubès, Jérôme

2015-03-01

The extension of very-long-chain fatty acids (VLCFAs) for the synthesis of specialized apoplastic lipids requires unique biochemical machinery. Condensing enzymes catalyze the first reaction in fatty acid elongation and determine the chain length of fatty acids accepted and produced by the fatty acid elongation complex. Although necessary for the elongation of all VLCFAs, known condensing enzymes cannot efficiently synthesize VLCFAs longer than 28 carbons, despite the prevalence of C28 to C34 acyl lipids in cuticular wax and the pollen coat. The eceriferum2 (cer2) mutant of Arabidopsis (Arabidopsis thaliana) was previously shown to have a specific deficiency in cuticular waxes longer than 28 carbons, and heterologous expression of CER2 in yeast (Saccharomyces cerevisiae) demonstrated that it can modify the acyl chain length produced by a condensing enzyme from 28 to 30 carbon atoms. Here, we report the physiological functions and biochemical specificities of the CER2 homologs CER2-LIKE1 and CER2-LIKE2 by mutant analysis and heterologous expression in yeast. We demonstrate that all three CER2-LIKEs function with the same small subset of condensing enzymes, and that they have different effects on the substrate specificity of the same condensing enzyme. Finally, we show that the changes in acyl chain length caused by each CER2-LIKE protein are of substantial importance for cuticle formation and pollen coat function. © 2015 American Society of Plant Biologists. All Rights Reserved.

ECERIFERUM2-LIKE Proteins Have Unique Biochemical and Physiological Functions in Very-Long-Chain Fatty Acid Elongation1[OPEN

PubMed Central

Haslam, Tegan M.; Haslam, Richard; Thoraval, Didier; Pascal, Stéphanie; Delude, Camille; Domergue, Frédéric; Fernández, Aurora Mañas; Beaudoin, Frédéric; Napier, Johnathan A.; Kunst, Ljerka; Joubès, Jérôme

2015-01-01

The extension of very-long-chain fatty acids (VLCFAs) for the synthesis of specialized apoplastic lipids requires unique biochemical machinery. Condensing enzymes catalyze the first reaction in fatty acid elongation and determine the chain length of fatty acids accepted and produced by the fatty acid elongation complex. Although necessary for the elongation of all VLCFAs, known condensing enzymes cannot efficiently synthesize VLCFAs longer than 28 carbons, despite the prevalence of C28 to C34 acyl lipids in cuticular wax and the pollen coat. The eceriferum2 (cer2) mutant of Arabidopsis (Arabidopsis thaliana) was previously shown to have a specific deficiency in cuticular waxes longer than 28 carbons, and heterologous expression of CER2 in yeast (Saccharomyces cerevisiae) demonstrated that it can modify the acyl chain length produced by a condensing enzyme from 28 to 30 carbon atoms. Here, we report the physiological functions and biochemical specificities of the CER2 homologs CER2-LIKE1 and CER2-LIKE2 by mutant analysis and heterologous expression in yeast. We demonstrate that all three CER2-LIKEs function with the same small subset of condensing enzymes, and that they have different effects on the substrate specificity of the same condensing enzyme. Finally, we show that the changes in acyl chain length caused by each CER2-LIKE protein are of substantial importance for cuticle formation and pollen coat function. PMID:25596184

Effect of Backbone Chemistry on the Structure of Polyurea Films Deposited by Molecular Layer Deposition

DOE PAGES

Bergsman, David S.; Closser, Richard G.; Tassone, Christopher J.; ...

2017-01-01

An experimental investigation into the growth of polyurea films by molecular layer deposition was performed by examining trends in the growth rate, crystallinity, and orientation of chains as a function of backbone flexibility. Growth curves obtained for films containing backbones of aliphatic and phenyl groups indicate that an increase in backbone flexibility leads to a reduction in growth rate from 4 to 1 Å/cycle. Crystallinity measurements collected using grazing incidence X-ray diffraction and Fourier transform infrared spectroscopy suggest that some chains form paracrystalline, out-of-plane stacks of polymer segments with packing distances ranging from 4.4 to 3.7 Å depending on themore » monomer size. Diffraction intensity is largely a function of the homogeneity of the backbone. Near-edge X-ray absorption fine structure measurements for thin and thick samples show an average chain orientation of ~25° relative to the substrate across all samples, suggesting that changes in growth rate are not caused by differences in chain angle but instead may be caused by differences in the frequency of chain terminations. In conclusion, these results suggest a model of molecular layer deposition-based chain growth in which films consist of a mixture of upward growing chains and horizontally aligned layers of paracrystalline polymer segments.« less

Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain.

PubMed

Wilbur, Jeremy D; Chen, Chih-Ying; Manalo, Venus; Hwang, Peter K; Fletterick, Robert J; Brodsky, Frances M

2008-11-21

The huntingtin-interacting protein family members (Hip1 and Hip1R in mammals and Sla2p in yeast) link clathrin-mediated membrane traffic to actin cytoskeleton dynamics. Genetic data in yeast have implicated the light chain subunit of clathrin in regulating this link. To test this hypothesis, the biophysical properties of mammalian Hip1 and Hip1R and their interaction with clathrin light chain and actin were analyzed. The coiled-coil domains (clathrin light chain-binding) of Hip1 and Hip1R were found to be stable homodimers with no propensity to heterodimerize in vitro. Homodimers were also predominant in vivo, accounting for cellular segregation of Hip1 and Hip1R functions. Coiled-coil domains of Hip1 and Hip1R differed in their stability and flexibility, correlating with slightly different affinities for clathrin light chain and more markedly with effects of clathrin light chain binding on Hip protein-actin interactions. Clathrin light chain binding induced a compact conformation of both Hip1 and Hip1R and significantly reduced actin binding by their THATCH domains. Thus, clathrin is a negative regulator of Hip-actin interactions. These observations necessarily change models proposed for Hip protein function.

Actin Binding by Hip1 (Huntingtin-interacting Protein 1) and Hip1R (Hip1-related Protein) Is Regulated by Clathrin Light Chain*S⃞

PubMed Central

Wilbur, Jeremy D.; Chen, Chih-Ying; Manalo, Venus; Hwang, Peter K.; Fletterick, Robert J.; Brodsky, Frances M.

2008-01-01

The huntingtin-interacting protein family members (Hip1 and Hip1R in mammals and Sla2p in yeast) link clathrin-mediated membrane traffic to actin cytoskeleton dynamics. Genetic data in yeast have implicated the light chain subunit of clathrin in regulating this link. To test this hypothesis, the biophysical properties of mammalian Hip1 and Hip1R and their interaction with clathrin light chain and actin were analyzed. The coiled-coil domains (clathrin light chain-binding) of Hip1 and Hip1R were found to be stable homodimers with no propensity to heterodimerize in vitro. Homodimers were also predominant in vivo, accounting for cellular segregation of Hip1 and Hip1R functions. Coiled-coil domains of Hip1 and Hip1R differed in their stability and flexibility, correlating with slightly different affinities for clathrin light chain and more markedly with effects of clathrin light chain binding on Hip protein-actin interactions. Clathrin light chain binding induced a compact conformation of both Hip1 and Hip1R and significantly reduced actin binding by their THATCH domains. Thus, clathrin is a negative regulator of Hip-actin interactions. These observations necessarily change models proposed for Hip protein function. PMID:18790740

Exploration Supply Chain Simulation

NASA Technical Reports Server (NTRS)

2008-01-01

The Exploration Supply Chain Simulation project was chartered by the NASA Exploration Systems Mission Directorate to develop a software tool, with proper data, to quantitatively analyze supply chains for future program planning. This tool is a discrete-event simulation that uses the basic supply chain concepts of planning, sourcing, making, delivering, and returning. This supply chain perspective is combined with other discrete or continuous simulation factors. Discrete resource events (such as launch or delivery reviews) are represented as organizational functional units. Continuous resources (such as civil service or contractor program functions) are defined as enabling functional units. Concepts of fixed and variable costs are included in the model to allow the discrete events to interact with cost calculations. The definition file is intrinsic to the model, but a blank start can be initiated at any time. The current definition file is an Orion Ares I crew launch vehicle. Parameters stretch from Kennedy Space Center across and into other program entities (Michaud Assembly Facility, Aliant Techsystems, Stennis Space Center, Johnson Space Center, etc.) though these will only gain detail as the file continues to evolve. The Orion Ares I file definition in the tool continues to evolve, and analysis from this tool is expected in 2008. This is the first application of such business-driven modeling to a NASA/government-- aerospace contractor endeavor.

SPPS of protected peptidyl aminoalkyl amides.

PubMed

Karavoltsos, Manolis; Mourtas, Spyros; Gatos, Dimitrios; Barlos, Kleomenis

2002-11-01

Monophthaloyl diamines derived from naturally occurring amino acids were attached through their free amino functions to resins of the trityl type. The phthaloyl groups were removed by hydrazinolysis, and peptide chains were assembled using Fmoc/tBu-amino acids on the liberated amino functions. The peptidyl aminoalkyl amides obtained were cleaved from the resins by mild acidolysis, with the tBu-side chain protection remaining intact.

Finding the Missing Physics: Simulating Polydisperse Polymer Melts

NASA Astrophysics Data System (ADS)

Rorrer, Nichoals; Dorgan, John

2014-03-01

A Monte Carlo algorithm has been developed to model polydisperse polymer melts. For the first time, this enables the specification of a predetermined molecular weight distribution for lattice based simulations. It is demonstrated how to map an arbitrary probability distributions onto a discrete number of chains residing on an fcc lattice. The resulting algorithm is able to simulate a wide variety of behaviors for polydisperse systems including confinement effects, shear flow, and parabolic flow. The dynamic version of the algorithm accurately captures Rouse dynamics for short polymer chains, and reptation-like dynamics for longer chain lengths.1 When polydispersity is introduced, smaller Rouse times and broadened the transition between different scaling regimes are observed. Rouse times also decrease under confinement for both polydisperse and monodisperse systems and chain length dependent migration effects are observed. The steady-state version of the algorithm enables the simulation of flow and when polydisperse systems are subject to parabolic (Poiseulle) flow, a migration phenomenon based on chain length is again present. These and other phenomena highlight the importance of including polydispersity in obtaining physically realistic simulations of polymeric melts. 1. Dorgan, J.R.; Rorrer, N.A.; Maupin, C.M., Macromolecules 2012, 45(21), 8833-8840. Work funded by the Fluid Dynamics program of the National Science Foundation under grant CBET-1067707.

The emerging complexity of ubiquitin architecture.

PubMed

Ohtake, Fumiaki; Tsuchiya, Hikaru

2017-02-01

Ubiquitylation is an essential post-translational modification (PTM) of proteins with diverse cellular functions. Polyubiquitin chains with different topologies have different cellular roles, and are referred to as a 'ubiquitin code'. Recent studies have begun to reveal that more complex ubiquitin architectures function as important signals in several biological pathways. These include PTMs of ubiquitin itself, such as acetylated ubiquitin and phospho-ubiquitin. Moreover, important roles for heterogeneous polyubiquitin chains, such as mixed or branched chains, have been reported, which significantly increase the diversity of the ubiquitin code. In this review, we describe mass spectrometry-based methods to characterize the ubiquitin signal. We also describe recent advances in our understanding of complex ubiquitin architectures, including our own findings concerning ubiquitin acetylation and branching within polyubiquitin chains. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Comparison of several classical density functional theories for the adsorption of flexible chain molecules into cylindrical nanopores.

PubMed

Hlushak, S P; Cummings, P T; McCabe, C

2013-12-21

Adsorption of flexible oligomers into narrow cylindrical pores has been studied by means of several versions of classical density functional theory (CDFT) and Monte Carlo simulation. The adsorption process is interesting to study due to the competition between the entropic depletion of oligomers from the pores and the wall-oligomer attraction. It is also challenging to describe using current CDFTs, which tend to overestimate the amount of the adsorbed fluid. From a comparison of several different CDFT approaches, we find that this is due to the assumption of ideal or freely jointed chain conformations. Moreover, it is demonstrated that it is impossible to obtain a reasonable description of the adsorption isotherms without taking into account accurate contact values in the distribution functions describing the structure of the reference monomer fluid. At low densities, more accurate result are obtained in comparison with Monte Carlo simulation data when accurate contact values are incorporated into the theory rather than the more commonly used hard-sphere contact value. However, even the CDFT with accurate contact values still overestimates the amount of the adsorbed fluid due to the ideal or freely jointed chain approximation, used for the description of chain conformations in most CDFT approaches. We find that significant improvement can achieved by employing self-consistent field theory, which samples self-avoiding chain conformations and decreases the number of possible chain conformations, and, consequently, the amount of the adsorbed fluid.

