Engineering Monolignol p-Coumarate Conjugates into Poplar and Arabidopsis Lignins1

PubMed Central

Smith, Rebecca A.; Gonzales-Vigil, Eliana; Karlen, Steven D.; Park, Ji-Young; Lu, Fachuang; Wilkerson, Curtis G.; Samuels, Lacey; Ralph, John; Mansfield, Shawn D.

2015-01-01

Lignin acylation, the decoration of hydroxyls on lignin structural units with acyl groups, is common in many plant species. Monocot lignins are decorated with p-coumarates by the polymerization of monolignol p-coumarate conjugates. The acyltransferase involved in the formation of these conjugates has been identified in a number of model monocot species, but the effect of monolignol p-coumarate conjugates on lignification and plant growth and development has not yet been examined in plants that do not inherently possess p-coumarates on their lignins. The rice (Oryza sativa) p-COUMAROYL-Coenzyme A MONOLIGNOL TRANSFERASE gene was introduced into two eudicots, Arabidopsis (Arabidopsis thaliana) and poplar (Populus alba × grandidentata), and a series of analytical methods was used to show the incorporation of the ensuing monolignol p-coumarate conjugates into the lignin of these plants. In poplar, specifically, the addition of these conjugates did not occur at the expense of the naturally incorporated monolignol p-hydroxybenzoates. Plants expressing the p-COUMAROYL-Coenzyme A MONOLIGNOL TRANSFERASE transgene can therefore produce monolignol p-coumarate conjugates essentially without competing with the formation of other acylated monolignols and without drastically impacting normal monolignol production. PMID:26511914

New Generation of Photosensitizers: Conjugates of Chlorin e 6 With Diamond Nanoparticles

NASA Astrophysics Data System (ADS)

Lapina, V. A.; Bushuk, S. B.; Pavich, T. A.; Vorobey, A. V.

2016-07-01

Conjugates of chlorin e 6 with diamond nanoparticles were synthesized by two methods. The spectral and luminescent properties of the obtained conjugates were studied. It was shown that chlorin e 6 retained its photosensitizing activity in the conjugate. It was established that chlorin e 6 immobilized directly on diamond nanoparticles had higher photosensitizing activity than that conjugated using a spacer. It was observed that chlorin e 6 in the conjugate had higher photolytic stability than the free form.

Ab-initio study of structural, electronic, and transport properties of zigzag GaP nanotubes.

PubMed

Srivastava, Anurag; Jain, Sumit Kumar; Khare, Purnima Swarup

2014-03-01

Stability and electronic properties of zigzag (3 ≤ n ≤ 16) gallium phosphide nanotubes (GaP NTs) have been analyzed by employing a systematic ab-intio approach based on density functional theory using generalized gradient approximation with revised Perdew Burke Ernzerhoff type parameterization. Diameter dependence of bond length, buckling, binding energy, and band gap has been investigated and the analysis shows that the bond length and buckling decreases with increasing diameter of the tube, highest binding energy of (16, 0) confirms this as the most stable amongst all the NTs taken into consideration. The present GaP NTs shows direct band gap and it increases with diameter of the tubes. Using a two probe model for (4, 0) NT the I-V relationship shows an exponential increase in current on applying bias voltage beyond 1.73 volt.

Unraveling metamaterial properties in zigzag-base folded sheets.

PubMed

Eidini, Maryam; Paulino, Glaucio H

2015-09-01

Creating complex spatial objects from a flat sheet of material using origami folding techniques has attracted attention in science and engineering. In the present work, we use the geometric properties of partially folded zigzag strips to better describe the kinematics of known zigzag/herringbone-base folded sheet metamaterials such as Miura-ori. Inspired by the kinematics of a one-degree of freedom zigzag strip, we introduce a class of cellular folded mechanical metamaterials comprising different scales of zigzag strips. This class of patterns combines origami folding techniques with kirigami. Using analytical and numerical models, we study the key mechanical properties of the folded materials. We show that our class of patterns, by expanding on the design space of Miura-ori, is appropriate for a wide range of applications from mechanical metamaterials to deployable structures at small and large scales. We further show that, depending on the geometry, these materials exhibit either negative or positive in-plane Poisson's ratios. By introducing a class of zigzag-base materials in the current study, we unify the concept of in-plane Poisson's ratio for similar materials in the literature and extend it to the class of zigzag-base folded sheet materials.

Self-Assembly and Nanostructures in Organogels Based on a Bolaform Cholesteryl Imide Compound with Conjugated Aromatic Spacer

PubMed Central

Jiao, Ti-Feng; Gao, Feng-Qing; Shen, Xi-Hai; Zhang, Qing-Rui; Zhang, Xian-Fu; Zhou, Jing-Xin; Gao, Fa-Ming

2013-01-01

The self-assembly of small functional molecules into supramolecular structures is a powerful approach toward the development of new nanoscale materials and devices. As a class of self-assembled materials, low weight molecular organic gelators, organized in special nanoarchitectures through specific non-covalent interactions, has become one of the hot topics in soft matter research due to their scientific values and many potential applications. Here, a bolaform cholesteryl imide compound with conjugated aromatic spacer was designed and synthesized. The gelation behaviors in 23 solvents were investigated as efficient low-molecular-mass organic gelator. The experimental results indicated that the morphologies and assembly modes of as-formed organogels can be regulated by changing the kinds of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecule self-assemble into different aggregates, from wrinkle and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes. Finally, some rational assembly modes in organogels were proposed and discussed. The present work may give some insight to the design and character of new organogelators and soft materials with special structures. PMID:28788428

Refined Zigzag Theory for Homogeneous, Laminated Composite, and Sandwich Plates: A Homogeneous Limit Methodology for Zigzag Function Selection

NASA Technical Reports Server (NTRS)

Tessler, Alexander; DiSciuva, Marco; Gherlone, marco

2010-01-01

The Refined Zigzag Theory (RZT) for homogeneous, laminated composite, and sandwich plates is presented from a multi-scale formalism starting with the inplane displacement field expressed as a superposition of coarse and fine contributions. The coarse kinematic field is that of first-order shear-deformation theory, whereas the fine kinematic field has a piecewise-linear zigzag distribution through the thickness. The condition of limiting homogeneity of transverse-shear properties is proposed and yields four distinct sets of zigzag functions. By examining elastostatic solutions for highly heterogeneous sandwich plates, the best-performing zigzag functions are identified. The RZT predictive capabilities to model homogeneous and highly heterogeneous sandwich plates are critically assessed, demonstrating its superior efficiency, accuracy ; and a wide range of applicability. The present theory, which is derived from the virtual work principle, is well-suited for developing computationally efficient CO-continuous finite elements, and is thus appropriate for the analysis and design of high-performance load-bearing aerospace structures.

p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates.

PubMed

Klos, C; Koob, M; Kramer, C; Dekant, W

1992-07-01

p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.

Theoretical study on p-type D-π-A sensitizers with modified π-spacers for dye-sensitized solar cells.

PubMed

Yan, Wen; Chaitanya, Kadali; Sun, Zhi-Dan; Ju, Xue-Hai

2018-02-24

Based on a prototype sensitizer W2, we designed triarylamine-based p-type sensitizers W2-1 to W2-7 that contain modified π-spacers (π'), a π-spacer and two anchors. For W2-1 to W2-4, instead of 2,1,3-benzothiadiazole in W2, thieno[3,4-b]-1,4-dioxin, thiophene, thieno[3,4-c][1,2,5]thiadizole, thiazolo[5,4-d]thiazole are π' and thiophene as π-spacer. For W2-5 to W2-8, π' and π are same, with 2,1,3-benzothiadiazole, thieno[3,4-b]-1,4-dioxin, thieno[3,4-c][1,2,5]thiadiazo, thiazolo[5,4-d]thiazole, respectively, as the π'-spacers. Structure optimization, electronic level and absorption characters were calculated with density functional theory (DFT) and time-dependent DFT (TDDFT) at the CAM-B3LYP/6-311G (d,p). The solvent effect was involved using a polarized continuum model in chloroform. The results showed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital guarantee sufficient hole injection (lower than -0.2 eV), and dye regeneration (lower than -0.2 eV). W2-4 has higher light-harvesting efficiency (LHE) (0.994) and larger overlap with the visible light from 400 nm to 600 nm. Finally, the results suggest that the driving force of hole injection, dye regeneration and charge recombination (ΔG inj , ΔG reg and ΔG CR ) of W2-4 are the best, with more negative ΔG inj (-4.33), ΔG reg (-1.74) and more positive ΔG CR (1.92). Replacing 2,1,3-benzothiadiazole with thiazolo[5,4-d]thiazole as π'-spacers is a effective way to improve the performance of the dyes. An introduction of thiazolo[5,4-d]thiazole group can improve the absorption ability and hinder charge recombination. Graphical abstract Absorption spectra of p-type D-π-A sensitizers with modified π-spacers.

Electroosmotic flow mixing in zigzag microchannels.

PubMed

Chen, Jia-Kun; Yang, Ruey-Jen

2007-03-01

In this study we performed numerical and experimental investigations into the mixing of EOFs in zigzag microchannels with two different corner geometries, namely sharp corners and flat corners. In the zigzag microchannel with sharp corners, the flow travels more rapidly near the inner wall of the corner than near the outer wall as a result of the higher electric potential drop. The resulting velocity gradient induces a racetrack effect, which enhances diffusion within the fluid and hence improves the mixing performance. The simulation results reveal that the mixing index is approximately 88.83%. However, the sharp-corner geometry causes residual liquid or bubbles to become trapped in the channel at the point where the flow is almost stationary, when the channel is in the process of cleaning. Accordingly, a zigzag microchannel with flat-corner geometry is developed. The flat-corner geometry forms a convergent-divergent type nozzle which not only enhances the mixing performance in the channel, but also prevents the accumulation of residual liquid or bubbles. Scaling analysis reveals that this corner geometry leads to an effective increase in the mixing length. The experimental results reveal that the mixing index is increased to 94.30% in the flat-corner zigzag channel. Hence, the results demonstrate that the mixing index of the flat-corner zigzag channel is better than that of the conventional sharp-corner microchannel. Finally, the results of Taguchi analysis indicate that the attainable mixing index is determined primarily by the number of corners in the microchannel and by the flow passing height at each corner.

Ligand Accessibility and Bioactivity of a Hormone-Dendrimer Conjugate Depend on pH and pH History

PubMed Central

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul; Carlson, Kathryn E.; Mayne, Christopher G.; Granick, Steve; Katzenellenbogen, Benita S.; Katzenellenbogen, John A.

2016-01-01

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the non-genomic actions of estrogens in target cells. In response to pH changes, however, these estrogen-dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine, TMR) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR-PAMAM reveal high ligand shielding above pH 7 and low shielding below pH 7. Furthermore, when pH was cycled from 8.5 (conditions of ligand-PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol and diphenolic acid PAMAM conjugates experience a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicate that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen-dendrimer conjugates appears to be metastable. This pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers. PMID:26186415

The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes.

PubMed

Shmakov, Sergey A; Sitnik, Vassilii; Makarova, Kira S; Wolf, Yuri I; Severinov, Konstantin V; Koonin, Eugene V

2017-09-19

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR "dark matter." We performed a comprehensive analysis of the spacers from all CRISPR- cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. IMPORTANCE The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers

Efficient self-assembly of DNA-functionalized fluorophores and gold nanoparticles with DNA functionalized silicon surfaces: the effect of oligomer spacers

PubMed Central

Milton, James A.; Patole, Samson; Yin, Huabing; Xiao, Qiang; Brown, Tom; Melvin, Tracy

2013-01-01

Although strategies for the immobilization of DNA oligonucleotides onto surfaces for bioanalytical and top-down bio-inspired nanobiofabrication approaches are well developed, the effect of introducing spacer molecules between the surface and the DNA oligonucleotide for the hybridization of nanoparticle–DNA conjugates has not been previously assessed in a quantitative manner. The hybridization efficiency of DNA oligonucleotides end-labelled with gold nanoparticles (1.4 or 10 nm diameter) with DNA sequences conjugated to silicon surfaces via hexaethylene glycol phosphate diester oligomer spacers (0, 1, 2, 6 oligomers) was found to be independent of spacer length. To quantify both the density of DNA strands attached to the surfaces and hybridization with the surface-attached DNA, new methodologies have been developed. Firstly, a simple approach based on fluorescence has been developed for determination of the immobilization density of DNA oligonucleotides. Secondly, an approach using mass spectrometry has been created to establish (i) the mean number of DNA oligonucleotides attached to the gold nanoparticles and (ii) the hybridization density of nanoparticle–oligonucleotide conjugates with the silicon surface–attached complementary sequence. These methods and results will be useful for application with nanosensors, the self-assembly of nanoelectronic devices and the attachment of nanoparticles to biomolecules for single-molecule biophysical studies. PMID:23361467

Multifunctional nanoparticle-protein conjugates with controllable bioactivity and pH responsiveness

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Ligand accessibility and bioactivity of a hormone–dendrimer conjugate depend on pH and pH history

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

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells in this paper. In response to pH changes, however, these estrogen–dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR–PAMAM revealed high ligand shielding abovemore » pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand–PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol– and diphenolic acid–PAMAM conjugates experienced a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen–dendrimer conjugates appears to be metastable. Finally, this pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers.« less

Ligand accessibility and bioactivity of a hormone–dendrimer conjugate depend on pH and pH history

DOE PAGES

Kim, Sung Hoon; Madak-Erdogan, Zeynep; Bae, Sung Chul; ...

2015-07-17

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells in this paper. In response to pH changes, however, these estrogen–dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR–PAMAM revealed high ligand shielding abovemore » pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand–PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol– and diphenolic acid–PAMAM conjugates experienced a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen–dendrimer conjugates appears to be metastable. Finally, this pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers.« less

Biomechanical Analysis of an Expandable Lumbar Interbody Spacer.

PubMed

Soriano-Baron, Hector; Newcomb, Anna G U S; Malhotra, Devika; Palma, Atilio E; Martinez-Del-Campo, Eduardo; Crawford, Neil R; Theodore, Nicholas; Kelly, Brian P; Kaibara, Taro

2018-06-01

Recently developed expandable interbody spacers are widely accepted in spinal surgery; however, the resulting biomechanical effects of their use have not yet been fully studied. We analyzed the biomechanical effects of an expandable polyetheretherketone interbody spacer inserted through a bilateral posterior approach with and without different modalities of posterior augmentation. Biomechanical nondestructive flexibility testing was performed in 7 human cadaveric lumbar (L2-L5) specimens followed by axial compressive loading. Each specimen was tested under 6 conditions: 1) intact, 2) bilateral L3-L4 cortical screw/rod (CSR) alone, 3) WaveD alone, 4) WaveD + CSR, 5) WaveD + bilateral L3-L4 pedicle screw/rod (PSR), and 6) WaveD + CSR/PSR, where CSR/PSR was a hybrid construct comprising bilateral cortical-level L3 and pedicle-level L4 screws interconnected by rods. The range of motion (ROM) with the interbody spacer alone decreased significantly compared with the intact condition during flexion-extension (P = 0.02) but not during lateral bending or axial rotation (P ≥ 0.19). The addition of CSR or PSR to the interbody spacer alone condition significantly decreased the ROM compared with the interbody spacer alone (P ≤ 0.002); and WaveD + CSR, WaveD + PSR, and WaveD + CSR/PSR (hybrid) (P ≥ 0.29) did not differ. The axial compressive stiffness (resistance to change in foraminal height during compressive loading) with the interbody spacer alone did not differ from the intact condition (P = 0.96), whereas WaveD + posterior instrumentation significantly increased compressive stiffness compared with the intact condition and the interbody spacer alone (P ≤ 0.001). The WaveD alone significantly reduced ROM during flexion-extension while maintaining the axial compressive stiffness. CSR, PSR, and CSR/PSR hybrid constructs were all effective in augmenting the expandable interbody spacer system and improving its stability. Copyright © 2018 Elsevier Inc. All

Magnetotransport Properties of Graphene Nanoribbons with Zigzag Edges

NASA Astrophysics Data System (ADS)

Wu, Shuang; Liu, Bing; Shen, Cheng; Li, Si; Huang, Xiaochun; Lu, Xiaobo; Chen, Peng; Wang, Guole; Wang, Duoming; Liao, Mengzhou; Zhang, Jing; Zhang, Tingting; Wang, Shuopei; Yang, Wei; Yang, Rong; Shi, Dongxia; Watanabe, Kenji; Taniguchi, Takashi; Yao, Yugui; Wang, Weihua; Zhang, Guangyu

2018-05-01

The determination of the electronic structure by edge geometry is unique to graphene. In theory, an evanescent nonchiral edge state is predicted at the zigzag edges of graphene. Up to now, the approach used to study zigzag-edged graphene has mostly been limited to scanning tunneling microscopy. The transport properties have not been revealed. Recent advances in hydrogen plasma-assisted "top-down" fabrication of zigzag-edged graphene nanoribbons (Z-GNRs) have allowed us to investigate edge-related transport properties. In this Letter, we report the magnetotransport properties of Z-GNRs down to ˜70 nm wide on an h -BN substrate. In the quantum Hall effect regime, a prominent conductance peak is observed at Landau ν =0 , which is absent in GNRs with nonzigzag edges. The conductance peak persists under perpendicular magnetic fields and low temperatures. At a zero magnetic field, a nonlocal voltage signal, evidenced by edge conduction, is detected. These prominent transport features are closely related to the observable density of states at the hydrogen-etched zigzag edge of graphene probed by scanning tunneling spectroscopy, which qualitatively matches the theoretically predicted electronic structure for zigzag-edged graphene. Our study gives important insights for the design of new edge-related electronic devices.

Multicolor Upconversion Nanoparticles for Protein Conjugation

PubMed Central

Wilhelm, Stefan; Hirsch, Thomas; Patterson, Wendy M.; Scheucher, Elisabeth; Mayr, Torsten; Wolfbeis, Otto S.

2013-01-01

We describe the preparation of monodisperse, lanthanide-doped hexagonal-phase NaYF4 upconverting luminescent nanoparticles for protein conjugation. Their core was coated with a silica shell which then was modified with a poly(ethylene glycol) spacer and N-hydroxysuccinimide ester groups. The nanoparticles were characterized by transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and dynamic light scattering. The N-hydroxysuccinimide ester functionalization renders them highly reactive towards amine nucleophiles (e.g., proteins). We show that such particles can be conjugated to proteins. The protein-reactive UCLNPs and their conjugates to streptavidin and bovine serum albumin display multicolor emissions upon 980-nm continuous wave laser excitation. Surface plasmon resonance studies were carried out to prove bioconjugation and to compare the affinity of the particles for proteins immobilized on a thin gold film. PMID:23606910

p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities.

PubMed

Pei, Kehan; Ou, Juanying; Huang, Junqing; Ou, Shiyi

2016-07-01

p-Coumaric acid (4-hydroxycinnamic acid) is a phenolic acid that has low toxicity in mice (LD50 = 2850 mg kg(-1) body weight), serves as a precursor of other phenolic compounds, and exists either in free or conjugated form in plants. Conjugates of p-coumaric acid have been extensively studied in recent years due to their bioactivities. In this review, the occurrence, bioavailability and bioaccessibility of p-coumaric acid and its conjugates with mono-, oligo- and polysaccharides, alkyl alcohols, organic acids, amine and lignin are discussed. Their biological activities, including antioxidant, anti-cancer, antimicrobial, antivirus, anti-inflammatory, antiplatelet aggregation, anxiolytic, antipyretic, analgesic, and anti-arthritis activities, and their mitigatory effects against diabetes, obesity, hyperlipaemia and gout are compared. Cumulative evidence from multiple studies indicates that conjugation of p-coumaric acid greatly strengthens its biological activities; however, the high biological activity but low absorption of its conjugates remains a puzzle. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Fabricating and Controlling Silicon Zigzag Nanowires by Diffusion-Controlled Metal-Assisted Chemical Etching Method.

PubMed

Chen, Yun; Zhang, Cheng; Li, Liyi; Tuan, Chia-Chi; Wu, Fan; Chen, Xin; Gao, Jian; Ding, Yong; Wong, Ching-Ping

2017-07-12

Silicon (Si) zigzag nanowires (NWs) have a great potential in many applications because of its high surface/volume ratio. However, fabricating Si zigzag NWs has been challenging. In this work, a diffusion-controlled metal-assisted chemical etching method is developed to fabricate Si zigzag NWs. By tailoring the composition of etchant to change its diffusivity, etching direction, and etching time, various zigzag NWs can be easily fabricated. In addition, it is also found that a critical length of NW (>1 μm) is needed to form zigzag nanowires. Also, the amplitude of zigzag increases as the location approaches the center of the substrate and the length of zigzag nanowire increases. It is also demonstrated that such zigzag NWs can help the silicon substrate for self-cleaning and antireflection. This method may provide a feasible and economical way to fabricate zigzag NWs and novel structures for broad applications.

Capacity improvement of the carbon-based electrochemical capacitor by zigzag-edge introduced graphene

NASA Astrophysics Data System (ADS)

Tamura, Naoki; Tomai, Takaaki; Oka, Nobuto; Honma, Itaru

2018-01-01

The electrochemical properties of graphene edge has been attracted much attention. Especially, zigzag edge has high electrochemical activity because neutral radical exits on edge. However, due to a lack of efficient production method for zigzag graphene, the electrochemical properties of zigzag edge have not been experimentally demonstrated and the capacitance enhancement of carbonaceous materials in energy storage devices by the control in their edge states is still challenge. In this study, we fabricated zigzag-edge-rich graphene by a one-step method combining graphene exfoliation in supercritical fluid and anisotropic etching by catalytic nanoparticles. This efficient production of zigzag-edge-rich graphene allows us to investigate the electrochemical activity of zigzag edge. By cyclic voltammetry, we revealed the zigzag edge-introduced graphene exhibited unique redox reaction in aqueous acid solution. Moreover, by the calculation on the density function theory (DFT), this unique redox potential for zigzag edge-introduced graphene can be attributed to the proton-insertion/-extraction reactions at the zigzag edge. This finding indicates that the graphene edge modification can contribute to the further increase in the capacitance of the carbon-based electrochemical capacitor.

Optimization of the nanotwin-induced zigzag surface of copper by electromigration

NASA Astrophysics Data System (ADS)

Chen, Hsin-Ping; Huang, Chun-Wei; Wang, Chun-Wen; Wu, Wen-Wei; Liao, Chien-Neng; Chen, Lih-Juann; Tu, King-Ning

2016-01-01

By adding nanotwins to Cu, the surface electromigration (EM) slows down. The atomic mobility of the surface step-edges is retarded by the triple points where a twin meets a free surface to form a zigzag-type surface. We observed that EM can alter the zigzag surface structure to optimize the reduction of EM, according to Le Chatelier's principle. Statistically, the optimal alternation is to change an arbitrary (111)/(hkl) zigzag pair to a pair having a very low index (hkl) plane, especially the (200) plane. Using in situ ultrahigh vacuum and high-resolution transmission electron microscopy, we examined the effects of different zigzag surfaces on the rate of EM. The calculated rate of surface EM can be decreased by a factor of ten.By adding nanotwins to Cu, the surface electromigration (EM) slows down. The atomic mobility of the surface step-edges is retarded by the triple points where a twin meets a free surface to form a zigzag-type surface. We observed that EM can alter the zigzag surface structure to optimize the reduction of EM, according to Le Chatelier's principle. Statistically, the optimal alternation is to change an arbitrary (111)/(hkl) zigzag pair to a pair having a very low index (hkl) plane, especially the (200) plane. Using in situ ultrahigh vacuum and high-resolution transmission electron microscopy, we examined the effects of different zigzag surfaces on the rate of EM. The calculated rate of surface EM can be decreased by a factor of ten. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05418d

Studies of paracetamol/phenacetin toxicity: isolation and characterization of p-aminophenol-glutathione conjugate.

PubMed

Eyanagi, R; Hisanari, Y; Shigematsu, H

1991-06-01

1. p-Aminophenol, a minor metabolite of phenacetin, is a potent nephrotoxic agent. 2. We have examined the binding of p-aminophenol to glutathione (GSH), a model amino acid, in the presence of horseradish peroxidase, which catalyses one electron oxidation. 3. The reaction product was purified by preparative h.p.l.c., and its structure was determined by FAB mass spectrometry and 1H-n.m.r. to be a p-aminophenol-GSH conjugate. The conjugate was formed between the ortho carbon of the amino group of p-aminophenol and the SH group of GSH. 4. It was confirmed by h.p.l.c. and 1H-n.m.r. that formation of the conjugate was catalysed in vitro by rat liver microsomes and cumene hydroperoxide.

Industrially prefabricated cement spacers: do vancomycin- and gentamicin-impregnated spacers offer any advantage?

PubMed

Corona, Pablo S; Barro, Victor; Mendez, Marye; Cáceres, Enric; Flores, Xavier

2014-03-01

Industrially preformed antibiotic-loaded cement spacers are useful to facilitate the second stage of two-stage exchange arthroplasty for infected THAs and TKAs. However, whether gentamicin alone or a combination of antibiotics (such as vancomycin and gentamicin) is more effective is not known. We therefore sought to compare industrially prefabricated spacers containing either gentamicin or gentamicin and vancomycin with respect to (1) infection control, (2) complications, and (3) quality of life, pain, and patient satisfaction. We performed a review of 51 patients with chronic infections treated at one center using either gentamicin or vancomycin and gentamicin-prefabricated spacers. The former were used exclusively from January 2006 until May 2009, and the latter from June 2009 until July 2011, and there was no overlap. We collected data on demographics, immunologic status (McPherson classification), prosthetic joint infection location, type of prosthesis, microbiologic results, and time between stages. We evaluated the primary outcome of infection control or recurrence after at least 12 months followup. We also recorded complications. Each patient completed a quality-of-life survey, VAS, and a self-administered satisfaction scale. The overall infection control rate was 83% after a mean followup of 35 months (range, 12.4-64.7 months). There were no differences between gentamicin and vancomycin and gentamicin spacers in terms of infection eradication (80 % versus 85 %, respectively; p = 0.73), nor in terms of complications, quality of life, pain, or satisfaction scores. Prefabricated, antibiotic-loaded cement spacers has been proven effective for infection control in TKAs and THAs but with the numbers available, we did not find any differences between a gentamicin or vancomycin and gentamicin-prefabricated spacer, and therefore, we are unable to validate the superiority of the combination of vancomycin and gentamicin over gentamicin alone. Because of the higher

FAST TRACK COMMUNICATION: Preferential functionalization on zigzag graphene nanoribbons: first-principles calculations

NASA Astrophysics Data System (ADS)

Lee, Hoonkyung

2010-09-01

We investigate the functionalization of functional groups to graphene nanoribbons with zigzag and armchair edges using first-principles calculations. We find that the formation energy for the configuration of the functional groups functionalized to the zigzag edge is ~ 0.2 eV per functional group lower than that to the armchair edge. The formation energy difference arises from a structural deformation on the armchair edge by the functionalization whereas there is no structural deformation on the zigzag edge. Selective functionalization on the zigzag edge takes place at a condition of the temperature and the pressure of ~ 25 °C and 10 - 5 atm. Our findings show that selective functionalization can offer the opportunity for an approach to the separation of zigzag graphene nanoribbons with their solubility change.

A Scheme for the Evaluation of Electron Delocalization and Conjugation Efficiency in Linearly π-Conjugated Systems.

PubMed

Bruschi, Maurizio; Limacher, Peter A; Hutter, Jürg; Lüthi, Hans Peter

2009-03-10

In this study, we present a scheme for the evaluation of electron delocalization and conjugation efficiency in lineraly π-conjugated systems. The scheme, based on the natural bond orbital theory, allows monitoring the evolution of electron delocalization along an extended conjugation path as well as its response to chemical modification. The scheme presented is evaluated and illustrated by means of a computational investigation of π-conjugation in all-trans polyacetylene [PA; H(-CH═CH)n-H], polydiacetylene [PDA, H(-C≡C-CH═CH)n-H], and polytriacetylene [PTA, H(-C≡C-CH═CH-C≡C)n-H] with up to 180 carbon atoms, all related by the number of ethynyl units incorporated in the chain. We are able to show that for short oligomers the incorporation of ethynyl spacers into the PA chain increases the π-delocalization energy, but, on the other hand, reduces the efficiency with which π-electron delocalization is promoted along the backbone. This explains the generally shorter effective conjugation lengths observed for the properties of the polyeneynes (PDA and PTA) relative to the polyenes (PA). It will also be shown that the reduced conjugation efficiency, within the NBO-based model presented in this work, can be related to the orbital interaction pattern along the π-conjugated chain. We will show that the orbital interaction energy pattern is characteristic for the type and the length of the backbone and may therefore serve as a descriptor for linearly π-conjugated chains.

Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

PubMed

Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

2008-03-04

The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

Novel conjugates of peptides and conjugated polymers for optoelectronics and neural interfaces

NASA Astrophysics Data System (ADS)

Bhagwat, Nandita

Peptide-polymer conjugates are a novel class of hybrid materials that take advantage of each individual component giving the opportunity to generate materials with unique physical, chemical, mechanical, optical, and electronic properties. In this dissertation peptide-polymer conjugates for two different applications are discussed. The first set of peptide-polymer conjugates were developed as templates to study the intermolecular interactions between electroactive molecules by manipulating the intermolecular distances at nano-scale level. A PEGylated, alpha-helical peptide template was employed to effectively display an array of organic chromophores (oxadiazole containing phenylenevinylene oligomers, Oxa-PPV). Three Oxa-PPV chromophores were strategically positioned on each template, at distances ranging from 6 to 17 A from each other, as dictated by the chemical and structural properties of the peptide. The Oxa-PPV modified PEGylated helical peptides (produced via Heck coupling strategies) were characterized by a variety of spectroscopic methods. Electronic contributions from multiple pairs of chromophores on a scaffold were detectable; the number and relative positioning of the chromophores dictated the absorbance and emission maxima, thus confirming the utility of these polymer--peptide templates for complex presentation of organic chromophores. The rest of the thesis is focused on using poly(3,4-alkylenedioxythiophene) based conjugated polymers as coatings for neural electrodes. This thiophene derivative is of considerable current interest for functionalizing the surfaces of a wide variety of devices including implantable biomedical electronics, specifically neural bio-electrodes. Toward these ends, copolymer films of 3,4-ethylenedioxythiophene (EDOT) with a carboxylic acid functional EDOT (EDOTacid) were electrochemically deposited and characterized as a systematic function of the EDOTacid content (0, 25, 50, 75, and 100%). The chemical surface characterization

Plasmid Capture by the Bacillus thuringiensis Conjugative Plasmid pXO16▿

PubMed Central

Timmery, Sophie; Modrie, Pauline; Minet, Olivier; Mahillon, Jacques

2009-01-01

Conjugation, mobilization, and retromobilization are three related mechanisms of horizontal gene transfer in bacteria. They have been extensively studied in gram-negative species, where retromobilization, the capture of DNA from a recipient by a donor cell, was shown to result from two successive steps: the transfer of the conjugative plasmid from the donor to the recipient followed by the retrotransfer of the mobilizable plasmid to the donor. This successive model was established for gram-negative bacteria but was lacking experimental data from the gram-positive counterparts. In the present work, the mobilization and retromobilization abilities of the conjugative plasmid pXO16 from Bacillus thuringiensis subsp. israelensis were studied using the mobilizable plasmids pUB110 and pE194 and the “nonmobilizable” element pC194 lacking the mob and oriT features (all from Staphylococcus aureus). Experimental data suggested a successive model, since different retromobilization frequencies were observed between the small plasmids. More importantly, retromobilization was shown to be delayed by 50 and 150 min for pUB110 and pE194, respectively, compared to pXO16 conjugation. Natural liquid foods (cow milk, soy milk, and rice milk) were used to evaluate the putative ecological impact of these transfers. In cow and soy milk, conjugation, mobilization, and retromobilization were shown to occur at frequencies of 8.0 × 10−1, 1.0 × 10−2, and 1.2 × 10−4 transconjugants per recipient, respectively. These data are comparable to those obtained with LB medium and about 10-fold lower than in the case of rice milk. Taken together, these results emphasize the potential role of plasmid capture played by B. thuringiensis in natural environments. PMID:19181805

Coupling of Armchair and Zigzag Tubes to a Free Electron Metal

NASA Technical Reports Server (NTRS)

Anantram, M. P.; Biegel, Bryan (Technical Monitor)

2001-01-01

The effect of nanotube chirality is of prime importance in determining its electronic properties. We address the issue of how chirality affects the coupling of a nanotube to metal contacts. We model coupling of armchair and zigzag nanotubes to metal contacts, in both the side- and end-contacted geometries. In the side-contacted geometry, the coupling of armchair and metallic-zigzag nanotubes to a free electron metal are significantly different. Namely, it is possible to drive a larger current through a metallic-zigzag nanotube. The predicted difference holds good when both (a) the entire circumference and (b) only a finite sector of the nanotube makes contact to the metal electrode. It might be possible to observe the predicted difference between armchair and zigzag nanotubes using gold contacts.

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence

PubMed Central

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-01-01

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction. PMID:26578773

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence.

PubMed

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-11-17

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction.

Improved Photo-Detection Using Zigzag TiO2 Nanostructures as an Active Medium.

PubMed

Tiwari, A K; Mondal, A; Mahajan, B K; Choudhuri, B; Goswami, T; Sarkar, M B; Chakrabartty, S; Ngangbam, C; Saha, S

2015-07-01

Zigzag TiO2 nanostructures were fabricated using oblique angle deposition technique. The field emission gun-scanning electron microscope (FEG-SEM) image shows that the TiO2 zigzag nanostructures were ~500 nm in length. Averagely two times enhanced UV-Vis absorption was recorded for zigzag structure compared to perpendicular TiO2 nanowires. The main band transition was observed at ~3.4 eV. The zigzag TiO2 exhibited high turn on voltage (+11 V) than that of nanowire (+2 V) detector under dark which were reduced to +0.2 V and +1.0 V under white light illumination, respectively. A maximum ~6 fold photo-responsivity was observed for the zigzag TiO2 compared with nanowire device at + 1.0 V applied potential. The maximum photo-responsivity of 0.36 A/W at 370 nm was measured for the zigzag TiO2 detector. The TiO2 zigzag detector showed slow response with rise time of 10.2 s and fall time of 10.3 s respectively. The UV (370 nm) to visible (450 nm) wavelength rejection ratio of photo-responsivity was recorded ~4 times for the detector.

A Two-Dimensional 'Zigzag' Silica Polymorph on a Metal Support.

PubMed

Kuhness, David; Yang, Hyun Jin; Klemm, Hagen W; Prieto, Mauricio; Peschel, Gina; Fuhrich, Alexander; Menzel, Dietrich; Schmidt, Thomas; Yu, Xin; Shaikhutdinov, Shamil; Lewandowski, Adrian; Heyde, Markus; Kelemen, Anna; Włodarczyk, Radosław; Usvyat, Denis; Schütz, Martin; Sauer, Joachim; Freund, Hans-Joachim

2018-05-16

We present a new polymorph of the two-dimensional (2D) silica film with a characteristic 'zigzag' line structure and a rectangular unit cell which forms on a Ru(0001) metal substrate. This new silica polymorph may allow for important insights into growth modes and transformations of 2D silica films as a model system for the study of glass transitions. Based on scanning tunneling microscopy, low energy electron diffraction, infrared reflection absorption spectroscopy, and X-ray photoelectron spectroscopy measurements on the one hand, and density functional theory calculations on the other, a structural model for the 'zigzag' polymorph is proposed. In comparison to established monolayer and bilayer silica, this 'zigzag' structure system has intermediate characteristics in terms of coupling to the substrate and stoichiometry. The silica 'zigzag' phase is transformed upon reoxidation at higher annealing temperature into a SiO 2 silica bilayer film which is chemically decoupled from the substrate.

pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery

NASA Astrophysics Data System (ADS)

Kang, Yang; Ha, Wei; Liu, Ying-Qian; Ma, Yuan; Fan, Min-Min; Ding, Li-Sheng; Zhang, Sheng; Li, Bang-Jing

2014-08-01

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4β-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4β-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.

pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery.

PubMed

Kang, Yang; Ha, Wei; Liu, Ying-Qian; Ma, Yuan; Fan, Min-Min; Ding, Li-Sheng; Zhang, Sheng; Li, Bang-Jing

2014-08-22

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4β-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4β-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC₅₀) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.

A Refined Zigzag Beam Theory for Composite and Sandwich Beams

NASA Technical Reports Server (NTRS)

Tessler, Alexander; Sciuva, Marco Di; Gherlone, Marco

2009-01-01

A new refined theory for laminated composite and sandwich beams that contains the kinematics of the Timoshenko Beam Theory as a proper baseline subset is presented. This variationally consistent theory is derived from the virtual work principle and employs a novel piecewise linear zigzag function that provides a more realistic representation of the deformation states of transverse-shear flexible beams than other similar theories. This new zigzag function is unique in that it vanishes at the top and bottom bounding surfaces of a beam. The formulation does not enforce continuity of the transverse shear stress across the beam s cross-section, yet is robust. Two major shortcomings that are inherent in the previous zigzag theories, shear-force inconsistency and difficulties in simulating clamped boundary conditions, and that have greatly limited the utility of these previous theories are discussed in detail. An approach that has successfully resolved these shortcomings is presented herein. Exact solutions for simply supported and cantilevered beams subjected to static loads are derived and the improved modelling capability of the new zigzag beam theory is demonstrated. In particular, extensive results for thick beams with highly heterogeneous material lay-ups are discussed and compared with corresponding results obtained from elasticity solutions, two other zigzag theories, and high-fidelity finite element analyses. Comparisons with the baseline Timoshenko Beam Theory are also presented. The comparisons clearly show the improved accuracy of the new, refined zigzag theory presented herein over similar existing theories. This new theory can be readily extended to plate and shell structures, and should be useful for obtaining relatively low-cost, accurate estimates of structural response needed to design an important class of high-performance aerospace structures.

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy

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

Mariados, Neil, E-mail: nmariados@ampofny.com; Sylvester, John; Shah, Dhiren

2015-08-01

Purpose: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Methods and Materials: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapymore » (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Results: Spacer application was rated as “easy” or “very easy” 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Conclusions: Spacer

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy.