A framework for the computer-aided planning and optimisation of manufacturing processes for components with functional graded properties

NASA Astrophysics Data System (ADS)

Biermann, D.; Gausemeier, J.; Heim, H.-P.; Hess, S.; Petersen, M.; Ries, A.; Wagner, T.

2014-05-01

In this contribution a framework for the computer-aided planning and optimisation of functional graded components is presented. The framework is divided into three modules - the "Component Description", the "Expert System" for the synthetisation of several process chains and the "Modelling and Process Chain Optimisation". The Component Description module enhances a standard computer-aided design (CAD) model by a voxel-based representation of the graded properties. The Expert System synthesises process steps stored in the knowledge base to generate several alternative process chains. Each process chain is capable of producing components according to the enhanced CAD model and usually consists of a sequence of heating-, cooling-, and forming processes. The dependencies between the component and the applied manufacturing processes as well as between the processes themselves need to be considered. The Expert System utilises an ontology for that purpose. The ontology represents all dependencies in a structured way and connects the information of the knowledge base via relations. The third module performs the evaluation of the generated process chains. To accomplish this, the parameters of each process are optimised with respect to the component specification, whereby the result of the best parameterisation is used as representative value. Finally, the process chain which is capable of manufacturing a functionally graded component in an optimal way regarding to the property distributions of the component description is presented by means of a dedicated specification technique.

Functionalizing graphene by embedded boron clusters

NASA Astrophysics Data System (ADS)

Quandt, Alexander; Özdoğan, Cem; Kunstmann, Jens; Fehske, Holger

2008-08-01

We present a model system that might serve as a blueprint for the controlled layout of graphene based nanodevices. The systems consists of chains of B7 clusters implanted in a graphene matrix, where the boron clusters are not directly connected. We show that the graphene matrix easily accepts these alternating B7-C6 chains and that the implanted boron components may dramatically modify the electronic properties of graphene based nanomaterials. This suggests a functionalization of graphene nanomaterials, where the semiconducting properties might be supplemented by parts of the graphene matrix itself, but the basic wiring will be provided by alternating chains of implanted boron clusters that connect these areas.

From Canterbury to Little Rock: The Struggle for Educational Equality for African Americans. Teaching with Historic Places.

ERIC Educational Resources Information Center

Hunter, Kathleen

Canterbury, Connecticut, and Little Rock, Arkansas, are links in a chain of events representing the struggle for equal educational opportunity for African Americans. Focusing on these two communities, this lesson plan highlights two important historic places and the role each played in testing the prevailing assumptions of the time regarding…

Evaluation of primer and probe mismatches in sensitivity of select RRT-PCR tests for avian influenza

USDA-ARS?s Scientific Manuscript database

The recent outbreak of pH1N1 in animals highlighted an imperfection of the matrix real-time reverse transcriptase-polymerase chain reaction (RRT-PCR) that has become the primary screening test for avian and swine influenza viruses. Four mismatches in one primer resulted in an important loss of sens...

Evaluating the Role of Drone-Produced Chemical Signals in Mediating Social Interactions in Honey Bees (Apis mellifera).

PubMed

Villar, Gabriel; Wolfson, Megan D; Hefetz, Abraham; Grozinger, Christina M

2018-01-01

Pheromones play a critical role in shaping societies of social insects, including honey bees, Apis mellifera. While diverse functions have been ascribed to queen- and worker-produced compounds, few studies have explored the identity and function of male-produced (drone) compounds. However, several lines of evidence suggest that drones engage in a variety of social interactions inside and outside of the colony. Here we elucidate the chemical composition of extracts of the drone mandibular gland, and test the hypothesis that compounds produced in these glands, or a synthetic blend consisting of the six main compounds, mediate drone social interactions in and out of the colony. Drone mandibular glands primarily produce a blend of saturated, unsaturated and methyl branched fatty acids ranging in chain length from nonanoic to docosanoic acids, and both gland extracts and synthetic blends of these chemicals serve to attract drones outside of the hive, but do not attract workers inside the hive. These studies shed light on the role drones and drone-produced chemicals have on mediating social interactions with other drones and highlight their potential importance in communicating with other castes.

Using Biomimetic Polymers in Place of Noncollagenous Proteins to Achieve Functional Remineralization of Dentin Tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, Yung-Ching; Tao, Jinhui; Saeki, Kuniko

In calcified tissues such as bones and teeth, mineralization is regulated by an extracellular matrix, which includes non-collagenous proteins (NCP). This natural process has been adapted or mimicked to restore tissues following physical damage or demineralization by using polyanionic acids in place of NCPs, but the remineralized tissues fail to fully recover their mechanical properties. Here we show that pre-treatment with certain amphiphilic peptoids, a class of peptide-like polymers consisting of N-substituted glycines that have defined monomer sequences, enhances ordering and mineralization of collagen and induces functional remineralization of dentin lesions in vitro. In the vicinity of dentin tubules, themore » newly formed apatite nano-crystals are co-aligned with the c-axis parallel to the tubular periphery and recovery of tissue ultrastructure is accompanied by development of high mechanical strength. The observed effects are highly sequence-dependent with alternating polar and non-polar groups leading to positive outcomes while diblock sequences have no effect. The observations suggest aromatic groups interact with the collagen while the hydrophilic side chains bind the mineralizing constituents and highlight the potential of synthetic sequence-defined biomimetic polymers to serve as NCP mimics in tissue remineralization.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uozumi, Naoki; Matsumoto, Hotaru; Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp

The amino-nucleoside antibiotic, puromycin, acts by covalently linking to elongating polypeptide chains on ribosomes to generate prematurely terminated immature polypeptides. The trafficking of puromycin-conjugated (puromycylated) immature polypeptides within cell has, however, remained elusive. In this study, using O-propargyl-puromycin (OP-Puro), the distribution of puromycylated polypeptides was assessed in HeLa cells by click chemistry. Under standard culture conditions, OP-Puro signals were detected in the cytoplasm and nucleus with the highest concentrations in the nucleolus. Intriguingly, when proteasome activities were aborted using MG132, OP-Puro signals began to accumulate at promyelocytic leukemia nuclear bodies (PML-NBs) in addition to the nucleolus. We also found promiscuousmore » association of OP-Puro signals with SUMO-2/3 and ubiquitin at PML-NBs, but not at the nucleolus, during abortive proteasome activities. This study reveals a previously unknown distribution of OP-Puro that argues for a nuclear function in regulating immature protein homeostasis. -- Highlights: •Click chemistry detects O-propargyl-puromycin (OP-Puro) signals in the nucleus. •OP-Puro accumulates at PML-NBs during abortive proteasome activities. •SUMO and ubiquitin are promiscuously associated with OP-Puro at PML-NBs. •The nucleus may function in immature protein homeostasis.« less

Dysbiosis of the microbiome in gastric carcinogenesis.

PubMed

Castaño-Rodríguez, Natalia; Goh, Khean-Lee; Fock, Kwong Ming; Mitchell, Hazel M; Kaakoush, Nadeem O

2017-11-21

The gastric microbiome has been proposed as an etiological factor in gastric carcinogenesis. We compared the gastric microbiota in subjects presenting with gastric cancer (GC, n = 12) and controls (functional dyspepsia (FD), n = 20) from a high GC risk population in Singapore and Malaysia. cDNA from 16S rRNA transcripts were amplified (515F-806R) and sequenced using Illumina MiSeq 2 × 250 bp chemistry. Increased richness and phylogenetic diversity but not Shannon's diversity was found in GC as compared to controls. nMDS clustered GC and FD subjects separately, with PERMANOVA confirming a significant difference between the groups. H. pylori serological status had a significant impact on gastric microbiome α-diversity and composition. Several bacterial taxa were enriched in GC, including Lactococcus, Veilonella, and Fusobacteriaceae (Fusobacterium and Leptotrichia). Prediction of bacterial metabolic contribution indicated that serological status had a significant impact on metabolic function, while carbohydrate digestion and pathways were enriched in GC. Our findings highlight three mechanisms of interest in GC, including enrichment of pro-inflammatory oral bacterial species, increased abundance of lactic acid producing bacteria, and enrichment of short chain fatty acid production pathways.

Smart Polymers with Special Wettability.

PubMed

Chang, Baisong; Zhang, Bei; Sun, Taolei

2017-01-01

Surface wettability plays a key role in addressing issues ranging from basic life activities to our daily life, and thus being able to control it is an attractive goal. Learning from nature, both of its structure and function, brings us much inspiration in designing smart polymers to tackle this major challenge. Life functions particularly depend on biomolecular recognition-induced interfacial properties from the aqueous phase onto either "soft" cell and tissue or "hard" inorganic bone and tooth surfaces. The driving force is noncovalent weak interactions rather than strong covalent combinations. An overview is provided of the weak interactions that perform vital actions in mediating biological processes, which serve as a basis for elaborating multi-component polymers with special wettabilities. The role of smart polymers from molecular recognitions to macroscopic properties are highlighted. The rationale is that highly selective weak interactions are capable of creating a dynamic synergetic communication in the building components of polymers. Biomolecules could selectively induce conformational transitions of polymer chains, and then drive a switching of physicochemical properties, e.g., roughness, stiffness and compositions, which are an integrated embodiment of macroscopic surface wettabilities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biophysics of protein evolution and evolutionary protein biophysics

PubMed Central

Sikosek, Tobias; Chan, Hue Sun

2014-01-01

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

Commensurability effects in one-dimensional Anderson localization: Anomalies in eigenfunction statistics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kravtsov, V.E., E-mail: kravtsov@ictp.it; Landau Institute for Theoretical Physics, 2 Kosygina st., 117940 Moscow; Yudson, V.I., E-mail: yudson@isan.troitsk.ru

Highlights: > Statistics of normalized eigenfunctions in one-dimensional Anderson localization at E = 0 is studied. > Moments of inverse participation ratio are calculated. > Equation for generating function is derived at E = 0. > An exact solution for generating function at E = 0 is obtained. > Relation of the generating function to the phase distribution function is established. - Abstract: The one-dimensional (1d) Anderson model (AM), i.e. a tight-binding chain with random uncorrelated on-site energies, has statistical anomalies at any rational point f=(2a)/({lambda}{sub E}) , where a is the lattice constant and {lambda}{sub E} is the demore » Broglie wavelength. We develop a regular approach to anomalous statistics of normalized eigenfunctions {psi}(r) at such commensurability points. The approach is based on an exact integral transfer-matrix equation for a generating function {Phi}{sub r}(u, {phi}) (u and {phi} have a meaning of the squared amplitude and phase of eigenfunctions, r is the position of the observation point). This generating function can be used to compute local statistics of eigenfunctions of 1d AM at any disorder and to address the problem of higher-order anomalies at f=p/q with q > 2. The descender of the generating function P{sub r}({phi}){identical_to}{Phi}{sub r}(u=0,{phi}) is shown to be the distribution function of phase which determines the Lyapunov exponent and the local density of states. In the leading order in the small disorder we derived a second-order partial differential equation for the r-independent ('zero-mode') component {Phi}(u, {phi}) at the E = 0 (f=1/2 ) anomaly. This equation is nonseparable in variables u and {phi}. Yet, we show that due to a hidden symmetry, it is integrable and we construct an exact solution for {Phi}(u, {phi}) explicitly in quadratures. Using this solution we computed moments I{sub m} = N< vertical bar {psi} vertical bar {sup 2m}> (m {>=} 1) for a chain of the length N {yields} {infinity} and found an essential difference between their m-behavior in the center-of-band anomaly and for energies outside this anomaly. Outside the anomaly the 'extrinsic' localization length defined from the Lyapunov exponent coincides with that defined from the inverse participation ratio ('intrinsic' localization length). This is not the case at the E = 0 anomaly where the extrinsic localization length is smaller than the intrinsic one. At E = 0 one also observes an anomalous enhancement of large moments compatible with existence of yet another, much smaller characteristic length scale.« less

Constructing and decoding unconventional ubiquitin chains.

PubMed

Behrends, Christian; Harper, J Wade

2011-05-01

One of the most notable discoveries in the ubiquitin system during the past decade is the extensive use of diverse chain linkages to control signaling networks. Although the utility of Lys48- and Lys63-linked chains in protein turnover and molecular assembly, respectively, are well known, we are only beginning to understand how unconventional chain linkages are formed on target proteins and how such linkages are decoded by specific binding proteins. In this review, we summarize recent efforts to elucidate the machinery and mechanisms controlling assembly of Lys11-linked and linear (or Met1-linked) ubiquitin chains, and describe current models for how these chain types function in immune signaling and cell-cycle control.

TCTEX1D4 Interactome in Human Testis: Unraveling the Function of Dynein Light Chain in Spermatozoa

PubMed Central

Freitas, Maria João; Korrodi-Gregório, Luís; Morais-Santos, Filipa; da Cruz e Silva, Edgar

2014-01-01

Abstract Studies were designed to identify the TCTEX1D4 interactome in human testis, with the purpose of unraveling putative protein complexes essential to male reproduction and thus novel TCTEX1D4 functions. TCTEX1D4 is a dynein light chain that belongs to the DYNT1/TCTEX1 family. In spermatozoa, it appears to be important to sperm motility, intraflagellar transport, and acrosome reaction. To contribute to the knowledge on TCTEX1D4 function in testis and spermatozoa, a yeast two-hybrid assay was performed in testis, which allowed the identification of 40 novel TCTEX1D4 interactors. Curiously, another dynein light chain, TCTEX1D2, was identified and its existence demonstrated for the first time in human spermatozoa. Immunofluorescence studies proved that TCTEX1D2 is an intra-acrosomal protein also present in the midpiece, suggesting a role in cargo movement in human spermatozoa. Further, an in silico profile of TCTEX1D4 revealed that most TCTEX1D4 interacting proteins were not previously characterized and the ones described present a very broad nature. This reinforces TCTEX1D4 as a dynein light chain that is capable of interacting with a variety of functionally different proteins. These observations collectively contribute to a deeper molecular understanding of the human spermatozoa function. PMID:24606217

Developing and sustaining human resources in the health supply chain in Ethiopia: barriers and enablers.

PubMed

Kälvemark Sporrong, Sofia; Traulsen, Janine M; Damene Kabtimer, Woynabeba; Mekasha Habtegiorgis, Bitsatab; Teshome Gebregeorgise, Dawit; Essah, Nana Am; Khan, Sara A; Brown, Andrew N

2016-01-01

The health supply chain is often the weakest link in achieving the health-related Millennium Development Goals and universal health coverage, requiring trained professionals who are often unavailable. In Ethiopia there have been recent developments in the area of health supply chain management. The aim of this study was to explore the current status of the development of human resources in health supply chain management in Ethiopia and to identify important factors affecting this development. A series of face-to-face interviews with key stakeholders was carried out in 2014. The interviews were conducted using a semi-structured interview guide. The interview guide comprised 51 questions. A qualitative analysis of transcripts was made. A total of 25 interviews were conducted. Three themes were identified: General changes: recognition, commitment and resources, Education and training, and Barriers and enablers. Results confirm the development of human resources in health supply chain management in many areas. However, several problems were identified including lack of coordination, partly due to the large number of stakeholders; reported high staff mobility; and a lack of overall strategy regarding the job/career structures necessary for maintaining human resources. Rural areas have a particular set of problems, including in transportation of goods and personnel, attracting and keeping personnel, and in communication and access to information. Ethiopia is on the way to developing a nationwide viable system for health supply chain management. However, there are still challenges. Short-term challenges include the importance of highlighting strategies and programs for human resources in health supply chain management. In the long term, commitments to financial support must be obtained. A strategy is needed for the further development and sustainability of human resources in the health supply chain in Ethiopia.

Single chain technology: Toward the controlled synthesis of polymer nanostructures

NASA Astrophysics Data System (ADS)

Lyon, Christopher

A technique for fabricating advanced polymer nanostructures enjoying recent popularity is the collapse or folding of single polymer chains in highly dilute solution mediated by intramolecular cross-linking. We term the resultant structures single-chain nanoparticles (SCNP). This technique has proven particularly valuable in the synthesis of nanomaterials on the order of 5 -- 20 nm. Many different types of covalent and non-covalent chemistries have been used to this end. This dissertation investigates the use of so-called single-chain technology to synthesize nanoparticles using modular techniques that allow for easy incorporation of functionality or special structural or characteristic features. Specifically, the synthesis of linear polymers functionalized with pendant monomer units and the subsequent intramolecular polymerization of these monomer units is discussed. In chapter 2, the synthesis of SCNP using alternating radical polymerization is described. Polymers functionalized with pendant styrene and stilbene groups are synthesized via a modular post-polymerization Wittig reaction. These polymers were exposed to radical initiators in the presence (and absence) of maleic anhydride and other electron deficient monomers in order to form intramolecular cross-links. Chapter 3 discusses templated acyclic diene metathesis (ADMET) polymerization using single-chain technology, starting with the controlled ring-opening polymerization of a glycidyl ether functionalized with an ADMET monomer. This polymer was then exposed to Grubbs' catalyst to polymerize the ADMET monomer units. The ADMET polymer was hydrolytically cleaved from the template and separated. Upon characterization, it was found that the daughter ADMET polymer had a similar degree of polymerization, but did not retain the low dispersity of the template. Chapter 4 details the synthesis of aldehyde- and diol-functionalized polymers toward the synthesis of SCNP containing dynamic, acid-degradable acetal cross-links. SCNP fabrication with these materials is beyond the scope of this dissertation.

A Toxoplasma gondii Class XIV Myosin, Expressed in Sf9 Cells with a Parasite Co-chaperone, Requires Two Light Chains for Fast Motility*

PubMed Central

Bookwalter, Carol S.; Kelsen, Anne; Leung, Jacqueline M.; Ward, Gary E.; Trybus, Kathleen M.

2014-01-01

Many diverse myosin classes can be expressed using the baculovirus/Sf9 insect cell expression system, whereas others have been recalcitrant. We hypothesized that most myosins utilize Sf9 cell chaperones, but others require an organism-specific co-chaperone. TgMyoA, a class XIVa myosin from the parasite Toxoplasma gondii, is required for the parasite to efficiently move and invade host cells. The T. gondii genome contains one UCS family myosin co-chaperone (TgUNC). TgMyoA expressed in Sf9 cells was soluble and functional only if the heavy and light chain(s) were co-expressed with TgUNC. The tetratricopeptide repeat domain of TgUNC was not essential to obtain functional myosin, implying that there are other mechanisms to recruit Hsp90. Purified TgMyoA heavy chain complexed with its regulatory light chain (TgMLC1) moved actin in a motility assay at a speed of ∼1.5 μm/s. When a putative essential light chain (TgELC1) was also bound, TgMyoA moved actin at more than twice that speed (∼3.4 μm/s). This result implies that two light chains bind to and stabilize the lever arm, the domain that amplifies small motions at the active site into the larger motions that propel actin at fast speeds. Our results show that the TgMyoA domain structure is more similar to other myosins than previously appreciated and provide a molecular explanation for how it moves actin at fast speeds. The ability to express milligram quantities of a class XIV myosin in a heterologous system paves the way for detailed structure-function analysis of TgMyoA and identification of small molecule inhibitors. PMID:25231988

Galactose-depleted xyloglucan is dysfunctional and leads to dwarfism in Arabidopsis.

PubMed

Kong, Yingzhen; Peña, Maria J; Renna, Luciana; Avci, Utku; Pattathil, Sivakumar; Tuomivaara, Sami T; Li, Xuemei; Reiter, Wolf-Dieter; Brandizzi, Federica; Hahn, Michael G; Darvill, Alan G; York, William S; O'Neill, Malcolm A

2015-04-01

Xyloglucan is a polysaccharide that has important roles in the formation and function of the walls that surround growing land plant cells. Many of these plants synthesize xyloglucan that contains galactose in two different side chains (L and F), which exist in distinct molecular environments. However, little is known about the contribution of these side chains to xyloglucan function. Here, we show that Arabidopsis (Arabidopsis thaliana) mutants devoid of the F side chain galactosyltransferase MURUS3 (MUR3) form xyloglucan that lacks F side chains and contains much less galactosylated xylose than its wild-type counterpart. The galactose-depleted xyloglucan is dysfunctional, as it leads to mutants that are dwarfed with curled rosette leaves, short petioles, and short inflorescence stems. Moreover, cell wall matrix polysaccharides, including xyloglucan and pectin, are not properly secreted and instead accumulate within intracellular aggregates. Near-normal growth is restored by generating mur3 mutants that produce no detectable amounts of xyloglucan. Thus, cellular processes are affected more by the presence of the dysfunctional xyloglucan than by eliminating xyloglucan altogether. To identify structural features responsible for xyloglucan dysfunction, xyloglucan structure was modified in situ by generating mur3 mutants that lack specific xyloglucan xylosyltransferases (XXTs) or that overexpress the XYLOGLUCAN L-SIDE CHAIN GALACTOSYLTRANSFERASE2 (XLT2) gene. Normal growth was restored in the mur3-3 mutant overexpressing XLT2 and in mur3-3 xxt double mutants when the dysfunctional xyloglucan was modified by doubling the amounts of galactosylated side chains. Our study assigns a role for galactosylation in normal xyloglucan function and demonstrates that altering xyloglucan side chain structure disturbs diverse cellular and physiological processes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia

PubMed Central

Page, Kathleen A.; Williamson, Anne; Yu, Namyi; McNay, Ewan C.; Dzuira, James; McCrimmon, Rory J.; Sherwin, Robert S.

2009-01-01

OBJECTIVE We examined whether ingestion of medium-chain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of β-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose. RESEARCH DESIGN AND METHODS A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic- (2 mU · kg−1 · min−1) euglycemic- (glucose ∼5.5 mmol/l) hypoglycemic (glucose ∼2.8 mmol/l) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of β-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced. RESULTS Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and β-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices β-hydroxybutyrate supported synaptic transmission under low-glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations. CONCLUSIONS Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia. PMID:19223595

Partitioning of electron flux between the respiratory chains of the yeast Candida parapsilosis: parallel working of the two chains.

PubMed

Guerin, M G; Camougrand, N M

1994-02-08

Partitioning of the electron flux between the classical and the alternative respiratory chains of the yeast Candida parapsilosis, was measured as a function of the oxidation rate and of the Q-pool redox poise. At low respiration rate, electrons from external NADH travelled preferentially through the alternative pathway as indicated by the antimycin A-insensitivity of electron flow. Inhibition of the alternative pathway by SHAM restored full antimycin A-sensitivity to the remaining electro flow. The dependence of the respiratory rate on the redox poise of the quinone pool was investigated when the electron flux was mediated either by the main respiratory chain (growth in the absence of antimycin A) or by the second respiratory chain (growth in the presence of antimycin A). In the former case, a linear relationship was found between these two parameters. In contrast, in the latter case, the relationship between Q-pool reduction level and electron flux was non-linear, but it could be resolved into two distinct curves. This second quinone is not reducible in the presence of antimycin A but only in the presence of high concentrations of myxothiazol or cyanide. Since two quinone species exist in C. parapsilosis, UQ9 and Qx (C33H54O4), we hypothesized that these two curves could correspond to the functioning of the second quinone engaged during the alternative pathway activity. Partitioning of electrons between both respiratory chains could occur upstream of complex III with the second chain functioning in parallel to the main one, and with the additional possibility of merging into the main one at the complex IV level.

How Messenger RNA and Nascent Chain Sequences Regulate Translation Elongation.

PubMed

Choi, Junhong; Grosely, Rosslyn; Prabhakar, Arjun; Lapointe, Christopher P; Wang, Jinfan; Puglisi, Joseph D

2018-06-20

Translation elongation is a highly coordinated, multistep, multifactor process that ensures accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of translated messenger RNA (mRNA). Although translation elongation is heavily regulated by external factors, there is clear evidence that mRNA and nascent-peptide sequences control elongation dynamics, determining both the sequence and structure of synthesized proteins. Advances in methods have driven experiments that revealed the basic mechanisms of elongation as well as the mechanisms of regulation by mRNA and nascent-peptide sequences. In this review, we highlight how mRNA and nascent-peptide elements manipulate the translation machinery to alter the dynamics and pathway of elongation.

Optical Properties of a Single Carbon Chain-Doped Silicene Nanoribbon

NASA Astrophysics Data System (ADS)

Lu, Dao-Bang; Song, Yu-Ling; Huang, Xiao-yu; Wang, Chong

2018-05-01

Using first-principles spin polarization density function theory calculations, we have studied the electronic and optical properties of zigzag-edge silicene nanoribbons (ZSiNRs) doped with a single carbon chain. Because of the doped carbon chain, there are several defect states in the band structures of ZSiNRs across the Fermi level, and the ferromagnetic ground state is metallic. The dielectric functions in all three dimensions are completely different from each other, and thus the system exhibits strong optical anisotropism. The carbon chain influenced the dielectric functions most at low energy. The first peak in the E//x direction of the dielectric spectrum exhibits a significant blueshift, and its value has changed as well. The main absorption wavelength depends on the polarization direction of the incident light, but occurs within the UV region for all polarization directions. The peaks of the energy loss spectra correspond to the trailing edges in the reflectivity spectrum, and the highest peak corresponds to a plasmon frequency. Our results could be useful for investigating nanodevices based on silicene nanoribbons.