PubMed

Mariados, Neil; Sylvester, John; Shah, Dhiren; Karsh, Lawrence; Hudes, Richard; Beyer, David; Kurtzman, Steven; Bogart, Jeffrey; Hsi, R Alex; Kos, Michael; Ellis, Rodney; Logsdon, Mark; Zimberg, Shawn; Forsythe, Kevin; Zhang, Hong; Soffen, Edward; Francke, Patrick; Mantz, Constantine; Rossi, Peter; DeWeese, Theodore; Hamstra, Daniel A; Bosch, Walter; Gay, Hiram; Michalski, Jeff

2015-08-01

Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Spacer application was well tolerated. Increased perirectal space reduced

Mobility of the native Bacillus subtilis conjugative plasmid pLS20 is regulated by intercellular signaling.

PubMed

Singh, Praveen K; Ramachandran, Gayetri; Ramos-Ruiz, Ricardo; Peiró-Pastor, Ramón; Abia, David; Wu, Ling J; Meijer, Wilfried J J

2013-10-01

Horizontal gene transfer mediated by plasmid conjugation plays a significant role in the evolution of bacterial species, as well as in the dissemination of antibiotic resistance and pathogenicity determinants. Characterization of their regulation is important for gaining insights into these features. Relatively little is known about how conjugation of Gram-positive plasmids is regulated. We have characterized conjugation of the native Bacillus subtilis plasmid pLS20. Contrary to the enterococcal plasmids, conjugation of pLS20 is not activated by recipient-produced pheromones but by pLS20-encoded proteins that regulate expression of the conjugation genes. We show that conjugation is kept in the default "OFF" state and identified the master repressor responsible for this. Activation of the conjugation genes requires relief of repression, which is mediated by an anti-repressor that belongs to the Rap family of proteins. Using both RNA sequencing methodology and genetic approaches, we have determined the regulatory effects of the repressor and anti-repressor on expression of the pLS20 genes. We also show that the activity of the anti-repressor is in turn regulated by an intercellular signaling peptide. Ultimately, this peptide dictates the timing of conjugation. The implications of this regulatory mechanism and comparison with other mobile systems are discussed.

Multicomponent Pt-Based Zigzag Nanowires as Selectivity Controllers for Selective Hydrogenation Reactions.

PubMed

Bai, Shuxing; Bu, Lingzheng; Shao, Qi; Zhu, Xing; Huang, Xiaoqing

2018-06-22

The selective hydrogenation of α, β-unsaturated aldehyde is an extremely important transformation, while developing efficient catalysts with desirable selectivity to highly value-added products is challenging, mainly due to the coexistence of two conjugated unsaturated functional groups. Herein, we report that a series of Pt-based zigzag nanowires (ZNWs) can be adopted as selectivity controllers for α, β-unsaturated aldehyde hydrogenation, where the excellent unsaturated alcohol (UOL) selectivity (>95%) and high saturated aldehyde (SA) selectivity (>94%) are achieved on PtFe ZNWs and PtFeNi ZNWs+AlCl 3 , respectively. The excellent UOL selectivity of PtFe ZNWs is attributed to the lower electron density of the surface Pt atoms, while the high SA selectivity of PtFeNi ZNWs+AlCl 3 is due to synergy between PtFeNi ZNWs and AlCl 3 , highlighting the importance of Pt-based NWs with precisely controlled surface and composition for catalysis and beyond.

A GEM readout with radial zigzag strips and linear charge-sharing response

DOE PAGES

Zhang, Aiwu; Hohlmann, Marcus; Azmoun, Babak; ...

2018-01-10

Here, we study the position sensitivity of radial zigzag strips intended to read out large GEM detectors for tracking at future experiments. Zigzag strips can cover a readout area with fewer strips than regular straight strips while maintaining good spatial resolution. Consequently, they can reduce the number of required electronic channels and related cost for large-area GEM detector systems. A non-linear relation between incident particle position and hit position measured from charge sharing among zigzag strips was observed in a previous study. We significantly reduce this non-linearity by improving the interleaving of adjacent physical zigzag strips. Zigzag readout structures aremore » implemented on PCBs and on a flexible foil and are tested using a 10 cm × 10 cm triple-GEM detector scanned with a strongly collimated X-ray gun on a 2D motorized stage. Lastly, angular resolutions of 60–84 μrad are achieved with a 1.37 mrad angular strip pitch at a radius of 784 mm. On a linear scale this corresponds to resolutions below 100 μm.« less

A GEM readout with radial zigzag strips and linear charge-sharing response

NASA Astrophysics Data System (ADS)

Zhang, Aiwu; Hohlmann, Marcus; Azmoun, Babak; Purschke, Martin L.; Woody, Craig

2018-04-01

We study the position sensitivity of radial zigzag strips intended to read out large GEM detectors for tracking at future experiments. Zigzag strips can cover a readout area with fewer strips than regular straight strips while maintaining good spatial resolution. Consequently, they can reduce the number of required electronic channels and related cost for large-area GEM detector systems. A non-linear relation between incident particle position and hit position measured from charge sharing among zigzag strips was observed in a previous study. We significantly reduce this non-linearity by improving the interleaving of adjacent physical zigzag strips. Zigzag readout structures are implemented on PCBs and on a flexible foil and are tested using a 10 cm × 10 cm triple-GEM detector scanned with a strongly collimated X-ray gun on a 2D motorized stage. Angular resolutions of 60-84 μrad are achieved with a 1.37 mrad angular strip pitch at a radius of 784 mm. On a linear scale this corresponds to resolutions below 100 μm.

Electronic transport across a junction between armchair graphene nanotube and zigzag nanoribbon. Transmission in an armchair nanotube without a zigzag half-line of dimers

NASA Astrophysics Data System (ADS)

Sharma, Basant Lal

2018-05-01

Based on the well known nearest-neighbor tight-binding approximation for graphene, an exact expression for the electronic conductance across a zigzag nanoribbon/armchair nanotube junction is presented for non-interacting electrons. The junction results from the removal of a half-row of zigzag dimers in armchair nanotube, or equivalently by partial rolling of zigzag nanoribbon and insertion of a half-row of zigzag dimers in between. From the former point of view, a discrete form of Dirichlet condition is imposed on a zigzag half-line of dimers assuming the vanishing of wave function outside the physical structure. A closed form expression is provided for the reflection and transmission moduli for the outgoing wave modes for each given electronic wave mode incident from either side of the junction. It is demonstrated that such a contact junction between the nanotube and nanoribbon exhibits negligible backscattering, and the transmission has been found to be nearly ballistic. In contrast to the previously reported studies for partially unzipped carbon nanotubes (CNTs), using the same tight binding model, it is found that due to the "defect" there is certain amount of mixing between the electronic wave modes with even and odd reflection symmetries. But the junction remains a perfect valley filter for CNTs at certain energy ranges. Applications aside from the electronic case, include wave propagation in quasi-one-dimensional honeycomb structures of graphene-like constitution. The paper includes several numerical calculations, analytical derivations, and graphical results, which complement the provision of succinct closed form expressions.

pA506, a Conjugative Plasmid of the Plant Epiphyte Pseudomonas fluorescens A506

PubMed Central

Stockwell, Virginia O.; Davis, Edward W.; Carey, Alyssa; Shaffer, Brenda T.; Mavrodi, Dmitri V.; Hassan, Karl A.; Hockett, Kevin; Thomashow, Linda S.; Paulsen, Ian T.

2013-01-01

Conjugative plasmids are known to facilitate the acquisition and dispersal of genes contributing to the fitness of Pseudomonas spp. Here, we report the characterization of pA506, the 57-kb conjugative plasmid of Pseudomonas fluorescens A506, a plant epiphyte used in the United States for the biological control of fire blight disease of pear and apple. Twenty-nine of the 67 open reading frames (ORFs) of pA506 have putative functions in conjugation, including a type IV secretion system related to that of MOBP6 family plasmids and a gene cluster for type IV pili. We demonstrate that pA506 is self-transmissible via conjugation between A506 and strains of Pseudomonas spp. or the Enterobacteriaceae. The origin of vegetative replication (oriV) of pA506 is typical of those in pPT23A family plasmids, which are present in many pathovars of Pseudomonas syringae, but pA506 lacks repA, a defining locus for pPT23A plasmids, and has a novel partitioning region. We selected a plasmid-cured derivative of A506 and compared it to the wild type to identify plasmid-encoded phenotypes. pA506 conferred UV resistance, presumably due to the plasmid-borne rulAB genes, but did not influence epiphytic fitness of A506 on pear or apple blossoms in the field. pA506 does not appear to confer resistance to antibiotics or other toxic elements. Based on the conjugative nature of pA506 and the large number of its genes that are shared with plasmids from diverse groups of environmental bacteria, the plasmid is likely to serve as a vehicle for genetic exchange between A506 and its coinhabitants on plant surfaces. PMID:23811504

Surface plasmon resonance in electrodynamically coupled Au NPs monolayer/dielectric spacer/Al film nanostructure: tuning by variation of spacer thickness

NASA Astrophysics Data System (ADS)

Yeshchenko, Oleg A.; Kozachenko, Viktor V.; Liakhov, Yuriy F.; Tomchuk, Anastasiya V.; Haftel, Michael; Pinchuk, Anatoliy O.

2017-10-01

Effects of plasmonic coupling between metal nanoparticles and thin metal films separated by thin dielectric film-spacers have been studied by means of light extinction in three-layer planar Au NPs monolayer/dielectric (shellac) film/Al film nanostructure. The influence of coupling on the spectral characteristics of the Au NPs SPR extinction peak has been analyzed with spacer thickness, varied from 3 to 200 nm. The main observed features are a strong red shift (160 nm), and non-monotonical behavior of the magnitude and width of Au NPs SPR, as the spacer thickness decreased. The appearance of an intensive gap mode peak was observed at a spacer thickness smaller than approximately 30 nm, caused by the hybridization of the Au NPs SPR mode and gap mode in the presence of the Al film. Additionally, the appreciable enhancement (5.6 times) of light extinction by the Au NPs monolayer in the presence of Al film has been observed. A certain value of dielectric spacer thickness (70 nm) exists at which such enhancement is maximal.

Two isotypic diphosphates LiM{sub 2}H{sub 3}(P{sub 2}O{sub 7}){sub 2} (M=Ni, Co) containing ferromagnetic zigzag MO{sub 6} chains

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

Yang Tao; Yang Sihai; Liao Fuhui

2008-06-15

Two new isotypic phosphates LiNi{sub 2}H{sub 3}(P{sub 2}O{sub 7}){sub 2} (1) and LiCo{sub 2}H{sub 3}(P{sub 2}O{sub 7}){sub 2} (2) have been hydrothermally synthesized and structurally characterized by the single-crystal X-ray diffraction technique. They crystallize in the monoclinic space group C2/c with the lattice: a=10.925(2) A, b=12.774(3) A, c=8.8833(18) A, {beta}=123.20(3){sup o} for 1 and a=10.999(2) A, b=12.863(3) A, c=8.9419(18) A, {beta}=123.00(3){sup o} for 2. The transition metal atoms are octahedrally coordinated, whereas the lithium and phosphorus atoms are all tetrahedrally coordinated. As the lithium-induced derivatives of MH{sub 2}P{sub 2}O{sub 7} (M=Ni, Co), 1 and 2 possess the same structure withmore » MH{sub 2}P{sub 2}O{sub 7} in terms of topology, comprising the MO{sub 6} zigzag chains and P{sub 2}O{sub 7} as the interchain groups. The magnetisms of 1 and 2 could be interpreted by adopting a quasi-one-dimensional (1D) zigzag chain model as that in their parent compounds: both 1 and 2 have ferromagnetic (FM) NiO{sub 6}/CoO{sub 6} chains; 1 shows a FM cluster glass behavior at low temperatures, which is originated from the possible antiferromagnetic (AFM) next-nearest-neighbour intrachain interactions; 2 shows a AFM ordering at T{sub N}=2.6 K and a metamagnetic transition at H{sub C}=4.2 kOe at 1.8 K. - Graphical abstract: LiNi{sub 2}H{sub 3}(P{sub 2}O{sub 7}){sub 2} (1) and LiCo{sub 2}H{sub 3}(P{sub 2}O{sub 7}){sub 2} (2) have been hydrothermally synthesized and structurally characterized. The MO{sub 6} octahedra share edges forming zigzag chains with P{sub 2}O{sub 7} as the interchain groups. Both of them are quasi-one-dimensional magnets and have ferromagnetic MO{sub 6} chains; 1 is a ferromagnet, whereas 2 is a metamagnet.« less

Comparison of Curvature Between the Zero-P Spacer and Traditional Cage and Plate After 3-Level Anterior Cervical Discectomy and Fusion: Mid-term Results.

PubMed

Chen, Yuanyuan; Liu, Yang; Chen, Huajiang; Cao, Peng; Yuan, Wen

2017-10-01

A retrospective study. To compare clinical and radiologic outcomes of 3-level anterior cervical discectomy and fusion between a zero-profile (Zero-P) spacer and a traditional plate in cases of symptomatic cervical spine spondylosis. Anterior cervical decompression and fusion is indicated for patients with anterior compression or stenosis of the spinal cord. The Zero-P spacers have been used for anterior cervical interbody fusion of 1 or 2 segments. However, there is a paucity of published clinical data regarding the exact impact of the device on cervical curvature of 3-level fixation. Clinical and radiologic data of 71 patients undergoing 3-level anterior cervical discectomy and fusion from January 2010 to January 2012 were collected. Zero-P spacer was implanted in 33 patients, and in 38 cases stabilization was accomplished using an anterior cervical plate and intervertebral cage. Patients were followed for a mean of 30.8 months (range, 24-36 mo) after surgery. Fusion rates, changes in cervical lordosis, and degeneration of adjacent segments were analyzed. Dysphagia was assessed using the Bazaz score, and clinical outcomes were analyzed using the Neck Disability Index and Japanese Orthopedic Association scoring system. Neurological outcomes did not differ significantly between groups. Significantly less dysphagia was seen at 2- and 6-month follow-up in patients with the Zero-P implant (P<0.05); however, there was significant less cervical lordosis and the lordosis across the fusion in patients with the Zero-P implant (both P<0.05). Degenerative changes in the adjacent segments occurred in 4 patients in the Zero-P group and 6 patients in the standard-plate group (P=0.742); however, no revision surgery was done. Clinical results for the Zero-P spacer were satisfactory. The device is superior to the traditional plate in preventing postoperative dysphagia; however, it is inferior at restoring cervical lordosis. It may not provide better sagittal cervical alignment

Priming in the Type I-F CRISPR-Cas system triggers strand-independent spacer acquisition, bi-directionally from the primed protospacer.

PubMed

Richter, Corinna; Dy, Ron L; McKenzie, Rebecca E; Watson, Bridget N J; Taylor, Corinda; Chang, James T; McNeil, Matthew B; Staals, Raymond H J; Fineran, Peter C

2014-07-01

Clustered regularly interspaced short palindromic repeats (CRISPR), in combination with CRISPR associated (cas) genes, constitute CRISPR-Cas bacterial adaptive immune systems. To generate immunity, these systems acquire short sequences of nucleic acids from foreign invaders and incorporate these into their CRISPR arrays as spacers. This adaptation process is the least characterized step in CRISPR-Cas immunity. Here, we used Pectobacterium atrosepticum to investigate adaptation in Type I-F CRISPR-Cas systems. Pre-existing spacers that matched plasmids stimulated hyperactive primed acquisition and resulted in the incorporation of up to nine new spacers across all three native CRISPR arrays. Endogenous expression of the cas genes was sufficient, yet required, for priming. The new spacers inhibited conjugation and transformation, and interference was enhanced with increasing numbers of new spacers. We analyzed ∼ 350 new spacers acquired in priming events and identified a 5'-protospacer-GG-3' protospacer adjacent motif. In contrast to priming in Type I-E systems, new spacers matched either plasmid strand and a biased distribution, including clustering near the primed protospacer, suggested a bi-directional translocation model for the Cas1:Cas2-3 adaptation machinery. Taken together these results indicate priming adaptation occurs in different CRISPR-Cas systems, that it can be highly active in wild-type strains and that the underlying mechanisms vary. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

PubMed

Han, Hwa Seung; Lee, Minchang; An, Jae Yoon; Son, Soyoung; Ko, Hyewon; Lee, Hansang; Chae, Yee Soo; Kang, Young Mo; Park, Jae Hyung

2016-05-01

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy. © 2015 Wiley Periodicals, Inc.

Iris Segmentation and Normalization Algorithm Based on Zigzag Collarette

NASA Astrophysics Data System (ADS)

Rizky Faundra, M.; Ratna Sulistyaningrum, Dwi

2017-01-01

In this paper, we proposed iris segmentation and normalization algorithm based on the zigzag collarette. First of all, iris images are processed by using Canny Edge Detection to detect pupil edge, then finding the center and the radius of the pupil with the Hough Transform Circle. Next, isolate important part in iris based zigzag collarette area. Finally, Daugman Rubber Sheet Model applied to get the fixed dimensions or normalization iris by transforming cartesian into polar format and thresholding technique to remove eyelid and eyelash. This experiment will be conducted with a grayscale eye image data taken from a database of iris-Chinese Academy of Sciences Institute of Automation (CASIA). Data iris taken is the data reliable and widely used to study the iris biometrics. The result show that specific threshold level is 0.3 have better accuracy than other, so the present algorithm can be used to segmentation and normalization zigzag collarette with accuracy is 98.88%

p-π Conjugated Polymers Based on Stable Triarylborane with n-Type Behavior in Optoelectronic Devices.

PubMed

Meng, Bin; Ren, Yi; Liu, Jun; Jäkle, Frieder; Wang, Lixiang

2018-02-19

p-π conjugation with embedded heteroatoms offers unique opportunities to tune the electronic structure of conjugated polymers. An approach is presented to form highly electron-deficient p-π conjugated polymers based on triarylboranes, demonstrate their n-type behavior, and explore device applications. By combining alternating [2,4,6-tris(trifluoromethyl)phenyl]di(thien-2-yl)borane (FBDT) and electron-deficient isoindigo (IID)/pyridine-flanked diketopyrrolopyrrole (DPPPy) units, we achieve low-lying lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels, high electron mobilities, and broad absorptions in the visible region. All-polymer solar cells with these polymers as electron acceptors exhibit encouraging photovoltaic performance with power conversion efficiencies of up to 2.83 %. These results unambiguously prove the n-type behavior and demonstrate the photovoltaic applications of p-π conjugated polymers based on triarylborane. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: towards the development of potential dual action antimalarials.

PubMed

Pérez, Bianca C; Teixeira, Cátia; Figueiras, Marta; Gut, Jiri; Rosenthal, Philip J; Gomes, José R B; Gomes, Paula

2012-08-01

A series of cinnamic acid/4-aminoquinoline conjugates conceived to link, through a proper retro-enantio dipeptide, a heterocyclic core known to prevent hemozoin formation, to a trans-cinnamic acid motif capable of inhibiting enzyme catalytic Cys residues, were synthesized as potential dual-action antimalarials. The effect of amino acid configuration and the absence of the dipeptide spacer were also assessed. The replacement of the D-amino acids by their natural L counterparts led to a decrease in both anti-plasmodial and falcipain-inhibitory activity, suggesting that the former are preferable. Molecules with such spacer were active against blood-stage Plasmodium falciparum, in vitro, and hemozoin formation, implying that the dipeptide has a key role in mediating these two activities. In turn, compounds without spacer were better falcipain-2 inhibitors, likely because these compounds are smaller and have their vinyl bonds in closer vicinity to the catalytic Cys, as suggested by molecular modeling calculations. These novel conjugates constitute promising leads for the development of new antiplasmodials targeted at blood-stage malaria parasites. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Patterning monolayer graphene with zigzag edges on hexagonal boron nitride by anisotropic etching

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

Wang, Guole; Wu, Shuang; Zhang, Tingting

2016-08-01

Graphene nanostructures are potential building blocks for nanoelectronic and spintronic devices. However, the production of monolayer graphene nanostructures with well-defined zigzag edges remains a challenge. In this paper, we report the patterning of monolayer graphene nanostructures with zigzag edges on hexagonal boron nitride (h-BN) substrates by an anisotropic etching technique. We found that hydrogen plasma etching of monolayer graphene on h-BN is highly anisotropic due to the inert and ultra-flat nature of the h-BN surface, resulting in zigzag edge formation. The as-fabricated zigzag-edged monolayer graphene nanoribbons (Z-GNRs) with widths below 30 nm show high carrier mobility and width-dependent energy gaps atmore » liquid helium temperature. These high quality Z-GNRs are thus ideal structures for exploring their valleytronic or spintronic properties.« less

Photo-oxidative doping in π-conjugated zig-zag chain of carbon atoms with sulfur-functional group

NASA Astrophysics Data System (ADS)

Ikeura-Sekiguchi, Hiromi; Sekiguchi, Tetsuhiro

2017-12-01

Photo-oxidative doping processes were studied for the trans-polyacetylene backbone with the -SCH3 side group as a chemically representative of the precisely controlled S-functionalized zig-zag graphene nanoribbon edge. Sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy indicates that photochemical reaction of S-CH3 with atmospheric O2 forms selectively oxidized products such as -S(O)CH3 and -SO3- bound to the polyacetylene (PA) backbone. Using the correlation between the oxidation states of sulfur and the XANES peak positions, the partial charge distribution of CH3Sδ+-PAδ- has been estimated. Such positively charged sulfur atoms can attract higher electronegative oxygen atoms and expect to enhance the photooxidization capabilities. The formation of the -SO3- side group is evidently responsible for hole doping into the PA backbone. The results can provide some strategy for area-selective and controllable doping processes of atomic-scale molecular systems with the assistance of UV light.

Real-Life Outcomes for Patients with Asthma Prescribed Spacers for Use with Either Extrafine- or Fine-Particle Inhaled Corticosteroids.

PubMed

Guilbert, Theresa W; Colice, Gene; Grigg, Jonathan; van Aalderen, Wim; Martin, Richard J; Israel, Elliot; Postma, Dirkje S; Roche, Nicolas; Phipatanakul, Wanda; Hillyer, Elizabeth V; Evans, Jennifer M; Dolovich, Myrna B; Price, David B

Spacers are often used with pressurized metered-dose inhalers (pMDIs) to eliminate the need for coordinating inhalation with actuation. To investigate the real-life effectiveness of spacers prescribed for use with either extrafine- or fine-particle inhaled corticosteroids (ICSs). This historical matched cohort study examined anonymous medical record data over 2 years (1-year baseline, 1-year outcome) for patients with asthma aged 12 to 80 years initiating ICSs by pMDI with or without prescribed spacer. We compared outcomes for spacer versus no-spacer arms, matched for key baseline and asthma-related characteristics, within 2 ICS cohorts: (1) extrafine-particle ICS (beclomethasone) and (2) fine-particle ICS (fluticasone). Effectiveness end points were compared using conditional regression methods. Matched spacer and no-spacer arms of the extrafine-particle ICS cohort each included 2090 patients (69% females; median age, 46-47 years) and the 2 arms of the fine-particle ICS cohort each included 444 patients (67% females; median age, 45 years). With extrafine-particle ICS, we observed no significant difference between spacer and no-spacer arms in severe exacerbation rate (primary end point): adjusted rate ratio, 1.01 (95% CI, 0.83-1.23). With fine-particle ICS, the severe exacerbation rate ratio with spacers was 0.77 (0.47-1.25). Oropharyngeal candidiasis incidence was low and similar in spacer and no-spacer arms for both ICS cohorts. We found no evidence that prescribed spacer devices are associated with improved asthma outcomes for extrafine- or fine-particle ICS administered by pMDI. These findings challenge long-standing assumptions that spacers should improve pMDI effectiveness and indicate the need for pragmatic trials of spacers in clinical practice. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Refined Zigzag Theory for Laminated Composite and Sandwich Plates

NASA Technical Reports Server (NTRS)

Tessler, Alexander; DiSciuva, Marco; Gherlone, Marco

2009-01-01

A refined zigzag theory is presented for laminated-composite and sandwich plates that includes the kinematics of first-order shear deformation theory as its baseline. The theory is variationally consistent and is derived from the virtual work principle. Novel piecewise-linear zigzag functions that provide a more realistic representation of the deformation states of transverse-shear-flexible plates than other similar theories are used. The formulation does not enforce full continuity of the transverse shear stresses across the plate s thickness, yet is robust. Transverse-shear correction factors are not required to yield accurate results. The theory is devoid of the shortcomings inherent in the previous zigzag theories including shear-force inconsistency and difficulties in simulating clamped boundary conditions, which have greatly limited the accuracy of these theories. This new theory requires only C(sup 0)-continuous kinematic approximations and is perfectly suited for developing computationally efficient finite elements. The theory should be useful for obtaining relatively efficient, accurate estimates of structural response needed to design high-performance load-bearing aerospace structures.

All-zigzag graphene nanoribbons for planar interconnect application

NASA Astrophysics Data System (ADS)

Chen, Po-An; Chiang, Meng-Hsueh; Hsu, Wei-Chou

2017-07-01

A feasible "lightning-shaped" zigzag graphene nanoribbon (ZGNR) structure for planar interconnects is proposed. Based on the density functional theory and non-equilibrium Green's function, the electron transport properties are evaluated. The lightning-shaped structure increases significantly the conductance of the graphene interconnect with an odd number of zigzag chains. This proposed technique can effectively utilize the linear I-V characteristic of asymmetric ZGNRs for interconnect application. Variability study accounting for width/length variation and the edge effect is also included. The transmission spectra, transmission eigenstates, and transmission pathways are analyzed to gain the physical insights. This lightning-shaped ZGNR enables all 2D material-based devices and circuits on flexible and transparent substrates.

Anisotropic thermoelectric behavior in armchair and zigzag mono- and fewlayer MoS2 in thermoelectric generator applications

PubMed Central

Arab, Abbas; Li, Qiliang

2015-01-01

In this work, we have studied thermoelectric properties of monolayer and fewlayer MoS2 in both armchair and zigzag orientations. Density functional theory (DFT) using non-equilibrium Green’s function (NEGF) method has been implemented to calculate the transmission spectra of mono- and fewlayer MoS2 in armchair and zigzag directions. Phonon transmission spectra are calculated based on parameterization of Stillinger-Weber potential. Thermoelectric figure of merit, ZT, is calculated using these electronic and phonon transmission spectra. In general, a thermoelectric generator is composed of thermocouples made of both n-type and p-type legs. Based on our calculations, monolayer MoS2 in armchair orientation is found to have the highest ZT value for both p-type and n-type legs compared to all other armchair and zigzag structures. We have proposed a thermoelectric generator based on monolayer MoS2 in armchair orientation. Moreover, we have studied the effect of various dopant species on thermoelectric current of our proposed generator. Further, we have compared output current of our proposed generator with those of Silicon thin films. Results indicate that thermoelectric current of MoS2 armchair monolayer is several orders of magnitude higher than that of Silicon thin films. PMID:26333948

Anisotropic thermoelectric behavior in armchair and zigzag mono- and fewlayer MoS2 in thermoelectric generator applications.

PubMed

Arab, Abbas; Li, Qiliang

2015-09-03

In this work, we have studied thermoelectric properties of monolayer and fewlayer MoS2 in both armchair and zigzag orientations. Density functional theory (DFT) using non-equilibrium Green's function (NEGF) method has been implemented to calculate the transmission spectra of mono- and fewlayer MoS2 in armchair and zigzag directions. Phonon transmission spectra are calculated based on parameterization of Stillinger-Weber potential. Thermoelectric figure of merit, ZT, is calculated using these electronic and phonon transmission spectra. In general, a thermoelectric generator is composed of thermocouples made of both n-type and p-type legs. Based on our calculations, monolayer MoS2 in armchair orientation is found to have the highest ZT value for both p-type and n-type legs compared to all other armchair and zigzag structures. We have proposed a thermoelectric generator based on monolayer MoS2 in armchair orientation. Moreover, we have studied the effect of various dopant species on thermoelectric current of our proposed generator. Further, we have compared output current of our proposed generator with those of Silicon thin films. Results indicate that thermoelectric current of MoS2 armchair monolayer is several orders of magnitude higher than that of Silicon thin films.

Nematic liquid crystals on sinusoidal channels: the zigzag instability.

PubMed

Silvestre, Nuno M; Romero-Enrique, Jose M; Telo da Gama, Margarida M

2017-01-11

Substrates which are chemically or topographically patterned induce a variety of liquid crystal textures. The response of the liquid crystal to competing surface orientations, typical of patterned substrates, is determined by the anisotropy of the elastic constants and the interplay of the relevant lengths scales, such as the correlation length and the surface geometrical parameters. Transitions between different textures, usually with different symmetries, may occur under a wide range of conditions. We use the Landau-de Gennes free energy to investigate the texture of nematics in sinusoidal channels with parallel anchoring bounded by nematic-air interfaces that favour perpendicular (hometropic) anchoring. In micron size channels 5CB was observed to exhibit a non-trivial texture characterized by a disclination line, within the channel, which is broken into a zigzag pattern. Our calculations reveal that when the elastic anisotropy of the nematic does not favour twist distortions the defect is a straight disclination line that runs along the channel, which breaks into a zigzag pattern with a characteristic period, when the twist elastic constant becomes sufficiently small when compared to the splay and bend constants. The transition occurs through a twist instability that drives the defect line to rotate from its original position. The interplay between the energetically favourable twist distortions that induce the defect rotation and the liquid crystal anchoring at the surfaces leads to the zigzag pattern. We investigate in detail the dependence of the periodicity of the zigzag pattern on the geometrical parameters of the sinusoidal channels, which in line with the experimental results is found to be non-linear.

Self-aligned quadruple patterning using spacer on spacer integration optimization for N5

NASA Astrophysics Data System (ADS)

Thibaut, Sophie; Raley, Angélique; Mohanty, Nihar; Kal, Subhadeep; Liu, Eric; Ko, Akiteru; O'Meara, David; Tapily, Kandabara; Biolsi, Peter

2017-04-01

To meet scaling requirements, the semiconductor industry has extended 193nm immersion lithography beyond its minimum pitch limitation using multiple patterning schemes such as self-aligned double patterning, self-aligned quadruple patterning and litho-etch / litho etch iterations. Those techniques have been declined in numerous options in the last few years. Spacer on spacer pitch splitting integration has been proven to show multiple advantages compared to conventional pitch splitting approach. Reducing the number of pattern transfer steps associated with sacrificial layers resulted in significant decrease of cost and an overall simplification of the double pitch split technique. While demonstrating attractive aspects, SAQP spacer on spacer flow brings challenges of its own. Namely, material set selections and etch chemistry development for adequate selectivities, mandrel shape and spacer shape engineering to improve edge placement error (EPE). In this paper we follow up and extend upon our previous learning and proceed into more details on the robustness of the integration in regards to final pattern transfer and full wafer critical dimension uniformity. Furthermore, since the number of intermediate steps is reduced, one will expect improved uniformity and pitch walking control. This assertion will be verified through a thorough pitch walking analysis.

Spacer grid assembly and locking mechanism

DOEpatents

Snyder, Jr., Harold J.; Veca, Anthony R.; Donck, Harry A.

1982-01-01

A spacer grid assembly is disclosed for retaining a plurality of fuel rods in substantially parallel spaced relation, the spacer grids being formed with rhombic openings defining contact means for engaging from one to four fuel rods arranged in each opening, the spacer grids being of symmetric configuration with their rhombic openings being asymmetrically offset to permit inversion and relative rotation of the similar spacer grids for improved support of the fuel rods. An improved locking mechanism includes tie bars having chordal surfaces to facilitate their installation in slotted circular openings of the spacer grids, the tie rods being rotatable into locking engagement with the slotted openings.

Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

PubMed

Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L; Esvelt, Kevin M; Villanueva, Laura; Liu, David R; Chen, Irene A

2011-01-01

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

Inhibition of Bacterial Conjugation by Phage M13 and Its Protein g3p: Quantitative Analysis and Model

PubMed Central

Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L.; Esvelt, Kevin M.; Villanueva, Laura; Liu, David R.; Chen, Irene A.

2011-01-01

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes. PMID:21637841

Fouling resilient perforated feed spacers for membrane filtration.

PubMed

Kerdi, Sarah; Qamar, Adnan; Vrouwenvelder, Johannes S; Ghaffour, Noreddine

2018-04-24

The improvement of feed spacers with optimal geometry remains a key challenge for spiral-wound membrane systems in water treatment due to their impact on the hydrodynamic performance and fouling development. In this work, novel spacer designs are proposed by intrinsically modifying cylindrical filaments through perforations. Three symmetric perforated spacers (1-Hole, 2-Hole, and 3-Hole) were in-house 3D-printed and experimentally evaluated in terms of permeate flux, feed channel pressure drop and membrane fouling. Spacer performance is characterized and compared with standard no perforated (0-Hole) design under constant feed pressure and constant feed flow rate. Perforations in the spacer filaments resulted in significantly lowering the net pressure drop across the spacer filled channel. The 3-Hole spacer was found to have the lowest pressure drop (50%-61%) compared to 0-Hole spacer for various average flow velocities. Regarding permeate flux production, the 0-Hole spacer produced 5.7 L m -2 .h -1 and 6.6 L m -2 .h -1 steady state flux for constant pressure and constant feed flow rate, respectively. The 1-Hole spacer was found to be the most efficient among the perforated spacers with 75% and 23% increase in permeate production at constant pressure and constant feed flow, respectively. Furthermore, membrane surface of 1-Hole spacer was found to be cleanest in terms of fouling, contributing to maintain higher permeate flux production. Hydrodynamic understanding of these perforated spacers is also quantified by performing Direct Numerical Simulation (DNS). The performance enhancement of these perforated spacers is attributed to the formation of micro-jets in the spacer cell that aided in producing enough unsteadiness/turbulence to clean the membrane surface and mitigate fouling phenomena. In the case of 1-Hole spacer, the unsteadiness intensity at the outlet of micro-jets and the shear stress fluctuations created inside the cells are higher than those

Two novel copper(II) complexes constructed from dicarboxylate ligands with different spacer lengths and 2-phenylimidazo[4,5- f]1,10-phenanthroline (PIP): Synthesis, structures and properties

NASA Astrophysics Data System (ADS)

Wang, X.-L.; Chen, Yongqiang; Liu, Guocheng; Lin, Hongyan; Zhang, Jinxia

2009-09-01

Two novel metal-organic coordination polymers [Cu(PIP)(bpea)(H 2O)]·H 2O ( 1) and [Cu(PIP)(1,4-bdc)] ( 2) have been obtained from hydrothermal reaction of copper(II) with the mixed ligands [biphenylethene-4,4'-dicarboxylic acid (bpea) for 1, benzene-1,4-dicarboxylic acid (1,4-H 2bdc) for 2, and 2-phenylimidazo[4,5- f]1,10-phenanthroline (PIP)]. Both complexes have been structurally characterized by elemental analyses, IR and single-crystal X-ray diffraction analyses. Structural analyses reveal that complex 1 possesses infinite one-dimensional zigzag chain, 2 exhibits a two-dimensional (4,4) network, both of which are extended into three-dimensional supramolecular network by weak interactions. The different structures of the title complexes illustrate the influence of the flexibility (the spacer length of carboxyl groups and the structural rigidity of the spacer) of organic dicarboxylate ligands on the formation of such coordination architectures. Moreover, the thermal properties and the voltammetric behavior of complexes 1 and 2 have been reported.

Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy.

PubMed

Wu, Xiang Lan; Kim, Jong Ho; Koo, Heebeom; Bae, Sang Mun; Shin, Hyeri; Kim, Min Sang; Lee, Byung-Heon; Park, Rang-Woon; Kim, In-San; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwangmeyung; Lee, Doo Sung

2010-02-17

Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(beta-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.

Target binding improves relaxivity in aptamer-gadolinium conjugates.

PubMed

Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

2012-12-01

MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

Generator stator core vent duct spacer posts

DOEpatents

Griffith, John Wesley; Tong, Wei

2003-06-24

Generator stator cores are constructed by stacking many layers of magnetic laminations. Ventilation ducts may be inserted between these layers by inserting spacers into the core stack. The ventilation ducts allow for the passage of cooling gas through the core during operation. The spacers or spacer posts are positioned between groups of the magnetic laminations to define the ventilation ducts. The spacer posts are secured with longitudinal axes thereof substantially parallel to the core axis. With this structure, core tightness can be assured while maximizing ventilation duct cross section for gas flow and minimizing magnetic loss in the spacers.

Carboxymethylcellulose-tetrahydrocurcumin conjugates for colon-specific delivery of a novel anti-cancer agent, 4-amino tetrahydrocurcumin.

PubMed

Plyduang, Thipapun; Lomlim, Luelak; Yuenyongsawad, Supreeya; Wiwattanapatapee, Ruedeekorn

2014-10-01

Several curcumin derivatives are now becoming increasingly of interest because of their bioactive attributes, especially their action as antioxidants and anti-carcinogenic activities. Tetrahydrocurcumin (THC), an active metabolite of curcumin, was selected to be a proper starting material for the work presented here as it is stable in physiological pH and has the typical pharmacological properties of curcumin. We have now reported that novel synthesized water-soluble polymeric macromolecule prodrugs can specifically deliver the drug to the colon. To study the drug loading and drug release, THC was conjugated with a hydrophilic polymer, carboxymethylcellulose (CMC) with the degree of substitution (DS) values of 0.7 and 1.2. THC was also attached to two different spacers including p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH) via an azo bond that was cleaved by the azoreductase activities of colonic bacteria. The novel active molecule, 4-amino-THC, was readily released from the conjugates in the colon (>62% within 24h) with only very small amounts released in the upper GI tract (<12% over 12h). The polymer conjugates showed chemical stability at various pH values along the gastrointestinal tract and increased water solubility of up to 5mg/mL. 4-Amino-THC demonstrated cytotoxic ability against the human colon adenocarcinoma cell lines (HT-29) with an IC50 of 28.67 ± 1.01 μg/mL, and even greater selectivity (∼ 4 folds) to inhibit HT-29 cells than to normal human colon epithelial cell lines while curcumin was a non-selective agent against both cell lines. Our study has demonstrated that the use of THC-CMC conjugates may be a promising colon-specific drug delivery system with its sustained release in the colon to be an effective treatment for colonic cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.