Expression and function of CD8 alpha/beta chains on rat and human mast cells.

PubMed

Kim, Mi-Sun; Kim, Sung-Hoon; Lee, Hye-Jung; Kim, Hyung-Min

2004-03-01

The expression and functional role of CD8 glycoprotein, a marker of cytotoxic/suppressor T lymphocytes and NK cells, were not studied on freshly isolated connective tissue type rat peritoneal mast cells, a rat mucosal type mast cell line (RBL 2H3), or human mast cell line (HMC-1). We used the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, immunohistochemistry and enzyme-linked immunosorbent assay. RT-PCR and Western blot analysis identified the presence of CD8 alpha/beta chains on the mast cells, and immunohistochemistry confirmed CD8alpha expression on rat or human mast cells. Functional studies demonstrated that stimulation of CD8 alpha/beta chains on rat mast cells induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), which are regarded as important mediators during infection. However, co-stimulation with stem cell factor had no effect on CD8-induced mediator secretion. Our findings demonstrate novel biological roles of CD8 molecules in mast cells.

Value of Conditioned Reinforcers as a Function of Temporal Context

ERIC Educational Resources Information Center

O'Daly, Matthew; Meyer, Steven; Fantino, Edmund

2005-01-01

In two experiments, pigeons were trained on a multiple-chain schedule, in which the initial link for one chain was a variable-interval (VI) 100s schedule and for the other chain a VI 10s schedule. The terminal links were both fixed-time 30s schedules signaled by differently colored stimuli. Following training, the pigeons had their preference for…

Distribution and Supply Chain Management: Educating the Army Officer

DTIC Science & Technology

2005-05-26

knowledge a logistics officer must have to function effectively in a supply chain and distribution management environment. It analyzes how officers...Educational Objectives. It discusses how the Army/DoD currently teaches supply chain and distribution management concepts in various programs, such as the...its educational curriculum, and that logisticians continue to gain operational experience in distribution management operations. The paper recommends

The spectral method and the central limit theorem for general Markov chains

NASA Astrophysics Data System (ADS)

Nagaev, S. V.

2017-12-01

We consider Markov chains with an arbitrary phase space and develop a modification of the spectral method that enables us to prove the central limit theorem (CLT) for non-uniformly ergodic Markov chains. The conditions imposed on the transition function are more general than those by Athreya-Ney and Nummelin. Our proof of the CLT is purely analytical.

Stretching of Single Polymer Chains Using the Atomic Force Microscope

NASA Astrophysics Data System (ADS)

Ortiz, C.; van der Vegte, E. W.; van Swieten, E.; Robillard, G. T.; Hadziioannou, G.

1998-03-01

A variety of macroscopic phenomenon involve "nanoscale" polymer deformation including rubber elasticity, shear yielding, strain hardening, stress relaxation, fracture, and flow. With the advent of new and improved experimental techniques, such as the atomic force microscope (AFM), the probing of physical properties of polymers has reached finer and finer scales. The development of mixed self-assembling monolayer techniques and the chemical functionalization of AFM probe tips has allowed for mechanical experiments on single polymer chains of molecular dimensions. In our experiments, mixed monolayers are prepared in which end-functionalized, flexible polymer chains of thiol-terminated poly(methacrylic acid) are covalently bonded, isolated, and randomly distributed on gold substrates. The coils are then imaged, tethered to a gold-coated AFM tip, and stretched between the tip and the substrate in a conventional force / distance experiment. An increase in the attractive force due to entropic, elastic resistance to stretching, as well as fracture of the polymer chain is observed. The effect of chain stiffness, topological constraints, strain rate, mechanical hysteresis, and stress relaxation were investigated. Force modulation techniques were also employed in order to image the viscoelastic character of the polymer chains. Parallel work includes similar studies of biological systems such as wheat gluten proteins and polypeptides.

A System-Oriented Approach for the Optimal Control of Process Chains under Stochastic Influences

NASA Astrophysics Data System (ADS)

Senn, Melanie; Schäfer, Julian; Pollak, Jürgen; Link, Norbert

2011-09-01

Process chains in manufacturing consist of multiple connected processes in terms of dynamic systems. The properties of a product passing through such a process chain are influenced by the transformation of each single process. There exist various methods for the control of individual processes, such as classical state controllers from cybernetics or function mapping approaches realized by statistical learning. These controllers ensure that a desired state is obtained at process end despite of variations in the input and disturbances. The interactions between the single processes are thereby neglected, but play an important role in the optimization of the entire process chain. We divide the overall optimization into two phases: (1) the solution of the optimization problem by Dynamic Programming to find the optimal control variable values for each process for any encountered end state of its predecessor and (2) the application of the optimal control variables at runtime for the detected initial process state. The optimization problem is solved by selecting adequate control variables for each process in the chain backwards based on predefined quality requirements for the final product. For the demonstration of the proposed concept, we have chosen a process chain from sheet metal manufacturing with simplified transformation functions.

Silicone derivatives for contact lenses: functionalization, chemical characterization, and cell compatibility assessment.

PubMed

Migonney, V; Lacroix, M D; Ratner, B D; Jozefowicz, M

1995-01-01

Epoxy ring-opening functionalization of polymers at random sites along chains with various chemical groups has been demonstrated. The reaction is performed in an aqueous solution under mild conditions in order to minimize degradation of the macromolecular chains. Silicone lenses made of copolymers with epoxy side chains were functionalized with 4-hydroxybutyric acid, sodium salt. The carboxylated silicone derivatives were characterized by ESCA and radiotracers. A mean value of 30% reaction yield was concluded, based upon data from both methods; nevertheless, the latter can be improved up to 50% or more if the conditions of preparation of the epoxydized silicone lenses are optimized. Derivatized silicones were coated in the wells of culture plates to evaluate the cell compatibility of these new polymers with a fibroblast cell line (McCoy's). No cellular toxicity was observed.

A Novel Method of Extraction of Blend Component Structure from SANS Measurements of Homopolymer Bimodal Blends.

PubMed

Smerdova, Olga; Graham, Richard S; Gasser, Urs; Hutchings, Lian R; De Focatiis, Davide S A

2014-05-01

A new method is presented for the extraction of single-chain form factors and interchain interference functions from a range of small-angle neutron scattering (SANS) experiments on bimodal homopolymer blends. The method requires a minimum of three blends, made up of hydrogenated and deuterated components with matched degree of polymerization at two different chain lengths, but with carefully varying deuteration levels. The method is validated through an experimental study on polystyrene homopolymer bimodal blends with [Formula: see text]. By fitting Debye functions to the structure factors, it is shown that there is good agreement between the molar mass of the components obtained from SANS and from chromatography. The extraction method also enables, for the first time, interchain scattering functions to be produced for scattering between chains of different lengths. [Formula: see text].

Chemically Realistic Tetrahedral Lattice Models for Polymer Chains: Application to Polyethylene Oxide.

PubMed

Dietschreit, Johannes C B; Diestler, Dennis J; Knapp, Ernst W

2016-05-10

To speed up the generation of an ensemble of poly(ethylene oxide) (PEO) polymer chains in solution, a tetrahedral lattice model possessing the appropriate bond angles is used. The distance between noncovalently bonded atoms is maintained at realistic values by generating chains with an enhanced degree of self-avoidance by a very efficient Monte Carlo (MC) algorithm. Potential energy parameters characterizing this lattice model are adjusted so as to mimic realistic PEO polymer chains in water simulated by molecular dynamics (MD), which serves as a benchmark. The MD data show that PEO chains have a fractal dimension of about two, in contrast to self-avoiding walk lattice models, which exhibit the fractal dimension of 1.7. The potential energy accounts for a mild hydrophobic effect (HYEF) of PEO and for a proper setting of the distribution between trans and gauche conformers. The potential energy parameters are determined by matching the Flory radius, the radius of gyration, and the fraction of trans torsion angles in the chain. A gratifying result is the excellent agreement of the pair distribution function and the angular correlation for the lattice model with the benchmark distribution. The lattice model allows for the precise computation of the torsional entropy of the chain. The generation of polymer conformations of the adjusted lattice model is at least 2 orders of magnitude more efficient than MD simulations of the PEO chain in explicit water. This method of generating chain conformations on a tetrahedral lattice can also be applied to other types of polymers with appropriate adjustment of the potential energy function. The efficient MC algorithm for generating chain conformations on a tetrahedral lattice is available for download at https://github.com/Roulattice/Roulattice .

Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis.

PubMed

Richard, John P; Amyes, Tina L; Reyes, Archie C

2018-04-17

The mystery associated with catalysis by what were once regarded as protein black boxes, diminished with the X-ray crystallographic determination of the three-dimensional structures of enzyme-substrate complexes. The report that several high-resolution X-ray crystal structures of orotidine 5'-monophosphate decarboxylase (OMPDC) failed to provide a consensus mechanism for enzyme-catalyzed decarboxylation of OMP to form uridine 5'-monophosphate, therefore, provoked a flurry of controversy. This controversy was fueled by the enormous 10 23 -fold rate acceleration for this enzyme, which had " jolted many biochemists' assumptions about the catalytic potential of enzymes." Our studies on the mechanism of action of OMPDC provide strong evidence that catalysis by this enzyme is not fundamentally different from less proficient catalysts, while highlighting important architectural elements that enable a peak level of performance. Many enzymes undergo substrate-induced protein conformational changes that trap their substrates in solvent occluded protein cages, but the conformational change induced by ligand binding to OMPDC is incredibly complex, as required to enable the development of 22 kcal/mol of stabilizing binding interactions with the phosphodianion and ribosyl substrate fragments of OMP. The binding energy from these fragments is utilized to activate OMPDC for catalysis of decarboxylation at the orotate fragment of OMP, through the creation of a tight, catalytically active, protein cage from the floppy, open, unliganded form of OMPDC. Such utilization of binding energy for ligand-driven conformational changes provides a general mechanism to obtain specificity in transition state binding. The rate enhancement that results from the binding of carbon acid substrates to enzymes is partly due to a reduction in the carbon acid p K a that is associated with ligand binding. The binding of UMP to OMPDC results in an unusually large >12 unit decrease in the p K a = 29 for abstraction of the C-6 substrate hydrogen, due to stabilization of an enzyme-bound vinyl carbanion, which is also an intermediate of OMPDC-catalyzed decarboxylation. The protein-ligand interactions operate to stabilize the vinyl carbanion at the enzyme active site compared to aqueous solution, rather than to stabilize the transition state for the concerted electrophilic displacement of CO 2 by H + that avoids formation of this reaction intermediate. There is evidence that OMPDC induces strain into the bound substrate. The interaction between the amide side chain of Gln-215 from the phosphodianion gripper loop and the hydroxymethylene side chain of Ser-154 from the pyrimidine umbrella of ScOMPDC position the amide side chain to interact with the phosphodianion of OMP. There are no direct stabilizing interactions between dianion gripper protein side chains Gln-215, Tyr-217, and Arg-235 and the pyrimidine ring at the decarboxylation transition state. Rather these side chains function solely to hold OMPDC in the catalytically active closed conformation. The hydrophobic side chains that line the active site of OMPDC in the region of the departing CO 2 product may function to stabilize the decarboxylation transition state by providing hydrophobic solvation of this product.

Photomechanical Deformation of Azobenzene-Functionalized Polyimides Synthesized with Bulky Substituents (Postprint)

DTIC Science & Technology

2017-12-06

mechanical response of the azobenzene- functionalized polyimide is correlated to the rotational freedom of the polyimide chains (resulting in extensive... correlated to the rotational freedom of the polyimide chains (resulting in extensive segmental mobility) and fractional free volume (FFV > 0.1...response has been described,34 and a recent simulation study on the stress relaxation dynamics of azo-polyimides has provided insights into the correlation

Command and Control: The Literature and Commentaries

DTIC Science & Technology

1993-09-01

orgeiiizational and intonination decisions. Prioi org4anizational decisions have established a chain of commnand for thle execution of- operational...to be discounted by sentiors inl thle chain of’ cointmnad, who would like to assumte that decisionls that are perfectly cleaýr ill thicir own muinds...Executive Functions." Chapter XV, The Fu~nctions of the IExecuth)ve. Cambiridge, MA: Harvard University Press, 195 1. Suply )emenatwy Reading~s on

Expanding the Bethe/Gauge dictionary

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Functional lignocellulosic materials prepared by ATRP from a wood scaffold.