PubMed

Esmaeili, Farnaz; Dinarvand, Rassoul; Ghahremani, Mohammad Hossein; Amini, Mohsen; Rouhani, Hasti; Sepehri, Nima; Ostad, Seyed Nasser; Atyabi, Fatemeh

2009-08-01

Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer. A high-performance liquid chromatography method was developed for the determination of DTX-albumin conjugate. T47D and SKOV3 cells were used for the evaluation of the in vitro cytotoxicity of the conjugate by MTT assay. Studies were then done on balb/c mice to elucidate the tissue distribution of conjugates after intravenous administration. The albumin-conjugated formulation of DTX with the particle size of 90-110 nm showed enhanced solubility and in vivo characteristics and significantly higher cytotoxicity against tumor cells, for example, IC50 of 6.30 +/- 0.73 nM for T47D cell line compared to free DTX with IC50 of 39.4 +/- 1.75 nM. Conjugation also maintained DTX plasma level at 16.19% up to 2 h after injection compared with 2.51% for Taxotere, hence increasing the chance of nanoparticles uptake by tumor cells. Copyright 2009 Wiley-Liss, Inc.

12P-conjugated PEG-modified gold nanorods combined with near-infrared laser for tumor targeting and photothermal therapy.

PubMed

Zhan, Tao; Li, Pengfei; Bi, Shan; Dong, Biao; Song, Hongwei; Ren, Hui; Wang, Liping

2012-09-01

Gold nanorods have been reported as potential tumor photothermal therapy in vivo and in vitro. However, development of the safe and efficient tumor-targeting gold nanorods for in vivo localized tumor therapy is still a challenge. In our present study, we synthesized the PEG modified gold nanorods and demonstrated its negligible cytotoxicity in vitro. These nanorods also have been demonstrated to efficiently ablate the different kinds of tumor cells in vitro after exposure to the near-infrared laser. When the PEG modified gold nanorods conjugated with the 12P (sequence: TACHQHVRMVRP), this conjugate showed great tumor-targeting and hyperthermia effects on the human liver cancer cell line HepG2 in vitro when coupled with the near-infrared laser treatment. To determine the potential hyperthermia effect of PEG modified gold nanorods or 12P conjugate on tumor cells in vivo, the mice hepatic cancer cells were used to induce the subcutaneous tumor-bearing model in ICR mice. The significant inhibition effects of near-infrared laser mediated PEG modified gold nanorods or 12P conjugate on the tumor growth were observed. These composite results suggest that the 12P-conjugated PEG modified gold nanorods exhibit great biocompatible, particular tumor-targeting and effective photothermal ablation of tumor cells, which warrant the potential therapeutic value of this conjugate for further application in in vivo localized tumor therapy.

The interobserver-validated relevance of intervertebral spacer materials in MRI artifacting

PubMed Central

Heidrich, G.; Bruening, T.; Krefft, S.; Buchhorn, G.; Klinger, H.M.

2006-01-01

Intervertebral spacers for anterior spine fusion are made of different materials, such as titanium, carbon or cobalt-chrome, which can affect the post-fusion MRI scans. Implant-related susceptibility artifacts can decrease the quality of MRI scans, thwarting proper evaluation. This cadaver study aimed to demonstrate the extent that implant-related MRI artifacting affects the post-fusion evaluation of intervertebral spacers. In a cadaveric porcine spine, we evaluated the post-implantation MRI scans of three intervertebral spacers that differed in shape, material, surface qualities and implantation technique. A spacer made of human cortical bone was used as a control. The median sagittal MRI slice was divided into 12 regions of interest (ROI). No significant differences were found on 15 different MRI sequences read independently by an interobserver-validated team of specialists (P>0.05). Artifact-affected image quality was rated on a score of 0-1-2. A maximum score of 24 points (100%) was possible. Turbo spin echo sequences produced the best scores for all spacers and the control. Only the control achieved a score of 100%. The carbon, titanium and cobalt-chrome spacers scored 83.3, 62.5 and 50%, respectively. Our scoring system allowed us to create an implant-related ranking of MRI scan quality in reference to the control that was independent of artifact dimensions. The carbon spacer had the lowest percentage of susceptibility artifacts. Even with turbo spin echo sequences, the susceptibility artifacts produced by the metallic spacers showed a high degree of variability. Despite optimum sequencing, implant design and material are relevant factors in MRI artifacting. PMID:16463200

Splicing of a group II intron involved in the conjugative transfer of pRS01 in lactococci.

PubMed

Mills, D A; McKay, L L; Dunny, G M

1996-06-01

Analysis of a region involved in the conjugative transfer of the lactococcal conjugative element pRS01 has revealed a bacteria] group II intron. Splicing of this lactococcal intron (designated Ll.ltrB) in vivo resulted in the ligation of two exon messages (ltrBE1 and ltrBE2) which encoded a putative conjugative relaxase essential for the transfer of pRS01. Like many group II introns, the Ll.ltrB intron possessed an open reading frame (ltrA) with homology to reverse transcriptases. Remarkably, sequence analysis of ltrA suggested a greater similarity to open reading frames encoded by eukaryotic mitochondrial group II introns than to those identified to date from other bacteria. Several insertional mutations within ltrA resulted in plasmids exhibiting a conjugative transfer-deficient phenotype. These results provide the first direct evidence for splicing of a prokaryotic group II intron in vivo and suggest that conjugative transfer is a mechanism for group II intron dissemination in bacteria.

Band-selective filter in a zigzag graphene nanoribbon.

PubMed

Nakabayashi, Jun; Yamamoto, Daisuke; Kurihara, Susumu

2009-02-13

Electric transport of a zigzag graphene nanoribbon through a steplike potential and a barrier potential is investigated by using the recursive Green's function method. In the case of the steplike potential, we demonstrate numerically that scattering processes obey a selection rule for the band indices when the number of zigzag chains is even; the electrons belonging to the "even" ("odd") bands are scattered only into the even (odd) bands so that the parity of the wave functions is preserved. In the case of the barrier potential, by tuning the barrier height to be an appropriate value, we show that it can work as the "band-selective filter", which transmits electrons selectively with respect to the indices of the bands to which the incident electrons belong. Finally, we suggest that this selection rule can be observed in the conductance by applying two barrier potentials.

The Bacillus subtilis Conjugative Plasmid pLS20 Encodes Two Ribbon-Helix-Helix Type Auxiliary Relaxosome Proteins That Are Essential for Conjugation.

PubMed

Miguel-Arribas, Andrés; Hao, Jian-An; Luque-Ortega, Juan R; Ramachandran, Gayetri; Val-Calvo, Jorge; Gago-Córdoba, César; González-Álvarez, Daniel; Abia, David; Alfonso, Carlos; Wu, Ling J; Meijer, Wilfried J J

2017-01-01

Bacterial conjugation is the process by which a conjugative element (CE) is transferred horizontally from a donor to a recipient cell via a connecting pore. One of the first steps in the conjugation process is the formation of a nucleoprotein complex at the origin of transfer ( oriT ), where one of the components of the nucleoprotein complex, the relaxase, introduces a site- and strand specific nick to initiate the transfer of a single DNA strand into the recipient cell. In most cases, the nucleoprotein complex involves, besides the relaxase, one or more additional proteins, named auxiliary proteins, which are encoded by the CE and/or the host. The conjugative plasmid pLS20 replicates in the Gram-positive Firmicute bacterium Bacillus subtilis . We have recently identified the relaxase gene and the oriT of pLS20, which are separated by a region of almost 1 kb. Here we show that this region contains two auxiliary genes that we name aux1 LS20 and aux2 LS20 , and which we show are essential for conjugation. Both Aux1 LS20 and Aux2 LS20 are predicted to contain a Ribbon-Helix-Helix DNA binding motif near their N-terminus. Analyses of the purified proteins show that Aux1 LS20 and Aux2 LS20 form tetramers and hexamers in solution, respectively, and that they both bind preferentially to oriT LS20 , although with different characteristics and specificities. In silico analyses revealed that genes encoding homologs of Aux1 LS20 and/or Aux2 LS20 are located upstream of almost 400 relaxase genes of the Rel LS20 family (MOB L ) of relaxases. Thus, Aux1 LS20 and Aux2 LS20 of pLS20 constitute the founding member of the first two families of auxiliary proteins described for CEs of Gram-positive origin.

Redox-Enabled, pH-Disabled Pyrazoline-Ferrocene INHIBIT Logic Gates.

PubMed

Scerri, Glenn J; Cini, Miriam; Schembri, Jonathan S; da Costa, Paola F; Johnson, Alex D; Magri, David C

2017-07-05

Pyrazoline-ferrocene conjugates with an "electron-donor-spacer-fluorophore-receptor" format are demonstrated as redox-fluorescent two-input INHIBIT logic gates. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Charge Transport in 4 nm Molecular Wires with Interrupted Conjugation: Combined Experimental and Computational Evidence for Thermally Assisted Polaron Tunneling.

PubMed

Taherinia, Davood; Smith, Christopher E; Ghosh, Soumen; Odoh, Samuel O; Balhorn, Luke; Gagliardi, Laura; Cramer, Christopher J; Frisbie, C Daniel

2016-04-26

We report the synthesis, transport measurements, and electronic structure of conjugation-broken oligophenyleneimine (CB-OPI 6) molecular wires with lengths of ∼4 nm. The wires were grown from Au surfaces using stepwise aryl imine condensation reactions between 1,4-diaminobenzene and terephthalaldehyde (1,4-benzenedicarbaldehyde). Saturated spacers (conjugation breakers) were introduced into the molecular backbone by replacing the aromatic diamine with trans-1,4-diaminocyclohexane at specific steps during the growth processes. FT-IR and ellipsometry were used to follow the imination reactions on Au surfaces. Surface coverages (∼4 molecules/nm(2)) and electronic structures of the wires were determined by cyclic voltammetry and UV-vis spectroscopy, respectively. The current-voltage (I-V) characteristics of the wires were acquired using conducting probe atomic force microscopy (CP-AFM) in which an Au-coated AFM probe was brought into contact with the wires to form metal-molecule-metal junctions with contact areas of ∼50 nm(2). The low bias resistance increased with the number of saturated spacers, but was not sensitive to the position of the spacer within the wire. Temperature dependent measurements of resistance were consistent with a localized charge (polaron) hopping mechanism in all of the wires. Activation energies were in the range of 0.18-0.26 eV (4.2-6.0 kcal/mol) with the highest belonging to the fully conjugated OPI 6 wire and the lowest to the CB3,5-OPI 6 wire (the wire with two saturated spacers). For the two other wires with a single conjugation breaker, CB3-OPI 6 and CB5-OPI 6, activation energies of 0.20 eV (4.6 kcal/mol) and 0.21 eV (4.8 kcal/mol) were found, respectively. Computational studies using density functional theory confirmed the polaronic nature of charge carriers but predicted that the semiclassical activation energy of hopping should be higher for CB-OPI molecular wires than for the OPI 6 wire. To reconcile the experimental and

Structure of p73 DNA-binding domain tetramer modulates p73 transactivation

PubMed Central

Ethayathulla, Abdul S.; Tse, Pui-Wah; Monti, Paola; Nguyen, Sonha; Inga, Alberto; Fronza, Gilberto; Viadiu, Hector

2012-01-01

The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation. PMID:22474346

Study on zigzag maneuver characteristics of V-U very large crude oil (VLCC) tankers

NASA Astrophysics Data System (ADS)

Jaswar, Maimun, A.; Wahid, M. A.; Priyanto, A.; Zamani, Pauzi, Saman

2012-06-01

The Department of Marine Technology at the Faculty of Mechanical Engineering, University Teknologi Malaysia has recently developed an Ship Maneuverability tool which intends to upgrade student's level understanding the application of fluid dynamic on interaction between hull, propeller, and rudder during maneuvering. This paper discusses zigzag maneuver for conventional Very Large Crude Oil (VLCC) ships with the same principal dimensions but different stern flame shape. 10/10 zigzag maneuver characteristics of U and V types of VLCC ships are investigated. Simulation results for U-type show a good agreement with the experimental data, but V-type not good agreement with experimental one. Further study on zigzag maneuver characteristics are required.

MDI with DIY Spacer versus Nebulizer for Bronchodilator Therapy in Children Admitted with Asthmatic Attack.

PubMed

Leelathipkul, Lalit; Tanticharoenwiwat, Pattara; Ithiawatchakul, Jutinan; Prommin, Danu; Sirisalee, Pasu; Junhunee, Parinya; Poachanukoon, Orapan

2016-07-01

Inhaled bronchodilator treatment given via the pressurized metered-dose inhaler (pMDI) with spacer has been recommended for an acute asthma treatment. Unfortunately, most of commercially available spacers are at high cost while a do-it-yourself (DIY) spacer has lower cost as it is made from plastic bottle and siphon pump which are inexpensive and easilyfound materials. This study aims to compare treatment response in nebulizer and DIY spacer used for asthmatic children. A prospective, randomized control study was conducted in children aged 1-15 years old hospitalized for mild to moderate asthmatic attack at Thammasat University Hospital between June 2014 and March 2015. The patients were divided into 2 groups, receiving β2-agonist via nebulization and via pMDI with DIY spacer. Their vital signs and oxygen saturation were monitored and asthma scores were also recorded at admission, 24 hours, 48 hours, and before discharge. The satisfaction of equipment use was evaluated employing questionnaires. 40 childrens were enrolled with male at 72.5% and mean age at 3.1±1.6 years old. There was no significant difference in efficacy of β2-agonist among 2 groups when comparing in consideration of vital signs, oximetry, asthma scores and hospital stay. However, there were significantly different on side effect in which the DIY spacer had less tachycardia and agitation. Satisfaction of parents and healthcare workers were higher in DIY spacer. MDI with DIY spacer was able to be used effectively when compared with nebulization to treat mild to moderate acute exacerbations of asthma in children admitted in hospital.

Optimal number of spacers in CRISPR arrays

PubMed Central

Severinov, Konstantin; Ispolatov, Iaroslav

2017-01-01

Prokaryotic organisms survive under constant pressure of viruses. CRISPR-Cas system provides its prokaryotic host with an adaptive immune defense against viruses that have been previously encountered. It consists of two components: Cas-proteins that cleave the foreign DNA and CRISPR array that suits as a virus recognition key. CRISPR array consists of a series of spacers, short pieces of DNA that originate from and match the corresponding parts of viral DNA called protospacers. Here we estimate the number of spacers in a CRISPR array of a prokaryotic cell which maximizes its protection against a viral attack. The optimality follows from a competition between two trends: too few distinct spacers make host vulnerable to an attack by a virus with mutated corresponding protospacers, while an excessive variety of spacers dilutes the number of the CRISPR complexes armed with the most recent and thus most useful spacers. We first evaluate the optimal number of spacers in a simple scenario of an infection by a single viral species and later consider a more general case of multiple viral species. We find that depending on such parameters as the concentration of CRISPR-Cas interference complexes and its preference to arm with more recently acquired spacers, the rate of viral mutation, and the number of viral species, the predicted optimal number of spacers lies within a range that agrees with experimentally-observed values. PMID:29253874

Cervical interfacet spacers and maintenance of cervical lordosis.

PubMed

Tan, Lee A; Straus, David C; Traynelis, Vincent C

2015-05-01

OBJECT The cervical interfacet spacer (CIS) is a relatively new technology that can increase foraminal height and area by facet distraction. These offer the potential to provide indirect neuroforaminal decompression while simultaneously enhancing fusion potential due to the relatively large osteoconductive surface area and compressive forces exerted on the grafts. These potential benefits, along with the relative ease of implantation during posterior cervical fusion procedures, make the CIS an attractive adjuvant in the management of cervical pathology. One concern with the use of interfacet spacers is the theoretical risk of inducing iatrogenic kyphosis. This work tests the hypothesis that interfacet spacers are associated with loss of cervical lordosis. METHODS Records from patients undergoing posterior cervical fusion at Rush University Medical Center between March 2011 and December 2012 were reviewed. The FacetLift CISs were used in all patients. Preoperative and postoperative radiographic data were reviewed and the Ishihara indices and cervical lordotic angles were measured and recorded. Statistical analyses were performed using STATA software. RESULTS A total of 64 patients were identified in whom 154 cervical levels were implanted with machined allograft interfacet spacers. Of these, 15 patients underwent anterior-posterior fusions, 4 underwent anterior-posterior-anterior fusions, and the remaining 45 patients underwent posterior-only fusions. In the 45 patients with posterior-only fusions, a total of 110 levels were treated with spacers. There were 14 patients (31%) with a single level treated, 16 patients (36%) with two levels treated, 5 patients (11%) with three levels treated, 5 patients (11%) with four levels treated, 1 patient (2%) with five levels treated, and 4 patients (9%) with six levels treated. Complete radiographic data were available in 38 of 45 patients (84%). On average, radiographic follow-up was obtained at 256.9 days (range 48-524 days

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH

PubMed Central

Bandyopadhyay, Anupam

2015-01-01

Bioorthogonal reactions that are fast and reversible under physiologic conditions are in high demand for biological applications. Herein, we show that an ortho boronic acid substituent makes aryl ketones to rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 102 to 103 M−1 s−1, comparable to the fastest bioorthogonal conjugations known to date. 11B-NMR analysis reveals varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiologic conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. PMID:26311464

Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

PubMed

Zhou, Zilan; Badkas, Apurva; Stevenson, Max; Lee, Joo-Youp; Leung, Yuet-Kin

2015-06-20

A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel tumor-targeted RGD peptide-camptothecin conjugates: synthesis and biological evaluation.

PubMed

Dal Pozzo, Alma; Ni, Ming-Hong; Esposito, Emiliano; Dallavalle, Sabrina; Musso, Loana; Bargiotti, Alberto; Pisano, Claudio; Vesci, Loredana; Bucci, Federica; Castorina, Massimo; Foderà, Rosanna; Giannini, Giuseppe; Aulicino, Concetta; Penco, Sergio

2010-01-01

Five RGD peptide-camptothecin (CPT) conjugates were designed and synthesized with the purpose to improve the therapeutic index of this antitumoral drug family. New RGD cyclopeptides were selected on the basis of their high affinity to alpha(v) integrin receptors overexpressed by tumor cells and their metabolic stability. The conjugates can be divided in two groups: in the first the peptide was attached to the drug through an amide bond, in the second through a hydrazone bond. The main difference between the two spacers lies in their acid stability. Affinity to the receptors was maintained for all conjugates and their internalization into tumor cells was demonstrated. The first group conjugates showed lower in vitro and in vivo activity than the parent drug, probably due to the excessive stability of the amide bond, even inside the tumor cells. Conversely, the hydrazone conjugates exhibited in vitro tumor cell inhibition similar to the parent drug, indicating high conversion in the culture medium and/or inside the cells, but their poor solubility hampered in vivo experiments. On the basis of these results, information was acquired for additional development of derivatives with different linkers and better solubility for in vivo evaluation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Comparison of dual-k spacer and single-k spacer for single NWFET and 3-stack NWFET

NASA Astrophysics Data System (ADS)

Ko, Hyungwoo; Kim, Jongsu; Kim, Minsoo; Kang, Myounggon; Shin, Hyungcheol

2018-02-01

The investigation of the Dual-k spacer through comparative analysis of single nanowire-FET(NWFET)/3-stack NWFET and underlap/overlap channel is conducted. It is known that the dug 3-stack NWFET has better delay characteristics than single NWFET with the use of high permittivity material of Cin in Dual-k spacer structure. In addition, there is no difference of delay between overlap and underlap channel when it used Dual-k spacer structure but underlap channel of Dual-k 3-stack NWFET shows better short channel immunity.

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

PubMed

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

Plasmid DNA-encapsulating liposomes: effect of a spacer between the cationic head group and hydrophobic moieties of the lipids on gene expression efficiency.

PubMed

Obata, Yosuke; Saito, Shunsuke; Takeda, Naoya; Takeoka, Shinji

2009-05-01

We have synthesized a series of cationic amino acid-based lipids having a spacer between the cationic head group and hydrophobic moieties and examined the influence of the spacer on a liposome gene delivery system. As a comparable spacer, a hydrophobic spacer with a hydrocarbon chain composed of 0, 3, 5, 7, or 11 carbons, and a hydrophilic spacer with an oxyethylene chain (10 carbon and 3 oxygen molecules) were investigated. Plasmid DNA (pDNA)-encapsulating liposomes were prepared by mixing an ethanol solution of the lipids with an aqueous solution of pDNA. The zeta potentials and cellular uptake efficiency of the cationic liposomes containing each synthetic lipid were almost equivalent. However, the cationic lipids with the hydrophobic spacer were subject to fuse with biomembrane-mimicking liposomes. 1,5-Dihexadecyl-N-lysyl-N-heptyl-l-glutamate, having a seven carbon atom spacer, exhibited the highest fusogenic potential among the synthetic lipids. Increased fusion potential correlated with enhanced gene expression efficiency. By contrast, an oxyethylene chain spacer showed low gene expression efficiency. We conclude that a hydrophobic spacer between the cationic head group and hydrophobic moieties is a key component for improving pDNA delivery.

Success of Two-Stage Reimplantation in Patients Requiring an Interim Spacer Exchange.

PubMed

George, Jaiben; Miller, Evan M; Curtis, Gannon L; Klika, Alison K; Barsoum, Wael K; Mont, Michael A; Higuera, Carlos A

2018-03-23

Some patients undergoing a 2-stage revision for a periprosthetic joint infection require a repeat spacer in the interim (removal of existing spacer with insertion of a new spacer or spacer exchange) due to persistent infection. The objectives of this study are to (1) determine the factors associated with patients who receive a repeat spacer and (2) compare the infection-free survival (overall and stratified by joint type) of reimplantation in patients who did or did not receive a repeat spacer. From 2001 to 2014, 347 hip or knee 2-stage revisions that finally underwent reimplantation and had a minimum 2-year follow-up were identified. An interim spacer exchange was performed in 59 (17%) patients (exchange cohort). Patient-related and organism-related factors were compared between the exchange and non-exchange cohorts. Kaplan-Meier survival curves were performed to assess the success (absence of signs of infection, reoperation for infection, periprosthetic joint infection-related mortality) of both cohorts. Patients in the exchange group had higher comorbidity score (P = .020), prolonged time to reimplantation (P < .001), and higher prevalence of resistant organisms, though not statistically significant (P = .091). The 5-year infection-free survival rates were 64% (knee 62%, hip 64%) in the exchange cohort, and 78% (knee 77%, hip 78%) in the non-exchange cohort (P = .020). Patients requiring an interim spacer exchange were found to have more comorbidities, prolonged treatment period, and were more likely to be infected with a resistant organism. About one-third of such patients became reinfected within 5 years compared to only one-fifth of the patients without an interim spacer exchange. Copyright © 2018 Elsevier Inc. All rights reserved.

Thermally induced spin-dependent current based on Zigzag Germanene Nanoribbons

NASA Astrophysics Data System (ADS)

Majidi, Danial; Faez, Rahim

2017-02-01

In this paper, using first principle calculation and non-equilibrium Green's function, the thermally induced spin current in Hydrogen terminated Zigzag-edge Germanene Nanoribbon (ZGeNR-H) is investigated. In this model, because of the difference between the source and the drain temperature of ZGeNR device, the spin up and spin down currents flow in the opposite direction with two different threshold temperatures (Tth). Hence, a pure spin polarized current which belongs to spin down is obtained. It is shown that, for temperatures above the threshold temperature spin down current increases with the increasing temperature up to 75 K and then decreases. But spin up current rises steadily and in the high temperature we can obtain polarized spin up current. In addition, we show an acceptable spin current around the room temperature for ZGeNR. The transmission peaks in ZGeNR which are closer to the Fermi level rather than Zigzag Graphene Nanoribbon (ZGNRS) which causes ZGeNR to have spin current at higher temperatures. Finally, it is indicated that by tuning the back gate voltage, the spin current can be completely modulated and polarized. Simulation results verify the Zigzag Germanene Nanoribbon as a promising candidate for spin caloritronics devices, which can be applied in future low power consumption technology.

Spacer effect on nanostructures and self-assembly in organogels via some bolaform cholesteryl imide derivatives with different spacers

PubMed Central

2013-01-01

In this paper, new bolaform cholesteryl imide derivatives with different spacers were designed and synthesized. Their gelation behaviors in 23 solvents were investigated, and some of them were found to be low molecular mass organic gelators. The experimental results indicated that these as-formed organogels can be regulated by changing the flexible/rigid segments in spacers and organic solvents. Suitable combination of flexible/rigid segments in molecular spacers in the present cholesteryl gelators is favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle and belt to fiber with the change of spacers and solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes, depending on the substituent spacers in molecular skeletons. The present work may give some insight into the design and character of new organogelators and soft materials with special molecular structures. PMID:24083361

Spacer effect on nanostructures and self-assembly in organogels via some bolaform cholesteryl imide derivatives with different spacers

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Gao, Fengqing; Zhang, Qingrui; Zhou, Jingxin; Gao, Faming

2013-10-01

In this paper, new bolaform cholesteryl imide derivatives with different spacers were designed and synthesized. Their gelation behaviors in 23 solvents were investigated, and some of them were found to be low molecular mass organic gelators. The experimental results indicated that these as-formed organogels can be regulated by changing the flexible/rigid segments in spacers and organic solvents. Suitable combination of flexible/rigid segments in molecular spacers in the present cholesteryl gelators is favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle and belt to fiber with the change of spacers and solvents. Spectral studies indicated that there existed different H-bond formations between imide groups and assembly modes, depending on the substituent spacers in molecular skeletons. The present work may give some insight into the design and character of new organogelators and soft materials with special molecular structures.

Application of the Refined Zigzag Theory to the Modeling of Delaminations in Laminated Composites

NASA Technical Reports Server (NTRS)

Groh, Rainer M. J.; Weaver, Paul M.; Tessler, Alexander

2015-01-01

The Refined Zigzag Theory is applied to the modeling of delaminations in laminated composites. The commonly used cohesive zone approach is adapted for use within a continuum mechanics model, and then used to predict the onset and propagation of delamination in five cross-ply composite beams. The resin-rich area between individual composite plies is modeled explicitly using thin, discrete layers with isotropic material properties. A damage model is applied to these resin-rich layers to enable tracking of delamination propagation. The displacement jump across the damaged interfacial resin layer is captured using the zigzag function of the Refined Zigzag Theory. The overall model predicts the initiation of delamination to within 8% compared to experimental results and the load drop after propagation is represented accurately.

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.

PubMed

Bandyopadhyay, Anupam; Gao, Jianmin

2015-10-12

Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene delivery

PubMed Central

Sawant, Rupa R.; Sriraman, Shravan Kumar; Navarro, Gemma; Biswas, Swati; Dalvi, Riddhi A.; Torchilin, Vladimir P.

2012-01-01

A low molecular weight polyethyleneimine (PEI 1.8 kDa) was modified with dioleoylphosphatidylethanolamine (PE) to form the PEI-PE conjugate investigated as a transfection vector. The optimized PEI-PE/pDNA complexes at an N/P ratio of 16 had a particle size of 225 nm, a surface charge of +31 mV, and protected the pDNA from the action of DNase I. The PEI-PE conjugate had a critical micelle concentration (CMC) of about 34 μg/ml and exhibited no toxicity compared to a high molecular weight PEI (PEI 25 kDa) as tested with B16-F10 melanoma cells. The B16-F10 cells transfected with PEI-PE/pEGFP complexes showed protein expression levels higher than with PEI-1.8 or PEI-25 vectors. Complexes prepared with YOYO 1-labeled pEGFP confirmed the enhanced delivery of the plasmid with PEI-PE compared to PEI-1.8 and PEI-25. The PEI-PE/pDNA complexes were also mixed with various amounts of micelle-forming material, polyethylene glycol (PEG)-PE to improve biocompatibility. The resulting particles exhibited a neutral surface charge, resistance to salt-induced aggregation, and good transfection activity in the presence of serum in complete media. The use of the low-pH-degradable PEG-hydrazone-PE produced particles with transfection activity sensitive to changes in pH consistent with the relatively acidic tumor environment. PMID:22365809

Intensity Modulated Proton and Photon Therapy for Early Prostate Cancer With or Without Transperineal Injection of a Polyethylen Glycol Spacer: A Treatment Planning Comparison Study

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

Weber, Damien C., E-mail: damien.weber@unige.ch; Zilli, Thomas; Vallee, Jean Paul

2012-11-01

Purpose: Rectal toxicity is a serious adverse effect in early-stage prostate cancer patients treated with curative radiation therapy (RT). Injecting a spacer between Denonvilliers' fascia increases the distance between the prostate and the anterior rectal wall and may thus decrease the rectal radiation-induced toxicity. We assessed the dosimetric impact of this spacer with advanced delivery RT techniques, including intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton beam RT (IMPT). Methods and Materials: Eight prostate cancer patients were simulated for RT with or without spacer. Plans were computed for IMRT, VMAT, and IMPT using the Eclipsemore » treatment planning system using both computed tomography spacer+ and spacer- data sets. Prostate {+-} seminal vesicle planning target volume [PTV] and organs at risk (OARs) dose-volume histograms were calculated. The results were analyzed using dose and volume metrics for comparative planning. Results: Regardless of the radiation technique, spacer injection decreased significantly the rectal dose in the 60- to 70-Gy range. Mean V{sub 70Gy} and V{sub 60Gy} with IMRT, VMAT, and IMPT planning were 5.3 {+-} 3.3%/13.9 {+-} 10.0%, 3.9 {+-} 3.2%/9.7 {+-} 5.7%, and 5.0 {+-} 3.5%/9.5 {+-} 4.7% after spacer injection. Before spacer administration, the corresponding values were 9.8 {+-} 5.4% (P=.012)/24.8 {+-} 7.8% (P=.012), 10.1 {+-} 3.0% (P=.002)/17.9 {+-} 3.9% (P=.003), and 9.7 {+-} 2.6% (P=.003)/14.7% {+-} 2.7% (P=.003). Importantly, spacer injection usually improved the PTV coverage for IMRT. With this technique, mean V{sub 70.2Gy} (P=.07) and V{sub 74.1Gy} (P=0.03) were 100 {+-} 0% to 99.8 {+-} 0.2% and 99.1 {+-} 1.2% to 95.8 {+-} 4.6% with and without Spacer, respectively. As a result of spacer injection, bladder doses were usually higher but not significantly so. Only IMPT managed to decrease the rectal dose after spacer injection for all dose levels, generally with no

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone.

PubMed

Piras, Anna Maria; Zambito, Ylenia; Burgalassi, Susi; Monti, Daniela; Tampucci, Silvia; Terreni, Eleonora; Fabiano, Angela; Balzano, Federica; Uccello-Barretta, Gloria; Chetoni, Patrizia

2018-03-30

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

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.

Direction-dependent waist-shift-difference of Gaussian beam in a multiple-pass zigzag slab amplifier and geometrical optics compensation method.

PubMed

Li, Zhaoyang; Kurita, Takashi; Miyanaga, Noriaki

2017-10-20

Zigzag and non-zigzag beam waist shifts in a multiple-pass zigzag slab amplifier are investigated based on the propagation of a Gaussian beam. Different incident angles in the zigzag and non-zigzag planes would introduce a direction-dependent waist-shift-difference, which distorts the beam quality in both the near- and far-fields. The theoretical model and analytical expressions of this phenomenon are presented, and intensity distributions in the two orthogonal planes are simulated and compared. A geometrical optics compensation method by a beam with 90° rotation is proposed, which not only could correct the direction-dependent waist-shift-difference but also possibly average the traditional thermally induced wavefront-distortion-difference between the horizontal and vertical beam directions.

Charge transport in doped zigzag phosphorene nanoribbons

NASA Astrophysics Data System (ADS)

Nourbakhsh, Zahra; Asgari, Reza

2018-06-01

The effects of lattice distortion and chemical disorder on charge transport properties of two-terminal zigzag phosphorene nanoribbons (zPNRs), which shows resonant tunneling behavior under an electrical applied bias, are studied. Our comprehensive study is based on ab initio quantum transport calculations on the basis of the Landauer theory. We use nitrogen and silicon substitutional dopant atoms, and employ different physical quantities such as the I -V curve, voltage drop behavior, transmission spectrum, transmission pathway, and atomic current to explore the transport mechanism of zPNR devices under a bias voltage. The calculated transmission pathways show the transition from a ballistic transport regime to a diffusive and in some particular cases to localized transport regimes. Current flowing via the chemical bonds and hopping are monitored; however, the conductance originates mainly from the charge traveling through the chemical bonds in the vicinity of the zigzag edges. Our results show that in the doped systems, the device conductance decreases and the negative differential resistance characteristic becomes weak or is eliminated. Besides, the conductance in a pure zPNR system is almost independent of the ribbon width.

Impact of a protective vest and spacer garment on exercise-heat strain.

PubMed

Cheuvront, Samuel N; Goodman, Daniel A; Kenefick, Robert W; Montain, Scott J; Sawka, Michael N

2008-03-01

Protective vests worn by global security personnel, and weighted vests worn by athletes, may increase physiological strain due to added load, increased clothing insulation and vapor resistance. The impact of protective vest clothing properties on physiological strain, and the potential of a spacer garment to reduce physiological strain, was examined. Eleven men performed 3 trials of intermittent treadmill walking over 4 h in a hot, dry environment (35 degrees C, 30% rh). Volunteers wore the US Army battledress uniform (trial B), B + protective vest (trial P), and B + P + spacer garment (trial S). Biophysical clothing properties were determined and found similar to many law enforcement, industry, and sports ensembles. Physiological measurements included core (T (c)), mean skin (T (sk)) and chest (T (chest)) temperatures, heart rate (HR), and sweating rate (SR). The independent impact of clothing was determined by equating metabolic rate in all trials. In trial P, HR was +7 b/min higher after 1 h of exercise and +19 b/min by the fourth hour compared to B (P < 0.05). T (c) (+0.30 degrees C), T (sk) (+1.0 degrees C) and Physiological Strain Index were all higher in P than B (P < 0.05). S did not abate these effects except to reduce T (sk) (P > S) via a lower T (chest) (-0.40 degrees C) (P < 0.05). SR was higher (P < 0.05) in P and S versus B, but the magnitude of differences was small. A protective vest increases physiological strain independent of added load, while a spacer garment does not alter this outcome.

Polymeric anticancer drugs with pH-controlled activation.

PubMed

Ulbrich, Karel; Subr, Vladimír

2004-04-23

Use of macromolecular water-soluble carriers of anti-cancer drugs represents a promising approach to cancer therapy. Release of drugs from the carrier system is a prerequisite for therapeutic activity of most macromolecular anti-cancer conjugates. Incorporation of acid-sensitive spacers between the drug and carrier enables release of an active drug from the carrier in a tumor tissue, either in slightly acidic extracellular fluids or, after endocytosis, in endosomes or lysosomes of cancer cells. This paper reviews advances in development and study of properties of various acid-sensitive macromolecular drug delivery systems, starting from simple polymer-drug conjugates to ending with site-specific antibody-targeted polymer-drug conjugates.

The ribosomal gene spacer region in archaebacteria

NASA Technical Reports Server (NTRS)

Achenbach-Richter, L.; Woese, C. R.

1988-01-01

Sequences for the spacer regions that separate the 16S and 23S ribosomal RNA genes have been determined for four more (strategically placed) archaebacteria. These confirm the general rule that methanogens and extreme halophiles have spacers that contain a single tRNAala gene, while tRNA genes are not found in the spacer region of the true extreme thermophiles. The present study also shows that the spacer regions from the sulfate reducing Archaeglobus and the extreme thermophile Thermococcus (both of which cluster phylogenetically with the methanogens and extreme halophiles) contain each a tRNAala gene. Thus, not only all methanogens and extreme halophiles show this characteristic, but all organisms on the "methanogen branch" of the archaebacterial tree appear to do so. The finding of a tRNA gene in the spacer region of the extreme thermophile Thermococcus celer is the first known phenotypic property that links this organism with its phylogenetic counterparts, the methanogens, rather than with its phenotypic counterparts, the sulfur-dependent extreme thermophiles.

Anti-P-glycoprotein conjugated nanoparticles for targeting drug delivery in cancer treatment.

PubMed

Iangcharoen, Pantiwa; Punfa, Wanisa; Yodkeeree, Supachai; Kasinrerk, Watchara; Ampasavate, Chadarat; Anuchapreeda, Songyot; Limtrakul, Pornngarm

2011-10-01

Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB-3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane.

Synthesis and characterization of silver nanowires with zigzag morphology in N, N-dimethylformamide

NASA Astrophysics Data System (ADS)

He, Xin; Zhao, Xiujian; Chen, Yunxia; Feng, Jinyang; Sun, Zhenya

2007-08-01

Zigzag silver nanowires with a uniform diameter of 20±5 nm were prepared by reducing silver nitrate (AgNO 3) with N, N-dimethylformamide (DMF) in the presence of tetrabutyl titanate (TBT) and acetylacetone (AcAc) at 373 K for 18 h. X-ray and selected area electron diffraction (XRD and SAED) patterns reveal that the prepared product is made of pure silver with face centered cubic structure. Transmission electron microscopy (TEM) investigations suggest that the amount of silver nanowires is enhanced with increase in reaction time, and the end-to-end assemblies of silver nanorods are observed during the reaction process. After 18 h reaction, silver nanowires with zigzag morphology are obtained. In this paper, a possible growth process of silver nanowires with this interesting shape is described. Silver nanoparticles with small sizes were obtained by reducing Ag + ions with DMF, providing seeds for homogeneous growth of silver nanorods. With the extending reaction time, the synthesized silver nanorods were connected in an end-to-end manner, and the interface between the connections of two nanorods gradually disappeared. The final product shows zigzag morphology with various angles. The angles between two connecting straight parts of zigzag nanowires exhibit an alterable range of 74-151°. These silver nanowires show tremendous potential applications in future nanoscale electronic circuits.

pH dependent conjugation of Ibuprofen to PEGylated nanoparticles

NASA Astrophysics Data System (ADS)

Bharti, Shivani; Jain, Shikshita; Kaur, Gurvir; Gupta, Shikha; Tripathi, S. K.

2018-04-01

In this paper, Ibuprofen, a water insoluble drug was covalently attached to PEGylated nanoparticles. Firstly, Surface functionalization of water dispersed core/shell nanoparticles had been done using hydrophilic polymer PEG-diamine. Therefore, PEGylated nanoparticles contain NH2 groups over the surface of nanoparticles and can be used for the further attachment of biomolecules. Ibuprofen was covalently loaded on the PEGylated core/shell nanoparticles using carbodiimide reaction. The synthesis had been carried out under two different pH environments, as the solubility of Ibuprofen is pH dependent. The resultant samples were characterized using UV-Vis absorption and FT-IR spectroscopy. The results strongly suggest the successful chemical conjugation of Ibuprofen to PEGylated nanoparticles in aqueous media and they could be further used for drug delivery applications.

Functionalized Congeners of P2Y1 Receptor Antagonists:

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

de Castro, Sonia; Maruoka, Hiroshi; Hong, Kunlun

2010-01-01

The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of anmore » intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM

Control of the hierarchical assembly of π-conjugated optoelectronic peptides by pH and flow

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

Mansbach, Rachael A.; Ferguson, Andrew L.

Self-assembled nanoaggregates of p-conjugated peptides possess optoelectronic properties due to electron delocalization over the conjugated peptide groups that make them attractive candidates for the fabrication of bioelectronic materials. We present a computational and theoretical study to resolve the microscopic effects of pH and flow on the non-equilibrium morphology and kinetics of early-stage assembly of an experimentally-realizable optoelectronic peptide that displays pH triggerable assembly. Employing coarse-grained molecular dynamics simulations, we probe the effects of pH on growth kinetics and aggregate morphology to show that control of the peptide protonation state by pH can be used to modulate the assembly rates, degreemore » of molecular alignment, and resulting morphologies within the self-assembling nanoaggregates. We also quantify the time and length scales at which convective flows employed in directed assembly compete with microscopic diffusion to show that flow influences cluster alignment and assembly rate during early-stage assembly only at extremely high shear rates. This suggests that observed improvements in optoelectronic properties at experimentally-accessible shear rates are due to the alignment of large aggregates of hundreds of monomers on time scales in excess of hundreds of nanoseconds. Lastly, our work provides new fundamental understanding of the effects of pH and flow to control the morphology and kinetics of early-stage assembly of p-conjugated peptides and lays the groundwork for the rational manipulation of environmental conditions to direct assembly and the attendant emergent optoelectronic properties.« less

Control of the hierarchical assembly of π-conjugated optoelectronic peptides by pH and flow

DOE PAGES

Mansbach, Rachael A.; Ferguson, Andrew L.

2017-01-01

Self-assembled nanoaggregates of p-conjugated peptides possess optoelectronic properties due to electron delocalization over the conjugated peptide groups that make them attractive candidates for the fabrication of bioelectronic materials. We present a computational and theoretical study to resolve the microscopic effects of pH and flow on the non-equilibrium morphology and kinetics of early-stage assembly of an experimentally-realizable optoelectronic peptide that displays pH triggerable assembly. Employing coarse-grained molecular dynamics simulations, we probe the effects of pH on growth kinetics and aggregate morphology to show that control of the peptide protonation state by pH can be used to modulate the assembly rates, degreemore » of molecular alignment, and resulting morphologies within the self-assembling nanoaggregates. We also quantify the time and length scales at which convective flows employed in directed assembly compete with microscopic diffusion to show that flow influences cluster alignment and assembly rate during early-stage assembly only at extremely high shear rates. This suggests that observed improvements in optoelectronic properties at experimentally-accessible shear rates are due to the alignment of large aggregates of hundreds of monomers on time scales in excess of hundreds of nanoseconds. Lastly, our work provides new fundamental understanding of the effects of pH and flow to control the morphology and kinetics of early-stage assembly of p-conjugated peptides and lays the groundwork for the rational manipulation of environmental conditions to direct assembly and the attendant emergent optoelectronic properties.« less

Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding.

PubMed

Bonache, M Angeles; Alaimo, Alessandro; Malo, Covadonga; Millet, Oscar; Villarroel, Alvaro; González-Muñiz, Rosario

2014-11-28

The recombinant Kv7.2 calmodulin (CaM) binding site (Q2AB CaMBD) shows a high tendency to aggregate, thus complicating biochemical and structural studies. To facilitate these studies we have conceived bis-PEG-peptide CaMBD-mimetics linking helices A and B in single, easy to handle molecules. Short PEG chains were selected as spacers between the two peptide molecules, and a Cu(i)-catalyzed cycloaddition (CuAAC) protocol was used to assemble the final bis-PEG-peptide conjugate, by the convenient functionalization of PEG arms with azide and alkyne groups. The resulting conjugates, with a certain helical character in TFE solutions (CD), showed nanomolar affinity in a fluorescence CaM binding in vitro assay, higher than just the sum of the precursor PEG-peptide affinities, thus validating our design. The approach to these first described examples of Kv7.2 CaMBD-mimetics could pave the way to chimeric conjugates merging helices A and B from different Kv7 subunits.

PEG-poly(amino acid) block copolymer micelles for tunable drug release.

PubMed

Ponta, Andrei; Bae, Younsoo

2010-11-01

To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

Exciton transport in π-conjugated polymers with conjugation defects.

PubMed

Meng, Ruixuan; Li, Yuan; Li, Chong; Gao, Kun; Yin, Sun; Wang, Luxia

2017-09-20

In π-conjugated polymers for photovoltaic applications, intrinsic conjugation defects are known to play crucial roles in impacting exciton transport after photoexcitation. However, the understanding of the associated microscopic processes still remains limited. Here, we present a theoretical investigation of the effects of different conjugation defects on the dynamics of exciton transport in two linearly coupled poly(p-phenylene vinylene) (PPV) molecules. The model system is constructed by employing an extended version of the Su-Schrieffer-Heeger model and the exciton behaviors are simulated by means of a quantum nonadiabatic dynamics. We identify two types of conjugation defects, i.e., weakening conjugation and strengthening conjugation, which are demonstrated to play different roles in impacting the dynamics of exciton transport in the system. The weakening conjugation acts as an energy well inclined to trap a moving exciton, while the strengthening conjugation acts as an energy barrier inclined to block the exciton. We also systematically simulate both intrachain and interchain dynamics of exciton transport, and find that an exciton could experience a "short-time delaying", "trapping", "blocking", or "hopping" process, which is determined by the defect type, strength, and position. These findings provide a microscopic understanding of how the exciton transport dynamics can be impacted by conjugation defects in an actual polymer system.

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

NASA Astrophysics Data System (ADS)

Swami, Rajan; Singh, Indu; Kulhari, Hitesh; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

2015-06-01

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

Nuclear reactor spacer grid and ductless core component

DOEpatents

Christiansen, David W.; Karnesky, Richard A.

1989-01-01

The invention relates to a nuclear reactor spacer grid member for use in a liquid cooled nuclear reactor and to a ductless core component employing a plurality of these spacer grid members. The spacer grid member is of the egg-shell type and is constructed so that the walls of the cell members of the grid member are formed of a single thickness of metal to avoid tolerance problems. Within each cell member is a hydraulic spring which laterally constrains the nuclear material bearing rod which passes through each cell member against a hardstop in response to coolant flow through the cell member. This hydraulic spring is also suitable for use in a water cooled nuclear reactor. A core component constructed of, among other components, a plurality of these spacer grid members, avoids the use of a full length duct by providing spacer sleeves about the sodium tubes passing through the spacer grid members at locations between the grid members, thereby maintaining a predetermined space between adjacent grid members.

Zigzag laser with reduced optical distortion

DOEpatents

Albrecht, G.F.; Comaskey, B.; Sutton, S.B.

1994-04-19

The architecture of the present invention has been driven by the need to solve the beam quality problems inherent in Brewster's angle tipped slab lasers. The entrance and exit faces of a solid state slab laser are cut perpendicular with respect to the pump face, thus intrinsically eliminating distortion caused by the unpumped Brewster's angled faces. For a given zigzag angle, the residual distortions inherent in the remaining unpumped or lightly pumped ends may be reduced further by tailoring the pump intensity at these ends. 11 figures.

Zigzag laser with reduced optical distortion

DOEpatents

Albrecht, Georg F.; Comaskey, Brian; Sutton, Steven B.

1994-01-01

The architecture of the present invention has been driven by the need to solve the beam quality problems inherent in Brewster's angle tipped slab lasers. The entrance and exit faces of a solid state slab laser are cut perpendicular with respect to the pump face, thus intrinsically eliminating distortion caused by the unpumped Brewster's angled faces. For a given zigzag angle, the residual distortions inherent in the remaining unpumped or lightly pumped ends may be reduced further by tailoring the pump intensity at these ends.

Evolution and comparative genomics of pAQU-like conjugative plasmids in Vibrio species.

PubMed

Li, Ruichao; Ye, Lianwei; Wong, Marcus Ho Yin; Zheng, Zhiwei; Chan, Edward Wai Chi; Chen, Sheng

2017-09-01

To investigate a set of MDR conjugative plasmids found in Vibrio species and characterize the underlying evolution process. pAQU-type plasmids from Vibrio species were sequenced using both Illumina and PacBio platforms. Bioinformatics tools were utilized to analyse the typical MDR regions and core genes in the plasmids. The nine pAQU-type plasmids ranged from ∼160 to 206 kb in size and were found to harbour as many as 111 core genes encoding conjugative, replication and maintenance functions. Eight plasmids were found to carry a typical MDR region, which contained various accessory and resistance genes, including ISCR1-blaPER-1-bearing complex class 1 integrons, ISCR2-floR, ISCR2-tet(D)-tetR-ISCR2, qnrVC6, a Tn10-like structure and others associated with mobile elements. Comparison between a plasmid without resistance genes and different MDR plasmids showed that integration of different mobile elements, such as IS26, ISCR1, ISCR2, IS10 and IS6100, into the plasmid backbone was the key mechanism by which foreign resistance genes were acquired during the evolution process. This study identified pAQU-type plasmids as emerging MDR conjugative plasmids among important pathogens from different origins in Asia. These findings suggest that aquatic bacteria constitute a major reservoir of resistance genes, which may be transmissible to other human pathogens during food production and processing. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bendamustine-PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo Pharmacokinetics: A Sustainable Delivery Tactic.

PubMed

Gothwal, Avinash; Khan, Iliyas; Kumar, Pramod; Raza, Kaisar; Kaul, Ankur; Mishra, Anil Kumar; Gupta, Umesh

2018-06-04

Successful delivery of a chemotherapeutic agent like bendamustine still remains a challenge in clinical conditions like chronic lymphatic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma. We have conjugated bendamustine to polyamidoamine (PAMAM) dendrimers after conjugating with N-(hydroxyethyl)maleimide (spacer) via an ester bond. The particle size of PAMAM-bendamustine conjugate was 49.8 ± 2.5 nm. In vitro drug release resulted in sustained release with improved solution stability of drug up to 72 h. In a 24 h cytotoxicity study by MTT assay against human monoblastic leukemia cells (THP-1), the IC50 value for PAMAM-bendamustine was 32.1 ± 4.8 μM compared to 50.42 ± 3.4 μM and 2303 ± 106.5 μM for bendamustine and PAMAM dendrimer, respectively. Significantly higher cell uptake and apoptosis were observed in THP-1 cells by PAMAM-bendamustine conjugate which was confirmed by flow cytometry and confocal laser scanning microscopy. Preliminary in vivo studies undertaken included pharmacokinetics studies, organ distribution studies, and tumor inhibition studies. In healthy Wistar rat model (1CBM IV push model), the pharmacokinetic studies revealed that bioavailability and t 1/2 increased significantly, i.e., almost 8.5-fold (193.8 ± 1.116 vs 22.8 ± 0.158 μg mL -1 /h) and 5.1-fold (0.75 ± 0.005 vs 3.85 ± 0.015 h), respectively, for PAMAM-bendamustine conjugate compared to pure bendamustine ( p < 0.05), however, clearance and volume of distribution were found to be decreased compared to those of free drug. The study suggests that PAMAM-bendamustine conjugate was not only stable for the longer period but also least toxic and highly taken up by THP-1 cells to exert an anticancer effect at the reduced dose. Tumor inhibition and biodistribution studies in tumor-bearing BALB/c mice revealed that PAMAM-bendamustine conjugate was more effective than the pure drug and showed higher accumulation in the tumor.

Zigzagging Across Pluto

NASA Image and Video Library

2015-12-16

This high-resolution swat of Pluto sweeps over the cratered plains at the west of the New Horizons' encounter hemisphere and across numerous prominent faults, skimming the eastern margin of the dark, forbidding region informally known as Cthulhu Regio, and finally passing over the mysterious, possibly cryovolcanic edifice Wright Mons, before reaching the terminator or day-night line. Among the many notable details shown are the overlapping and infilling relationships between units of the relatively smooth, bright volatile ices from Sputnik Planum (at the edge of the mosaic) and the dark edge or "shore" of Cthulhu. The pictures in this mosaic were taken by the Long Range Reconnaissance Imager (LORRI) in "ride-along" mode with the LEISA spectrometer, which accounts for the 'zigzag' or step pattern. Taken shortly before New Horizons' July 14 closest approach to Pluto, details as small as 500 yards (500 meters) can be seen. http://photojournal.jpl.nasa.gov/catalog/PIA20286

Sensory Organ Like Response of Zigzag Edge Graphene Nanoribbons

NASA Astrophysics Data System (ADS)

Shenoy, Vijay; Bhowmick, Somnath

2011-03-01

Using a continuum Dirac theory, we study the density and spin response of zigzag edge terminated graphene ribbons subjected to edge potentials and Zeeman fields. Our analytical calculations of the density and spin responses of the closed system (fixed particle number) to the static edge fields, show a highly nonlinear Weber-Fechner type behavior where the response depends logarithmically on the edge potential. The dependence of the response on the size of the system (e.g.~width of a nanoribbon) is also uncovered. Zigzag edge graphene nanoribbons, therefore, provide a realization of response of organs such as the eye and ear that obey Weber-Fechner law. We validate our analytical results with tight binding calculations. These results are crucial in understanding important effects of electron-electron interactions in graphene nanoribbons such as edge magnetism etc., and also suggest possibilities for device applications of graphene nanoribbons. Work supported by DST, India through MONAMI and Ramanujan grants.

Trestle #1, detail of stringers and spacers on northeast end ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Trestle #1, detail of stringers and spacers on northeast end of deck. View to southwest - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates

PubMed Central

1980-01-01

A method is presented for covalently bonding Haemophilus influenzae type b capsular polysaccharide (HIB Ps) to several proteins. The method is efficient and relies upon the use of adipic dihydrazide as a spacer between the capsular polysaccharide and the carrier protein. In contrast to the poor immunogenicity of the purified HIB Ps in mice and rabbits, the HIB Ps-protein conjugates induced serum anti-type b antibodies having bactericidal activity at levels shown to be protective in humans when low doses were injected subcutaneously in a saline solution. The antibody response in mice was related to the dose of the conjugates, increased with the number of injections, and could be primed by the previous injection of the carrier protein. The HIB Ps- protein conjugates were immunogenic in three different mouse strains. The importance of the carrier molecule for the enhanced immunogenicity of the HIB Ps-protein conjugates was shown by the failure of HIB Ps hybrids prepared with either the homologous polysaccharide or pneumococcus type 3 polysaccharide to induce antibodie in mice. Rabbits injected with the HIB Ps-protein conjugates emulsified in Freund's adjuvant produced high levels of serum anti-type b antibodies which induced a bactericidal effect upon H. influenzae type b organisms. It is proposed that the HIB Ps component of the polysaccharide protein conjugates has been converted to a thymic-dependent immunogen. This method may be used to prepare protein-polysaccharide conjugates with HIB Ps and other polysaccharides to be considered for human use. PMID:6967514

Horizontal transfer of chromosomal markers mediated by the large conjugative plasmid pXO16 from Bacillus thuringiensis serovar israelensis.

PubMed

Makart, Lionel; Commans, Florian; Gillis, Annika; Mahillon, Jacques

2017-05-01

pXO16, a large plasmid originating from Bacillus thuringiensis serovar israelensis, displays unique conjugation capacities: besides efficient self-transfer, it is able to mobilize and retro-mobilize non-conjugative plasmids, including those missing an oriT and/or a mob gene, also known as "non-mobilizable" plasmids. In this paper, another peculiar transfer property of pXO16 is described. This element is indeed able to transfer chromosomal loci at frequencies of ca. 10 -5 -10 -6 transconjugants/donor cell. Whereas most other chromosomal transfer systems occur via the integration of the conjugative elements into the chromosome prior to its transfer, pXO16 appears to transfer the chromosomal markers in the absence of physical integration, but rather through a "donation-type" mobilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Trestle #1, detail of spacer, bolt, and spikes on northeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Trestle #1, detail of spacer, bolt, and spikes on northeast end of deck. View to southwest - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

Synthesis and characterization of a pH-sensitive conjugate of isoniazid with Fe3O4@SiO2 magnetic nanoparticles.

PubMed

Sedlák, Miloš; Bhosale, Dattatry Shivajirao; Beneš, Ludvík; Palarčík, Jiří; Kalendová, Andrea; Královec, Karel; Imramovský, Aleš

2013-08-15

The Letter describes the preparation and characterization of a conjugate of isoniazid (INH) with magnetic nanoparticles Fe3O4@SiO2 115±60 nm in size. The INH molecules were attached to the surface of nanoparticles by a covalent pH-sensitive amidine bond. The conjugate was characterized by X-ray diffraction, SEM, dynamic light scattering, IR spectroscopy and microanalysis. The conjugate released isoniazid under in vitro conditions (pH=4; 37 °C; t1/2≈115 s). In addition, the cytotoxicity of the Fe3O4@SiO2-INH conjugate was evaluated in SK-BR-3 cells using the xCELLigence system. Copyright © 2013 Elsevier Ltd. All rights reserved.

How to use an inhaler - with spacer

MedlinePlus

... MDIs) usually have 3 parts: A mouthpiece A cap that goes over the mouthpiece A canister full ... Take the cap off the inhaler and spacer. Shake the inhaler hard. Attach the spacer to the inhaler. If you have ...

Comparison of internal transcribed spacers and intergenic spacer regions of five common Iranian sheep bursate nematodes.

PubMed

Nabavi, Reza; Conneely, Brendan; McCarthy, Elaine; Good, Barbara; Shayan, Parviz; DE Waal, Theo

2014-09-01

Accurate identification of sheep nematodes is a critical point in epidemiological studies and monitoring of drug resistance in flocks. However, due to a close morphological similarity between the eggs and larval stages of many of these nematodes, such identification is not a trivial task. There are a number of studies showing that molecular targets in ribosomal DNA (Internal transcribed spacer 1, 2 and Intergenic spacer) are suitable for accurate identification of sheep bursate nematodes. The objective of present study was to compare the ITS1, ITS2 and IGS regions of Iranian common bursate nematodes in order to choose best target for specific identification methods. The first and second internal transcribed spacers (ITS1and ITS2) and intergenic spacer (IGS) of the ribosomal DNA (rDNA) of 5 common Iranian bursate nematodes of sheep were sequenced. The sequences of some non-Iranian isolates were used for comparison in order to evaluate the variation in sequence homology between geographically different nematode populations. Comparison of the ITS1 and ITS2 sequences of Iranian nematodes showed greatest similarity among Teladorsagia circumcincta and Marshallagia marshalli of 94% and 88%, respectively. While Trichostrongylus colubriformis and M. marshalli showed the highest homology (99%) in the IGS sequences. Comparison of the spacer sequences of Iranian with non-Iranian isolates showed significantly higher variation in Haemonchus contortus compared to the other species. Both the ITS1 and ITS2 sequences are convenient targets to have species-specific identification of Iranian bursate nematodes. On the other hand the IGS region may be a less suitable molecular target.

Refinement of Timoshenko Beam Theory for Composite and Sandwich Beams Using Zigzag Kinematics

NASA Technical Reports Server (NTRS)

Tessler, Alexander; DiSciuva, Marco; Gherlone, Marco

2007-01-01

A new refined theory for laminated-composite and sandwich beams that contains the kinematics of the Timoshenko Beam Theory as a proper baseline subset is presented. This variationally consistent theory is derived from the virtual work principle and employs a novel piecewise linear zigzag function that provides a more realistic representation of the deformation states of transverse shear flexible beams than other similar theories. This new zigzag function is unique in that it vanishes at the top and bottom bounding surfaces of a beam. The formulation does not enforce continuity of the transverse shear stress across the beam s cross-section, yet is robust. Two major shortcomings that are inherent in the previous zigzag theories, shear-force inconsistency and difficulties in simulating clamped boundary conditions, and that have greatly limited the utility of these previous theories are discussed in detail. An approach that has successfully resolved these shortcomings is presented herein. This new theory can be readily extended to plate and shell structures, and should be useful for obtaining accurate estimates of structural response of laminated composites.

Modifying exchange-spring behavior of CoPt/NiFe bilayer by inserting a Pt or Ru spacer

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

Hsu, Jen-Hwa, E-mail: jhhsu@phys.ntu.edu.tw; Tsai, C. L.; Lee, C.-M.

2015-05-07

We herein explore the possibility of obtaining tunable tilted magnetic anisotropy in ordered-CoPt (5 nm)/NiFe(t{sub NiFe}) bilayers through modifying their exchange spring behavior by inserting Pt and Ru-spacers. The tuning process of tilt angle magnetization of NiFe-layer was systematically investigated by varying the Pt or Ru thickness (t{sub Pt} or t{sub Ru}) from 0 to 8 nm at different thicknesses of NiFe (t{sub NiFe} = 1.5, 4.0, and 6.0 nm). Polar magneto-optic Kerr effect (p-MOKE) studies reveal that the bilayers grown in absence of spacers exhibit almost a rectangular hysteresis loop. With the insertion of Pt-spacer, the loop becomes more and more tilted as t{submore » Pt} increases; whereas, in the case of Ru-spacer, the nature of the loops is not simply changing in one direction. The estimated SQR{sub ⊥} (= θ{sub r}/θ{sub s}) values from the p-MOKE loops are found to monotonically decrease with increasing t{sub Pt} when t{sub Pt} ≦ 4 nm. In contrast, in the case of Ru-spacer, an oscillatory behavior for the SQR{sub ⊥} values is apparent when t{sub Ru} ≦ 4 nm. As a result, an oscillatory tilted angle of NiFe spin configuration was obtained in the case of Ru-spacer; while a decoupling effect was prominent for the Pt-spacer. The results of present study reveal that the insertion of Pt and Ru-spacers as an appropriate means for realizing tunable tilted magnetic anisotropy in the CoPt/NiFe exchange springs.« less

The application of zero-profile anchored spacer in anterior cervical discectomy and fusion.

PubMed

Wang, Zhiwen; Jiang, Weimin; Li, Xuefeng; Wang, Heng; Shi, Jinhui; Chen, Jie; Meng, Bin; Yang, Huilin

2015-01-01

We aimed to analyze the clinical efficacy of the zero-profile anchored spacers in the treatment of one-level or two-level cervical degenerative disc disease. From April 2011 to April 2013, a total of 63 consecutive patients with cervical degenerative disc disease who underwent one- or two-level ACDF using either the zero-profile anchored spacer or the stand-alone cages and a titanium plate fixation were reviewed for the radiological and clinical outcomes and complications. The zero-profile anchored spacers were used in 30 patients (anchored group) and stand-alone cages with an anterior cervical plate were implanted in 33 cases (non-anchored group). Operative time, intraoperative blood loss, clinical and radiological results were compared between the anchored group and the non-anchored group. All patients were followed up for at least 12 months. There were not bolt loosening or rupture of anchoring clips, screws or titanium plates observed in two groups during follow-up period. There were no significant difference in neck disability index scores, Japanese Orthopedic Association scores, fusion rate, and cervical lordosis during follow-up between two groups (P > 0.05), but significant difference in the operation time, blood loss and the presence of dysphagia were found (P < 0.05). There were no adjacent disc degeneration and instability observed in two groups. The zero-profile anchored spacer achieved similar clinical outcomes compared to ACDF with anterior plating for the treatment of the cervical degenerative disc disease. However, zero-profile anchored spacer was associated with a lower risk of postoperative dysphagia, shorter operation time, less blood loss, and relatively greater simplicity than the stand-alone cage with a titanium plate.

Magnetic resonance imaging evaluation of intervertebral test spacers: an experimental comparison of magnesium versus titanium and carbon fiber reinforced polymers as biomaterials.

PubMed

Ernstberger, T; Buchhorn, G; Heidrich, G

2010-03-01

Intervertebral spacers are made of different materials, which can affect the postfusion magnetic resonance imaging (MRI) scans. Susceptibility artifacts, especially for metallic implants, can decrease the image quality. This study aimed to determine whether magnesium as a lightweight and biocompatible metal is suitable as a biomaterial for spinal implants based on its MRI artifacting behavior. To compare artifacting behaviors, we implanted into one porcine cadaveric spine different test spacers made of magnesium, titanium, and CFRP. All test spacers were scanned using two T1-TSE MRI sequences. The artifact dimensions were traced on all scans and statistically analyzed. The total artifact volume and median artifact area of the titanium spacers were statistically significantly larger than magnesium spacers (P < 0.001), while magnesium and CFRP spacers produced almost identical artifacting behaviors (P > 0.05). Our results suggest that spinal implants made with magnesium alloys will behave more like CFRP devices in MRI scans.

A new security solution to JPEG using hyper-chaotic system and modified zigzag scan coding

NASA Astrophysics Data System (ADS)

Ji, Xiao-yong; Bai, Sen; Guo, Yu; Guo, Hui

2015-05-01

Though JPEG is an excellent compression standard of images, it does not provide any security performance. Thus, a security solution to JPEG was proposed in Zhang et al. (2014). But there are some flaws in Zhang's scheme and in this paper we propose a new scheme based on discrete hyper-chaotic system and modified zigzag scan coding. By shuffling the identifiers of zigzag scan encoded sequence with hyper-chaotic sequence and accurately encrypting the certain coefficients which have little relationship with the correlation of the plain image in zigzag scan encoded domain, we achieve high compression performance and robust security simultaneously. Meanwhile we present and analyze the flaws in Zhang's scheme through theoretical analysis and experimental verification, and give the comparisons between our scheme and Zhang's. Simulation results verify that our method has better performance in security and efficiency.

Impact of Alkyl Spacer Length on Aggregation Pathways in Kinetically Controlled Supramolecular Polymerization.

PubMed

Ogi, Soichiro; Stepanenko, Vladimir; Thein, Johannes; Würthner, Frank

2016-01-20

We have investigated the kinetic and thermodynamic supramolecular polymerizations of a series of amide-functionalized perylene bisimide (PBI) organogelator molecules bearing alkyl spacers of varied lengths (ethylene to pentylene chains, PBI-1-C2 to PBI-1-C5) between the amide and PBI imide groups. These amide-functionalized PBIs form one-dimensional fibrous nanostructures as the thermodynamically favored states in solvents of low polarity. Our in-depth studies revealed, however, that the kinetic behavior of their supramolecular polymerization is dependent on the spacer length. Propylene- and pentylene-tethered PBIs follow a similar polymerization process as previously observed for the ethylene-tethered PBI. Thus, the monomers of these PBIs are kinetically trapped in conformationally restricted states through intramolecular hydrogen bonding between the amide and imide groups. In contrast, the intramolecularly hydrogen-bonded monomers of butylene-tethered PBI spontaneously self-assemble into nanoparticles, which constitute an off-pathway aggregate state with regard to the thermodynamically stable fibrous supramolecular polymers obtained. Thus, for this class of π-conjugated system, an unprecedented off-pathway aggregate with high kinetic stability could be realized for the first time by introducing an alkyl linker of optimum length (C4 chain) between the amide and imide groups. Our current system with an energy landscape of two competing nucleated aggregation pathways is applicable to the kinetic control over the supramolecular polymerization by the seeding approach.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

PubMed

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Naphtho[1,2-b:5,6-b']dithiophene-Based Conjugated Polymers for Fullerene-Free Inverted Polymer Solar Cells.

PubMed

Jiang, Zhaoyan; Li, Huan; Wang, Zhen; Zhang, Jianqi; Zhang, Yajie; Lu, Kun; Wei, Zhixiang

2018-03-23

Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT-T-1,3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2-ethylhexyl)benzo[1,2-c:4,5-c']-dithiophene-4,8-dione (BDD), PzNDT-TT-BDD, and PzNDTP-T-BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π-bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2'-[(4,4,9,9-tetrahexyl-4,9-dihydro-sindaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis[methylidyne(3-oxo-1H-indene-2,1(3H)-diylidene)

Simple introduction of carboxyl head group with alkyl spacer onto multiwalled carbon nanotubes by solution plasma process

NASA Astrophysics Data System (ADS)

Nemoto, Shimpei; Ueno, Tomonaga; Watthanaphanit, Anyarat; Hieda, Junko; Bratescu, Maria Antoaneta; Saito, Nagahiro

2017-09-01

A simple method of fabricating carboxyl-terminated multiwalled carbon nanotubes (MWCNTs) with alkyl spacers was developed to improve the dispersion quality of MWCNTs in aqueous solutions using solution plasma (SP) in a 6-aminocaproic acid solution. The formation of SP in the solution led to better dispersion of MWCNTs in aqueous solutions. Fourier transform infrared spectroscopy (FT-IR) results indicate that a carboxyl group with an alkyl spacer can be introduced by SP treatment in the 6-aminocaproic acid solution. Sedimentation tests show that the SP-treated MWCNTs in the 6-aminocaproic acid solution retained their good dispersion quality in aqueous solutions of pHs 5, 6, and 9. The alkyl spacer plays an important role in the preservation of dispersion states particularly at pH 6.

Influence of Spacer Systems on Heat Transfer in Evacuated Glazing

NASA Astrophysics Data System (ADS)

Swimm, K.; Weinläder, H.; Ebert, H.-P.

2009-06-01

One attractive possibility to essentially improve the insulation properties of glazing is to evacuate the space between the glass panes. This eliminates heat transport due to convection between the glass panes and suppresses the thermal conductivity of the remaining low pressure filling gas atmosphere. The glass panes can be prevented from collapsing by using a matrix of spacers. These spacers, however, increase heat transfer between the glass panes. To quantify this effect, heat transfer through samples of evacuated glazing was experimentally determined. The samples were prepared with different kinds of spacer materials and spacer distances. The measurements were performed with a guarded hot-plate apparatus under steady-state conditions and at room temperature. The measuring chamber of the guarded hot plate was evacuated to < 10-2 Pa. An external pressure load of 0.1 MPa was applied on the samples to ensure realistic system conditions. Radiative heat transfer was significantly reduced by preparing the samples with a low- ɛ coating on one of the glass panes. In a first step, measurements without any spacers allowed quantification of the amount of radiative heat transfer. With these data, the measurements with spacers could be corrected to separate the effect of the spacers on thermal heat transfer. The influence of the thermal conductivity of the spacer material, as well as the distance between the spacers and the spacer geometry, was experimentally investigated and showed good agreement with simulation results. For mechanically stable matrices with cylindrical spacers, experimental thermal conductance values ≤0.44W·m-2 ·K-1 were found. This shows that U g -values of about 0.5W · m-2 · K-1 are achievable in evacuated glazing, if highly efficient low-emissivity coatings are used.

Trestle #1, detail of spacer and bolt assembly with tie ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Trestle #1, detail of spacer and bolt assembly with tie and guard timber, southwest end of deck. View to east-northeast - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

Vancomycin-Loaded Polymethylmethacrylate Spacers Fail to Eradicate Periprosthetic Joint Infection in a Clinically Representative Mouse Model.

PubMed

Carli, Alberto V; Bhimani, Samrath; Yang, Xu; de Mesy Bentley, Karen L; Ross, F Patrick; Bostrom, Mathias P G

2018-06-06

Periprosthetic joint infection (PJI) remains a devastating complication following total joint arthroplasty. Current animal models of PJI do not effectively recreate the clinical condition and thus provide limited help in understanding why treatments fail. We developed a mouse model of the first-stage surgery of a 2-stage revision for PJI involving a 3-dimensionally printed Ti-6Al-4V implant and a mouse-sized cement spacer that elutes vancomycin. Vancomycin was mixed with polymethylmethacrylate (PMMA) cement and inserted into custom-made mouse-sized spacer molds. Twenty C57BL/6 mice received a proximal tibial implant and an intra-articular injection of 3 × 10 colony-forming units of Staphylococcus aureus Xen36. At 2 weeks, 9 mice underwent irrigation and debridement of the leg with revision of the implant to an articulating vancomycin-loaded PMMA spacer. Postoperatively, mice underwent radiography and serum inflammatory-marker measurements. Following euthanasia of the mice at 6 weeks, bone and soft tissues were homogenized to quantify bacteria within periprosthetic tissues. Implants and articulating spacers were either sonicated to quantify adherent bacteria or examined under scanning electron microscopy (SEM) to characterize the biofilm. Vancomycin-loaded PMMA spacers eluted vancomycin for ≤144 hours and retained antimicrobial activity. Control mice had elevated levels of inflammatory markers, radiographic evidence of septic loosening of the implant, and osseous destruction. Mice treated with a vancomycin-loaded PMMA spacer had significantly lower levels of inflammatory markers (p < 0.01), preserved tibial bone, and no intra-articular purulence. Retrieved vancomycin-loaded spacers exhibited significantly lower bacterial counts compared with implants (p < 0.001). However, bacterial counts in periprosthetic tissue did not significantly differ between the groups. SEM identified S. aureus encased within biofilm on control implants, while vancomycin-loaded spacers

Catalyst-free growth of Al-doped SnO2 zigzag-nanobelts for low ppm detection of organic vapours

NASA Astrophysics Data System (ADS)

Sinha, Sudip Kumar; Ghosh, Saptarshi

2016-10-01

In this effort, we report on development of specific sensors dedicated for detection of two of these volatiles, namely ethanol and acetone, below the prescribed statutory limits. Single crystalline Al-doped SnO2 zigzag nanobelt structures were deposited on Si substrate by a catalyst-free thermal evaporation method. The Al-doped SnO2 zigzag nanostructures exhibit high sensitivity and repeatability together with coveted features like fast response and excellent stability. Structural attributes involving the crystal quality and morphology of Al-doped SnO2 zigzag nanobelts were analyzed using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy and transmission electron microscopy. The microscopic images revealed formation of randomly oriented 'zigzag-like' nanobelts with characteristic width between 60 nm and 200 nm and length of 50-300 μm. The Al-doping was observed to have a discerning effect in enhancing the sensitivity in comparison to the pristine nanowires by creating excess oxygen vacancies in the crystal lattice, confirmed through XPS and PL spectra.

Photodynamic inactivation of bacteria using polyethylenimine-chlorin(e6) conjugates: Effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH.

PubMed

Huang, Liyi; Zhiyentayev, Timur; Xuan, Yi; Azhibek, Dulat; Kharkwal, Gitika B; Hamblin, Michael R

2011-04-01

Antimicrobial photodynamic therapy (APDT) is a novel technique to treat local infections. Previously we reported that the attachment of chlorin(e6) to polyethylenimine (PEI) polymers to form PEI-ce6 conjugates is an effective way to improve ce6 PDT activity against bacteria. The aim of this work was to explore how the polymer molecular weight, substitution ratio (SR) of ce6 and pH value affect the PDT efficacy. We have synthesized PEI-ce6(10) (MW = 60,000, SR = 1) and PEI-ce6(11) (MW = 60,000, SR = 5) and compared these with the previous PEI-ce6(9) (MW = 10,000, SR = 1). We tested the PDT efficacy of these three conjugates against Gram-negative E. coli and Gram-positive bacteria (S. aureus and E. fecalis) at three different pH values (5.0, 7.4, 10.0) that may affect the charge on both the bacterial cells and on the conjugate (that has both basic and acidic groups). PEI-ce6(9) and PEI-ce6(10) were the most effective against these tested bacteria. The PDT effect of all three conjugates depended on pH values. The effective order was pH = 10.0 > pH = 7.4 > pH = 5.0 on E. coli. For S. aureus and E. fecalis the order was pH = 5.0 > pH = 10.0 > pH = 7.4. PEI-ce6(11) PDT activity was worse than PEI-ce6(10) activity which is probably connected to the fact that ce6 molecules are self-quenched within the PEI-ce6(11) molecule. Ce6 quenching within the PEI-ce6 molecules was proved by analyzing fluorescence spectra of PEI-ce6 conjugates at different pH values. There were no differences in bacterial uptake between different pH values in three PEI-ce6 conjugates. We assume high pH (rather than low pH as was hypothesized) disaggregates the conjugates, so the higher pH was more effective than the lower pH against E. coli. But for Gram-positive bacteria, low pH was more effective possibly due to more overall positive charge on the conjugate. Copyright © 2011 Wiley-Liss, Inc.

Bioinformatics analyses of Shigella CRISPR structure and spacer classification.

PubMed

Wang, Pengfei; Zhang, Bing; Duan, Guangcai; Wang, Yingfang; Hong, Lijuan; Wang, Linlin; Guo, Xiangjiao; Xi, Yuanlin; Yang, Haiyan

2016-03-01

Clustered regularly interspaced short palindromic repeats (CRISPR) are inheritable genetic elements of a variety of archaea and bacteria and indicative of the bacterial ecological adaptation, conferring acquired immunity against invading foreign nucleic acids. Shigella is an important pathogen for anthroponosis. This study aimed to analyze the features of Shigella CRISPR structure and classify the spacers through bioinformatics approach. Among 107 Shigella, 434 CRISPR structure loci were identified with two to seven loci in different strains. CRISPR-Q1, CRISPR-Q4 and CRISPR-Q5 were widely distributed in Shigella strains. Comparison of the first and last repeats of CRISPR1, CRISPR2 and CRISPR3 revealed several base variants and different stem-loop structures. A total of 259 cas genes were found among these 107 Shigella strains. The cas gene deletions were discovered in 88 strains. However, there is one strain that does not contain cas gene. Intact clusters of cas genes were found in 19 strains. From comprehensive analysis of sequence signature and BLAST and CRISPRTarget score, the 708 spacers were classified into three subtypes: Type I, Type II and Type III. Of them, Type I spacer referred to those linked with one gene segment, Type II spacer linked with two or more different gene segments, and Type III spacer undefined. This study examined the diversity of CRISPR/cas system in Shigella strains, demonstrated the main features of CRISPR structure and spacer classification, which provided critical information for elucidation of the mechanisms of spacer formation and exploration of the role the spacers play in the function of the CRISPR/cas system.

Unique helicase determinants in the essential conjugative TraI factor from Salmonella enterica serovar Typhimurium plasmid pCU1.

PubMed

McLaughlin, Krystle J; Nash, Rebekah P; Redinbo, Mathew R

2014-09-01

The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. In this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Unique Helicase Determinants in the Essential Conjugative TraI Factor from Salmonella enterica Serovar Typhimurium Plasmid pCU1

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

McLaughlin, K. J.; Nash, R. P.; Redinbo, M. R.