PubMed

Cabane, Etienne; Keplinger, Tobias; Künniger, Tina; Merk, Vivian; Burgert, Ingo

2016-08-10

Wood, a natural and abundant source of organic polymers, has been used as a scaffold to develop novel wood-polymer hybrid materials. Through a two-step surface-initiated Atom Transfer Radical Polymerization (ATRP), the porous wood structure can be effectively modified with polymer chains of various nature. In the present study, polystyrene and poly(N-isopropylacrylamide) were used. As shown with various characterization techniques including confocal Raman microscopy, FTIR, and SEM/EDX, the native wood ultrastructure and features are retained and the polymer chains can be introduced deep within the wood, i.e. inside the wood cell walls. The physical properties of the new materials have been studied, and results indicate that the insertion of polymer chains inside the wood cell wall alters the intrinsic properties of wood to yield a hybrid composite material with new functionalities. This approach to the functionalization of wood could lead to the fabrication of a new class of interesting functional materials and promote innovative utilizations of the renewable resource wood.

A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription.

PubMed

Zhou, Xin X; Zou, Xinzhi; Chung, Hokyung K; Gao, Yuchen; Liu, Yanxia; Qi, Lei S; Lin, Michael Z

2018-02-16

Optical control of CRISPR-Cas9-derived proteins would be useful for restricting gene editing or transcriptional regulation to desired times and places. Optical control of Cas9 functions has been achieved with photouncageable unnatural amino acids or by using light-induced protein interactions to reconstitute Cas9-mediated functions from two polypeptides. However, these methods have only been applied to one Cas9 species and have not been used for optical control of different perturbations at two genes. Here, we use photodissociable dimeric fluorescent protein domains to engineer single-chain photoswitchable Cas9 (ps-Cas9) proteins in which the DNA-binding cleft is occluded at baseline and opened upon illumination. This design successfully controlled different species and functional variants of Cas9, mediated transcriptional activation more robustly than previous optogenetic methods, and enabled light-induced transcription of one gene and editing of another in the same cells. Thus, a single-chain photoswitchable architecture provides a general method to control a variety of Cas9-mediated functions.

Atomistic Simulations of Hydrodynamic and Interaction Forces on Functionalized Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Lane, J. Matthew D.; Ismail, Ahmed E.; Chandross, Michael; Lorenz, Christian D.; Grest, Gary S.

2009-03-01

It is often desired to prevent the flocculation and phase separation of nanoparticles in solution. This can be accomplished either by manipulating the solvent or by tailoring the surface chemistry of the nanoparticles through functionalization with a monolayer of oligomer chains. Since it is not known how these functionalized coatings affect the interactions between nanoparticles and with the surrounding solvent, we present results from a series of molecular dynamics simulations of polyethylene oxide (PEO) coated silica nanoparticles of varying size (5 to 20 nm diameter) in water. For a single nanoparticle we determined the Stokes drag on the nanoparticle as it moves through the solvent and as it approaches a wall. Due to hydrodynamic interactions there are large finite size effects which we estimate by varying the size of the simulation cell. We also determined both solvent-mediated (velocity-independent) and lubrication (velocity-dependent) forces between two nanoparticles as a function of the coverage and chain length of the PEO chains.

Functional lignocellulosic materials prepared by ATRP from a wood scaffold

PubMed Central

Cabane, Etienne; Keplinger, Tobias; Künniger, Tina; Merk, Vivian; Burgert, Ingo

2016-01-01

Wood, a natural and abundant source of organic polymers, has been used as a scaffold to develop novel wood-polymer hybrid materials. Through a two-step surface-initiated Atom Transfer Radical Polymerization (ATRP), the porous wood structure can be effectively modified with polymer chains of various nature. In the present study, polystyrene and poly(N-isopropylacrylamide) were used. As shown with various characterization techniques including confocal Raman microscopy, FTIR, and SEM/EDX, the native wood ultrastructure and features are retained and the polymer chains can be introduced deep within the wood, i.e. inside the wood cell walls. The physical properties of the new materials have been studied, and results indicate that the insertion of polymer chains inside the wood cell wall alters the intrinsic properties of wood to yield a hybrid composite material with new functionalities. This approach to the functionalization of wood could lead to the fabrication of a new class of interesting functional materials and promote innovative utilizations of the renewable resource wood. PMID:27506369

Developing new methods for the mono-end functionalization of living ring opening metathesis polymers.

PubMed

Kilbinger, Andreas F M

2012-01-01

In this article we present a review of our recent results in one area of research we are involved in. All research efforts in our group focus on functional polymers and new ways of gaining higher levels of control with regard to the placement of functional groups within these polymers. Here, the living ring opening metathesis polymerization (ROMP) will be reviewed for which end-functionalization methods had been rare until very recently. Polymers carrying particular functional groups only at the chain-ends are, however, very interesting for a variety of industrial and academic applications. Polymeric surfactants and polymer-protein conjugates are two examples for the former and polymer-β-sheet-peptide conjugates one example for the latter. The functionalization of macroscopic or nanoscopic surfaces often relies on mono-end functional polymers. Complex macromolecular architectures are often constructed from macromolecules carrying exactly one functional group at their chain- end. The ring opening metathesis polymerization is particularly interesting in this context as it is one of the most functional group tolerant polymerization methods known. Additionally, high molecular weight polymers are readily accessible with this technique, a feature that living radical polymerizations often struggle to achieve. Finding new ways of functionalizing the polymer chain-end of ROMP polymers has therefore been a task long overdue. Here, we present our contribution to this area of research.

Identification of the gene for fly non-muscle myosin heavy chain: Drosophila myosin heavy chains are encoded by a gene family.

PubMed Central

Kiehart, D P; Lutz, M S; Chan, D; Ketchum, A S; Laymon, R A; Nguyen, B; Goldstein, L S

1989-01-01

In contrast to vertebrate species Drosophila has a single myosin heavy chain gene that apparently encodes all sarcomeric heavy chain polypeptides. Flies also contain a cytoplasmic myosin heavy chain polypeptide that by immunological and peptide mapping criteria is clearly different from the major thoracic muscle isoform. Here, we identify the gene that encodes this cytoplasmic isoform and demonstrate that it is distinct from the muscle myosin heavy chain gene. Thus, fly myosin heavy chains are the products of a gene family. Our data suggest that the contractile function required to power myosin based movement in non-muscle cells requires myosin diversity beyond that available in a single heavy chain gene. In addition, we show, that accumulation of cytoplasmic myosin transcripts is regulated in a developmental stage specific fashion, consistent with a key role for this protein in the movements of early embryogenesis. Images PMID:2498088

Canonical Structure and Orthogonality of Forces and Currents in Irreversible Markov Chains

NASA Astrophysics Data System (ADS)

Kaiser, Marcus; Jack, Robert L.; Zimmer, Johannes

2018-03-01

We discuss a canonical structure that provides a unifying description of dynamical large deviations for irreversible finite state Markov chains (continuous time), Onsager theory, and Macroscopic Fluctuation Theory (MFT). For Markov chains, this theory involves a non-linear relation between probability currents and their conjugate forces. Within this framework, we show how the forces can be split into two components, which are orthogonal to each other, in a generalised sense. This splitting allows a decomposition of the pathwise rate function into three terms, which have physical interpretations in terms of dissipation and convergence to equilibrium. Similar decompositions hold for rate functions at level 2 and level 2.5. These results clarify how bounds on entropy production and fluctuation theorems emerge from the underlying dynamical rules. We discuss how these results for Markov chains are related to similar structures within MFT, which describes hydrodynamic limits of such microscopic models.

The condition of a finite Markov chain and perturbation bounds for the limiting probabilities

NASA Technical Reports Server (NTRS)

Meyer, C. D., Jr.

1979-01-01

The inequalities bounding the relative error the norm of w- w squiggly/the norm of w are exhibited by a very simple function of E and A. Let T denote the transition matrix of an ergodic chain, C, and let A = I - T. Let E be a perturbation matrix such that T squiggly = T - E is also the transition matrix of an ergodic chain, C squiggly. Let w and w squiggly denote the limiting probability (row) vectors for C and C squiggly. The inequality is the best one possible. This bound can be significant in the numerical determination of the limiting probabilities for an ergodic chain. In addition to presenting a sharp bound for the norm of w-w squiggly/the norm of w an explicit expression for w squiggly will be derived in which w squiggly is given as a function of E, A, w and some other related terms.

Quasi-Block Copolymers Based on a General Polymeric Chain Stopper.

PubMed

Sanguramath, Rajashekharayya A; Nealey, Paul F; Shenhar, Roy

2016-07-11

Quasi-block copolymers (q-BCPs) are block copolymers consisting of conventional and supramolecular blocks, in which the conventional block is end-terminated by a functionality that interacts with the supramolecular monomer (a "chain stopper" functionality). A new design of q-BCPs based on a general polymeric chain stopper, which consists of polystyrene end-terminated with a sulfonate group (PS-SO3 Li), is described. Through viscosity measurements and a detailed diffusion-ordered NMR spectroscopy study, it is shown that PS-SO3 Li can effectively cap two types of model supramolecular monomers to form q-BCPs in solution. Furthermore, differential scanning calorimetry data and structural characterization of thin films by scanning force microscopy suggests the existence of the q-BCP architecture in the melt. The new design considerably simplifies the synthesis of polymeric chain stoppers; thus promoting the utilization of q-BCPs as smart, nanostructured materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An ab initio molecular dynamics and density functional theory study of the formation of phosphate chains from metathiophosphates.

PubMed

Mosey, Nicholas J; Woo, Tom K

2006-09-04

The reactions that occur between metathiophosphate (MTP) molecules are identified and examined through ab initio molecular dynamics simulations and static quantum chemical calculations at the density functional level of theory. The simulations show that certain types of MTPs can react to yield phosphate chains, while others only dimerize. These differences are rationalized in terms of reaction energies and the electronic structures of these molecules. In the reaction leading to the formation of phosphate chains, the reactive center, a tri-coordinate phosphorus atom, is continually regenerated. A polymerization mechanism linking MTPs to phosphate chains is developed on the basis of these results. This information sheds light on the underlying processes that may be responsible for the formation of phosphates under high-temperature conditions and may prove useful in the development of protocols for the rational synthesis of complex phosphate structures.

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

Clustering and visualizing similarity networks of membrane proteins.

PubMed

Hu, Geng-Ming; Mai, Te-Lun; Chen, Chi-Ming

2015-08-01

We proposed a fast and unsupervised clustering method, minimum span clustering (MSC), for analyzing the sequence-structure-function relationship of biological networks, and demonstrated its validity in clustering the sequence/structure similarity networks (SSN) of 682 membrane protein (MP) chains. The MSC clustering of MPs based on their sequence information was found to be consistent with their tertiary structures and functions. For the largest seven clusters predicted by MSC, the consistency in chain function within the same cluster is found to be 100%. From analyzing the edge distribution of SSN for MPs, we found a characteristic threshold distance for the boundary between clusters, over which SSN of MPs could be properly clustered by an unsupervised sparsification of the network distance matrix. The clustering results of MPs from both MSC and the unsupervised sparsification methods are consistent with each other, and have high intracluster similarity and low intercluster similarity in sequence, structure, and function. Our study showed a strong sequence-structure-function relationship of MPs. We discussed evidence of convergent evolution of MPs and suggested applications in finding structural similarities and predicting biological functions of MP chains based on their sequence information. © 2015 Wiley Periodicals, Inc.

[Maintenance of cold chain for the delivery of immunobiological drugs by the indicators of heating and freezing controls].

PubMed

Smirnov, D V; Buianov, V V; Kolesnikov, N V; Minaev, V A; Demina, A M; Suprun, I P

2004-01-01

The paper deals with an objective evaluation of a qualitative storage of immunobiological drugs including all stages of "cold chain". The results of technological research and of designing related with constructing a system of indicators for monitoring the temperature regime to maintain the "cold chain" functioning are presented. The suggested devices are comparatively described.

Thermodynamic perturbation theory for fused sphere hard chain fluids using nonadditive interactions

NASA Astrophysics Data System (ADS)

Abu-Sharkh, Basel F.; Sunaidi, Abdallah; Hamad, Esam Z.

2004-03-01

A model is developed for the equation of state of fused chains based on Wertheim thermodynamic perturbation theory and nonadditive size interactions. The model also assumes that the structure (represented by the radial distribution function) of the fused chain fluid is the same as that of the touching hard sphere chain fluid. The model is completely based on spherical additive and nonadditive size interactions. The model has the advantage of offering good agreement with simulation data while at the same time being independent of fitted parameters. The model is most accurate for short chains, small values of Δ (slightly fused spheres) and at intermediate (liquidlike) densities.