The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. Inmore » this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity.« less

p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy.

PubMed

Tsuchiya, Megumi; Ogawa, Hidesato; Koujin, Takako; Mori, Chie; Osakada, Hiroko; Kobayashi, Shouhei; Hiraoka, Yasushi; Haraguchi, Tokuko

2018-03-01

Autophagy is a bulk degradation pathway, and selective autophagy to remove foreign entities is called xenophagy. The conjugation of ubiquitin to target pathogens is an important process in xenophagy but when and where this ubiquitination occurs remains unclear. Here, we analyzed the temporal sequence and subcellular location of ubiquitination during xenophagy using time-lapse observations, with polystyrene beads mimicking invading pathogens. Results revealed accumulation of a ubiquitination marker around the beads within 3 min after endosome rupture. Recruitment of ubiquitin to the beads was significantly delayed in p62-knockout murine embryonic fibroblast cells, and this delay was rescued by ectopic p62 expression. Ectopic expression of a phosphorylation-mimicking p62 mutated at serine residue 405 (equivalent to human serine residue 403) rescued this delay, but its unphosphorylated form did not. These results indicate that ubiquitination mainly occurs after endosome rupture and suggest that p62, specifically the phosphorylated form, promotes ubiquitin conjugation to target proteins in xenophagy.

pHTβ-promoted mobilization of non-conjugative resistance plasmids from Enterococcus faecium to Enterococcus faecalis.

PubMed

Di Sante, Laura; Morroni, Gianluca; Brenciani, Andrea; Vignaroli, Carla; Antonelli, Alberto; D'Andrea, Marco Maria; Di Cesare, Andrea; Giovanetti, Eleonora; Varaldo, Pietro E; Rossolini, Gian Maria; Biavasco, Francesca

2017-09-01

To analyse the recombination events associated with conjugal mobilization of two multiresistance plasmids, pRUM17i48 and pLAG (formerly named pDO1-like), from Enterococcus faecium 17i48 to Enterococcus faecalis JH2-2. The plasmids from two E. faecalis transconjugants (JH-4T, tetracycline resistant, and JH-8E, erythromycin resistant) and from the E. faecium donor (also carrying a pHTβ-like conjugative plasmid, named pHTβ17i48) were investigated by several methods, including PCR mapping and sequencing, S1-PFGE followed by Southern blotting and hybridization, and WGS. Two locations of repApHTβ were detected in both transconjugants, one on a ∼50 kb plasmid (as in the donor) and the other on plasmids of larger sizes. In JH-4T, WGS disclosed an 88.6 kb plasmid resulting from the recombination of pHTβ17i48 (∼50 kb) and a new plasmid, named pLAG (35.3 kb), carrying the tet(M), tet(L), lsa(E), lnu(B), spw and aadE resistance genes. In JH-8E, a 75 kb plasmid resulting from the recombination of pHTβ17i48 and pRUM17i48 was observed. In both cases, the cointegrates were apparently derived from replicative transposition of an IS1216 present in each of the multiresistance plasmids into pHTβ17i48. The cointegrates could resolve to yield the multiresistance plasmids and a pHTβ17i48 derivative carrying an IS1216 (unlike the pHTβ17i48 of the donor). Our results completed the characterization of the multiresistance plasmids carried by the E. faecium 17i48, confirming the role of pHT plasmids in the mobilization of non-conjugative antibiotic resistance elements among enterococci. Results also revealed that mobilization to E. faecalis was associated with the generation of cointegrate plasmids promoted by IS1216-mediated transposition. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Zigzagging causility model of EPR correlations and on the interpretation of quantum mechanics

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

de Beauregard, O.C.

1988-09-01

Being formalized inside the S-matrix scheme, the zigzagging causility model of EPR correlations has full Lorentz and CPT invariance. EPR correlations, proper or reversed, and Wheeler's smoky dragon metaphor are respectively pictured in a spacetime or in the momentum-energy space, as V-shaped, anti LAMBDA-shaped, or C-shaped ABC zigzags, with a summation at B over virtual states absolute value B>=*. The reversibility = * implies that causality is CPT-invariant, or arrowless, at the microlevel. Arrowed causality is a macroscopic emergence, corollary to wave retardation and probability increase. Factlike irreversibility states repression, not suppression, of blind statistical retrodiction- that is, of finalmore » cause.« less

The effect of varied pH on the luminescence characteristics of antibody-mercaptoacetic acid conjugated ZnS nanowires

NASA Astrophysics Data System (ADS)

Chaudhry, Madeeha; Rehman, Malik Abdul; Gul, Asghari; Qamar, Raheel; Bhatti, Arshad Saleem

2017-11-01

We demonstrate here that the effect of varied pH of the media on the photoluminescence (PL) properties of mercaptoacetic acid (MAA) and digoxin antibody (Ab) conjugated zinc sulphide (ZnS) nanowires. The charge-transfer kinetics from MAA to ZnS and vice versa showed a profound effect on the luminescence of ZnS defect states. The PL intensity of the ZnS defect states showed strong dependence on the value of pH with respect to the pKa of MAA. The carboxyl and thiol group of MAA in the protonated (pH < pKa) and deprotonated (pH > pKa) states resulted in the quenched PL intensity. While for pH ∼ pKa, the PL intensity was regained as there was equal probability of both protonated and deprotonated carboxyl and thiol groups. These findings indicated that pH of the environment is a key parameter for the use of MAA-Ab conjugated ZnS nanowires as an optical biomarker.

Vanishing Thermal Conductance of Carbon Nanotube upon Encapsulation by Zigzag Sulfur Chain.

PubMed

Koley, Sayantanu; Sen, Sabyasachi; Chakrabarti, Swapan

2018-06-07

We report an unprecedented enhancement of thermoelectric properties of a single-walled carbon nanotube upon encapsulation of a zigzag sulfur chain inside the nanocore. Our calculations on a 70 Å long [5, 5] carbon nanotube reveal that the encapsulation of zigzag sulfur chain will lead to a 10 7 % increase in the thermoelectric figure of merit and concomitant quenching of thermal conductance by 90%. We have noticed that finite transmission gradient at the Fermi level combined with destructive quantum interference at the sulfur sites and structural conformation-dependent scattering-induced damping of phonon transmission are attributed to the dramatic improvement of thermoelectric behavior of this material. This finding indeed will help circumvent the long-standing problem in the fabrication of carbon-nanotube-based ultrafast device.

The Effect of Acceleration Sprint and Zig-zag Drill Combination to Increase Students’ Speed and Agility

NASA Astrophysics Data System (ADS)

Bana, O.; Mintarto, E.; Kusnanik, N. W.

2018-01-01

The purpose of this research is to analyze the following factors: (1) how far the effect of exercise acceleration sprint on the speed and agility (2) how much influence the zig-zag drill combination to the speed and agility (3) and is there any difference between the effects of exercise acceleration sprint and practice zig-zag drill combination of the speed and agility. This research is quantitative with quasi-experimental approach. The design of this study is matching only design.This study was conducted on 33 male students who take part in extracurricular and divided into 3 groups with 11 students in each group. Group 1 was given training of acceleration sprint, group 2 was given zig-zag training combination drills of conventional and exercises for group 3, for 8 weeks. The data collection was using sprint 30 meter to test the speed and agility t-test to test agility. Data were analyzed using t-test and analysis of variance. The conclusion of the research is (1) there is a significant effect of exercise acceleration sprint for the speed and agility, (2) there is a significant influence combination zig-zag drills, on speed and agility (3) and exercise acceleration sprint have more effect on the speed and agility.

Pressurised metered dose inhaler-spacer technique in young children improves with video instruction.

PubMed

Shaw, Nicole; Le Souëf, Peter; Turkovic, Lidija; McCahon, Lucy; Kicic, Anthony; Sly, Peter D; Devadason, Sunalene; Schultz, André

2016-07-01

The importance of good device technique to maximise delivery of aerosolised medications is widely recognised. Pressurised metered dose inhaler (pMDI)-spacer technique was investigated in 122 children, aged 2-7 years, with asthma. Eight individual steps of device technique were evaluated before and after viewing an instructional video for correct device technique. Video measurements were repeated every three months for nine months. Device technique improved directly after video instruction at the baseline study visit (p < 0.001) but had no immediate effect at subsequent visits. Additionally, pMDI-spacer technique improved with successive visits over one year for the group overall as evidenced by increases in the proportion of children scoring maximal (p = 0.02) and near-maximal (p = 0.04) scores. Repeated video instruction over time improves inhaler technique in young children. • Correct device technique is considered essential for sufficient delivery of inhaled medication. • Poor inhaler use is common in young asthmatic children using pressurised metered dose inhalers and spacers. What is New: • Video instruction could be used as a strategy to improve device technique in young children.

p -Carborane Conjugation in Radical Anions of Cage–Cage and Cage–Phenyl Compounds

DOE PAGES

Cook, Andrew R.; Valášek, Michal; Funston, Alison M.; ...

2017-12-14

Optical electron transfer (intervalence) transitions in radical anions of p-carborane oligomers attest to delocalization of electrons between two p-carboranes cages or a p-carborane and a phenyl ring. Oligomers of the 12 vertex p-carborane (C 2B 10H 12) cage, [12], with up to 3 cages were synthesized, as well as p-carboranes with one or two trimethylsilylphenyl groups, [6], attached to the carbon termini. Pulse radiolysis in tetrahydrofuran produced radical anions, determined redox potentials by equilibria and measured their absorption spectra. Density functional theory computations provided critical insight into the optical electron transfer bands and electron delocalization. One case, [6–12–6], showed bothmore » Robin–Day class II and III transitions. The class III transition resulted from a fully delocalized excess electron across both benzene rings and the central p-carborane, with an electronic coupling H ab = 0.46 eV between the cage and either benzene. This unprecedented finding shows that p-carborane bridges are not simply electron withdrawing insulators. In other cases with more than ~1/2 of the excess electron localized on a [12], large cage distortions were triggered, producing a partially open cage with a nido-like structure. This resulted in class II transitions with similar Hab but massive reorganization energies. The computations also predicted delocalization in radical cations, but complexities in cation formation allowed only tentative experimental support of the predictions. Thus, the results with anions provide clear evidence for carborane conjugation that might be exploited in molecular wire materials, which are classically composed of all π-conjugated molecules.« less

p -Carborane Conjugation in Radical Anions of Cage–Cage and Cage–Phenyl Compounds

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

Cook, Andrew R.; Valášek, Michal; Funston, Alison M.

Optical electron transfer (intervalence) transitions in radical anions of p-carborane oligomers attest to delocalization of electrons between two p-carboranes cages or a p-carborane and a phenyl ring. Oligomers of the 12 vertex p-carborane (C 2B 10H 12) cage, [12], with up to 3 cages were synthesized, as well as p-carboranes with one or two trimethylsilylphenyl groups, [6], attached to the carbon termini. Pulse radiolysis in tetrahydrofuran produced radical anions, determined redox potentials by equilibria and measured their absorption spectra. Density functional theory computations provided critical insight into the optical electron transfer bands and electron delocalization. One case, [6–12–6], showed bothmore » Robin–Day class II and III transitions. The class III transition resulted from a fully delocalized excess electron across both benzene rings and the central p-carborane, with an electronic coupling H ab = 0.46 eV between the cage and either benzene. This unprecedented finding shows that p-carborane bridges are not simply electron withdrawing insulators. In other cases with more than ~1/2 of the excess electron localized on a [12], large cage distortions were triggered, producing a partially open cage with a nido-like structure. This resulted in class II transitions with similar Hab but massive reorganization energies. The computations also predicted delocalization in radical cations, but complexities in cation formation allowed only tentative experimental support of the predictions. Thus, the results with anions provide clear evidence for carborane conjugation that might be exploited in molecular wire materials, which are classically composed of all π-conjugated molecules.« less

C2-streptavidin mediates the delivery of biotin-conjugated tumor suppressor protein p53 into tumor cells.

PubMed

Fahrer, Jörg; Schweitzer, Brigitte; Fiedler, Katja; Langer, Torben; Gierschik, Peter; Barth, Holger

2013-04-17

We have previously generated a recombinant C2-streptavidin fusion protein for the delivery of biotin-labeled molecules of low molecular weight into the cytosol of mammalian cells. A nontoxic moiety of Clostridium botulinum C2 toxin mediates the cellular uptake, whereas the streptavidin unit serves as a binding platform for biotin-labeled cargo molecules. In the present study, we used the C2-streptavidin transporter to introduce biotin-conjugated p53 protein into various mammalian cell lines. The p53 tumor suppressor protein is inactivated in many human cancers by multiple mechanisms and therefore the restoration of its activity in tumor cells is of great therapeutic interest. Recombinant p53 was expressed in insect cells and biotin-labeled. Biotin-p53 retained its specific high-affinity DNA-binding as revealed by gel-shift analysis. Successful conjugation of biotin-p53 to the C2-streptavidin transporter was monitored by an overlay blot technique and confirmed by real-time surface plasmon resonance, providing a KD-value in the low nM range. C2-streptavidin significantly enhanced the uptake of biotin-p53 into African Green Monkey (Vero) epithelial cells as shown by flow cytometry. Using cell fractionation, the cytosolic translocation of biotin-p53 was detected in Vero cells as well as in HeLa cervix carcinoma cells. In line with this finding, confocal microscopy displayed cytoplasmic staining of biotin-p53 in HeLa and HL60 leukemia cells. Internalized biotin-p53 partially colocalized with early endosomes, as confirmed by confocal microscopy. In conclusion, our results demonstrate the successful conjugation of biotin-p53 to C2-streptavidin and its subsequent receptor-mediated endocytosis into different human tumor cell lines.

Optical absorption of zigzag single walled boron nitride nanotubes

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Chegel, Raad; Behzad, Somayeh

2010-11-01

In a realistic three-dimensional model, optical matrix element and linear optical absorption of zigzag single walled boron nitride nanotubes (BNNTs) in the tight binding approximation are studied. In terms of absolute value of dipole matrix elements of the first three direct transitions at kz=0, we divided the zigzag BNNTs into three groups and investigated their optical absorption spectrum in energy ranges E<5, 77.5 eV. We found that in lower energies, E<5 eV, all groups show different behaviors while in the higher energies, 77.5 eV, their behaviors depend on their even or odd nanotube index. We also found that in the energy range 7

Polypyrrole polyvinylidene difluoride composite stripe and zigzag actuators for use in facial robotics

NASA Astrophysics Data System (ADS)

Tadesse, Yonas; Priya, Shashank; Ramannair Chenthamarakshan, C.; de Tacconi, Norma R.; Rajeshwar, Krishnan

2008-04-01

Composite stripe and zigzag actuators consisting of a sandwich polypyrrole (PPy)/polyvinylidene difluoride (PVDF)/PPy structure were synthesized using potentiodynamic film growth on gold electrodes. The synthesis was done from an aqueous solution containing tetrabutylammonium perchlorate and pyrrole by polymerization at room temperature. The actuator displacement was modeled using finite element simulations. For depositing thin PPy films and thereby minimizing the response time, experimental optimization of the deposition conditions was performed. The number of current-potential (potentiodynamic) growth cycles and the thickness of the deposited PPy film were highly correlated in the initial stages of polymer film growth. The actuation response measurements indicate that the zigzag shaped actuators provide promising properties to develop artificial muscle.

Which nanowire couples better electrically to a metal contact: Armchair or zigzag nanotube?

NASA Technical Reports Server (NTRS)

Anantram, M. P.; Biegel, Bryan (Technical Monitor)

2001-01-01

The fundamental question of how chirality affects tile electronic coupling of a nanotube to metal contacts is important for tile application of nanotubes as nanowires. We show that metallic-zigzag nanotubes are superior to armchair nanotubes as nanowires, by modeling the metal-nanotube interface. More specifically, we show that as a function of coupling strength, the total electron transmission of armchair nanotubes increases and tends to be pinned close to unity for a metal with Fermi wave vector close to that of gold. In contrast, the transmission probability of zigzag nanotubes increases to the maximum possible value of two. The origin of these effects lies in the details of the wave function, which is explained.

Giant magnetoresistance in perpendicularly magnetized synthetic antiferromagnetic coupling with Ir spacer

NASA Astrophysics Data System (ADS)

Fukushima, A.; Taniguchi, T.; Sugihara, A.; Yakushiji, K.; Kubota, H.; Yuasa, S.

2018-05-01

Perpendicularly magnetized magnetic tunnel junction (p-MTJ) is a key element for developing high-density spin-transfer torque switching magnetoresistive random access memory. Recently, a large exchange coupling (IEC) in the synthetic antiferromagnetic reference layer with Ir interlayer was observed in p-MTJs. The evaluation of the IEC is, however, difficult due to the electrostatic breakdown of MTJs. This study demonstrates the evaluation of the IEC with Ir interlayer in giant magnetoresistive (GMR) nanopillar. We fabricated three kinds of perpendicularly magnetized GMR elements; bottom-free structures with Cu or Ir spacer, and top-free structure with Ir spacer. The magnetoresistance (RH) loops of all samples show sharp changes of the magnetoresistance at the magnetic fields over ±10 kOe, indicating the existence of the large IECs. In particular, a sharp change of the magnetoresistance at the field over ±20 kOe was found for the element with Cu of 2 nm thickness.

Pillared graphene on the basis of zigzag carbon nanotubes for adsorption in medicine: mechanical properties

NASA Astrophysics Data System (ADS)

Kolesnikova, Anna S.; Mazepa, Margarita M.

2018-02-01

In nowadays the nanoscale materials are actively used in medicine, based on the properties of adsorption. One of the main problems of this field of medicine is the increase in specific surface of sorbent. We proposed to use carbon composites consisting of an extended in its directions graphene sheet with attached to it by chemical bonds zigzag carbon nanotubes (CNT). This paper presents the results of a theoretical study of the mechanical properties of graphene based on the CNT zigzag depending on the geometric dimensions of the composite (length and diameter of CNTs).

A structural and electronic comparison of armchair and zigzag epitaxial graphene sidewall nanoribbons

NASA Astrophysics Data System (ADS)

Nevius, Meredith; Wang, F.; Palacio, I.; Celis, A.; Tejeda, A.; Taleb-Ibrahimi, A.; de Heer, W.; Berger, C.; Conrad, E.

2014-03-01

Graphene grown on sidewalls of trenches etched in SiC shows particular promise as a candidate for post-Si CMOS electronics because of its ballistic transport, exceptional mobilities, low intrinsic doping, and the opening of a large band gap. However, before definitive progress can be made toward epitaxial graphene-based transistors, we must fully understand the nuances of graphene ribbon growth on different SiC facets. We have now confirmed that sidewall ribbons grown in graphene's two primary crystallographic directions (``armchair'' and ``zigzag'') differ greatly in both structure and electronic band-structure. We present data from both geometries obtained using low-energy electron microscopy (LEEM), low-energy electron diffraction (LEED), angle-resolved photoemission spectroscopy (ARPES), photoemission electron microscopy (PEEM), micro-ARPES and dark-field micro-ARPES. We demonstrate that while graphene grows on stable facets of trenches oriented for armchair edge growth, trenches oriented for zigzag edge growth prefer narrow ribbons of graphene on the (0001) surface near the trench edge. The structure of these zigzag edge graphene ribbons is complex and paramount to understanding their transport. This work was supported by the NSF under grants DMR-1005880 and DMR-0820382, the W. M. Keck Foundation and the Partner University Fund from the Embassy of France

High power tube solid-state laser with zigzag propagation of pump and laser beam

NASA Astrophysics Data System (ADS)

Savich, Michael

2015-02-01

A novel resonator and pumping design with zigzag propagation of pumping and laser beams permits to design an improved tube Solid State Laser (SSL), solving the problem of short absorption path to produce a high power laser beam (100 - 1000kW). The novel design provides an amplifier module and laser oscillator. The tube-shaped SSL includes a gain element fiber-optically coupled to a pumping source. The fiber optic coupling facilitates light entry at compound Brewster's angle of incidence into the laser gain element and uses internal reflection to follow a "zigzag" path in a generally spiral direction along the length of the tube. Optics are arranged for zigzag propagation of the laser beam, while the cryogenic cooling system is traditional. The novel method of lasing uses advantages of cylindrical geometry to reach the high volume of gain medium with compactness and structural rigidity, attain high pump density and uniformity, and reach a low threshold without excessive increase of the temperature of the crystal. The design minimizes thermal lensing and stress effects, and provides high gain amplification, high power extraction from lasing medium, high pumping and lasing efficiency and a high beam quality.

A Conserved Helicase Processivity Factor Is Needed for Conjugation and Replication of an Integrative and Conjugative Element

PubMed Central

Thomas, Jacob; Lee, Catherine A.; Grossman, Alan D.

2013-01-01

Integrative and conjugative elements (ICEs) are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT) by the ICE–encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP), encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability. PMID:23326247

[Identification of medicinal plant Dendrobium based on the chloroplast psbK-psbI intergenic spacer].

PubMed

Yao, Hui; Yang, Pei; Zhou, Hong; Ma, Shuang-jiao; Song, Jing-yuan; Chen, Shi-lin

2015-06-01

In this paper, the chloroplast psbK-psbI intergenic spacers of 18 species of Dendrobium and their adulterants were amplified and sequenced, and then the sequence characteristics were analyzed. The sequence lengths of chloroplast psbK-psbI regions of Dendrobium ranged from 474 to 513 bp and the GC contents were 25.4%-27.6%. The variable sites were 71 while the informative sites were 46. The inter-specific genetic distances calculated by Kimura 2-parameter (K2P) of Dendrobium were 0.006 1-0.058 1, with an average of 0.028 4. The K2P genetic distances between Dendrobium species and Bulbophyllum odoratissimum were 0.093 2-0.120 4. The NJ tree showed that the Dendrobium species can be easily differentiated from each other and 6 samples of the inspected Dendrobium species were identified successfully through sequencing the psbK-psbI intergenic spacer. Therefore, the chloroplast psbK-psbI intergenic spacer can be used as a candidate marker to identify Dendrobium species and its adulterants.

Vectorization of agrochemicals: amino acid carriers are more efficient than sugar carriers to translocate phenylpyrrole conjugates in the Ricinus system.

PubMed

Wu, Hanxiang; Marhadour, Sophie; Lei, Zhi-Wei; Yang, Wen; Marivingt-Mounir, Cécile; Bonnemain, Jean-Louis; Chollet, Jean-François

2018-05-01

Producing quality food in sufficient quantity while using less agrochemical inputs will be one of the great challenges of the twenty-first century. One way of achieving this goal is to greatly reduce the doses of plant protection compounds by improving the targeting of pests to eradicate. Therefore, we developed a vectorization strategy to confer phloem mobility to fenpiclonil, a contact fungicide from the phenylpyrrole family used as a model molecule. It consists in coupling the antifungal compound to an amino acid or a sugar, so that the resulting conjugates are handled by active nutrient transport systems. The method of click chemistry was used to synthesize three conjugates combining fenpiclonil to glucose or glutamic acid with a spacer containing a triazole ring. Systemicity tests with the Ricinus model have shown that the amino acid promoiety was clearly more favorable to phloem mobility than that of glucose. In addition, the transport of the amino acid conjugate is carrier mediated since the derivative of the L series was about five times more concentrated in the phloem sap than its counterpart of the D series. The systemicity of the L-derivative is pH dependent and almost completely inhibited by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). These data suggest that the phloem transport of the L-derivative is governed by a stereospecific amino acid carrier system energized by the proton motive force.

Advanced hole patterning technology using soft spacer materials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Park, Jong Keun; Hustad, Phillip D.; Aqad, Emad; Valeri, David; Wagner, Mike D.; Li, Mingqi

2017-03-01

A continuing goal in integrated circuit industry is to increase density of features within patterned masks. One pathway being used by the device manufacturers for patterning beyond the 80nm pitch limitation of 193 immersion lithography is the self-aligned spacer double patterning (SADP). Two orthogonal line space patterns with subsequent SADP can be used for contact holes multiplication. However, a combination of two immersion exposures, two spacer deposition processes, and two etch processes to reach the desired dimensions makes this process expensive and complicated. One alternative technique for contact hole multiplication is the use of an array of pillar patterns. Pillars, imaged with 193 immersion photolithography, can be uniformly deposited with spacer materials until a hole is formed in the center of 4 pillars. Selective removal of the pillar core gives a reversal of phases, a contact hole where there was once a pillar. However, the highly conformal nature of conventional spacer materials causes a problem with this application. The new holes, formed between 4 pillars, by this method have a tendency to be imperfect and not circular. To improve the contact hole circularity, this paper presents the use of both conventional spacer material and soft spacer materials. Application of soft spacer materials can be achieved by an existing coating track without additional cost burden to the device manufacturers.

Optimizing Soft Tissue Management and Spacer Design in Segmental Bone Defects

DTIC Science & Technology

2016-12-01

proximal and distal bone segments. 3. Debride 10 grams of tibialis anterior and gastrocnemius muscles. 4. Place an interlocking intramedullary nail ...using a custom spacer to maintain 5-cm defect length. 5. Place a pre-molded 5 cm long x 2 cm diameter PMMA spacer around the nail in the defect. 6...tibia. 3. Open the IM surrounding the PMMA spacer using a “bomb bay door opening”. 4. Remove the spacer without damaging the membrane or nail . 5

Measurements and sensitivities of LWR in poly spacers

NASA Astrophysics Data System (ADS)

Ayal, Guy; Shauly, Eitan; Levi, Shimon; Siany, Amit; Adan, Ofer; Shacham-Diamand, Yosi

2010-03-01

LER and LWR have long been considered a primary issue in process development and monitoring. Development of a low power process flavors emphasizes the effect of LER, LWR on different aspects of the device. Gate level performance, particularly leakage current at the front end of line, resistance and reliability in the back-end layers. Traditionally as can be seen in many publications, for the front end of line the focus is mainly on Poly and Active area layers. Poly spacers contribution to the gate leakage, for example, is rarely discussed. Following our research done on sources of gate leakage, we found leakage current (Ioff) in some processes to be highly sensitive to changes in the width of the Poly spacers - even more strongly to the actual Poly gate CDs. Therefore we decided to measure Poly spacers LWR, its correlation to the LWR in the poly, and its sensitivity to changes in layout and OPC. In our last year publication, we defined the terms LLER (Local Line Edge Roughness) and LLWR (Local Line Width Roughness). The local roughness is measured as the 3-sigma value of the line edge/width in a 5-nm segment around the measurement point. We will use these terms in this paper to evaluate the Poly roughness impact on Poly spacer's roughness. A dedicated test chip was designed for the experiments, having various transistors layout configurations with different densities to cover the all range of process design rules. Applied Materials LER and LWR innovative algorithms were used to measure and characterize the spacer roughness relative to the distance from the active edges and from other spaces. To accurately measure all structures in a reasonable time, the recipes were automatically generated from CAD. On silicon, after poly spacers generation, the transistors no longer resemble the Poly layer CAD layout, their morphology is different compared with Photo/Etch traditional structures , and dimensions vary significantly. In this paper we present metrology and

Molecular authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii by ITS and 5S rRNA spacer sequencing.

PubMed

Sun, Ye; Shaw, Pang-Chui; Fung, Kwok-Pui

2007-01-01

In the present study, we examined nuclear DNA sequences in an attempt to reveal the relationships between Pueraria lobata (Willd). Ohwi, P. thomsonii Benth., and P. montana (Lour.) Merr. We found that internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA are highly divergent in P. lobata and P. thomsonii, and four types of ITS with different length are found in the two species. On the other hand, DNA sequences of 5S rRNA gene spacer are highly conserved across multiple copies in P. lobata and P. thomsonii, they could be used to identify P. lobata, P. thomsonii, and P. montana of this complex, and may serve as a useful tool in medical authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii.

Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

PubMed

Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing

2016-11-01

The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1 H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher K a and P eff than CsA suspension in the duodenum and jejunum segments (p <  0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

Mobilization of the relaxable Staphylococcus aureus plasmid pC221 by the conjugative plasmid pGO1 involves three pC221 loci.

PubMed Central

Projan, S J; Archer, G L

1989-01-01

The Staphylococcus aureus plasmid pC221, a 4.6-kilobase multicopy chloramphenicol resistance plasmid that forms plasmid-protein relaxation complexes, was mobilized for transfer by the conjugative plasmid pGO1. Two open reading frames on the pC221 genome, now designated mobA and mobB, as well as a cis-acting locus, the putative oriT, were shown to be in involved in pC221 mobilization. The mobA (but not mobB) and oriT loci were required for pC221 relaxation, and relaxation was necessary but not sufficient for pC221 mobilization by pGO1. oriT was cloned onto a pE194 derivative and complemented in trans for both relaxation and mobilization. Mobilization of relaxable plasmids in S. aureus appears to be analogous to mobilization by donation observed in gram-negative bacteria. Images PMID:2703461

Orthognathic model surgery with LEGO key-spacer.

PubMed

Tsang, Alfred Chee-Ching; Lee, Alfred Siu Hong; Li, Wai Keung

2013-12-01

A new technique of model surgery using LEGO plates as key-spacers is described. This technique requires less time to set up compared with the conventional plaster model method. It also retains the preoperative setup with the same set of models. Movement of the segments can be measured and examined in detail with LEGO key-spacers. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Meta-Analysis Comparing Zero-Profile Spacer and Anterior Plate in Anterior Cervical Fusion.

PubMed

Dong, Jun; Lu, Meng; Lu, Teng; Liang, Baobao; Xu, Junkui; Zhou, Jun; Lv, Hongjun; Qin, Jie; Cai, Xuan; Huang, Sihua; Li, Haopeng; Wang, Dong; He, Xijing

2015-01-01

Anterior plate fusion is an effective procedure for the treatment of cervical spinal diseases but is accompanied by a high incidence of postoperative dysphagia. A zero profile (Zero-P) spacer is increasingly being used to reduce postoperative dysphagia and other potential complications associated with surgical intervention. Studies comparing the Zero-P spacer and anterior plate have reported conflicting results. A meta-analysis was conducted to compare the safety, efficacy, radiological outcomes and complications associated with the use of a Zero-P spacer versus an anterior plate in anterior cervical spine fusion for the treatment of cervical spinal disease. We comprehensively searched PubMed, Embase, the Cochrane Library and other databases and performed a meta-analysis of all randomized controlled trials (RCTs) and prospective or retrospective comparative studies assessing the two techniques. Ten studies enrolling 719 cervical spondylosis patients were included. The pooled data showed significant differences in the operation time [SMD = -0.58 (95% CI = -0.77 to 0.40, p < 0.01)] and blood loss [SMD = -0.40, 95% CI (-0.59 to -0.21), p < 0.01] between the two groups. Compared to the anterior plate group, the Zero-P group exhibited a significantly improved JOA score and reduced NDI and VAS. However, anterior plate fusion had greater postoperative segmental and cervical Cobb's angles than the Zero-P group at the last follow-up. The fusion rate in the two groups was similar. More importantly, the Zero-P group had a lower incidence of earlier and later postoperative dysphagia. Compared to anterior plate fusion, Zero-P is a safer and effective procedure, with a similar fusion rate and lower incidence of earlier and later postoperative dysphagia. However, the results of this meta-analysis should be accepted with caution due to the limitations of the study. Further evaluation and large-sample RCTs are required to confirm and update the results of this study.

Complementation of Conjugation Functions of Streptomyces lividans Plasmid pIJ101 by the Related Streptomyces Plasmid pSB24.2

PubMed Central

Pettis, Gregg S.; Prakash, Shubha

1999-01-01

A database search revealed extensive sequence similarity between Streptomyces lividans plasmid pIJ101 and Streptomyces plasmid pSB24.2, which is a deletion derivative of Streptomyces cyanogenus plasmid pSB24.1. The high degree of relatedness between the two plasmids allowed the construction of a genetic map of pSB24.2, consisting of putative transfer and replication loci. Two pSB24.2 loci, namely, the cis-acting locus for transfer (clt) and the transfer-associated korB gene, were shown to be capable of complementing the pIJ101 clt and korB functions, respectively, a result that is consistent with the notion that pIJ101 and the parental plasmid pSB24.1 encode highly similar, if not identical, conjugation systems. PMID:10419972

Conjugation of isoniazid to a zinc phthalocyanine via hydrazone linkage for pH-dependent liposomal controlled release

NASA Astrophysics Data System (ADS)

Nkanga, Christian Isalomboto; Krause, Rui Werner Maçedo

2018-05-01

Tuberculosis (TB) remains the leading cause of mortality from infectious diseases. Extended TB treatment and frequent adverse effects, due to poor bioavailability of anti-tubercular drugs (ATBDs), represent the main rationales behind liposomal encapsulation for controlled delivery. Liposomes have been reported as potential vehicles for targeted delivery of ATBDs due to their rapid uptake by macrophages, which are known as the main host cells for TB causative agent (Mycobacterium tuberculosis). Additionally, the need for controlled release of ATBDs arises because leakage is part of the key liposome challenges for hydrophilic compounds like isoniazid (INH). In this study, INH was conjugated to a highly hydrophobic photosensitizer, zinc (II) phthalocyanine (PC), through hydrazone bonding. The obtained conjugate (PC-INH) was encapsulated in liposomes by film hydration method. PC-INH loaded liposomes (PILs) were characterized using dynamic light scattering, transmission electron microscopy, energy-dispersive X-ray spectrometry and UV-Vis absorption spectrometry, which was used also for estimation of encapsulation efficiency (%EE). INH release was evaluated in different pH media using dialysis. Particle size, zeta potential and %EE of PILs were about 506 nm, - 55 mV and 72%, respectively. Over 12 h, PILs exhibited 22, 41, 97 and 100% of INH, respectively, released in pH 7.4, 6.4, 5.4 and 4.4 media. This pH-dependent behavior is attractive for site-specific delivery. These findings suggest the conjugation of chemotherapeutics to phthalocyanines using pH-labile linkages as a potential strategy for liposomal controlled release.

[Aerosol deposition and clinical performance verified with a spacer device made in Brazil

PubMed

Camargos, P A; Rubim, J A; Simal, C J; Lasmar, L M

2000-01-01

OBJECTIVE: To assess the lung deposition pattern of radioaerosol and the clinical performance of a spacer developed and made in Brazil. METHODS: Qualitative - in a patient with cystic fibrosis - and semi-quantitative - in two healthy volunteers - assessment of pulmonary deposition of (99)mtechnetium was done using the Aerogama Medical oxigen driven nebulizer system attached to the spacer and a gama-camera (Siemens, model Orbiter) connected to a microcomputer. In the next step, clinical assessment was carried out in 50 asthmatic children, aged from four months to 13 years old with an acute attack, using conventional doses of albuterol through a metered dose inhaler attached to the spacer device. RESULTS: Qualitative assessment revealed a lung silhouette comparable with those obtained in the inhalation scintigraphy and semiquantitative assessment reveals that 7.5% to 8.0% of the inhaled (99m)technetium reached the volunteerś lungs. Statistically significant differences (p < 0.001) were observed comparing clinical scores at admission with those verified 20 and 40 minutes after albuterol inhalation; conversely, no significance was obtained for scores taken at 60 and 80 minutes. CONCLUSIONS: Although we used an alternative method, the scintigraphic assessment reveals an expected pattern of pulmonary deposition. Similarly, clinical performance in the treatment of an acute attack showed results comparable with those obtained with other spacers devices.

Characterization of replication and conjugation of plasmid pWTY27 from a widely distributed Streptomyces species

PubMed Central

2012-01-01

Background Streptomyces species are widely distributed in natural habitats, such as soils, lakes, plants and some extreme environments. Replication loci of several Streptomyces theta-type plasmids have been reported, but are not characterized in details. Conjugation loci of some Streptomyces rolling-circle-type plasmids are identified and mechanism of conjugal transferring are described. Results We report the detection of a widely distributed Streptomyces strain Y27 and its indigenous plasmid pWTY27 from fourteen plants and four soil samples cross China by both culturing and nonculturing methods. The complete nucleotide sequence of pWTY27 consisted of 14,288 bp. A basic locus for plasmid replication comprised repAB genes and an adjacent iteron sequence, to a long inverted-repeat (ca. 105 bp) of which the RepA protein bound specifically in vitro, suggesting that RepA may recognize a second structure (e.g. a long stem-loop) of the iteron DNA. A plasmid containing the locus propagated in linear mode when the telomeres of a linear plasmid were attached, indicating a bi-directional replication mode for pWTY27. As for rolling-circle plasmids, a single traA gene and a clt sequence (covering 16 bp within traA and its adjacent 159 bp) on pWTY27 were required for plasmid transfer. TraA recognized and bound specifically to the two regions of the clt sequence, one containing all the four DC1 of 7 bp (TGACACC) and one DC2 (CCCGCCC) and most of IC1, and another covering two DC2 and part of IC1, suggesting formation of a high-ordered DNA-protein complex. Conclusions This work (i) isolates a widespread Streptomyces strain Y27 and sequences its indigenous theta-type plasmid pWTY27; (ii) identifies the replication and conjugation loci of pWTY27 and; (iii) characterizes the binding sequences of the RepA and TraA proteins. PMID:23134842

Co-assembly of Zn(SPh){sub 2} and organic linkers into helical and zig-zag polymer chains

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

Liu Yi; Yu Lingmin; Loo, Say Chye Joachim

2012-07-15

Two novel one-dimensional coordination polymers, single helicate [Zn(SPh){sub 2}(TPyTA)(EG)]{sub n} (EG=ethylene glycol) (1) and zig-zag structure [Zn(SPh){sub 2}(BPyVB)]{sub n} (2), were synthesized under solvothermal conditions at 150 Degree-Sign C or room temperature by the co-assembly of Zn(SPh){sub 2} and organic linkers such as 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPyTA) and 1,3-bis(trans-4-pyridylvinyl)benzene (BPyVB). X-ray crystallography study reveals that both polymers 1 and 2 crystallize in space group P2{sub 1}/c of the monoclinic system. The solid-state UV-vis absorption spectra show that 1 and 2 have maxium absorption onsets at 400 nm and 420 nm, respectively. TGA analysis indicates that 1 and 2 are stable up tomore » 110 Degree-Sign C and 210 Degree-Sign C. - Graphical abstract: Two novel one-dimensional coordination polymers, single helicate [Zn(SPh){sub 2}(TPyTA)(EG)]{sub n} (1) and zig-zag structure [Zn(SPh){sub 2}(BPyVB)]{sub n} (2), were synthesized. Solid-state UV-vis absorptions show that 1 and 2 have maxium absorption onsets at 400 nm and 420 nm, respectively. TGA analysis indicates that 1 and 2 are stable up to 110 Degree-Sign C and 210 Degree-Sign C. Highlights: Black-Right-Pointing-Pointer Two novel one-dimensional coordination polymers have been synthesized. Black-Right-Pointing-Pointer TPyTA results in helical structures in 1 while BPyVB leads to zig-zag chains in 2. Black-Right-Pointing-Pointer Solid-state UV-vis absorption spectra and TGA analysis of the title polymers were studied.« less

Outcomes of Articulating Spacers With Autoclaved Femoral Components in Total Knee Arthroplasty Infection.