Method for fabricating hafnia films

DOEpatents

Hu, Michael Z [Knoxville, TN

2007-08-21

The present invention comprises a method for fabricating hafnia film comprising the steps of providing a substrate having a surface that allows formation of a self-assembled monolayer thereon via covalent bonding; providing an aqueous solution that provides homogeneous hafnium ionic complexes and hafnium nanoclusters wherein the aqueous solution is capable of undergoing homogeneous precipitation under controlled conditions for a desired period of time at a controlled temperature and controlled solution acidity for desired nanocluster nucleation and growth kinetics, desired nanocluster size, desired growth rate of film thickness and desired film surface characteristics. The method further comprising forming the self-assembled monolayer on the surface of the substrate wherein the self-assembled monolayer comprises a plurality of hydrocarbon chains cross-linked together along the surface of the substrate, the hydrocarbon chains being uniformly spaced from one another and wherein each of the hydrocarbon chains having a functional anchoring group at a first end of the chain covalently bonded with the surface of the substrate and each of the hydrocarbon chains having a functional terminating group projected away from the surface wherein the functional terminating group provides a bonding site for the hafnium film to grow; and exposing the substrate to the aqueous solution for a desired period of time at a controlled temperature wherein the hafnium ionic complexes and the hafnium nanoclusters are deposited on the bonding site of the functional terminating group thereby forming the hafnia film wherein the hafnium bonded to the hydrocarbons and to one another provide a uniform ordered arrangement defined by the uniform arrangement of the hydrocarbons.

Applying Alkyl-Chain Surface Functionalizations in Mesoporous Inorganic Structures: Their Impact on Gas Flow and Selectivity Depending on Temperature.

PubMed

Besser, Benjamin; Ahmed, Atiq; Baune, Michael; Kroll, Stephen; Thöming, Jorg; Rezwan, Kurosch

2016-10-12

Porous inorganic capillary membranes are prepared to serve as model structures for the experimental investigation of the gas transport in functionalized mesopores. The porous structures possess a mean pore diameter of 23 nm which is slightly reduced to 20 nm after immobilizing C 16 -alkyl chains on the surface. Gas permeation measurements are performed at temperatures ranging from 0 to 80 °C using Ar, N 2 , and CO 2 . Nonfunctionalized structures feature a gas transport according to Knudsen diffusion with regard to gas flow and selectivity. After C 16 -functionalization, the gas flow is reduced by a factor of 10, and the ideal selectivities deviate from the Knudsen theory. CO 2 adsorption measurements show a decrease in total amount of adsorbed gas and isosteric heat of adsorption. It is hypothesized that the immobilized C 16 -chains sterically influence the gas transport behavior without a contribution from adsorption effects. The reduced gas flow derives from an additional surface resistance caused by the C 16 -chains spacially limiting the adsorption and desorption directions for gas molecules propagating through the structure, resulting in longer diffusion paths. In agreement, the gas flow is found to correlate with the molecular diameter of the gas species (CO 2 < Ar < N 2 ) increasing the resistance for larger molecules. This affects the ideal selectivities with the relation [Formula: see text]. The influence on selectivity increases with increasing temperature which leads to the conclusion that the temperature induced movement of the C 16 -chains is responsible for the stronger interaction between gas molecules and surface functional groups.

Does an early onset and continuous chain of rehabilitation improve the long-term functional outcome of patients with severe traumatic brain injury?

PubMed

Andelic, Nada; Bautz-Holter, Erik; Ronning, Pal; Olafsen, Kjell; Sigurdardottir, Solrun; Schanke, Anne-Kristine; Sveen, Unni; Tornas, Sveinung; Sandhaug, Maria; Roe, Cecilie

2012-01-01

There are currently no international guidelines regarding treatment in the early rehabilitation phase for persons with severe traumatic brain injury (TBI), and only a few studies have investigated the effect of integrating rehabilitation into acute TBI care. The aim of the study was to evaluate whether a continuous chain of rehabilitation that begins with the acute phase could improve the functional outcome of severe TBI patients, compared to a broken chain of rehabilitation that starts in the sub-acute phase of TBI. A total of 61 surviving patients with severe TBI were included in a quasi-experimental study conducted at the Level I trauma center in Eastern Norway. In the study, 31 patients were in the early rehabilitation group (Group A) and 30 patients were in the delayed rehabilitation group (Group B). The functional outcomes were assessed 12 months post-injury with the Glasgow Outcome Scale Extended (GOSE) and the Disability Rating Scale (DRS). A favorable outcome (GOSE 6-8) occurred in 71% of the patients from Group A versus 37% in Group B (p=0.007). The DRS score was significantly better in Group A (p=0.03). The ordinal logistic regression analysis was used to quantify the relationship between the type of rehabilitation chain and the GOSE. A better GOSE outcome was found in patients from Group A (unadjusted OR 3.25 and adjusted OR 2.78, respectively). These results support the hypothesis that better functional outcome occurs in patients who receive early onset and a continuous chain of rehabilitation.

Comprehensive Study on the Impact of the Cation Alkyl Side Chain Length on the Solubility of Water in Ionic Liquids.

PubMed

Kurnia, Kiki A; Neves, Catarina M S S; Freire, Mara G; Santos, Luís M N B F; Coutinho, João A P

2015-10-01

A comprehensive study on the phase behaviour of two sets of ionic liquids (ILs) and their interactions with water is here presented through combining experimental and theoretical approaches. The impact of the alkyl side chain length and the cation symmetry on the water solubility in the asymmetric [C N- 1 C 1 im][NTf 2 ] and symmetric [C N- 1 C N- 1 im][NTf 2 ] series of ILs ( N up to 22), from 288.15 K to 318.15 K and at atmospheric pressure, was studied. The experimental data reveal that the solubility of water in ILs with an asymmetric cation is higher than in those with the symmetric isomer. Several trend shifts on the water solubility as a function of the alkyl side chain length were identified, namely at [C 6 C 1 im][NTf 2 ] for asymmetric ILs and at [C 4 C 4 im][NTf 2 ] and [C 7 C 7 im][NTf 2 ] for the symmetric ILs. To complement the experimental data and to further investigate the molecular-level mechanisms behind the dissolution process, Density Functional Theory calculations, using the Conductor-like Screening Model for Real Solvents (COSMO-RS) and the Electrostatic potential-derived CHelpG, were performed. The COSMO-RS model is able to qualitatively predict water solubility as function of temperature and alkyl chain lengths of both symmetric and asymmetric cations. Furthermore, the model is also capable to predict the somewhat higher water solubility in the asymmetric cation, as well as the trend shift as function of alkyl chain lengths experimentally observed. Both COSMO-RS and the electrostatic potential-derived CHelpG show that the interactions of water and the IL cation take place on the IL polar region, namely on the aromatic head and adjacent methylene groups what explains the differences in water solubility observed for cations with different chain lengths. Furthermore, the CHelpG calculations for the isolated cations in the gas phase indicates that the trend shift of water solubility as function of alkyl chain lengths and the difference of water solubility in symmetric may also result from the partial positive charge distribution/contribution of the cation.

Design and preparation of bi-functionalized short-chain modified zwitterionic nanoparticles.

PubMed

Hu, Fenglin; Chen, Kaimin; Xu, Hong; Gu, Hongchen

2018-05-01

An ideal nanomaterial for use in the bio-medical field should have a distinctive surface capable of effectively preventing nonspecific protein adsorption and identifying target bio-molecules. Recently, the short-chain zwitterion strategy has been suggested as a simple and novel approach to create outstanding anti-fouling surfaces. In this paper, the carboxyl end group of short-chain zwitterion-coated silica nanoparticles (SiO 2 -ZWS) was found to be difficult to functionalize via a conventional EDC/NHS strategy due to its rapid hydrolysis side-reactions. Hence, a series of bi-functionalized silica nanoparticles (SiO 2 -ZWS/COOH) were designed and prepared by controlling the molar ratio of 3-aminopropyltriethoxysilane (APTES) to short-chain zwitterionic organosiloxane (ZWS) in order to achieve above goal. The synthesized SiO 2 -ZWS/COOH had similar excellent anti-fouling properties compared with SiO 2 -ZWS, even in 50% fetal bovine serum characterized by DLS and turbidimetric titration. Subsequently, SiO 2 -ZWS/COOH 5/1 was chosen as a representative and then demonstrated higher detection signal intensity and more superior signal-to-noise ratios compare with the pure SiO 2 -COOH when they were used as a bio-carrier for chemiluminescence enzyme immunoassay (CLEIA). These unique bi-functionalized silica nanoparticles have many potential applications in the diagnostic and therapeutic fields. Reducing nonspecific protein adsorption and enhancing the immobilized efficiency of specific bio-probes are two of the most important issues for bio-carriers, particularly for a nanoparticle based bio-carrier. Herein, we designed and prepared a bi-functional nanoparticle with anti-fouling property and bio conjugation capacity for further bioassay by improving the short-chain zwitterionic modification strategy we have proposed previously. The heterogeneous surface of this nanoparticle showed effective anti-fouling properties both in model protein solutions and fetal bovine serum (FBS). The modified nanoparticles can also be successfully functionalized with a specific antibody for CLEIA assay with a prominent bio-detection performance even in 50% FBS. In this paper, we also investigated an unexpectedly fast hydrolysis behavior of NHS-activated carboxylic groups within the pure short-chain zwitterionic molecule that led to no protein binding in the short-chain zwitterion modified nanoparticle. Our findings pave a new way for the designing of high performance bio-carriers, demonstrating their strong potential as a robust platform for diagnosis and therapy. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Linear rheology and structure of molecular bottlebrushes with short side chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Barrón, Carlos R., E-mail: carlos.r.lopez-barron@exxonmobil.com; Brant, Patrick; Crowther, Donna J.

We investigate the microstructure and linear viscoelasticity of model molecular bottlebrushes (BBs) using rheological and small-angle X-ray and neutron scattering measurements. Our polymers have short atactic polypropylene (aPP) side chains of molecular weight ranging from 119 g/mol to 259 g/mol and narrow molecular weight distribution (M{sub w}/M{sub n} 1.02–1.05). The side chain molecular weights are a small fraction of the entanglement molecular weight of the corresponding linear polymer (M{sub e,aPP}= 7.05 kg/mol), and as such, they are unentangled. The morphology of the aPP BBs is characterized as semiflexible thick chains with small side chain interdigitation. Their dynamic master curves, obtained by time-temperature superposition,more » reveal two sequential relaxation processes corresponding to the segmental relaxation and the relaxation of the BB backbone. Due to the short length of the side chains, their fast relaxation could not be distinguished from the glassy relaxation. The fractional free volume is an increasing function of the side chain length (N{sub SC}). Therefore, the glassy behavior of these polymers as well as their molecular friction and dynamic properties are influenced by their N{sub SC} values. The apparent flow activation energies are a decreasing function of N{sub SC}, and their values explain the differences in zero-shear viscosity measured at different temperatures.« less

Silo Effect a Prominence Factor to Decrease Efficiency of Pharmaceutical Industry

PubMed Central

Vatanpour, Hossein; Khorramnia, Atoosa; Forutan, Naghmeh

2013-01-01

To be sure, all the industries try to be involved in globalization with a constant trend to find out ways to increase productivity across different functions within an organization to maintain competitive advantage world. Pharmaceutical industries are not exceptional and further are based on fragmentation. So these kind of companies need to cope with several barriers such as silo mentality that may affect efficiency of their business activity. Due to eliminate a part of resources such as raw materials, new molecule developed, financial and human resources and so on, companies can gradually loss their competitive potentials in the market and increase their expenses. Furthermore, to avoid any business disturbances in financially connected companies due to silo effect, they should arrange their management to integrated organization form. Otherwise, actions taken by one business member of the chain can influence the profitability of all the other members in the chain. That is why recently supply chain has generated much interest in many business units. In this paper, it has been tried to investigate the different aspects of silo effect which can affect integrate supply chain. Finally, a fluent communication, high level of information exchange, fragmentation management, cross-functional control in a supply chain management format are needed to reduce or control silo effect within entire chain of the holding company by Supply chain management. PMID:24250690

Silo effect a prominence factor to decrease efficiency of pharmaceutical industry.