PubMed

Goltz, Daniel E; Sutter, E Grant; Bolognesi, Michael P; Wellman, Samuel S

2018-03-30

In 2-stage revision of total knee arthroplasty (TKA) infection, articulating antibiotic spacers show similar eradication rates and superior range of motion compared with static spacers. This study evaluated infection control and other outcomes in articulating spacers with an autoclaved index femoral component. We reviewed 59 patients who underwent 2-stage treatment of TKA infection using articulating antibiotic spacers with an autoclaved femoral component with at least 2-year follow-up (mean: 5.0 years) from spacer placement. Reinfection was defined as any subsequent infection; recurrence was defined as reinfection with the same organism, need for chronic antibiotics, or conversion directly to amputation/arthrodesis. Nine patients (15%) experienced a recurrence and 22 patients (37%) experienced a reinfection. Incidence of diabetes mellitus was significantly higher in patients who became reinfected. Other comorbidities, revision history, prior spacer, or presence of virulent organisms did not predict infection recurrence. Forty-seven spacers underwent reimplantation, 6 (13%) of these went on to above-knee amputation, 6 (13%) received another 2-stage procedure, and 3 (6%) underwent subsequent irrigation and debridement. Three patients (5%) proceeded directly from spacer to above-knee amputation (2) or arthrodesis (1). Nine spacers (15%) in 7 patients were retained indefinitely (mean: 3.4 years), with overall good motion and function. Accounting for methodology, articulating spacers with autoclaved femoral components provide similar infection control to previous reports. Most patients with reinfection grew different organisms compared with initial infection, suggesting that some subsequent infections may be host related. Some patients retained spacers definitively with overall good patient satisfaction. Copyright © 2018 Elsevier Inc. All rights reserved.

Experimental Study of Two Phase Flow Behavior Past BWR Spacer Grids

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

Ratnayake, Ruwan K.; Hochreiter, L.E.; Ivanov, K.N.

2002-07-01

Performance of best estimate codes used in the nuclear industry can be significantly improved by reducing the empiricism embedded in their constitutive models. Spacer grids have been found to have an important impact on the maximum allowable Critical Heat Flux within the fuel assembly of a nuclear reactor core. Therefore, incorporation of suitable spacer grids models can improve the critical heat flux prediction capability of best estimate codes. Realistic modeling of entrainment behavior of spacer grids requires understanding the different mechanisms that are involved. Since visual information pertaining to the entrainment behavior of spacer grids cannot possibly be obtained frommore » operating nuclear reactors, experiments have to be designed and conducted for this specific purpose. Most of the spacer grid experiments available in literature have been designed in view of obtaining quantitative data for the purpose of developing or modifying empirical formulations for heat transfer, critical heat flux or pressure drop. Very few experiments have been designed to provide fundamental information which can be used to understand spacer grid effects and phenomena involved in two phase flow. Air-water experiments were conducted to obtain visual information on the two-phase flow behavior both upstream and downstream of Boiling Water Reactor (BWR) spacer grids. The test section was designed and constructed using prototypic dimensions such as the channel cross-section, rod diameter and other spacer grid configurations of a typical BWR fuel assembly. The test section models the flow behavior in two adjacent sub channels in the BWR core. A portion of a prototypic BWR spacer grid accounting for two adjacent channels was used with industrial mild steel rods for the purpose of representing the channel internals. Symmetry was preserved in this practice, so that the channel walls could effectively be considered as the channel boundaries. Thin films were established on the rod

Gallium(III) complexes of NOTA-bis (phosphonate) conjugates as PET radiotracers for bone imaging.

PubMed

Holub, Jan; Meckel, Marian; Kubíček, Vojtěch; Rösch, Frank; Hermann, Petr

2015-01-01

Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT. Copyright © 2014 John Wiley & Sons, Ltd.

The Conjugate Acid-Base Chart.

ERIC Educational Resources Information Center

Treptow, Richard S.

1986-01-01

Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

Enhancement of thermoelectric figure of merit in zigzag graphene nanoribbons with periodic edge vacancies

NASA Astrophysics Data System (ADS)

Kolesnikov, D. V.; Sadykova, O. G.; Osipov, V. A.

2017-06-01

The influence of periodic edge vacancies and antidot arrays on the thermoelectric properties of zigzag graphene nanoribbons (ZGNRs) are investigated. Using Green’s function method, the tight-binding approximation for the electron Hamiltonian and the 4th nearest neighbor approximation for the phonon dynamical matrix, we calculate the Seebeck coefficient and the thermoelectric figure of merit. It is found that, at a certain periodic arrangement of vacancies on both edges of zigzag nanoribbon, a finite band gap opens and almost twofold degenerate energy levels appear. As a result, a marked increase in the Seebeck coefficient takes place. It is shown that an additional enhancement of the thermoelectric figure of merit can be achieved by a combination of periodic edge defects with an antidot array.

Impact of ZnO embedded feed spacer on biofilm development in membrane systems.

PubMed

Ronen, Avner; Semiat, Raphael; Dosoretz, Carlos G

2013-11-01

The concept of suppressing biofouling formation using an antibacterial feed spacer was investigated in a bench scale-cross flow system mimicking a spiral wound membrane configuration. An antibacterial composite spacer containing zinc oxide-nanoparticles was constructed by modification of a commercial polypropylene feed spacer using sonochemical deposition. The ability of the modified spacers to repress biofilm development on membranes was evaluated in flow-through cells simulating the flow conditions in commercial spiral wound modules. The experiments were performed at laminar flow (Re = 300) with a 200 kDa molecular weight cut off polysulfone ultrafiltration membrane using Pseudomonas putida S-12 as model biofilm bacteria. The modified spacers reduced permeate flux decrease at least by 50% compared to the unmodified spacers (control). The physical properties of the modified spacer and biofilm development were evaluated using high resolution/energy dispersive spectrometry-scanning electron microscopy, atomic force microscopy and confocal laser scanning microscopy imaging (HRSEM, EDS, AFM and CLSM). HRSEM images depicted significantly less bacteria attached to the membranes exposed to the modified spacer, mainly scattered and in a sporadic monolayer structure. AFM analysis indicated the influence of the modification on the spacer surface including a phase change on the upper surface. Dead-live staining assay by CLSM indicated that most of the bacterial cells attached on the membranes exposed to the modified spacer were dead in contrast to a developed biofilm which was predominant in the control samples. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ultrafast intersystem-crossing in platinum containing π-conjugated polymers with tunable spin-orbit coupling.

PubMed

Sheng, C-X; Singh, S; Gambetta, A; Drori, T; Tong, M; Tretiak, S; Vardeny, Z V

2013-01-01

The development of efficient organic light-emitting diodes (OLED) and organic photovoltaic cells requires control over the dynamics of spin sensitive excitations. Embedding heavy metal atoms in π-conjugated polymer chains enhances the spin-orbit coupling (SOC), and thus facilitates intersystem crossing (ISC) from the singlet to triplet manifolds. Here we use various nonlinear optical spectroscopies such as two-photon absorption and electroabsorption in conjunction with electronic structure calculations, for studying the energies, emission bands and ultrafast dynamics of spin photoexcitations in two newly synthesized π-conjugated polymers that contain intrachain platinum (Pt) atoms separated by one (Pt-1) or three (Pt-3) organic spacer units. The controllable SOC in these polymers leads to a record ISC time of <~1 ps in Pt-1 and ~6 ps in Pt-3. The tunable ultrafast ISC rate modulates the intensity ratio of the phosphorescence and fluorescence emission bands, with potential applications for white OLEDs.

Impact of spacer thickness on biofouling in forward osmosis.

PubMed

Valladares Linares, R; Bucs, Sz S; Li, Z; AbuGhdeeb, M; Amy, G; Vrouwenvelder, J S

2014-06-15

Forward osmosis (FO) indirect desalination systems integrate wastewater recovery with seawater desalination. Niche applications for FO systems have been reported recently, due to the demonstrated advantages compared to conventional high-pressure membrane processes such as nanofiltration (NF) and reverse osmosis (RO). Among them, wastewater recovery has been identified to be particularly suitable for practical applications. However, biofouling in FO membranes has rarely been studied in applications involving wastewater effluents. Feed spacers separating the membrane sheets in cross-flow systems play an important role in biofilm formation. The objective of this study was to determine the influence of feed spacer thickness (28, 31 and 46 mil) on biofouling development and membrane performance in a FO system, using identical cross-flow cells in parallel studies. Flux development, biomass accumulation, fouling localization and composition were determined and analyzed. For all spacer thicknesses, operated at the same feed flow and the same run time, the same amount of biomass was found, while the flux reduction decreased with thicker spacers. These observations are in good agreement with biofouling studies for RO systems, considering the key differences between FO and RO. Our findings contradict previous cross-flow studies on particulate/colloidal fouling, where higher cross-flow velocities improved system performance. Thicker spacers reduced the impact of biofouling on FO membrane flux. Copyright © 2014 Elsevier Ltd. All rights reserved.

Properties of new Escherichia coli Hfr strains constructed by integration of pSC101-derived conjugative plasmids.

PubMed Central

François, V; Conter, A; Louarn, J M

1990-01-01

Conjugative temperature-sensitive plasmids were derived from pSC101. These plasmids are useful in genetic analysis for two reasons: (i) they render possible the construction of new Hfr lines by plasmid integration at predetermined chromosomal loci via Tn10 inverse transposition, and (ii) the Hfr characters are transducible via bacteriophage P1. We also showed that replication from pSC101 origin is deleterious for the plasmid-chromosome fusion. PMID:2155201

Apparatus and methods for aligning holes through wheels and spacers and stacking the wheels and spacers to form a turbine rotor

DOEpatents

Berry, Robert Randolph; Palmer, Gene David; Wilson, Ian David

2000-01-01

A gas turbine rotor stacking fixture includes upstanding bolts for reception in aligned bolt holes in superposed aft disk, wheels and spacers and upstanding alignment rods received in openings of the disk, wheels and spacers during the rotor stacking assembly. The axially registering openings enable insertion of thin-walled tubes circumferentially about the rim of the rotor, with tight tolerances to the openings to provide supply and return steam for cooling buckets. The alignment rods have radial dimensions substantially less than their dimensions in a circumferential direction to allow for radial opening misalignment due to thermal expansion, tolerance stack-up and wheel-to-spacer mismatch due to rabbet mechanical growth. The circumferential dimension of the alignment rods affords tightly toleranced alignment of the openings through which the cooling tubes are installed.

Optimized Design of Spacer in Electrodialyzer Using CFD Simulation Method

NASA Astrophysics Data System (ADS)

Jia, Yuxiang; Yan, Chunsheng; Chen, Lijun; Hu, Yangdong

2018-06-01

In this study, the effects of length-width ratio and diversion trench of the spacer on the fluid flow behavior in an electrodialyzer have been investigated through CFD simulation method. The relevant information, including the pressure drop, velocity vector distribution and shear stress distribution, demonstrates the importance of optimized design of the spacer in an electrodialysis process. The results show width of the diversion trench has a great effect on the fluid flow compared with length. Increase of the diversion trench width could strength the fluid flow, but also increase the pressure drop. Secondly, the dead zone of the fluid flow decreases with increase of length-width ratio of the spacer, but the pressure drop increases with the increase of length-width ratio of the spacer. So the appropriate length-width ratio of the space should be moderate.

An Implementation of RC4+ Algorithm and Zig-zag Algorithm in a Super Encryption Scheme for Text Security

NASA Astrophysics Data System (ADS)

Budiman, M. A.; Amalia; Chayanie, N. I.

2018-03-01

Cryptography is the art and science of using mathematical methods to preserve message security. There are two types of cryptography, namely classical and modern cryptography. Nowadays, most people would rather use modern cryptography than classical cryptography because it is harder to break than the classical one. One of classical algorithm is the Zig-zag algorithm that uses the transposition technique: the original message is unreadable unless the person has the key to decrypt the message. To improve the security, the Zig-zag Cipher is combined with RC4+ Cipher which is one of the symmetric key algorithms in the form of stream cipher. The two algorithms are combined to make a super-encryption. By combining these two algorithms, the message will be harder to break by a cryptanalyst. The result showed that complexity of the combined algorithm is θ(n2 ), while the complexity of Zig-zag Cipher and RC4+ Cipher are θ(n2 ) and θ(n), respectively.

Degradation Signals Recognized by the Ubc6p-Ubc7p Ubiquitin-Conjugating Enzyme Pair

PubMed Central

Gilon, Tamar; Chomsky, Orna; Kulka, Richard G.

2000-01-01

Proteolysis by the ubiquitin-proteasome system is highly selective. Specificity is achieved by the cooperation of diverse ubiquitin-conjugating enzymes (Ubcs or E2s) with a variety of ubiquitin ligases (E3s) and other ancillary factors. These recognize degradation signals characteristic of their target proteins. In a previous investigation, we identified signals directing the degradation of β-galactosidase and Ura3p fusion proteins via a subsidiary pathway of the ubiquitin-proteasome system involving Ubc6p and Ubc7p. This pathway has recently been shown to be essential for the degradation of misfolded and regulated proteins in the endoplasmic reticulum (ER) lumen and membrane, which are transported to the cytoplasm via the Sec61p translocon. Mutant backgrounds which prevent retrograde transport of ER proteins (hrd1/der3Δ and sec61-2) did not inhibit the degradation of the β-galactosidase and Ura3p fusions carrying Ubc6p/Ubc7p pathway signals. We therefore conclude that the ubiquitination of these fusion proteins takes place on the cytosolic face of the ER without prior transfer to the ER lumen. The contributions of different sequence elements to a 16-amino-acid-residue Ubc6p-Ubc7p-specific signal were analyzed by mutation. A patch of bulky hydrophobic residues was an essential element. In addition, positively charged residues were found to be essential. Unexpectedly, certain substitutions of bulky hydrophobic or positively charged residues with alanine created novel degradation signals, channeling the degradation of fusion proteins to an unidentified proteasomal pathway not involving Ubc6p and Ubc7p. PMID:10982838

Method of forming a spacer for field emission flat panel displays

DOEpatents

Bernhardt, Anthony F.; Contolini, Robert J.

1997-01-01

Spacers for applications such as field emission flat panel displays and vacuum microelectronics, and which involves the application of aerogel/xerogel technology to the formation of the spacer. In a preferred approach the method uses a mold and mold release agent wherein the gel precursor is a liquid which can be applied to the mold filling holes which expose the substrate (either the baseplate or the faceplate). A release agent is applied to the mold prior to precursor application to ease removal of the mold after formation of the dielectric spacer. The shrinkage of the gel during solvent extraction also improves mold removal. The final spacer material is a good dielectric, such as silica, secured to the substrate.

In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler

PubMed Central

Nair, Arun; Menzies, Daniel; Hopkinson, Pippa; McFarlane, Lesley; Lipworth, Brian J

2009-01-01

AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P = 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P = 0.009); the Nebuchamber 57% greater suppression (P = 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. PMID:19220273

Wheeze in childhood: is the spacer good enough?

PubMed Central

Rajkumar, Veena; Rajendra, Barathi; How, Choon How; Ang, Seng Bin

2014-01-01

Max was treated with SABA using an MDI and spacer with facemask and responded well to the initial treatment. You explained to the parents that nebulisers are neither required nor recommended in the treatment of wheezing in their child’s situation. You advised the parents on the proper technique of MDI use with spacer and facemask, as well as care of the equipment. You also gave them a clearly written action plan regarding the efficient management of the next episode of wheeze with MDI and spacer. You further explained the side effects of oral bronchodilators and nebulisers, and why you refrained from using them. Max was given a follow-up appointment to assess his progress, and his parents were advised on the situations when they should go to a doctor or the emergency department. PMID:25631964

Heterogeneous diversity of spacers within CRISPR

NASA Astrophysics Data System (ADS)

Deem, Michael; He, Jiankui

2011-03-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of anti-viral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face. 1) J. He and M. W. Deem, Phys. Rev. Lett. 105 (2010) 128102

Tube support grid and spacer therefor

DOEpatents

Ringsmuth, Richard J.; Kaufman, Jay S.

1986-01-01

A tube support grid and spacers therefor provide radially inward preloading of heat exchange tubes to minimize stress upon base welds due to differential thermal expansion. The grid comprises a concentric series of rings and spacers with opposing concave sides for conforming to the tubes and V-shaped ends to provide resilient flexibility. The flexibility aids in assembly and in transmitting seismic vibrations from the tubes to a shroud. The tube support grid may be assembled in place to achieve the desired inwardly radial preloading of the heat exchange tubes. Tab and slot assembly further minimizes stresses in the system. The radii of the grid rings may be preselected to effect the desired radially inward preloading.

Magnonic quantum spin Hall state in the zigzag and stripe phases of the antiferromagnetic honeycomb lattice

NASA Astrophysics Data System (ADS)

Lee, Ki Hoon; Chung, Suk Bum; Park, Kisoo; Park, Je-Geun

2018-05-01

We investigated the topological property of magnon bands in the collinear magnetic orders of zigzag and stripe phases for the antiferromagnetic honeycomb lattice and identified Berry curvature and symmetry constraints on the magnon band structure. Different symmetries of both zigzag and stripe phases lead to different topological properties, in particular, the magnon bands of the stripe phase being disentangled with a finite Dzyaloshinskii-Moriya (DM) term with nonzero spin Chern number. This is corroborated by calculating the spin Nernst effect. Our study establishes the existence of a nontrivial magnon band topology for all observed collinear antiferromagnetic honeycomb lattices in the presence of the DM term.

The application of pH-sensitive fluorescent dyes in lactic acid bacteria reveals distinct extrusion systems for unmodified and conjugated dyes.

PubMed

Glaasker, E; Konings, W N; Poolman, B

1996-01-01

Intracellular pH in bacteria can be measured efficiently between internal pH values of 6.5 and 8.5 with the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5[and-6]-carboxyfluorescein (BCECF). A new fluorescent pH probe with a lower pKa(app) than BCECF was synthesized from fluorescein isothiocyanate and glutamate. The new probe, N-(fluorescein thio-ureanyl)-glutamate (FTUG), was much less sensitive to changes in concentrations of KCl than was BCECF. Similar to BCECF, an efflux of FTUG independent of the proton motive force, but dependent on ATP, was observed both in Lactobacillus plantarum and Lactococcus lactis. Corrections for probe efflux allowed accurate measurements of the pHin. Similar intracellular pH values were determined with FTUG and BCECF, in the range where both probes can be applied, and the pH values correlated well with those estimated from the distribution of radio-labelled benzoic acid. Since FITC can easily be coupled to substrates containing an amino group, it is possible to develop other FITC derivatives as well. The mechanisms of probe excretion and the nature of the excreted product(s) were studied in further detail for BCECF and FTUG. BCECF was excreted from wild-type L. lactis in an unmodified form as was determined by chromatographic and mass spectrometry analysis. In the case of FTUG, the excreted product was a conjugated derivative. Unmodified FTUG was not excreted, although it was present in cellular extracts from L. lactis. Exit of BCECF was completely inhibited in a BCECF efflux mutant (Bef-) of L. lactis, whereas FTUG-conjugate efflux in this mutant was similar to the wild-type. Addition of indomethacin, a known inhibitor of BCECF efflux in human epithelial cells, resulted in complete inhibition of BCECF efflux in wild-type L. lactis, whereas FTUG-conjugate exit was only slightly affected. The results of the mutant and inhibitor studies suggest that FTUG-conjugate and BCECF efflux in L. lactis are mediated by different ATP

Pb4(OH)4(BrO3)3(NO3): An Example of SHG Crystal in Metal Bromates Containing π-Conjugated Planar Triangle.

PubMed

Kong, Fang; Hu, Chun-Li; Liang, Ming-Li; Mao, Jiang-Gao

2016-01-19

The first example of SHG crystal in the metal bromates containing π-conjugated planar triangle systems, namely, Pb4(OH)4(BrO3)3(NO3), was successfully synthesized via the hydrothermal method. Furthermore, a single crystal of centrosymmetric Pb8O(OH)6(BrO3)6(NO3)2·H2O was also obtained. Both compounds contain similar [Pb4(OH)4] cubane-like tetranuclear clusters, but they display different one-dimensional (1D) chain structures. Pb4(OH)4(BrO3)3(NO3) features a zigzag [Pb4(OH)4(BrO3)3](+) 1D chain, while Pb8O(OH)6(BrO3)6(NO3)2·H2O is composed of two different orthogonal chains: the linear [Pb4(OH)4(BrO3)2](2+) 1D chain along the b-axis and the zigzag [Pb4O2(OH)2(BrO3)4](2-) 1D chain along the a-axis. The NO3 planar triangles of the compounds are all isolated and located in the spaces of the structures. Pb4(OH)4(BrO3)3(NO3) exhibits the first example of SHG crystal in the metal bromates with π-conjugated planar triangle. The second-harmonic generation (SHG) efficiency of Pb4(OH)4(BrO3)3(NO3) is approximately equal to that of KDP and it is phase-matchable. Dipole moment and theory calculations indicate that BrO3, NO3, and PbO4 groups are the origin of its SHG efficiency, although some of the contributions cancel each other out.

Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and cinnamic acid-Pluronic F127 conjugate.

PubMed

Zhang, Hong; Kim, Jin-Chul

2016-01-01

Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.

COMPARISON OF PRESSURE DROP PRODUCED BY SPIRAL WRAPS, COOKIE CUTTERS AND OTHER ROD BUNDLE SPACERS

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

Noyes, R.C.

The problem of predicting pressure drop due to various fuel bundle spacers is considered in some detail. Three sets of experimental data are reviewed and presented in reduced form. These data are compared to several semitheoretical approaches to pressure drop prediction and a best method is selected to make the required predictions. The comparison between predictions for the ASCR spiral wrap spacer and cookie cutter spacer shows that both types of spacers produce about the same pressure drop. Spacer pressure drop is shown to be strongly dependent on spacer frontal area and pitch. (auth)

Thermal Lens Measurement in Diode-Pumped Nd:YAG Zig-Zag Slab

NASA Technical Reports Server (NTRS)

Smoak, M. C.; Kay, R. B.; Coyle, D. B.; Hopf, D.

1998-01-01

A major advantage that solid state zig-zag slab lasers have over conventional rod-based designs is that a much weaker thermal lens is produced in the slab when side-pumped with Quasi-CW laser diode arrays, particularly if the pump radiation is kept well away from the Brewster-cut ends. This paper reports on a rather strong thermal lens produced when diode pump radiation is collimated into a narrow portion of the zig-zag slab. The collimation of multi-bar pump packages to increase brightness and improve overlap is a direct consequence of designs which seek to maximize performance and efficiency. Our slab design employed a 8.1 cm x 2.5 mm x 5 mm slab with opposing Brewster end faces. It was pumped through the 2.5 mm direction by seven laser diode array packages, each housing four 6OW diode bars, 1 cm in width. The pump face, anti-reflection (AR) coated at 809 nm, was 6.8 cm in width and the 8.1 cm opposing side, high-reflection (HR) coated at 809 nm, reflected the unabsorbed pump beam for a second pass through the slab.

Annular flow in rod-bundle: Effect of spacer on disturbance waves

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

Pham, Son H.; Kunugi, Tomoaki

2016-08-01

A high-speed camera technique is used to study the effect of spacers on the disturbance waves present in annular two-phase flow within a rod-bundle geometry. Images obtained using a backlight configuration to visualize the spacer-wave interactions at the micro-scale resolution (in time and space) are discussed. This paper also presents additional images obtained using a reflected light configuration which provides new observations of the disturbance waves. These images show the separation effect caused by the spacer on the liquid film in which the size of generated liquid droplets can be controlled by the gas superficial velocity. Furthermore, the data confirmmore » that the spacer breaks the circumferential coherent structures of the waves.« less

Method of forming a spacer for field emission flat panel displays

DOEpatents

Bernhardt, A.F.; Contolini, R.J.

1997-08-19

Spacers are disclosed for applications such as field emission flat panel displays and vacuum microelectronics, and which involves the application of aerogel/xerogel technology to the formation of the spacer. In a preferred approach the method uses a mold and mold release agent wherein the gel precursor is a liquid which can be applied to the mold filling holes which expose the substrate (either the baseplate or the faceplate). A release agent is applied to the mold prior to precursor application to ease removal of the mold after formation of the dielectric spacer. The shrinkage of the gel during solvent extraction also improves mold removal. The final spacer material is a good dielectric, such as silica, secured to the substrate. 3 figs.

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

PubMed

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intramedullary rod and cement static spacer construct in chronically infected total knee arthroplasty.

PubMed

Kotwal, Suhel Y; Farid, Yasser R; Patil, Suresh S; Alden, Kris J; Finn, Henry A

2012-02-01

Two-stage reimplantation, with interval antibiotic-impregnated cement spacer, is the preferred treatment of prosthetic knee joint infections. In medically compromised hosts with prior failed surgeries, the outcomes are poor. Articulating spacers in such patients render the knee unstable; static spacers have risks of dislocation and extensor mechanism injury. We examined 58 infected total knee arthroplasties with extensive bone and soft tissue loss, treated with resection arthroplasty and intramedullary tibiofemoral rod and antibiotic-laden cement spacer. Thirty-seven patients underwent delayed reimplantation. Most patients (83.8%) were free from recurrent infection at mean follow-up of 29.4 months. Reinfection occurred in 16.2%, which required debridement. Twenty-one patients with poor operative risks remained with the spacer for 11.4 months. All patients, during spacer phase, had brace-free ambulation with simulated tibiofemoral fusion, without bone loss or loss of limb length. Copyright © 2012 Elsevier Inc. All rights reserved.

Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.

PubMed

Shankaraiah, Nagula; Nekkanti, Shalini; Brahma, Uma Rani; Praveen Kumar, Niggula; Deshpande, Namrata; Prasanna, Daasi; Senwar, Kishna Ram; Jaya Lakshmi, Uppu

2017-09-01

A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely, lung (A549 and NCI-H460), prostate (DU-145 and PC-3), colon (HCT-15 and HCT-116), and brain (U-87 glioblastoma) by MTT assay. Notably, among all the tested compounds, 4a exhibited potent cytotoxicity on NCI-H460 (lung cancer) cells with IC 50 of 1.48±0.19µM. The compound 4a showed significant inhibition of tubulin polymerization and disruption of the formation of microtubules (IC 50 of 9.66±0.06μM). Moreover, phase contrast microscopy and DAPI staining studies indicated that compound 4a can induce apoptosis in NCI-H460 cells. Further, the flow-cytometry analysis revealed that compound 4a arrests NCI-H460 cells in the G2/M phase of the cell cycle. In addition, molecular docking studies of the most active compounds 4a and 4b into the colchicine site of the tubulin, revealed the possible mode of interaction by these new conjugates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Separator-spacer for electrochemical systems

DOEpatents

Grimes, Patrick G.; Einstein, Harry; Newby, Kenneth R.; Bellows, Richard J.

1983-08-02

An electrochemical cell construction features a novel co-extruded plastic electrode in an interleaved construction with a novel integral separator-spacer. Also featured is a leak and impact resistant construction for preventing the spill of corrosive materials in the event of rupture.

Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

PubMed

Karami, Zahra; Sadighian, Somayeh; Rostamizadeh, Kobra; Parsa, Maliheh; Rezaee, Saeed

2016-04-01

A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz. Copyright © 2015 Elsevier B.V. All rights reserved.

WE-FG-BRA-02: Docetaxel Eluting Brachytherapy Spacers for Local Chemo-Radiation Therapy in Prostate Cancer

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

Belz, J; Kumar, R; Sridhar, S

Purpose: We propose an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a sustained drug delivery platform in the form of a spacer to locally radio-sensitize the prostate with Docetaxel (DTX) enabling a synergistic cure with the use of lower radiation doses. These biodegradable spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but are now loaded with formulations of DTX. Methods: Spacers were loaded with ∼500µg Docetaxel (DTX) for prostate cancer studies. The implants were characterized in vitro using SEM and HPLC. The release kinetic studies were carried out in buffer (pH 6.0)more » at 37°C. Subcutaneous PC3 tumors were xenografted in nude mice. Prostate cancer studies were done with and without radiation using SARRP at 5Gy, 10Gy, and 15Gy. Drug-loaded implants were injected once intratumorally using an 18G brachytherapy needle. Results: The release study in vitro showed a highly sustained release for multiple weeks at therapeutically relevant doses. The monotherapy with local DTX spacer showed sustained tumor inhibition compared to empty implants and an equivalent DTX dose given systemically. At 40 days, 89% survival was observed for mice treated with DTX implants compared with 0% in all other treatment groups. The combined treatment with local DTX spacer and radiation (10Gy) showed the highest degree of tumor suppression (significant tumor growth inhibition by day 90). The control mice showed continuous tumor growth and were scarified by day 56. Groups of mice treated with DTX-spacer or radiation alone showed initial tumor suppression but growth continued after day 60. A larger experiment is ongoing. Conclusion: This approach provides localized delivery of the chemotherapeutic sensitizer directly to the tumor and avoids the toxicities associated with both brachytherapy and current systemic delivery of docetaxel. Sustained release of DTX is an effective chemotherapy option

Bandgaps and directional properties of two-dimensional square beam-like zigzag lattices

NASA Astrophysics Data System (ADS)

Wang, Yan-Feng; Wang, Yue-Sheng; Zhang, Chuanzeng

2014-12-01

In this paper we propose four kinds of two-dimensional square beam-like zigzag lattice structures and study their bandgaps and directional propagation of elastic waves. The band structures are calculated by using the finite element method. Both the in-plane and out-of-plane waves are investigated simultaneously via the three-dimensional Euler beam elements. The mechanism of the bandgap generation is analyzed by studying the vibration modes at the bandgap edges. The effects of the geometry parameters of the xy- and z-zigzag lattices on the bandgaps are investigated and discussed. Multiple complete bandgaps are found owing to the separation of the degeneracy by introducing bending arms. The bandgaps are sensitive to the geometry parameters of the periodic systems. The deformed displacement fields of the harmonic responses of a finite lattice structure subjected to harmonic loads at different positions are illustrated to show the directional wave propagation. An extension of the proposed concept to the hexagonal lattices is also presented. The research work in this paper is relevant to the practical design of cellular structures with enhanced vibro-acoustics performance.

pH-responsive fluorescence chemical sensor constituted by conjugated polymers containing pyridine rings.

PubMed

Adachi, Naoya; Kaneko, Yuki; Sekiguchi, Kazuki; Sugiyama, Hiroki; Sugeno, Masafumi

2015-12-01

Poly(p-pyridinium phenylene ethynylene)s (PPyPE) functionalized with alternating donor-acceptor repeat units were synthesized by a Pd-catalyzed Sonogashira coupling reaction between diethynyl monomer and di-iodopyridine for use as a pH-responsive fluorescence chemical sensor. The synthesized PPyPE, containing pyridine units, was characterized by FT-IR, (1)H and (13)C NMR, UV-visible and fluorescence spectroscopies. We investigated the relationship between changes of optical properties and protonation/deprotonation of PPyPE containing pyridine units in solution. Addition of HCl decreased and red-shifted the fluorescence intensity of the conjugated polymers that contained pyridine rings; fluorescence intensity of the polymers increased upon addition of NaOH solution. The synthesized PPyPE was found to be an effective and reusable chemical sensor for pH sensing. Copyright © 2015 John Wiley & Sons, Ltd.

Study of structural and optical properties of ZnS zigzag nanostructured thin films

NASA Astrophysics Data System (ADS)

Rahchamani, Seyyed Zabihollah; Rezagholipour Dizaji, Hamid; Ehsani, Mohammad Hossein

2015-11-01

Zinc sulfide (ZnS) nanostructured thin films of different thicknesses with zigzag shapes have been deposited on glass substrates by glancing angle deposition (GLAD) technique. Employing a homemade accessory attached to the substrate holder enabled the authors to control the substrate temperature and substrate angle. The prepared samples were subjected to X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and UV-VIS. spectroscopy techniques. The structural studies revealed that the film deposited at room temperature crystallized in cubic structure. The FESEM images of the samples confirmed the formation of zigzag nano-columnar shape with mean diameter about 60-80 nm. By using the data obtained from optical studies, the real part of the refractive index (n), the absorption coefficient (α) and the band gap (Eg) of the samples were calculated. The results show that the refractive indices of the prepared films are very sensitive to deposition conditions.

Targeting biofilms and persisters of ESKAPE pathogens with P14KanS, a kanamycin peptide conjugate.

PubMed

Mohamed, Mohamed F; Brezden, Anna; Mohammad, Haroon; Chmielewski, Jean; Seleem, Mohamed N

2017-04-01

The worldwide emergence of antibiotic resistance represents a serious medical threat. The ability of these resistant pathogens to form biofilms that are highly tolerant to antibiotics further aggravates the situation and leads to recurring infections. Thus, new therapeutic approaches that adopt novel mechanisms of action are urgently needed. To address this significant problem, we conjugated the antibiotic kanamycin with a novel antimicrobial peptide (P14LRR) to develop a kanamycin peptide conjugate (P14KanS). Antibacterial activities were evaluated in vitro and in vivo using a Caenorhabditis elegans model. Additionally, the mechanism of action, antibiofilm activity and anti-inflammatory effect of P14KanS were investigated. P14KanS exhibited potent antimicrobial activity against ESKAPE pathogens. P14KanS demonstrated a ≥128-fold improvement in MIC relative to kanamycin against kanamycin-resistant strains. Mechanistic studies confirmed that P14KanS exerts its antibacterial effect by selectively disrupting the bacterial cell membrane. Unlike many antibiotics, P14KanS demonstrated rapid bactericidal activity against stationary phases of both Gram-positive and Gram-negative pathogens. Moreover, P14KanS was superior in disrupting adherent bacterial biofilms and in killing intracellular pathogens as compared to conventional antibiotics. Furthermore, P14KanS demonstrated potent anti-inflammatory activity via the suppression of LPS-induced proinflammatory cytokines. Finally, P14KanS protected C. elegans from lethal infections of both Gram-positive and Gram-negative pathogens. The potent in vitro and in vivo activity of P14KanS warrants further investigation as a potential therapeutic agent for bacterial infections. This study demonstrates that equipping kanamycin with an antimicrobial peptide is a promising method to tackle bacterial biofilms and address bacterial resistance to aminoglycosides. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrogel-coated feed spacers in two-phase flow cleaning in spiral wound membrane elements: a novel platform for eco-friendly biofouling mitigation.

PubMed

Wibisono, Yusuf; Yandi, Wetra; Golabi, Mohsen; Nugraha, Roni; Cornelissen, Emile R; Kemperman, Antoine J B; Ederth, Thomas; Nijmeijer, Kitty

2015-03-15

Biofouling is still a major challenge in the application of nanofiltration and reverse osmosis membranes. Here we present a platform approach for environmentally friendly biofouling control using a combination of a hydrogel-coated feed spacer and two-phase flow cleaning. Neutral (polyHEMA-co-PEG10MA), cationic (polyDMAEMA) and anionic (polySPMA) hydrogels have been successfully grafted onto polypropylene (PP) feed spacers via plasma-mediated UV-polymerization. These coatings maintained their chemical stability after 7 days incubation in neutral (pH 7), acidic (pH 5) and basic (pH 9) environments. Anti-biofouling properties of these coatings were evaluated by Escherichia coli attachment assay and nanofiltration experiments at a TMP of 600 kPag using tap water with additional nutrients as feed and by using optical coherence tomography. Especially the anionic polySPMA-coated PP feed spacer shows reduced attachment of E. coli and biofouling in the spacer-filled narrow channels resulting in delayed biofilm growth. Employing this highly hydrophilic coating during removal of biofouling by two-phase flow cleaning also showed enhanced cleaning efficiency, feed channel pressure drop and flux recoveries. The strong hydrophilic nature and the presence of negative charge on polySPMA are most probably responsible for the improved antifouling behavior. A combination of polySPMA-coated PP feed spacers and two-phase flow cleaning therefore is promising and an environmentally friendly approach to control biofouling in NF/RO systems employing spiral-wound membrane modules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adiabatic quantum pump in a zigzag graphene nanoribbon junction

NASA Astrophysics Data System (ADS)

Zhang, Lin

2015-11-01

The adiabatic electron transport is theoretically studied in a zigzag graphene nanoribbon (ZGNR) junction with two time-dependent pumping electric fields. By modeling a ZGNR p-n junction and applying the Keldysh Green’s function method, we find that a pumped charge current is flowing in the device at a zero external bias, which mainly comes from the photon-assisted tunneling process and the valley selection rule in an even-chain ZGNR junction. The pumped charge current and its ON and OFF states can be efficiently modulated by changing the system parameters such as the pumping frequency, the pumping phase difference, and the Fermi level. A ferromagnetic ZGNR device is also studied to generate a pure spin current and a fully polarized spin current due to the combined spin pump effect and the valley valve effect. Our finding might pave the way to manipulate the degree of freedom of electrons in a graphene-based electronic device. Project supported by the National Natural Science Foundation of China (Grant No. 110704033), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK2010416), and the Natural Science Foundation for Colleges and Universities in Jiangsu Province, China (Grant No. 13KJB140005).

Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A.