PubMed

Vatanpour, Hossein; Khorramnia, Atoosa; Forutan, Naghmeh

2013-01-01

To be sure, all the industries try to be involved in globalization with a constant trend to find out ways to increase productivity across different functions within an organization to maintain competitive advantage world. Pharmaceutical industries are not exceptional and further are based on fragmentation. So these kind of companies need to cope with several barriers such as silo mentality that may affect efficiency of their business activity. Due to eliminate a part of resources such as raw materials, new molecule developed, financial and human resources and so on, companies can gradually loss their competitive potentials in the market and increase their expenses. Furthermore, to avoid any business disturbances in financially connected companies due to silo effect, they should arrange their management to integrated organization form. Otherwise, actions taken by one business member of the chain can influence the profitability of all the other members in the chain. That is why recently supply chain has generated much interest in many business units. In this paper, it has been tried to investigate the different aspects of silo effect which can affect integrate supply chain. Finally, a fluent communication, high level of information exchange, fragmentation management, cross-functional control in a supply chain management format are needed to reduce or control silo effect within entire chain of the holding company by Supply chain management.

Pyridylamination as a means of analyzing complex sugar chains

PubMed Central

Hase, Sumihiro

2010-01-01

Herein, I describe pyridylamination for versatile analysis of sugar chains. The reducing ends of the sugar chains are tagged with 2-aminopyridine and the resultant chemically stable fluorescent derivatives are used for structural/functional analysis. Pyridylamination is an effective “operating system” for increasing sensitivity and simplifying the analytical procedures including mass spectrometry and NMR. Excellent separation of isomers is achieved by reversed-phase HPLC. However, separation is further improved by two-dimensional HPLC, which involves a combination of reversed-phase HPLC and size-fractionation HPLC. Moreover, a two-dimensional HPLC map is also useful for structural analysis. I describe a simple procedure for preparing homogeneous pyridylamino sugar chains that is less laborious than existing techniques and can be used for functional analysis (e.g., sugar-protein interaction). This novel approach was applied and some of the results are described: i) a glucosyl-serine type sugar chain found in blood coagulation factors; ii) discovery of endo-β-mannosidase (EC 3.2.1.152) and a new type plant α1,2-l-fucosidase; and iii) novel substrate specificity of a cytosolic α-mannosidase. Moreover, using homogeneous sugar chains of a size similar to in vivo substrates we were able to analyze interactions between sugar chains and proteins such as enzymes and lectins in detail. Interestingly, our studies reveal that some enzymes recognize a wider region of the substrate than anticipated. PMID:20431262

Eliminating the Cuspidal Temperature Profile of a Non-equilibrium Chain

NASA Astrophysics Data System (ADS)

Cândido, Michael M.; M. Morgado, Welles A.; Duarte Queirós, Sílvio M.

2017-06-01

In 1967, Z. Rieder, J. L. Lebowitz, and E. Lieb (RLL) introduced a model of heat conduction on a crystal that became a milestone problem of non-equilibrium statistical mechanics. Along with its inability to reproduce Fourier's law—which subsequent generalizations have been trying to amend—the RLL model is also characterized by awkward cusps at the ends of the non-equilibrium chain, an effect that has endured all these years without a satisfactory answer. In this paper, we first show that such trait stems from the insufficiency of pinning interactions between the chain and the substrate. Assuming the possibility of pinning the chain, the analysis of the temperature profile in the space of parameters reveals that for a proper combination of the border and bulk pinning values, the temperature profile may shift twice between the RLL cuspidal behavior and the expected monotonic local temperature evolution along the system, as a function of the pinning. At those inversions, the temperature profile along the chain is characterized by perfect plateaux: at the first threshold, the cumulants of the heat flux reach their maxima and the vanishing of the two-point velocity correlation function for all sites of the chain so that the system behaves similarly to a "phonon box." On the other hand, at the second change of the temperature profile, we still have the vanishing of the two-point correlation function but only for the bulk, which explains the emergence of the temperature plateau and thwarts the reaching of the maximal values of the cumulants of the heat flux.

Non-local electron transport through normal and topological ladder-like atomic systems

NASA Astrophysics Data System (ADS)

Kurzyna, Marcin; Kwapiński, Tomasz

2018-05-01

We propose a locally protected ladder-like atomic system (nanoconductor) on a substrate that is insensitive to external perturbations. The system corresponds to coupled atomic chains fabricated on different surfaces. Electron transport properties of such conductors are studied theoretically using the model tight-binding Su-Schriffer-Hegger (SSH) Hamiltonian and Green's function formalism. We have found that the conductance of the system is almost insensitive to single adatoms and oscillates as a function of the side chain length with very large periods. Non-local character of the electron transport was observed also for topological SSH chains where nontrivial end states survive in the presence of disturbances as well as for different substrates. We have found that the careful inspection of the density of states or charge waves can provide the information about the atom energy levels and hopping amplitudes. Moreover, the ladder-like geometry allows one to distinguish between normal and topological zero-energy states. It is important that topological chains do not reveal Friedel oscillations which are observed in non-topological chains.

Atomic scale real-space mapping of holes in YBa2Cu3O(6+δ).

PubMed

Gauquelin, N; Hawthorn, D G; Sawatzky, G A; Liang, R X; Bonn, D A; Hardy, W N; Botton, G A

2014-07-15

The high-temperature superconductor YBa2Cu3O(6+δ) consists of two main structural units--a bilayer of CuO2 planes that are central to superconductivity and a CuO(2+δ) chain layer. Although the functional role of the planes and chains has long been established, most probes integrate over both, which makes it difficult to distinguish the contribution of each. Here we use electron energy loss spectroscopy to directly resolve the plane and chain contributions to the electronic structure in YBa2Cu3O6 and YBa2Cu3O7. We directly probe the charge transfer of holes from the chains to the planes as a function of oxygen content, and show that the change in orbital occupation of Cu is large in the chain layer but modest in CuO2 planes, with holes in the planes doped primarily into the O 2p states. These results provide direct insight into the local electronic structure and charge transfers in this important high-temperature superconductor.

Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity

PubMed Central

Waddington, Amelia; Appleby, Peter A.; De Kamps, Marc; Cohen, Netta

2012-01-01

Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds. Previous studies have suggested that the development of synfire chains requires either initial sparse connectivity or strong topological constraints, in addition to any synaptic learning rules. Here, we show that this necessity can be removed by using a previously reported but hitherto unconsidered spike-timing-dependent plasticity (STDP) rule and activity-dependent excitability. Under this rule the network develops stable synfire chains that possess a non-trivial, scalable multi-layer structure, in which relative layer sizes appear to follow a universal function. Using computational modeling and a coarse grained random walk model, we demonstrate the role of the STDP rule in growing, molding and stabilizing the chain, and link model parameters to the resulting structure. PMID:23162457

Automotive Lithium-ion Battery Supply Chain and U.S. Competitiveness Considerations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Donald; Elgqvist, Emma; Santhanagopalan, Shriram

2015-06-01

This study highlights the U.S. foothold in automotive lithium-ion battery (LIB) production, globally. U.S.-based manufacturers comprise 17% of global production capacity. With increasing demand for electric and hybrid electric vehicles and U.S. vehicle manufacturers' proximity to customers, there is a growing opportunity for the United States to compete globally in the automotive LIB market.

Parametric and Generative Design Techniques for Digitalization in Building Industry: the Case Study of Glued- Laminated-Timber Industry

NASA Astrophysics Data System (ADS)

Pasetti Monizza, G.; Matt, D. T.; Benedetti, C.

2016-11-01

According to Wortmann classification, the Building Industry (BI) can be defined as engineer-to-order (ETO) industry: the engineering-process starts only when an order is acquired. This definition implies that every final product (building) is almost unique’ and processes cannot be easily standardized or automated. Because of this, BI is one of the less efficient industries today’ mostly leaded by craftsmanship. In the last years’ several improvements in process efficiency have been made focusing on manufacturing and installation processes only. In order to improve the efficiency of design and engineering processes as well, the scientific community agrees that the most fruitful strategy should be Front-End Design (FED). Nevertheless, effective techniques and tools are missing. This paper discusses outcomes of a research activity that aims at highlighting whether Parametric and Generative Design techniques allow reducing wastes of resources and improving the overall efficiency of the BI, by pushing the Digitalization of design and engineering processes of products. Focusing on the Glued-Laminated-Timber industry, authors will show how Parametric and Generative Design techniques can be introduced in a standard supply-chain system, highlighting potentials and criticism on the supply-chain system as a whole.

Biased immunoglobulin light chain gene usage in the shark1

PubMed Central

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-01-01

This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

Biased Immunoglobulin Light Chain Gene Usage in the Shark.

PubMed

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-10-15

This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. Copyright © 2015 by The American Association of Immunologists, Inc.

Formation and structural phase transition in Co atomic chains on a Cu(775) surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syromyatnikov, A. G.; Kabanov, N. S.; Saletsky, A. M.

The formation of Co atomic chains on a Cu(775) surface is investigated by the kinetic Monte Carlo method. It is found that the length of Co atomic chains formed as a result of self-organization during epitaxial growth is a random quantity and its mean value depends on the parameters of the experiment. The existence of two structural phases in atomic chains is detected using the density functional theory. In the first phase, the separations between an atom and its two nearest neighbors in a chain are 0.230 and 0.280 nm. In the second phase, an atomic chain has identical atomicmore » spacings of 0.255 nm. It is shown that the temperature of the structural phase transition depends on the length of the atomic chain.« less

Molecular cloning and expression in mammalian cells of ricin B chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, M.

1987-01-01

In these studies, the cDNA encoding the B chain of ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with {sup 35}S-methionine and {sup 35}S-cysteine and demonstrating secretion of a protein with a Mr of 30-32,000 which was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B chain antibody. The amount of recombinant B chain secreted by the COS-M6 cells was determined by radioimmunoassay to be 1-10 ng/ml of media. Virtually all the recombinant B chain formedmore » active ricin when mixed with native A chain; it could also bind as effectively as native B chain to the galactose-containing glycoprotein, asialofetuin. These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function.« less

Side-Chain Effects on the Thermoelectric Properties of Fluorene-Based Copolymers.

PubMed

Liang, Ansheng; Zhou, Xiaoyan; Zhou, Wenqiao; Wan, Tao; Wang, Luhai; Pan, Chengjun; Wang, Lei

2017-09-01

Three conjugated polymers with alkyl chains of different lengths are designed and synthesized, and their structure-property relationship as organic thermoelectric materials is systematically elucidated. All three polymers show similar photophysical properties, thermal properties, and mechanical properties; however, their thermoelectric performance is influenced by the length of their side chains. The length of the alkyl chain significantly influences the electrical conductivity of the conjugated polymers, and polymers with a short alkyl chain exhibit better conductivity than those with a long alkyl chain. The length of the alkyl chain has little effect on the Seebeck coefficient. Only a slight increase in the Seebeck coefficient is observed with the increasing length of the alkyl chain. The purpose of this study is to provide comprehensive insight into fine-tuning the thermoelectric properties of conjugated polymers as a function of side-chain engineering, thereby providing a novel perspective into the design of high-performance thermoelectric conjugated polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress towards Sustainable Utilisation and Management of Food Wastes in the Global Economy.

PubMed

Ghosh, Purabi R; Fawcett, Derek; Sharma, Shashi B; Poinern, Gerrard Eddy Jai

2016-01-01

In recent years, the problem of food waste has attracted considerable interest from food producers, processors, retailers, and consumers alike. Food waste is considered not only a sustainability problem related to food security, but also an economic problem since it directly impacts the profitability of the whole food supply chain. In developed countries, consumers are one of the main contributors to food waste and ultimately pay for all wastes produced throughout the food supply chain. To secure food and reduce food waste, it is essential to have a comprehensive understanding of the various sources of food wastes throughout the food supply chain. The present review examines various reports currently in the literature and quantifies waste levels and examines the trends in wastage for various food sectors such as fruit and vegetable, fisheries, meat and poultry, grain, milk, and dairy. Factors contributing to food waste, effective cost/benefit food waste utilisation methods, sustainability and environment considerations, and public acceptance are identified as hurdles in preventing large-scale food waste processing. Thus, we highlight the need for further research to identify and report food waste so that government regulators and food supply chain stakeholders can actively develop effective waste utilisation practices.

Progress towards Sustainable Utilisation and Management of Food Wastes in the Global Economy

PubMed Central

Ghosh, Purabi R.; Fawcett, Derek; Sharma, Shashi B.

2016-01-01

In recent years, the problem of food waste has attracted considerable interest from food producers, processors, retailers, and consumers alike. Food waste is considered not only a sustainability problem related to food security, but also an economic problem since it directly impacts the profitability of the whole food supply chain. In developed countries, consumers are one of the main contributors to food waste and ultimately pay for all wastes produced throughout the food supply chain. To secure food and reduce food waste, it is essential to have a comprehensive understanding of the various sources of food wastes throughout the food supply chain. The present review examines various reports currently in the literature and quantifies waste levels and examines the trends in wastage for various food sectors such as fruit and vegetable, fisheries, meat and poultry, grain, milk, and dairy. Factors contributing to food waste, effective cost/benefit food waste utilisation methods, sustainability and environment considerations, and public acceptance are identified as hurdles in preventing large-scale food waste processing. Thus, we highlight the need for further research to identify and report food waste so that government regulators and food supply chain stakeholders can actively develop effective waste utilisation practices. PMID:27847805

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

PubMed

Perlin, Pesach; Gharakhanian, Eric G; Deming, Timothy J

2018-06-12

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified.

Introduction to fatty acids and lipids.

PubMed

Burdge, Graham C; Calder, Philip C

2015-01-01

The purpose of this article is to describe the structure, function and metabolism of fatty acids and lipids that are of particular importance in the context of parenteral nutrition. Lipids are a heterogeneous group of molecules that share the common property of hydrophobicity. Lipids range in structure from simple short hydrocarbon chains to more complex molecules, including triacylglycerols, phospholipids and sterols and their esters. Lipids within each class may differ structurally. Fatty acids are common components of complex lipids, and these differ according to chain length and the presence, number and position of double bonds in the hydrocarbon chain. Structural variation among complex lipids and among fatty acids gives rise to functional differences that result in different impacts upon metabolism and upon cell and tissue responses. Fatty acids and complex lipids exhibit a variety of structural variations that influence their metabolism and their functional effects. © 2015 S. Karger AG, Basel.

High performance current and spin diode of atomic carbon chain between transversely symmetric ribbon electrodes.

PubMed

Dong, Yao-Jun; Wang, Xue-Feng; Yang, Shuo-Wang; Wu, Xue-Mei

2014-08-21

We demonstrate that giant current and high spin rectification ratios can be achieved in atomic carbon chain devices connected between two symmetric ferromagnetic zigzag-graphene-nanoribbon electrodes. The spin dependent transport simulation is carried out by density functional theory combined with the non-equilibrium Green's function method. It is found that the transverse symmetries of the electronic wave functions in the nanoribbons and the carbon chain are critical to the spin transport modes. In the parallel magnetization configuration of two electrodes, pure spin current is observed in both linear and nonlinear regions. However, in the antiparallel configuration, the spin-up (down) current is prohibited under the positive (negative) voltage bias, which results in a spin rectification ratio of order 10(4). When edge carbon atoms are substituted with boron atoms to suppress the edge magnetization in one of the electrodes, we obtain a diode with current rectification ratio over 10(6).

High performance current and spin diode of atomic carbon chain between transversely symmetric ribbon electrodes

PubMed Central

Dong, Yao-Jun; Wang, Xue-Feng; Yang, Shuo-Wang; Wu, Xue-Mei

2014-01-01

We demonstrate that giant current and high spin rectification ratios can be achieved in atomic carbon chain devices connected between two symmetric ferromagnetic zigzag-graphene-nanoribbon electrodes. The spin dependent transport simulation is carried out by density functional theory combined with the non-equilibrium Green's function method. It is found that the transverse symmetries of the electronic wave functions in the nanoribbons and the carbon chain are critical to the spin transport modes. In the parallel magnetization configuration of two electrodes, pure spin current is observed in both linear and nonlinear regions. However, in the antiparallel configuration, the spin-up (down) current is prohibited under the positive (negative) voltage bias, which results in a spin rectification ratio of order 104. When edge carbon atoms are substituted with boron atoms to suppress the edge magnetization in one of the electrodes, we obtain a diode with current rectification ratio over 106. PMID:25142376

Structure determination and characterization of two rare-earth molybdenum borate compounds: LnMoBO(6) (Ln = La, Ce).

PubMed

Zhao, Dan; Cheng, Wen-Dan; Zhang, Hao; Hang, Shu-Ping; Fang, Ming

2008-07-28

The structural, optical, and electronic properties of two rare-earth molybdenum borate compounds, LnMoBO(6) (Ln = La, Ce), have been investigated by means of single-crystal X-ray diffraction, elemental analyses, and spectral measurements, as well as calculations of energy band structures, density of states, and optical response functions by the density functional method. The title compounds, which crystallize in monoclinic space group P2(1)/c, possess a similar network of interconnected [Ce(2)(MoO(4))(2)](2+) chains and [BO(2)](-) wavy chains. Novel 1D molybdenum oxide chains are contained in their three-dimensional (3D) networks. The calculated results of crystal energy band structure by the density functional theory (DFT) method show that the solid-state compound LaMoBO(6) is a semiconductor with indirect band gaps.

Searching for a 4 α linear-chain structure in excited states of 16O with covariant density functional theory

NASA Astrophysics Data System (ADS)

Yao, J. M.; Itagaki, N.; Meng, J.

2014-11-01

A study of the 4 α linear-chain structure in high-lying collective excitation states of 16O with covariant density functional theory is presented. The low-spin states are obtained by configuration mixing of particle-number and angular-momentum projected quadrupole deformed mean-field states with the generator coordinate method. The high-spin states are determined by cranking calculations. These two calculations are based on the same energy density functional PC-PK1. We have found a rotational band at low spin with the dominant intrinsic configuration considered to be the one whereby 4 α clusters stay along a common axis. The strongly deformed rod shape also appears in the high-spin region with the angular momentum 13 ℏ to18 ℏ ; however, whether the state is a pure 4 α linear chain is less obvious than for the low-spin states.

A fuzzy cost-benefit function to select economical products for processing in a closed-loop supply chain

NASA Astrophysics Data System (ADS)

Pochampally, Kishore K.; Gupta, Surendra M.; Cullinane, Thomas P.

2004-02-01

The cost-benefit analysis of data associated with re-processing of used products often involves the uncertainty feature of cash-flow modeling. The data is not objective because of uncertainties in supply, quality and disassembly times of used products. Hence, decision-makers must rely on "fuzzy" data for analysis. The same parties that are involved in the forward supply chain often carry out the collection and re-processing of used products. It is therefore important that the cost-benefit analysis takes the data of both new products and used products into account. In this paper, a fuzzy cost-benefit function is proposed that is used to perform a multi-criteria economic analysis to select the most economical products to process in a closed-loop supply chain. Application of the function is detailed through an illustrative example.

Meta-Analysis of Structured Triglyceride versus Physical Mixture Medium- and Long-Chain Triglycerides for PN in Liver Resection Patients.

PubMed

Zhao, Yajie; Wang, Chengfeng

2017-01-01

The use of total parenteral nutrition can affect liver function, causing a series of problems such as cholestasis. The aim of this meta-analysis was to compare structured triglyceride- (STG-) based lipid emulsions with physical medium-chain triglyceride (MCT)/long-chain triglyceride (LCT) mixtures in patients who had undergone liver surgery to identify any differences between these two types of parenteral nutrition. We searched the databases of PubMed, the Cochrane Library, Web of Science, EMBASE, and Chinese Biomedicine Database from January 2007 to March 2017 and included studies that compared STG-based lipid emulsions with physical MCT/LCT mixtures for surgical patients with liver disease. The STG was more beneficial than physical MCT/LCT on recovery of liver function and immune function. Therefore, STGs may represent a promising alternative to other types of lipid emulsions for hepatic surgery patients.

Event-chain algorithm for the Heisenberg model: Evidence for z≃1 dynamic scaling.

PubMed

Nishikawa, Yoshihiko; Michel, Manon; Krauth, Werner; Hukushima, Koji

2015-12-01

We apply the event-chain Monte Carlo algorithm to the three-dimensional ferromagnetic Heisenberg model. The algorithm is rejection-free and also realizes an irreversible Markov chain that satisfies global balance. The autocorrelation functions of the magnetic susceptibility and the energy indicate a dynamical critical exponent z≈1 at the critical temperature, while that of the magnetization does not measure the performance of the algorithm. We show that the event-chain Monte Carlo algorithm substantially reduces the dynamical critical exponent from the conventional value of z≃2.

[Development of wireless monitoring system based on Zigbee technology in blood and bacterin cold chain].

PubMed

Zhao, Peng; Sun, Jian-Jun; Wu, Tai-Hu

2008-11-01

Real-time monitoring for temperature is required in cold chain for the medical products that are sensible with temperature, such as blood and bacterin, to guarantee the quality and reduce their wastage. This wireless monitoring system in cold chain is developed with Zigbee technology. Functions such as real-time monitoring, analyzing, alarming are realized. The system boasts such characteristics as low power consumption, low cost, big capacity and high reliability, and could improve the capability of real-time monitoring and management in cold chain effectively.

Distribution Free Approach for Coordination of a Supply Chain with Consumer Return

NASA Astrophysics Data System (ADS)

Hu, Jinsong; Xu, Yuanji

Consumer return is considered in a coordination of a supply chain consisting of one manufacturer and one retailer. A distribution free approach is employed to deal with a centralized decision model and a decentralized model which are constructed under the situation with only knowing the demand function's mean and variance, respectively. A markdown money contract is designed to coordinate the supply chain, and it is also proved that the contract can make the supply chain perfectly coordinated. Several numerical examples are given at the end of this paper.

PubMed Central

Di Mauro, S.

2010-01-01

In this brief review, I have highlighted recent advances in several areas of mitochondrial medicine, including mtDNA-related diseases, mendelian mitochondrial encephalomyopathies, and therapy. The pathogenic mechanisms of mtDNA mutations, especially those affecting mitochondrial protein synthesis, are still largely unknown. The pathogenicity of homoplasmic mtDNA mutations has become evident but has also called attention to modifying nuclear genes, yet another example of impaired intergenomic signaling. The functional significance of the homoplasmic changes associated with mitochondrial haplogroups has been confirmed. Among the mendelian disorders, a new form of “indirect hit” has been described, in which the ultimate pathogenesis is toxic damage to the respiratory chain. Three therapeutic strategies look promising: (i) allogeneic hematopoietic stem cell transplantation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy); (ii) bezafibrate, an activator of PGC-1α, has proven effective in animal models of mitochondrial myopathy; and (iii) pronucleus transfer into a normal oocyte is effective in eliminating maternal transmission of mtDNA, thus preventing the appearance of mtDNA-related disorders. PMID:21314015

Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer

PubMed Central

Mohankumar, Swathi

2016-01-01

Analysis of extracellular vesicles (EV) and their contents may be useful as disease biomarkers if they reflect the contents of cells of origin, differ between normal and diseased tissue and can be reliably detected. An increasing number of long noncoding RNA (lncRNA) are being reported to be aberrantly expressed in human cancers. These tumor-associated lncRNA may have potential as new biomarkers of disease. In this review, we highlight lncRNAs that are commonly associated with hepatocellular cancer, and summarize their potential biological roles and underlying molecular mechanisms. While lncRNA can be detected in the circulation, their low expression within circulating vesicles will require the use of highly sensitive detection technologies such as digital polymerase chain reaction or next-generation sequencing. While the integrity and functional role of tumor-specific lncRNAs within EV have yet to be established, their presence or enrichment within tumor cell-derived EV offers promise for their potential as disease biomarkers. PMID:26634812

Viscoelasticity promotes collective swimming of sperm

NASA Astrophysics Data System (ADS)

Tung, Chih-Kuan; Harvey, Benedict B.; Fiore, Alyssa G.; Ardon, Florencia; Suarez, Susan S.; Wu, Mingming

From flocking birds to swarming insects, interactions of organisms large and small lead to the emergence of collective dynamics. Here, we report striking collective swimming of bovine sperm, with sperm orienting in the same direction within each cluster, enabled by the viscoelasticity of the fluid. A long-chain polyacrylamide solution was used as a model viscoelastic fluid such that its rheology can be fine-tuned to mimic that of bovine cervical mucus. In viscoelastic fluid, sperm formed dynamic clusters, and the cluster size increased with elasticity of the polyacrylamide solution. In contrast, sperm swam randomly and individually in Newtonian fluids of similar viscosity. Analysis of the fluid motion surrounding individual swimming sperm indicated that sperm-fluid interaction is facilitated by the elastic component of the fluid. We note that almost all biological fluids (e.g. mucus and blood) are viscoelastic in nature, this finding highlights the importance of fluid elasticity in biological function. We will discuss what the orientation fluctuation within a cluster reveals about the interaction strength. Supported by NIH Grant 1R01HD070038.

BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei

PubMed Central

Oppenheim, Rebecca D.; Limenitakis, Julien; Polonais, Valerie; Seeber, Frank; Barrett, Michael P.; Billker, Oliver; McConville, Malcolm J.; Soldati-Favre, Dominique

2014-01-01

While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens. PMID:25032958