PubMed

Mustafa, Golam; Anderson, Ethan M; Bokrand-Donatelli, Yvonne; Neubert, John K; Caudle, Robert M

2013-11-01

Neuropathic pain is a debilitating condition resulting from damage to sensory transmission pathways in the peripheral and central nervous system. A potential new way of treating chronic neuropathic pain is to target specific pain-processing neurons based on their expression of particular receptor molecules. We hypothesized that a toxin-neuropeptide conjugate would alter pain by first being taken up by specific receptors for the neuropeptide expressed on the neuronal cells. Then, once inside the cell the toxin would inhibit the neurons' activity without killing the neurons, thereby providing pain relief without lesioning the nervous system. In an effort to inactivate the nociceptive neurons in the trigeminal nucleus caudalis in mice, we targeted the NK1 receptor (NK1R) using substance P (SP). The catalytically active light chain of botulinum neurotoxin type A (LC/A) was conjugated with SP. Our results indicate that the conjugate BoNT/A-LC:SP is internalized in cultured NK1R-expressing neurons and also cleaves the target of botulinum toxin, a component-docking motif necessary for release of neurotransmitters called SNAP-25. The conjugate was next tested in a murine model of Taxol-induced neuropathic pain. An intracisternal injection of BoNT/A-LC:SP decreased thermal hyperalgesia as measured by the operant orofacial nociception assay. These findings indicate that conjugates of the light chain of botulinum toxin are extremely promising agents for use in suppressing neuronal activity for extended time periods, and that BoNT/A-LC:SP may be a useful agent for treating chronic pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The Tcp conjugation system of Clostridium perfringens.

PubMed

Wisniewski, Jessica A; Rood, Julian I

2017-05-01

The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

A distributed parameter electromechanical model for bimorph piezoelectric energy harvesters based on the refined zigzag theory

NASA Astrophysics Data System (ADS)

Chen, Chung-De

2018-04-01

In this paper, a distributed parameter electromechanical model for bimorph piezoelectric energy harvesters based on the refined zigzag theory (RZT) is developed. In this model, the zigzag function is incorporated into the axial displacement, and the zigzag distribution of the displacement between the adjacent layers of the bimorph structure can be considered. The governing equations, including three equations of motions and one equation of circuit, are derived using Hamilton’s principle. The natural frequency, its corresponding modal function and the steady state response of the base excitation motion are given in exact forms. The presented results are benchmarked with the finite element method and two beam theories, the first-order shear deformation theory and the classical beam theory. Comparing examples shows that the RZT provides predictions of output voltage and generated power at high accuracy, especially for the case of a soft middle layer. Variation of the parameters, such as the beam thickness, excitation frequencies and the external electrical loads, is investigated and its effects on the performance of the energy harvesters are studied by using the RZT developed in this paper. Based on this refined theory, analysts and engineers can capture more details on the electromechanical behavior of piezoelectric harvesters.

The mechanism and control of DNA transfer by the conjugative relaxase of resistance plasmid pCU1

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

Nash, Rebekah Potts; Habibi, Sohrab; Cheng, Yuan

2010-11-15

Bacteria expand their genetic diversity, spread antibiotic resistance genes, and obtain virulence factors through the highly coordinated process of conjugative plasmid transfer (CPT). A plasmid-encoded relaxase enzyme initiates and terminates CPT by nicking and religating the transferred plasmid in a sequence-specific manner. We solved the 2.3 {angstrom} crystal structure of the relaxase responsible for the spread of the resistance plasmid pCU1 and determined its DNA binding and nicking capabilities. The overall fold of the pCU1 relaxase is similar to that of the F plasmid and plasmid R388 relaxases. However, in the pCU1 structure, the conserved tyrosine residues (Y18,19,26,27) that aremore » required for DNA nicking and religation were displaced up to 14 {angstrom} out of the relaxase active site, revealing a high degree of mobility in this region of the enzyme. In spite of this flexibility, the tyrosines still cleaved the nic site of the plasmid's origin of transfer, and did so in a sequence-specific, metal-dependent manner. Unexpectedly, the pCU1 relaxase lacked the sequence-specific DNA binding previously reported for the homologous F and R388 relaxase enzymes, despite its high sequence and structural similarity with both proteins. In summary, our work outlines novel structural and functional aspects of the relaxase-mediated conjugative transfer of plasmid pCU1.« less

First principles study on the electronic structures and transport properties of armchair/zigzag edge hybridized graphene nanoribbons

NASA Astrophysics Data System (ADS)

Yi, Xiuying; Long, Mengqiu; Liu, Anhua; Li, Mingjun; Xu, Hui

2018-05-01

Graphene nanoribbons (GNRs) can be mainly classified into armchair graphene nanoribbons (aGNRs) and zigzag graphene nanoribbons (zGNRs) by different edge chiral directions. In this work, by introducing Stone-Wales defects on the edges of the V-shaped aGNRs, we propose a kind of armchair/zigzag edge hybridized GNRs (a/zHGNRs) and using the density functional theory and the nonequilibrium Green's function method, the band structures and electronic transport properties of the a/zHGNRs have been calculated. Our results show that an indirect bandgap appears in the band structures of the a/zHGNRs, which is very different from the direct bandgap of aGNRs and gapless of zGNRs. We also find that the valance band is mainly derived from the armchair partial atoms on the hybridized edge, while the conduction band comes mainly from the zigzag partial atoms of the hybridized edge. Meanwhile, the bandgap also oscillates with a period of three when the ribbon width increases. In addition, our quantum transport calculations show that there is a remarkable transition between the semiconductor and the metal with different ribbon widths in the a/zHGNRs devices, and the corresponding physical analysis is given.

Soliton Analysis in Complex Molecular Systems: A Zig-Zag Chain

NASA Astrophysics Data System (ADS)

Christiansen, P. L.; Savin, A. V.; Zolotaryuk, A. V.

1997-06-01

A simple numerical method for seeking solitary wavesolutions of a permanent profile in molecular systems of big complexity is presented. The method is essentially based on the minimization of a finite-dimensional function which is chosen under an appropriate discretization of time derivatives in equations of motion. In the present paper, it is applied to a zig-zag chain backbone of coupled particles, each of which has twodegrees of freedom (longitudinal and transverse). Both topological and nontopological soliton solutions are treated for this chain when it is (i) subjected to a two-dimensional periodic substrate potential or (ii) considered as an isolated object, respectively. In the first case, which may be considered as a zig-zag generalization of the Frenkel-Kontorova chain model, two types of kink solutions with different topological charges, describing vacancies of one or two atoms (I- or II-kinks) and defects with excess one or two atoms in the chain (I- or II-antikinks), have been found. The second case (isolated chain) is a generalization of the well-known Fermi-Pasta-Ulam chain model, which takes into account transverse degrees of freedom of the chain molecules. Two types of stable nontopological soliton solutions which describe either (i) a supersonic solitary wave of longitudinal stretching accompanied by transverse slendering or (ii) supersonic pulses of longitudinal compression propagating together with localized transverse thickening (bulge) have been obtained.

A New, Simple and Versatile Strategy for the Synthesis of Short Segments of Zigzag-Type Carbon Nanotubes.

PubMed

André, Etienne; Boutonnet, Baptiste; Charles, Pauline; Martini, Cyril; Aguiar-Hualde, Juan-Manuel; Latil, Sylvain; Guérineau, Vincent; Hammad, Karim; Ray, Priyanka; Guillot, Régis; Huc, Vincent

2016-02-24

Short segments of zigzag single-walled carbon nanotubes (SWCNTs) were obtained from a calixarene scaffold by using a completely new, simple and expedited strategy that allowed fine-tuning of their diameters. This new approach also allows for functionalised short segments of zigzag SWCNTs to be obtained; a prerequisite towards their lengthening. These new SWCNT short segments/calixarene composites show interesting behaviour in solution. DFT analysis of these new compounds also suggests interesting photophysical behaviour. Along with the synthesis of various SWCNTs segments, this approach also constitutes a powerful tool for the construction of new, radially oriented π systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spacer geometry and particle deposition in spiral wound membrane feed channels.

PubMed

Radu, A I; van Steen, M S H; Vrouwenvelder, J S; van Loosdrecht, M C M; Picioreanu, C

2014-11-01

Deposition of microspheres mimicking bacterial cells was studied experimentally and with a numerical model in feed spacer membrane channels, as used in spiral wound nanofiltration (NF) and reverse osmosis (RO) membrane systems. In-situ microscopic observations in membrane fouling simulators revealed formation of specific particle deposition patterns for different diamond and ladder feed spacer orientations. A three-dimensional numerical model combining fluid flow with a Lagrangian approach for particle trajectory calculations could describe very well the in-situ observations on particle deposition in flow cells. Feed spacer geometry, positioning and cross-flow velocity sensitively influenced the particle transport and deposition patterns. The deposition patterns were not influenced by permeate production. This combined experimental-modeling approach could be used for feed spacer geometry optimization studies for reduced (bio)fouling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two-stage revision of septic knee prosthesis with articulating knee spacers yields better infection eradication rate than one-stage or two-stage revision with static spacers.

PubMed

Romanò, C L; Gala, L; Logoluso, N; Romanò, D; Drago, L

2012-12-01

The best method for treating chronic periprosthetic knee infection remains controversial. Randomized, comparative studies on treatment modalities are lacking. This systematic review of the literature compares the infection eradication rate after two-stage versus one-stage revision and static versus articulating spacers in two-stage procedures. We reviewed full-text papers and those with an abstract in English published from 1966 through 2011 that reported the success rate of infection eradication after one-stage or two-stage revision with two different types of spacers. In all, 6 original articles reporting the results after one-stage knee exchange arthoplasty (n = 204) and 38 papers reporting on two-stage revision (n = 1,421) were reviewed. The average success rate in the eradication of infection was 89.8% after a two-stage revision and 81.9% after a one-stage procedure at a mean follow-up of 44.7 and 40.7 months, respectively. The average infection eradication rate after a two-stage procedure was slightly, although significantly, higher when an articulating spacer rather than a static spacer was used (91.2 versus 87%). The methodological limitations of this study and the heterogeneous material in the studies reviewed notwithstanding, this systematic review shows that, on average, a two-stage procedure is associated with a higher rate of eradication of infection than one-stage revision for septic knee prosthesis and that articulating spacers are associated with a lower recurrence of infection than static spacers at a comparable mean duration of follow-up. IV.

The structures and electronic properties of zigzag silicene nanoribbons with periodically embedded with four- and eight-membered rings

NASA Astrophysics Data System (ADS)

Tan, Guiping; Lu, Junzhe; Zhu, Hengjiang; Li, Fangfang; Ma, Miaomiao; Wang, Xiaoning

2018-07-01

Using density functional theory (DFT), we have studied the structure of a zigzag silicene nanoribbons (SiNRs) with periodically embedded with four- and eight-membered rings, and studied their electronic properties by calculating its band structures and density of states (DOS). The results showed that the zigzag SiNRs have a sp2 hybridization, in addition, the band gap gradually decreased with the increase of the width by layer, and gradually changed from semiconductor properties to metal properties. The existence of vacancy defects increased the band gap and energies, but their positions could not change the structure and the electronic properties.

Articulating spacers used in two-stage revision of infected hip and knee prostheses abrade with time.

PubMed

Fink, Bernd; Rechtenbach, Annett; Büchner, Hubert; Vogt, Sebastian; Hahn, Michael

2011-04-01

Articulating spacers used in two-stage revision surgery of infected prostheses have the potential to abrade and subsequently induce third-body wear of the new prosthesis. We asked whether particulate material abraded from spacers could be detected in the synovial membrane 6 weeks after implantation when the spacers were removed for the second stage of the revision. Sixteen hip spacers (cemented prosthesis stem articulating with a cement cup) and four knee spacers (customized mobile cement spacers) were explanted 6 weeks after implantation and the synovial membranes were removed at the same time. The membranes were examined by xray fluorescence spectroscopy, xray diffraction for the presence of abraded particles originating from the spacer material, and analyzed in a semiquantitative manner by inductively coupled plasma mass spectrometry. Histologic analyses also were performed. We found zirconium dioxide in substantial amounts in all samples, and in the specimens of the hip synovial lining, we detected particles that originated from the metal heads of the spacers. Histologically, zirconium oxide particles were seen in the synovial membrane of every spacer and bone cement particles in one knee and two hip spacers. The observations suggest cement spacers do abrade within 6 weeks. Given the presence of abrasion debris, we recommend total synovectomy and extensive lavage during the second-stage reimplantation surgery to minimize the number of abraded particles and any retained bacteria.

Spectroscopy of nitrophenolates in vacuo: effect of spacer, configuration, and microsolvation on the charge-transfer excitation energy.

PubMed

Brøndsted Nielsen, Steen; Brøndsted Nielsen, Mogens; Rubio, Angel

2014-04-15

In a charge-transfer (CT) transition, electron density moves from one end of the molecule (donor) to the other end (acceptor). This type of transition is of paramount importance in nature, for example, in photosynthesis, and it governs the excitation of several protein biochromophores and luminophores such as the oxyluciferin anion that accounts for light emission from fireflies. Both transition energy and oscillator strength are linked to the coupling between the donor and acceptor groups: The weaker the coupling, the smaller the excitation energy. But a weak coupling necessarily also causes a low oscillator strength possibly preventing direct excitation (basically zero probability in the noncoupling case). The coupling is determined by the actual spacer between the two groups, and whether the spacer acts as an insulator or a conductor. However, it can be difficult or even impossible to distinguish the effect of the spacer from that of local solvent molecules that often cause large solvent shifts due to different ground-state and excited-state stabilization. This calls for gas-phase spectroscopy experiments where absorption by the isolated molecule is identified to unequivocally establish the intrinsic molecular properties with no perturbations from a microenvironment. From such insight, the effect of a protein microenvironment on the CT excited state can be deduced. In this Account, we review our results over the last 5 years from mass spectroscopy experiments using specially designed apparatus on several charged donor-acceptor ions that are based on the nitrophenolate moiety and π-extended derivatives, which are textbook examples of donor-acceptor chromophores. The phenolate oxygen is the donor, and the nitro group is the acceptor. The choice of this system is also based on the fact that phenolate is a common structural motif of biochromophores and luminophores, for example, it is a constituent of the oxyluciferin anion. A presentation of the setups used for

CRISPR interference and priming varies with individual spacer sequences

PubMed Central

Xue, Chaoyou; Seetharam, Arun S.; Musharova, Olga; Severinov, Konstantin; J. Brouns, Stan J.; Severin, Andrew J.; Sashital, Dipali G.

2015-01-01

CRISPR–Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems allow bacteria to adapt to infection by acquiring ‘spacer’ sequences from invader DNA into genomic CRISPR loci. Cas proteins use RNAs derived from these loci to target cognate sequences for destruction through CRISPR interference. Mutations in the protospacer adjacent motif (PAM) and seed regions block interference but promote rapid ‘primed’ adaptation. Here, we use multiple spacer sequences to reexamine the PAM and seed sequence requirements for interference and priming in the Escherichia coli Type I-E CRISPR–Cas system. Surprisingly, CRISPR interference is far more tolerant of mutations in the seed and the PAM than previously reported, and this mutational tolerance, as well as priming activity, is highly dependent on spacer sequence. We identify a large number of functional PAMs that can promote interference, priming or both activities, depending on the associated spacer sequence. Functional PAMs are preferentially acquired during unprimed ‘naïve’ adaptation, leading to a rapid priming response following infection. Our results provide numerous insights into the importance of both spacer and target sequences for interference and priming, and reveal that priming is a major pathway for adaptation during initial infection. PMID:26586800

Under Pressure: The Utility of Spacers in Univalved Fiberglass Casts.

PubMed

Kleis, Kevin; Schlechter, John A; Doan, Joshua D; Farnsworth, Christine L; Edmonds, Eric W

2017-02-24

Univalving fiberglass casts after fracture manipulation or extremity surgery reduces the risk of developing compartment syndrome (CS). Previous experiments have demonstrated that univalving decreases intracompartmental pressures (ICPs), but increases the risk for loss of fracture reduction due to altering the mechanical properties of the cast. The purpose of this study was to correlate cast valve width within a univalved cast model to decreasing ICP. Saline bags (1 L) were covered with stockinette, Webril, and fiberglass tape then connected to an arterial pressure line monitor. Resting pressure was recorded. A water column was added to simulate 2 groups (n=5 each) of clinical CS: low pressure CS (LPCS range, 28 to 31 mm Hg) and high pressure CS (HPCS, range, 64 to 68 mm Hg). After the designated pressure was reached, the fiberglass was cut (stockinette and Webril remained intact). Cast spacers were inserted into each univalve and secured with varying widths: position #1 (3 mm wide), #2 (6 mm), #3 (9 mm), and #4 (12 mm). Pressure was recorded after cutting the fiberglass and following each spacer placement. In LPCS and HPCS groups, after univalve and placement of spacer position #1, pressure dropped by a mean of 52% and 58%, respectively. Spacer #2, decreased the pressure by a mean of 78% and 80%, respectively. Both spacer sizes significantly decreased the underlying pressure in both groups. Spacer #3 and #4 progressively reduced pressure within the cast, but not statistically significantly more than the previous spacer widths. This experimental model replicates the iatrogenic elevation in interstitial compartment pressure due to rigid cast application, not necessarily a self-sustained true CS. Increasing the univalved cast spread by ≥9 mm of the initial cast diameter will reduce pressure to a pre-CS level; however, a spread of only 6 mm can effectively reduce the pressure to <30 mm Hg depending on the initial elevated ICP. Cutting the Webril and stockinette in

Efficient double-emitting layer inverted organic light-emitting devices with different spacer layers

NASA Astrophysics Data System (ADS)

Nie, Qu-yang; Zhang, Fang-hui

2017-09-01

Double-emitting layer inverted organic light-emitting devices (IOLEDs) with different spacer layers were investigated, where 2,20,7,70-tetrakis(carbazol-9-yl)-9,9-spirobifluorene (CBP), 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP), 4,7-diphenyl-1,10-phenanthroline (Bphen) and 4,40,400-tris(N-carbazolyl)-triphenylamine (TCTA) were used as spacer layers, respectively, and GIr1 and R-4b were used as green and red guest phosphorescent materials, respectively. The results show that the device with BCP spacer layer has the best performance. The maximum current efficiency of the BCP spacer layer device reaches up to 24.15 cd·A-1 when the current density is 3.99 mA·cm-2, which is 1.23 times bigger than that of the CBP spacer layer device. The performance is better than that of corresponding conventional device observably. The color coordinate of the device with BCP spacer layer only changes from (0.625 1, 0.368 0) to (0.599 5, 0.392 8) when the driving voltage increases from 6 V to 10 V, so it shows good stability in color coordinate, which is due to the adoption of the co-doping evaporation method for cladding luminous layer and the effective restriction of spacer layer to carriers in emitting layer.

Quantum phase transitions in effective spin-ladder models for graphene zigzag nanoribbons

NASA Astrophysics Data System (ADS)

Koop, Cornelie; Wessel, Stefan

2017-10-01

We examine the magnetic correlations in quantum spin models that were derived recently as effective low-energy theories for electronic correlation effects on the edge states of graphene nanoribbons. For this purpose, we employ quantum Monte Carlo simulations to access the large-distance properties, accounting for quantum fluctuations beyond mean-field-theory approaches to edge magnetism. For certain chiral nanoribbons, antiferromagnetic interedge couplings were previously found to induce a gapped quantum disordered ground state of the effective spin model. We find that the extended nature of the intraedge couplings in the effective spin model for zigzag nanoribbons leads to a quantum phase transition at a large, finite value of the interedge coupling. This quantum critical point separates the quantum disordered region from a gapless phase of stable edge magnetism at weak intraedge coupling, which includes the ground states of spin-ladder models for wide zigzag nanoribbons. To study the quantum critical behavior, the effective spin model can be related to a model of two antiferromagnetically coupled Haldane-Shastry spin-half chains with long-ranged ferromagnetic intrachain couplings. The results for the critical exponents are compared also to several recent renormalization-group calculations for related long-ranged interacting quantum systems.

Formation of Stone-Wales edge: Multistep reconstruction and growth mechanisms of zigzag nanographene.

PubMed

Dang, Jing-Shuang; Wang, Wei-Wei; Zheng, Jia-Jia; Nagase, Shigeru; Zhao, Xiang

2017-10-05

Although the existence of Stone-Wales (5-7) defect at graphene edge has been clarified experimentally, theoretical study on the formation mechanism is still imperfect. In particular, the regioselectivity of multistep reactions at edge (self-reconstruction and growth with foreign carbon feedstock) is essential to understand the kinetic behavior of reactive boundaries but investigations are still lacking. Herein, by using finite-sized models, multistep reconstructions and carbon dimer additions of a bared zigzag edge are introduced using density functional theory calculations. The zigzag to 5-7 transformation is proved as a site-selective process to generate alternating 5-7 pairs sequentially and the first step with largest barrier is suggested as the rate-determining step. Conversely, successive C 2 insertions on the active edge are calculated to elucidate the formation of 5-7 edge during graphene growth. A metastable intermediate with a triple sequentially fused pentagon fragment is proved as the key structure for 5-7 edge formation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Bandgaps and directional propagation of elastic waves in 2D square zigzag lattice structures

NASA Astrophysics Data System (ADS)

Wang, Yan-Feng; Wang, Yue-Sheng; Zhang, Chuanzeng

2014-12-01

In this paper we propose various types of two-dimensional (2D) square zigzag lattice structures, and we study their bandgaps and directional propagation of elastic waves. The band structures and the transmission spectra of the systems are calculated by using the finite element method. The effects of the geometry parameters of the 2D-zigzag lattices on the bandgaps are investigated and discussed. The mechanism of the bandgap generation is analyzed by studying the vibration modes at the bandgap edges. Multiple wide complete bandgaps are found in a wide porosity range owing to the separation of the degeneracy by introducing bending arms. The bandgaps are sensitive to the geometry parameters of the systems. The deformed displacement fields of the transient response of finite structures subjected to time-harmonic loads are presented to show the directional wave propagation. The research in this paper is relevant to the practical design of cellular structures with enhanced vibro-acoustics performance.

A Fortran 90 Hartree-Fock program for one-dimensional periodic π-conjugated systems using Pariser-Parr-Pople model

NASA Astrophysics Data System (ADS)

Kondayya, Gundra; Shukla, Alok

2012-03-01

Pariser-Parr-Pople (P-P-P) model Hamiltonian is employed frequently to study the electronic structure and optical properties of π-conjugated systems. In this paper we describe a Fortran 90 computer program which uses the P-P-P model Hamiltonian to solve the Hartree-Fock (HF) equation for infinitely long, one-dimensional, periodic, π-electron systems. The code is capable of computing the band structure, as also the linear optical absorption spectrum, by using the tight-binding and the HF methods. Furthermore, using our program the user can solve the HF equation in the presence of a finite external electric field, thereby, allowing the simulation of gated systems. We apply our code to compute various properties of polymers such as trans-polyacetylene, poly- para-phenylene, and armchair and zigzag graphene nanoribbons, in the infinite length limit. Program summaryProgram title: ppp_bulk.x Catalogue identifier: AEKW_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKW_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 87 464 No. of bytes in distributed program, including test data, etc.: 2 046 933 Distribution format: tar.gz Programming language: Fortran 90 Computer: PCs and workstations Operating system: Linux, Code was developed and tested on various recent versions of 64-bit Fedora including Fedora 14 (kernel version 2.6.35.12-90). Classification: 7.3 External routines: This program needs to link with LAPACK/BLAS libraries compiled with the same compiler as the program. For the Intel Fortran Compiler we used the ACML library version 4.4.0, while for the gfortran compiler we used the libraries supplied with the Fedora distribution. Nature of problem: The electronic structure of one-dimensional periodic π-conjugated systems is an intense area of research at

Low resistivity of graphene nanoribbons with zigzag-dominated edge fabricated by hydrogen plasma etching combined with Zn/HCl pretreatment

NASA Astrophysics Data System (ADS)

Liu, Fengkui; Li, Qi; Wang, Rubing; Xu, Jianbao; Hu, Junxiong; Li, Weiwei; Guo, Yufen; Qian, Yuting; Deng, Wei; Ullah, Zaka; Zeng, Zhongming; Sun, Mengtao; Liu, Liwei

2017-11-01

Graphene nanoribbons (GNRs) have attracted intensive research interest owing to their potential applications in high performance graphene-based electronics. However, the deterioration of electrical performance caused by edge disorder is still an important obstacle to the applications. Here, we report the fabrication of low resistivity GNRs with a zigzag-dominated edge through hydrogen plasma etching combined with the Zn/HCl pretreatment method. This method is based on the anisotropic etching properties of hydrogen plasma in the vicinity of defects created by sputtering zinc (Zn) onto planar graphene. The polarized Raman spectra measurement of GNRs exhibits highly polarization dependence, which reveals the appearance of the zigzag-dominated edge. The as-prepared GNRs exhibit high carrier mobility (˜1332.4 cm2 v-1 s-1) and low resistivity (˜0.7 kΩ) at room temperature. Particularly, the GNRs can carry large current density (5.02 × 108 A cm-2) at high voltage (20.0 V) in the air atmosphere. Our study develops a controllable method to fabricate zigzag edge dominated GNRs for promising applications in transistors, sensors, nanoelectronics, and interconnects.

Dual-channel current valve in a three terminal zigzag graphene nanoribbon junction

NASA Astrophysics Data System (ADS)

Zhang, L.

2017-02-01

We theoretically propose a dual-channel current valve based on a three terminal zigzag graphene nanoribbon (ZGNR) junction driven by three asymmetric time-dependent pumping potentials. By means of the Keldysh Green’s function method, we show that two asymmetric charge currents can be pumped in the different left-right terminals of the device at a zero bias, which mainly stems from the single photon-assisted pumping approximation and the valley valve effect in a ZGNR p-n junction. The ON and OFF states of pumped charge currents are crucially dependent on the even-odd chain widths of the three electrodes, the pumping frequency, the lattice potential and the Fermi level. Two-tunneling spin valves are also considered to spatially separate and detect 100% polarized spin currents owing to the combined spin pump effect and the valley selective transport in a three terminal ZGNR ferromagnetic junction. Our investigations might be helpful to control the spatial and spin degrees of freedom of electrons in graphene pumping devices.

Zero-profile Anchored Spacer Reduces Rate of Dysphagia Compared With ACDF With Anterior Plating.

PubMed

Hofstetter, Christoph P; Kesavabhotla, Kartik; Boockvar, John A

2015-06-01

Retrospective cohort study. To study clinical and radiologic outcomes after anterior cervical discectomy and fusion (ACDF) using a zero-profile anchored spacer compared with a standard interposition graft with anterior plating. Anterior plating increases fusion rates in ACDF but is associated with higher rates of postoperative dysphagia. Reduction of plate thickness or zero-profile fixation of the interposition graft have been suggested to decrease the incidence of postoperative dysphagia. Retrospective cohort study of 70 consecutive patients of whom the first 35 patients underwent ACDF with anterior plating and the remaining patients received an LDR device. Patient demographics, operative details, neurological impairment, complications, and radiographic imaging were reviewed. Dysphagia occurring in the immediate postoperative period and lasting for >3 months was recorded. Both the zero-profile anchored spacer and a standard interposition graft with anterior plating resulted in improvement of neurological outcome at a mean follow-up time of 13.9 months. Fusion rates were found to be similar between ACDF with anterior plating (96.0%) and LDR (95.2%). Evaluation of postoperative radiographs revealed significantly more swelling of the prevertebral space (20.4±0.9 mm) after implantation of an anterior locking plate compared with a zero-profile device (15.6±0.7 mm, P<0.001). This difference remained significant at 6-month follow-up (P=0.035). Seven patients (20%) with ACDF and plating complained about swallowing difficulties beyond 3 months compared with only 1 patient with the LDR device (P=0.027). The severity of dysphagia was mild in all but 2 patients. Both patients with moderate and severe swallowing difficulties had undergone ACDF with anterior plating. Zero-profile anchored spacers lead to similar clinical and radiographic outcomes compared with ACDF with plating and may carry a lower risk of postoperative dysphagia.

Pros and cons of symmetrical dual-k spacer technology in hybrid FinFETs

NASA Astrophysics Data System (ADS)

Pradhan, K. P.; Andrade, M. G. C.; Sahu, P. K.

2016-12-01

The symmetrical dual-k spacer technology in hybrid FinFETs has been widely explored for better electrostatic control of the fin-based devices in nanoscale region. Since, high-k tangible spacer materials are broadly became a matter of study due to their better immunity to the short channel effects (SCEs) in nano devices. However, the only cause that restricts the circuit designers from using high-k spacer is the unreasonable increasing fringing capacitances. This work quantitatively analyzed the benefits and drawbacks of considering two different dielectric spacer materials symmetrically in either sides of the channel for the hybrid device. From the demonstrated results, the inclusion of high-k spacer predicts an effective reduction in off-state leakage along with an improvement in drive current. However, these devices have paid the cost in terms of a high total gate-to-gate capacitance (Cgg) that consequently results poor cutoff frequency (fT) and delay.

In vitro antibody-enzyme conjugates with specific bactericidal activity.

PubMed

Knowles, D M; Sulivan, T J; Parker, C W; Williams, R C

1973-06-01

IgG with antibacterial antibody opsonic activity was isolated from rabbit antisera produced by intravenous hyperimmunization with several test strains of pneumococci, Group A beta-hemolytic streptococci, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli. Antibody-enzyme conjugates were prepared, using diethylmalonimidate to couple glucose oxidase to IgG antibacterial antibody preparations. Opsonic human IgG obtained from serum of patients with subacute bacterial endocarditis was also conjugated to glucose oxidase. Antibody-enzyme conjugates retained combining specificity for test bacteria as demonstrated by indirect immunofluorescence. In vitro test for bactericidal activity of antibody-enzyme conjugates utilized potassium iodide, lactoperoxidase, and glucose as cofactors. Under these conditions glucose oxidase conjugated to antibody generates hydrogen peroxide, and lactoperoxidase enzyme catalyzes the reduction of hydrogen peroxide with simultaneous oxidation of I(-) and halogenation and killing of test bacteria. Potent in vitro bactericidal activity of this system was repeatedly demonstrated for antibody-enzyme conjugates against pneumococci, streptococci, S. aureus, P. mirabilis, and E. coli. However, no bactericidal effect was demonstrable with antibody-enzyme conjugates and two test strains of P. aeruginosa. Bactericidal activity of antibody-enzyme conjugates appeared to parallel original opsonic potency of unconjugated IgG preparations. Antibody-enzyme conjugates at concentrations as low as 0.01 mg/ml were capable of intense bactericidal activity producing substantial drops in surviving bacterial counts within 30-60 min after initiation of assay. These in vitro bactericidal systems indicate that the concept of antibacterial antibody-enzyme conjugates may possibly be adaptable as a mechanism for treatment of patients with leukocyte dysfunction or fulminant bacteremia.

Synthesis and evaluation of macromolecule-bound derivatives of a peptidyl-1-beta-D-arabinofuranosylcytosine prodrug.

PubMed

Balajthy, Zoltan

2008-04-01

Macromolecule-bound Val-Leu-Lys-ara-C (1) prodrugs were synthesized with spacers (-HN-(CH(2))(x)-CO-; x =1,3,5) between the dextran carrier (T-70) and 1, in order to achieve a sustained-release drug delivery system dextran-NH-(CH(2))(x:1,3,5)-CO-Val-Leu-Lys-ara-C (5, 6 and 7). The conjugation increased the stability of 1 in aqueous buffer solutions by three times (t((1/2)) 53.0 h, pH 7.4). The length of spacer also regulated the rate of hydrolysis of the prodrugs in serum. The shortest spacer (-HN-(CH(2))-CO-, (2)) in 5 provided the best protection of 1 against the hydrolyzing ability of proteinase- alpha(2)-macroglobulin complexes, increasing its half-life approximately 30-fold. The conjugation procedure resulted in a growth arrest ability for macromolecular-bound prodrugs 5, 6 and 7 against L1210 with IC(50) of 0.01 microM in vitro, which is significantly lower than that of other ara-C-macromolecule conjugates. 5 and 6 arrested cell growth in a broader range of concentration, between 1 x 10(-5)-1.0 microM, than ara-C could.

Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate

PubMed Central

Berguig, Geoffrey Y.; Convertine, Anthony J.; Shi, Julie; Palanca-Wessels, Maria Corinna; Duvall, Craig L.; Pun, Suzie H.; Press, Oliver W.; Stayton, Patrick S.

2012-01-01

Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma cells where it is rapidly trafficked to the lysosomal compartment. To characterize the intracellular-releasing dynamics of the polymer-mAb conjugates, HD39-streptavidin (HD39/SA) was dual-labeled with pH-insensitive Alex Fluor 488 and pH-sensitive pHrodo fluorophores. The subcellular pH-distribution of the HD39/SA-polymer conjugates were quantified as a function of time by live-cell fluorescence microscopy, and the average intracellular pH values experienced by the conjugates were also characterized as a function of time by flow cytometry. PPAA was shown to strongly alter the intracellular trafficking kinetics compared to HD39/SA alone or HD39/SA conjugates with a control polymer, poly(methacryclic acid) (PMAA). Subcellular trafficking studies revealed that after 6 hours only 11% of the HD39/SA-PPAA conjugates had been trafficked to acidic lysosomal compartments with values at or below pH 5.6. In contrast the average intracellular pH of HD39/SA alone dropped from pH 6.7 ± 0.2 at 1 hour to pH 5.6 ± 0.5 after 3 hours and pH 4.7 ± 0.6 after 6 hours. Conjugation of the control PMAA to HD39/SA showed an average pH drop similar to HD39/SA. Subcellular fractionation studies with tritium-labeled HD39/SA demonstrated that after 6 hours, 89% of HD39/SA was associated with endosomes (Rab5+) and lysosomes (Lamp2+), while 45% of HD39/SA-PPAA was translocated to the cytosol (lactate dehydrogenase+). These results demonstrate the endosomal-releasing properties of PPAA with antibody-polymer conjugates and detail their intracellular trafficking dynamics and subcellular compartmental distributions over time. PMID:23075320

The direct exchange mechanism of induced spin polarization of low-dimensional π-conjugated carbon- and h-BN fragments at LSMO(001) MnO-terminated interfaces

NASA Astrophysics Data System (ADS)

Kuklin, Artem V.; Kuzubov, Alexander A.; Kovaleva, Evgenia A.; Lee, Hyosun; Sorokin, Pavel B.; Sakai, Seiji; Entani, Shiro; Naramoto, Hiroshi; Avramov, Paul

2017-10-01

Induced spin polarization of π-conjugated carbon and h-BN low dimensional fragments at the interfaces formed by deposition of pentacene molecule and narrow zigzag graphene and h-BN nanoribbons on MnO2-terminated LSMO(001) thin film was studied using GGA PBE+U PAW D3-corrected approach. Induced spin polarization of π-conjugated low-dimensional fragments is caused by direct exchange with Mn ions of LSMO(001) MnO-derived surface. Due to direct exchange, the pentacene molecule changes its diamagnetic narrow-band gap semiconducting nature to the ferromagnetic semiconducting state with 0.15 eV energy shift between spin-up and spin-down valence bands and total magnetic moment of 0.11 μB. Direct exchange converts graphene nanoribbon to 100% spin-polarized half-metal with large amplitude of spin-up electronic density at the Fermi level. The direct exchange narrows the h-BN nanoribbon band gap from 4.04 to 1.72 eV in spin-up channel and converts the h-BN ribbon semiconducting diamagnetic nature to a semiconducting magnetic one. The electronic structure calculations demonstrate a possibility to control the spin properties of low-dimensional π-conjugated carbon and h-BN fragments by direct exchange with MnO-derived LSMO(001) surface for spin-related applications.

Aspects of electron transport in zigzag graphene nanoribbons

NASA Astrophysics Data System (ADS)

Bhalla, Pankaj; Pratap, Surender

2018-05-01

In this paper, we investigate the aspects of electron transport in the zigzag graphene nanoribbons (ZGNRs) using the nonequilibrium Green’s function (NEGF) formalism. The latter is an esoteric tool in mesoscopic physics. It is used to perform an analysis of ZGNRs by considering potential well. Within this potential, the dependence of transmission coefficient, local density of states (LDOS) and electron transport properties on number of atoms per unit cell is discussed. It is observed that there is an increment in electron and thermal conductance with increasing number of atoms. In addition to these properties, the dependence of same is also studied in figure of merit. The results infer that the contribution of electrons to enhance the figure of merit is important above the crossover temperature.

Eccentric mastectomy and zigzag periareolar incision for gynecomastia.

PubMed

Tu, Lung-Chen; Tung, Kwang-Yi; Chen, Heng-Chang; Huang, Wen-Chen; Hsiao, Hung-Tao

2009-07-01

Gynecomastia is enlargement of the male breast caused by gland proliferation. Surgery is performed for symptom relief or for cosmetic reasons. The authors used a modified operative procedure, then evaluated the results and safety. Between 2001 and 2005, 22 men (median age, 26 years; range, 13-63 years) with gynecomastia underwent surgery. The operative procedure included a zigzag periareolar skin incision, eccentric subcutaneous mastectomy, and liposuction, with postoperative compression. All the patients were satisfied with the results of the surgery, which produced a chest contour resembling a normal male chest rather than simply a smaller breast. The only complication was a hematoma. One patient was found to have breast cancer. The normal male chest contour can be restored by the described method of eccentric subcutaneous mastectomy.

Modulation of Benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate

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

Schellenberger, Mario T.; Grova, Nathalie; Willieme, Stephanie

2009-10-01

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of bothmore » T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-{gamma}, IL-12, TNF-{alpha} production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.« less

[Relationship between family variables and conjugal adjustment].

PubMed

Jiménez-Picón, Nerea; Lima-Rodríguez, Joaquín-Salvador; Lima-Serrano, Marta

2018-04-01

To determine whether family variables, such as type of relationship, years of marriage, existence of offspring, number of members of family, stage of family life cycle, transition between stages, perceived social support, and/or stressful life events are related to conjugal adjustment. A cross-sectional and correlational study using questionnaires. Primary care and hospital units of selected centres in the province of Seville, Spain. Consecutive stratified sampling by quotas of 369 heterosexual couples over 18years of age, who maintained a relationship, with or without children, living in Seville. A self-report questionnaire for the sociodemographic variables, and the abbreviated version of the Dyadic Adjustment Scale, Questionnaire MOS Perceived Social Support, and Social Readjustment Rating Scale, were used. Descriptive and inferential statistics were performed with correlation analysis and multivariate regression. Statistically significant associations were found between conjugal adjustment and marriage years (r=-10: P<.05), stage of family life cycle (F=2.65; P<.05), the transition between stages (RPB=.11; P<.05) and perceived social support (r=.44; P<.001). The regression model showed the predictive power of perceived social support and the family life cycle stage (mature-aged stage) on conjugal adjustment (R2=.21; F=9.9; df=356; P<.001). Couples may be assessed from Primary Care and be provide with resources and support. In addition, it can identify variables that may help improve the conjugal relationship. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Asymmetric underlap spacer layer enabled nanoscale double gate MOSFETs for design of ultra-wideband cascode amplifiers

NASA Astrophysics Data System (ADS)

Roy, Debapriya; Biswas, Abhijit

2017-10-01

Using extensive numerical analysis we investigate effects of asymmetric sidewall spacers on various device parameters of 20-nm double gate MOSFETs associated with analog/RF applications. Our studies show that the device with underlap drain-side spacer length LED of 10 nm and source-side spacer length LES of 5 nm shows improvement in terms of the peak value of transconductance efficiency, voltage gain Av, unity-gain cut-off frequency fT and maximum frequency of oscillations fMAX by 8.6%, 51.7%, 5% and 10.3%, respectively compared to the symmetric 5 nm underlap spacer device with HfO2 spacer of dielectric constant k = 22. Additionally, a higher spacer dielectric constant increases the peak Av while decreasing both peak fT and fMAX. The detailed physical insight is exploited to design a cascode amplifier which yields an ultra-wide gain bandwidth of 2.48 THz at LED = 10 nm with a SiO2 spacer.

Bronchodilator Effect of Tiotropium via Respimat®Administered with a Spacer in Patients with Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Ogasawara, Takashi; Sakata, Jun; Aoshima, Yoichiro; Tanaka, Kazuki; Yano, Toshiaki; Kasamatsu, Norio

2017-09-15

Objective Among elderly patients with chronic obstructive pulmonary disease (COPD), there are some patients who cannot inhale tiotropium via Respimat ® due to poor hand-lung coordination. This study aimed to examine whether or not tiotropium inhalation therapy using Respimat ® with a spacer increased the forced expiratory volume in 1 s (FEV 1 ) in patients with COPD. Methods A randomized, crossover, single-center study was conducted in 18 patients with stable COPD. Tiotropium (5 μg) via Respimat ® with or without a spacer (AeroChamber ® ) was administered for 2 weeks. Following a 2-week washout period using a transdermal tulobuterol patch (2 mg per day), participants were then crossed over to the other inhalation therapy with respect to spacer use. The trough FEV 1 was measured at every visit using a spirometer. A questionnaire regarding inhalation therapy was administered to patients at the final visit. Results The administration of tiotropium via Respimat ® both with and without a spacer significantly increased the trough FEV 1 from baseline during each treatment period, with mean differences of 115.0±169.6 mL and 92.8±128.1 mL, respectively. There was no significant difference in the change in the trough FEV 1 between the 2 procedures (p=0.66). A total of 86% of patients reported that inhalation using a spacer was not difficult, and more than half also rated both the usage and maintenance of the AeroChamber ® as easy. Conclusion Tiotropium inhalation therapy administered via Respimat ® using a spacer exerted a bronchodilatory effect similar to that observed with tiotropium Respimat ® alone.

Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration

PubMed Central

Nivala, Jeff; Shipman, Seth L.; Church, George M.

2018-01-01

The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli. Considering whether such promiscuous Cas1-Cas2 activity could have an evolutionary role through the genesis of neo-CRISPR loci, we combed existing CRISPR databases and available genomes for evidence of off-target integration activity. This search uncovered several putative instances of naturally occurring off-target spacer integration events within the genomes of Yersinia pestis and Sulfolobus islandicus. These results are important in understanding alternative routes to CRISPR array genesis and evolution, as well as in the use of spacer acquisition in technological applications. PMID:29379209

New clustered regularly interspaced short palindromic repeat locus spacer pair typing method based on the newly incorporated spacer for Salmonella enterica.

PubMed

Li, Hao; Li, Peng; Xie, Jing; Yi, Shengjie; Yang, Chaojie; Wang, Jian; Sun, Jichao; Liu, Nan; Wang, Xu; Wu, Zhihao; Wang, Ligui; Hao, Rongzhang; Wang, Yong; Jia, Leili; Li, Kaiqin; Qiu, Shaofu; Song, Hongbin

2014-08-01

A clustered regularly interspaced short palindromic repeat (CRISPR) typing method has recently been developed and used for typing and subtyping of Salmonella spp., but it is complicated and labor intensive because it has to analyze all spacers in two CRISPR loci. Here, we developed a more convenient and efficient method, namely, CRISPR locus spacer pair typing (CLSPT), which only needs to analyze the two newly incorporated spacers adjoining the leader array in the two CRISPR loci. We analyzed a CRISPR array of 82 strains belonging to 21 Salmonella serovars isolated from humans in different areas of China by using this new method. We also retrieved the newly incorporated spacers in each CRISPR locus of 537 Salmonella isolates which have definite serotypes in the Pasteur Institute's CRISPR Database to evaluate this method. Our findings showed that this new CLSPT method presents a high level of consistency (kappa = 0.9872, Matthew's correlation coefficient = 0.9712) with the results of traditional serotyping, and thus, it can also be used to predict serotypes of Salmonella spp. Moreover, this new method has a considerable discriminatory power (discriminatory index [DI] = 0.8145), comparable to those of multilocus sequence typing (DI = 0.8088) and conventional CRISPR typing (DI = 0.8684). Because CLSPT only costs about $5 to $10 per isolate, it is a much cheaper and more attractive method for subtyping of Salmonella isolates. In conclusion, this new method will provide considerable advantages over other molecular subtyping methods, and it may become a valuable epidemiologic tool for the surveillance of Salmonella infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Phonon stiffen and soften at zigzag- and armchair-dominated edges of exfoliated bilayer graphene ribbon presented by Raman spectra

NASA Astrophysics Data System (ADS)

Xia, Minggang; Zhou, Xiaohua; Xin, Duqiang; Xu, Qiang

2018-01-01

The Raman spectra at the edge of the exfoliated bilayer graphene ribbon (GR) were investigated in detail. Results show that both G and 2D phonons stiffen (wave number increases) at zigzag-dominated edge, while they soften at armchair-dominated edge compared with those at the middle position in the GR. Furthermore, the full widths at half maximum intensity of both G and 2D Raman peaks narrow at the zigzag-dominated edge, while they broaden at the armchair-dominated edge. The stiffness and softness are attributed to the C-C bonds at the edge. For zigzag-dominated edge, the stiffness may originate in the increase of the force constant induced by the shrinking of C-C bond. For armchair-dominated edge, the softness may be due to the decrease of the force constant induced by the unsaturated hanging bonds at edge, which is different from Kohn anomaly and charge doping. The analysis is in agreement well with others calculation results about C-C bonds and the edge energy. These results may be useful to understand physical properties at the bilayer graphene edge and for applications in the device by taking advantage of the edge states in bilayer graphene.

Negative differential resistance and bias-modulated metal-to-insulator transition in zigzag C2N-h2D nanoribbon

NASA Astrophysics Data System (ADS)

He, Jing-Jing; Guo, Yan-Dong; Yan, Xiao-Hong

2017-04-01

Motivated by the fabrication of layered two-dimensional material C2N-h2D [Nat. Commun. 6, 6486 (2015)], we cut the single-layer C2N-h2D into a zigzag nanoribbon and perform a theoretical study. The results indicate that the band structure changes from semiconducting to metallic and a negative differential resistance effect occurs in the I-V curve. Interestingly, the current can be reduced to zero and this insulator-like state can be maintained as the bias increases. We find this unique property is originated from a peculiar band morphology, with only two subbands appearing around the Fermi level while others being far away. Furthermore the width and symmetry of the zigzag C2N-h2D nanoribbon can be used to tune the transport properties, such as cut-off bias and the maximum current. We also explore the electron transport property of an aperiodic model composed of two nanoribbons with different widths and obtain the same conclusion. This mechanism can be extended to other systems, e.g., hybrid BCN nanoribbons. Our discoveries suggest that the zigzag C2N-h2D nanoribbon has great potential in nanoelectronics applications.

Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate.

PubMed

Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Schroeder, Henri; Muller, Claude P

2013-09-01

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P-diphtheria toxoid (B[a]P-DT) conjugate vaccine were sub-acutely exposed to 2mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P-DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. Copyright © 2013 Elsevier Inc. All rights reserved.

A functional analysis of the spacer of V(D)J recombination signal sequences.

PubMed

Lee, Alfred Ian; Fugmann, Sebastian D; Cowell, Lindsay G; Ptaszek, Leon M; Kelsoe, Garnett; Schatz, David G

2003-10-01

During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

Optical absorption of zigzag single walled boron nitride nanotubes in axial magnetic field

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2013-11-01

We have investigated the effect of axial magnetic field on the band structure, dipole matrix elements and absorption spectrum in different energy ranges, using tight binding approximation. It is found that magnetic field breaks the degeneracy in the band structure and creates new allowed transitions in the dipole matrix which leads to creation of new peaks in the absorption spectrum. It is found that, unlike to CNTs which show metallic-semiconductor transition, the BNNTs remain semiconductor in any magnetic field strength. By calculation the diameter dependence of peak positions, we found that the positions of three first peaks in the lower energy region (E <5.3 eV) are proportional to n-2. In the middle energy region (7 < E < 7.5 eV) all (n, 0) zigzag BNNTs, with even and odd nanotube index, have two distinct peaks in the absence of magnetic field which these peaks may be used to identify zigzag BNNTs from other tube chiralities. For odd (even) tubes, in the middle energy region, applying the magnetic field leads to splitting of these two peaks into three (five) distinct peaks.

Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

NASA Astrophysics Data System (ADS)

Titanova, Elena O.; Burygin, Gennady L.

2016-04-01

Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate.

PubMed

Berguig, Geoffrey Y; Convertine, Anthony J; Shi, Julie; Palanca-Wessels, Maria Corinna; Duvall, Craig L; Pun, Suzie H; Press, Oliver W; Stayton, Patrick S

2012-12-03

Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma cells, where it is rapidly trafficked to the lysosomal compartment. To characterize the intracellular-release dynamics of the polymer-mAb conjugates, HD39-streptavidin (HD39/SA) was dual-labeled with pH-insensitive Alexa Fluor 488 and pH-sensitive pHrodo fluorophores. The subcellular pH distribution of the HD39/SA-polymer conjugates was quantified as a function of time by live-cell fluorescence microscopy, and the average intracellular pH value experienced by the conjugates was also characterized as a function of time by flow cytometry. PPAA was shown to alter the intracellular trafficking kinetics strongly relative to HD39/SA alone or HD39/SA conjugates with a control polymer, poly(methacryclic acid) (PMAA). Subcellular trafficking studies revealed that after 6 h, only 11% of the HD39/SA-PPAA conjugates had been trafficked to acidic lysosomal compartments with values at or below pH 5.6. In contrast, the average intracellular pH of HD39/SA alone dropped from 6.7 ± 0.2 at 1 h to 5.6 ± 0.5 after 3 h and 4.7 ± 0.6 after 6 h. Conjugation of the control polymer PMAA to HD39/SA showed an average pH drop similar to that of HD39/SA. Subcellular fractionation studies with tritium-labeled HD39/SA demonstrated that after 6 h, 89% of HD39/SA was associated with endosomes (Rab5+) and lysosomes (Lamp2+), while 45% of HD39/SA-PPAA was translocated to the cytosol (lactate dehydrogenase+). These results demonstrate the endosomal-releasing properties of PPAA with antibody-polymer conjugates and detail their intracellular trafficking dynamics and subcellular compartmental distributions over time.

Bacillus thuringiensis Conjugation in Simulated Microgravity

NASA Astrophysics Data System (ADS)

Beuls, Elise; van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques

2009-10-01

Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0-g position (simulated microgravity) were compared to those obtained under 1-g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

Bacillus thuringiensis conjugation in simulated microgravity.

PubMed

Beuls, Elise; Van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques

2009-10-01

Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0 g position (simulated microgravity) were compared to those obtained under 1 g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

Do dynamic cement-on-cement knee spacers provide better function and activity during two-stage exchange?

PubMed

Jaekel, David J; Day, Judd S; Klein, Gregg R; Levine, Harlan; Parvizi, Javad; Kurtz, Steven M

2012-09-01

Implantation of an antibiotic bone cement spacer is used to treat infection of a TKA. Dynamic spacers fashioned with cement-on-cement articulating surfaces potentially facilitate patient mobility and reduce bone loss as compared with their static counterparts, while consisting of a biomaterial not traditionally used for load-bearing articulations. However, their direct impact on patient mobility and wear damage while implanted remains poorly understood. We characterized patient activity, surface damage, and porous structure of dynamic cement-on-cement spacers. We collected 22 dynamic and 14 static knee antibiotic cement spacers at revision surgeries at times ranging from 0.5 to 13 months from implantation. For these patients, we obtained demographic data and UCLA activity levels. We characterized surface damage using the Hood damage scoring method and used micro-CT analysis to observe the internal structure, cracking, and porosity of the cement. The average UCLA score was higher for patients with dynamic spacers than for patients with static spacers, with no differences in BMI or age. Burnishing was the only prevalent damage mode on all the bearing surfaces. Micro-CT analysis revealed the internal structure of the spacers was porous and highly inhomogeneous, including heterogeneous dispersion of radiopaque material and cavity defects. The average porosity was 8% (range, 1%-29%) and more than ½ of the spacers had pores greater than 1 mm in diameter. Our observations suggest dynamic, cement-on-cement spacers allow for increased patient activity without catastrophic failure. Despite the antibiotic loading and internal structural inhomogeneity, burnishing was the only prevalent damage mode that could be consistently classified with no evidence of fracture or delamination. The porous structure of the spacers varied highly across the surfaces without influencing the material failure.

Membrane-spacer assembly for flow-electrode capacitive deionization

NASA Astrophysics Data System (ADS)

Lee, Ki Sook; Cho, Younghyun; Choo, Ko Yeon; Yang, SeungCheol; Han, Moon Hee; Kim, Dong Kook

2018-03-01

Flow-electrode capacitive deionization (FCDI) is a desalination process designed to overcome the limited desalination capacity of conventional CDI systems due to their fixed electrodes. Such a FCDI cell system is comprised of a current collector, freestanding ion-exchange membrane (IEM), gasket, and spacer for flowing saline water. To simplify the cell system, in this study we combined the membrane and spacer into a single unit, by coating the IEM on a porous ceramic structure that acts as the spacer. The combination of membrane with the porous structure avoids the use of costly freestanding IEM. Furthermore, the FCDI system can be readily scaled up by simply inserting the IEM-coated porous structures in between the channels for flow electrodes. However, coating the IEM on such porous ceramic structures can cause a sudden drop in the treatment capacity, if the coated IEM penetrates the ceramic pores and prevents these pores from acting as saline flow channels. To address this issue, we blocked the larger microscale pores on the outer surface with SiO2 and polymeric multilayers. Thus, the IEM is coated only onto the top surface of the porous structure, while the internal pores remain empty to function as water channels.

Immunochemical Parameters of Some Commercial Conjugates for the Fluorescent Treponemal Antibody-Absorption Test

PubMed Central

Hunter, E. F.; Smith, J. F.; Lewis, J. S.; McGrew, B. E.; Schmale, J. D.

1972-01-01

Fluorescein-labeled anti-human globulins were examined to determine the need for standardization of conjugates used in the fluorescent treponemal antibody-absorption (FTA-ABS) test. Twenty-one of 33 conjugates submitted by commercial manufacturers to the Reagents Control Activity, Venereal Disease Research Laboratory, for evaluation in the FTA-ABS test were available for study. Conjugates, after evaluation in FTA-ABS performance tests, were examined by immunoelectrophoresis, by titration against immunoglobulins G and M (IgG, IgM) with FTA-ABS techniques, and by the biuret protein and fluorescein diacetate methods for determining fluorescein to protein (F/P) ratios. The conjugates were predominately anti-IgG globulin with anti-light-chain activity. Differences were noted in the ability of some conjugates to detect IgM antibody. The F/P ratios of those conjugates that could be determined varied from 2.6 to 17.8 μg of fluorescein per mg of protein. The need to identify and standardize both the immunologic capabilities and the optimum F/P ratio for FTA-ABS test conjugates is presented. PMID:4564403

Molecular diodes based on conjugated diblock co-oligomers.

PubMed

Ng, Man-Kit; Lee, Dong-Chan; Yu, Luping

2002-10-09

This report describes synthesis and characterization of a molecular diode based upon a diblock conjugated oligomer system. This system consists of two conjugated blocks with opposite electronic demand. The molecular structure exhibits a built-in electronic asymmetry, much like a semiconductor p-n junction. Electrical measurements by scanning tunneling spectroscopy (STS) clearly revealed a pronounced rectifying effect. Definitive proof for the molecular nature of the rectifying effect in this conjugated diblock molecule is provided by control experiments with a structurally similar reference compound.

Afocal three-mirror anastigmat with zigzag optical axis for widened field of view and enlarged aperture

NASA Astrophysics Data System (ADS)

Li, Qi; Han, Lin; Jin, Yangming; Shen, Weimin

2016-10-01

In order to improve the detection accuracy and range of new generation of Forward Looking Infra-Red (FLIR) system for distant targets, its optical system, which usually consists of a fore afocal telescope and rear imaging lenses, is required to has wide spectral range, large entrance pupil aperture, and wide field of view (FOV). In this paper, a new afocal Three-Mirror Anastigmat (TMA) with widened field of view and high demagnification is suggested. Its mechanical structure remains coaxial, but it has zigzag optical axis through properly and slightly decentering and tilting of the three mirrors to avoid its secondary obscuration due to the third mirror as FOV increase. Compared with conventional off-axis TMA, the suggested zigzag-axis TMA is compact, easy-alignment and low-cost. The design method and optimum result of the suggested afocal TMA is presented. Its initial structural parameters are determined with its first-order relationship and primary aberration theory. Slight and proper decentration and tilt of each mirror is leaded in optimization so that its coaxial mechanical structure is held but attainable FOV and demagnification are respectively as wide and as high as possible. As an example, a 5.5-demagnification zigzag-axis afocal TMA with a wavelength range, an entrance pupil diameter, and FOV respectively from 3μm to 12μm, of 320mm, and 2×3.2 degrees and with a real exit pupil, is designed. Its imaging quality is diffraction limited. It is suitable for fore afocal telescope of the so-called third generation FLIR.

Optimal design of wavy microchannel and comparison of heat transfer characteristics with zigzag and straight geometries

NASA Astrophysics Data System (ADS)

Parlak, Zekeriya

2018-05-01

Design concept of microchannel heat exchangers is going to plan with new flow microchannel configuration to reduce the pressure drop and improve heat transfer performance. The study aims to find optimum microchannel design providing the best performance of flow and heat transfer characterization in a heat sink. Therefore, three different types of microchannels in which water is used, straight, wavy and zigzag have been studied. The optimization operation has been performed to find optimum geometry with ANSYS's Response Surface Optimization Tool. Primarily, CFD analysis has been performed by parameterizing a wavy microchannel geometry. Optimum wavy microchannel design has been obtained by the response surface created for the range of velocity from 0.5 to 5, the range of amplitude from 0.06 to 0.3, the range of microchannel height from 0.1 to 0.2, the range of microchannel width from 0.1 to 0.2 and range of sinusoidal wave length from 0.25 to 2.0. All simulations have been performed in the laminar regime for Reynolds number ranging from 100 to 900. Results showed that the Reynolds number range corresponding to the industrial pressure drop limits is between 100 and 400. Nu values obtained in this range for optimum wavy geometry were found at a rate of 10% higher than those of the zigzag channel and 40% higher than those of the straight channels. In addition, when the pressure values of the straight channel did not exceed 10 kPa, the inlet pressure data calculated for zigzag and wavy channel data almost coincided with each other.

Synthesis of highly water-soluble fluorescent conjugated glycopoly(p-phenylene)s for lectin and Escherichia coli.

PubMed

Xue, Cuihua; Jog, Sonali P; Murthy, Pushpalatha; Liu, Haiying

2006-09-01

Two facile, convenient, and versatile synthetic approaches are used to covalently attach carbohydrate residues to conjugated poly(p-phenylene)s (PPPs) for highly water-soluble PPPs bearing alpha-mannopyranosyl and beta-glucopyranosyl pendants (polymers A and B), which highly fluoresce in phosphate buffer (pH 7.0). The post-polymerization functionalization approach is to treat bromo-bearing PPP (polymer 1) with 1-thiolethyl-alpha-D-mannose tetraacetate or 1-thiol-beta-D-glucose tetraacetate in THF solution in the presence of K(2)CO(3) at room temperature through formation of thioether bridges, affording polymer 2a or 2b. The prepolymerization functionalization approach is to polymerize a well-defined sugar-carrying monomer, affording polymer 2a. Polymers 2a and 2b were deacetylated under Zemplén conditions in methanol and methylene chloride containing sodium methoxide, affording polymers A and B, respectively. The multivalent display of carbohydrates on the fluorescent conjugated glycopolymer overcomes the characteristic low binding affinity of the individual carbohydrates to their receptor proteins. Titration of concanavalin A (Con A) to alpha-mannose-bearing polymer A resulted in significant fluorescent quenching of the polymer with Stern-Volmer quenching constant of 4.5 x 10(7). Incubation of polymer A with Escherichia coli (E. coli) lead to formation of fluorescently stained bacterial clusters. Beta-glucose-bearing polymer B displayed no response to Con A and E. coli.

Comparison of noncovalent interactions of zigzag and armchair carbon nanotubes with heterocyclic and aromatic compounds: Imidazole and benzene, imidazophenazines, and tetracene

NASA Astrophysics Data System (ADS)

Zarudnev, Eugene S.; Stepanian, Stepan G.; Adamowicz, Ludwik; Leontiev, Victor S.; Karachevtsev, Victor A.

2017-02-01

We study non-covalent functionalization of SWCNT by linear heterocyclic compounds such as imidazophenazine (F1) and its derivatives (F2-F4). MP2 and DFT/M05-2X quantum-chemical methods are used to determine the structures and the interaction energies of complexes formed by F1-F4 with the zigzag(10,10) and armchair(6,6) nanotubes. The calculations show that for small diameter nanotubes the binding energies with zigzag nanotubes are stronger than with armchair nanotubes. But above the diameter of 1.4 nm the interaction energies for the armchair nanotubes become larger than for the zigzag nanotubes. Experimental measurements demonstrates that the ratio of the integral intensity of the resonance Raman bands assigned to the RBM modes of semiconducting nanotubes to the integral intensity of the metallic nanotubes increases for supernatant of SWCNT:F4 (1,2,3-triazole-[4,5-d]-phenazine) hybrids solved in 1-Methyl-2-pyrrolidone as compared to this ratio in sediment samples. It demonstrates that the linear heterocyclic compounds can be used for separating SWCNTs with different electron-conduction types.

The human ubiquitin-conjugating enzyme Cdc34 controls cellular proliferation through regulation of p27{sup Kip1} protein levels

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

Butz, Nicole; Ruetz, Stephan; Natt, Francois

2005-02-15

Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27{sup Kip1} was shown to be required for the activation of key cyclin-dependent kinases, thereby triggering the onset of DNA replication and cell cycle progression. Although the SCF{sup Skp2} ubiquitin ligase has been reported to mediate p27{sup Kip1} degradation, the nature of the human ubiquitin-conjugating enzyme involved in this process has not yet been determined at the cellular level. Here, we show that antisense oligonucleotides targeting the human ubiquitin-conjugating enzyme Cdc34 downregulate its expression, inhibit the degradation of p27{sup Kip1}, and prevent cellular proliferation. Elevation of p27{sup Kip1} protein level is found tomore » be the sole requirement for the inhibition of cellular proliferation induced upon downregulation of Cdc34. Indeed, reducing the expression of p27{sup Kip1} with a specific antisense oligonucleotide is sufficient to reverse the anti-proliferative phenotype elicited by the Cdc34 antisense. Furthermore, downregulation of Cdc34 is found to specifically increase the abundance of the SCF{sup Skp2} ubiquitin ligase substrate p27{sup Kip1}, but has no concomitant effect on the level of IkB{alpha} and {beta}-catenin, which are known substrates of a closely related SCF ligase.« less

Effect of edge defects on band structure of zigzag graphene nanoribbons

NASA Astrophysics Data System (ADS)

Wadhwa, Payal; Kumar, Shailesh; Dhilip Kumar, T. J.; Shukla, Alok; Kumar, Rakesh

2018-04-01

In this article, we report band structure studies of zigzag graphene nanoribbons (ZGNRs) on introducing defects (sp3 hybridized carbon atoms) in different concentrations at edges by varying the ratio of sp3 to sp2 hybridized carbon atoms. On the basis of theoretical analyses, bandgap values of ZGNRs are found to be strongly dependent on the relative arrangement of sp3 to sp2 hybridized carbon atoms at the edges for a defect concentration; so the findings would greatly help in understanding the bandgap of nanoribbons for their electronic applications.

Cysteine-Conjugated Metabolites of Ginger Components, Shogaols, Induce Apoptosis through Oxidative Stress-Mediated p53 Pathway in Human Colon Cancer Cells

PubMed Central

2015-01-01

Shogaols, the major constituents of thermally processed ginger, have been proven to be highly effective anticancer agents. Our group has identified cysteine-conjugated shogaols (M2, M2′, and M2″) as the major metabolites of [6]-, [8]-, and [10]-shogaol in human and found that M2 is a carrier of its parent molecule [6]-shogaol in cancer cells and in mice, while being less toxic to normal colon fibroblast cells. The objectives of this study are to determine whether M2′ and M2″ behave in a similar manner to M2, in both metabolism and efficacy as anticancer agents, and to further explore the biological pro-apoptotic mechanisms of the cysteine-conjugated shogaols against human colon cancer cells HCT-116 and HT-29. Our results show that [8]- and [10]-shogaol have similar metabolic profiles to [6]-shogaol and exhibit similar toxicity toward human colon cancer cells. M2′ and M2″ both show low toxicity against normal colon cells but retain potency against colon cancer cells, suggesting that they have similar activity to M2. We further demonstrate that the cysteine-conjugated shogaols can cause cancer cell death through the activation of the mitochondrial apoptotic pathway. Our results show that oxidative stress activates a p53 pathway that ultimately leads to p53 up-regulated modulator of apoptosis (PUMA) induction and down-regulation of B-cell lymphoma 2 (Bcl-2), followed by cytochrome c release, perturbation of inhibitory interactions of X-linked inhibitor of apoptosis protein (XIAP) with caspases, and finally caspase 9 and 3 activation and cleavage. A brief screen of the markers attenuated by the proapoptotic activity of M2 revealed similar results for [8]- and [10]-shogaol and their respective cysteine-conjugated metabolites M2′ and M2″. This study highlights the cysteine-conjugated metabolites of shogaols as novel dietary colon cancer preventive agents. PMID:24786146

Rotor bore and turbine rotor wheel/spacer heat exchange flow circuit

DOEpatents

Caruso, Philip M.; Eldrid, Sacheverel Quentin; Ladhani, Azad A.; DeMania, Alan Richard; Palmer, Gene David; Wilson, Ian David; Rathbun, Lisa Shirley; Akin, Robert Craig

2002-01-01

In a turbine having closed-circuit steam-cooling passages about the rim of the rotor during steady-state operation, compressor discharge air is supplied to the rotor bore for passage radially outwardly into the wheel space cavities between the wheels and spacers. Communicating slots and channels in the spacers and wheels at circumferentially spaced positions enable egress of the compressor discharge air into the hot gas flow path. At turbine startup, cooling air flows through the closed-circuit steam passages to cool the outer rim of the rotor while compressor discharge air pre-warms the wheels and spacers. At steady-state, cooling steam is supplied in the closed-circuit steam-cooling passages and compressor discharge air is supplied through the bore and into the wheel space cavities to cool the rotor.

Spin density waves predicted in zigzag puckered phosphorene, arsenene and antimonene nanoribbons

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

Wu, Xiaohua; Zhang, Xiaoli; Wang, Xianlong

2016-04-15

The pursuit of controlled magnetism in semiconductors has been a persisting goal in condensed matter physics. Recently, Vene (phosphorene, arsenene and antimonene) has been predicted as a new class of 2D-semiconductor with suitable band gap and high carrier mobility. In this work, we investigate the edge magnetism in zigzag puckered Vene nanoribbons (ZVNRs) based on the density functional theory. The band structures of ZVNRs show half-filled bands crossing the Fermi level at the midpoint of reciprocal lattice vectors, indicating a strong Peierls instability. To remove this instability, we consider two different mechanisms, namely, spin density wave (SDW) caused by electron-electronmore » interaction and charge density wave (CDW) caused by electron-phonon coupling. We have found that an antiferromagnetic Mott-insulating state defined by SDW is the ground state of ZVNRs. In particular, SDW in ZVNRs displays several surprising characteristics:1) comparing with other nanoribbon systems, their magnetic moments are antiparallelly arranged at each zigzag edge and almost independent on the width of nanoribbons; 2) comparing with other SDW systems, its magnetic moments and band gap of SDW are unexpectedly large, indicating a higher SDW transition temperature in ZVNRs; 3) SDW can be effectively modified by strains and charge doping, which indicates that ZVNRs have bright prospects in nanoelectronic device.« less

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

PubMed

Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05). The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Tight binding simulation study on zigzag single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Sharma, Deepa; Jaggi, Neena; Gupta, Vishu

2018-01-01

Tight binding simulation studies using the density functional tight binding (DFTB) model have been performed on various zigzag single-walled carbon-nanotubes (SWCNTs) to investigate their electronic properties using DFTB module of the Material Studio Software version 7.0. Various combinations of different eigen-solvers and charge mixing schemes available in the DFTB Module have been tried to chalk out the electronic structure. The analytically deduced values of the bandgap of (9, 0) SWCNT were compared with the experimentally determined value reported in the literature. On comparison, it was found that the tight binding approximations tend to drastically underestimate the bandgap values. However, the combination of Anderson charge mixing method with standard eigensolver when implemented using the smart algorithm was found to produce fairly close results. These optimized model parameters were then used to determine the band structures of various zigzag SWCNTs. (9, 0) Single-walled Nanotube which is extensively being used for sensing NH3, CH4 and NO2 has been picked up as a reference material since its experimental bandgap value has been reported in the literature. It has been found to exhibit a finite energy bandgap in contrast to its expected metallic nature. The study is of utmost significance as it not only probes and validates the simulation route for predicting suitable properties of nanomaterials but also throws light on the comparative efficacy of the different approximation and rationalization quantum mechanical techniques used in simulation studies. Such simulation studies if used intelligently prove to be immensely useful to the material scientists as they not only save time and effort but also pave the way to new experiments by making valuable predictions.

Purification of SUMO conjugating enzymes and kinetic analysis of substrate conjugation

PubMed Central

Yunus, Ali A.; Lima, Christopher D.

2009-01-01

SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417

Chemotherapeutic Drug-Conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA.

PubMed

Lin, Kevin N; Grandhi, Taraka Sai Pavan; Goklany, Sheba; Rege, Kaushal

2018-04-10

Plasmid DNA (pDNA) is an attractive therapeutic biomolecule in several diseases including cancer, AIDS, cystic fibrosis, Parkinson's disease, and Alzheimer's disease. Increasing demand for plasmid DNA as a therapeutic biomolecule for transgene expression or vaccine applications necessitate novel approaches to bioprocessing. The synthesis, characterization and evaluation of aminoglycoside-derived hydrogel microbeads (Amikabeads) for pDNA binding is described previously. Here, the generation and evaluation of novel chemotherapeutic drug-conjugated microbeads for application in pDNA binding and recovery is described. Chemotherapeutic drug-conjugated Amikabeads demonstrate higher binding of methylated pDNA compared to unmethylated pDNA in presence of high salt concentrations. Desorption of plasmids from drug-conjugated microbeads is facilitated by the use of organic modifiers. The observed differences in binding methylated versus unmethylated DNA can make drug-conjugated microbeads useful in diagnostic as well as therapeutic applications. These results demonstrate that anti-cancer drugs represent a diverse set of ligands that may be exploited for molecular engineering of novel DNA binding materials for applications in delivery, diagnostics, and biomanufacturing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unified model for singlet fission within a non-conjugated covalent pentacene dimer

NASA Astrophysics Data System (ADS)

Basel, Bettina S.; Zirzlmeier, Johannes; Hetzer, Constantin; Phelan, Brian T.; Krzyaniak, Matthew D.; Reddy, S. Rajagopala; Coto, Pedro B.; Horwitz, Noah E.; Young, Ryan M.; White, Fraser J.; Hampel, Frank; Clark, Timothy; Thoss, Michael; Tykwinski, Rik R.; Wasielewski, Michael R.; Guldi, Dirk M.

2017-05-01

When molecular dimers, crystalline films or molecular aggregates absorb a photon to produce a singlet exciton, spin-allowed singlet fission may produce two triplet excitons that can be used to generate two electron-hole pairs, leading to a predicted ~50% enhancement in maximum solar cell performance. The singlet fission mechanism is still not well understood. Here we report on the use of time-resolved optical and electron paramagnetic resonance spectroscopy to probe singlet fission in a pentacene dimer linked by a non-conjugated spacer. We observe the key intermediates in the singlet fission process, including the formation and decay of a quintet state that precedes formation of the pentacene triplet excitons. Using these combined data, we develop a single kinetic model that describes the data over seven temporal orders of magnitude both at room and cryogenic temperatures.

Unified model for singlet fission within a non-conjugated covalent pentacene dimer.

PubMed

Basel, Bettina S; Zirzlmeier, Johannes; Hetzer, Constantin; Phelan, Brian T; Krzyaniak, Matthew D; Reddy, S Rajagopala; Coto, Pedro B; Horwitz, Noah E; Young, Ryan M; White, Fraser J; Hampel, Frank; Clark, Timothy; Thoss, Michael; Tykwinski, Rik R; Wasielewski, Michael R; Guldi, Dirk M

2017-05-18

When molecular dimers, crystalline films or molecular aggregates absorb a photon to produce a singlet exciton, spin-allowed singlet fission may produce two triplet excitons that can be used to generate two electron-hole pairs, leading to a predicted ∼50% enhancement in maximum solar cell performance. The singlet fission mechanism is still not well understood. Here we report on the use of time-resolved optical and electron paramagnetic resonance spectroscopy to probe singlet fission in a pentacene dimer linked by a non-conjugated spacer. We observe the key intermediates in the singlet fission process, including the formation and decay of a quintet state that precedes formation of the pentacene triplet excitons. Using these combined data, we develop a single kinetic model that describes the data over seven temporal orders of magnitude both at room and cryogenic temperatures.

Unified model for singlet fission within a non-conjugated covalent pentacene dimer

PubMed Central

Basel, Bettina S.; Zirzlmeier, Johannes; Hetzer, Constantin; Phelan, Brian T.; Krzyaniak, Matthew D.; Reddy, S. Rajagopala; Coto, Pedro B.; Horwitz, Noah E.; Young, Ryan M.; White, Fraser J.; Hampel, Frank; Clark, Timothy; Thoss, Michael; Tykwinski, Rik R.; Wasielewski, Michael R.; Guldi, Dirk M.

2017-01-01

When molecular dimers, crystalline films or molecular aggregates absorb a photon to produce a singlet exciton, spin-allowed singlet fission may produce two triplet excitons that can be used to generate two electron–hole pairs, leading to a predicted ∼50% enhancement in maximum solar cell performance. The singlet fission mechanism is still not well understood. Here we report on the use of time-resolved optical and electron paramagnetic resonance spectroscopy to probe singlet fission in a pentacene dimer linked by a non-conjugated spacer. We observe the key intermediates in the singlet fission process, including the formation and decay of a quintet state that precedes formation of the pentacene triplet excitons. Using these combined data, we develop a single kinetic model that describes the data over seven temporal orders of magnitude both at room and cryogenic temperatures. PMID:28516916

The opposite induced magnetic moment in narrow zigzag graphene nanoribbons

NASA Astrophysics Data System (ADS)

Liu, Hong; Hu, Bian; Liu, Na

2016-11-01

Based on the analysis of band structure and edge states on zigzag graphene nanoribbons (ZGNRs), we can study theoretically the origination of two minimal quantum conductance. At the two energy points - 0.20 eV and 0.15 eV corresponding to the two dips of quantum conductance, the spin-polarized quantum conductance is about 45%. Furthermore, the two types of edge-localized carriers in the opposite transport directions along the two opposite edge sides form the quantum internal loop current, which can generate one big magnetic moment. At these two energy points - 0.17 eV and 0.15 eV the two induced magnetic moments are in opposite signals.

The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers

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

Luo, Michelle L.; Jackson, Ryan N.; Denny, Steven R.

Bacteria and archaea acquire resistance to foreign genetic elements by integrating fragments of foreign DNA into CRISPR (clustered regularly interspaced short palindromic repeats) loci. In Escherichia coli, CRISPR-derived RNAs (crRNAs) assemble with Cas proteins into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Cascade recognizes DNA targets via protein-mediated recognition of a protospacer adjacent motif and complementary base pairing between the crRNA spacer and the DNA target. Previously determined structures of Cascade showed that the crRNA is stretched along an oligomeric protein assembly, leading us to ask how crRNA length impacts the assembly and function of thismore » complex. We found that extending the spacer portion of the crRNA resulted in larger Cascade complexes with altered stoichiometry and preserved in vitro binding affinity for target DNA. Longer spacers also preserved the in vivo ability of Cascade to repress target gene expression and to recruit the Cas3 endonuclease for target degradation. Lastly, longer spacers exhibited enhanced silencing at particular target locations and were sensitive to mismatches within the extended region. These findings demonstrate the flexibility of the Type I-E CRISPR machinery and suggest that spacer length can be modified to fine-tune Cascade activity.« less

The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers

DOE PAGES

Luo, Michelle L.; Jackson, Ryan N.; Denny, Steven R.; ...

2016-05-12

Bacteria and archaea acquire resistance to foreign genetic elements by integrating fragments of foreign DNA into CRISPR (clustered regularly interspaced short palindromic repeats) loci. In Escherichia coli, CRISPR-derived RNAs (crRNAs) assemble with Cas proteins into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Cascade recognizes DNA targets via protein-mediated recognition of a protospacer adjacent motif and complementary base pairing between the crRNA spacer and the DNA target. Previously determined structures of Cascade showed that the crRNA is stretched along an oligomeric protein assembly, leading us to ask how crRNA length impacts the assembly and function of thismore » complex. We found that extending the spacer portion of the crRNA resulted in larger Cascade complexes with altered stoichiometry and preserved in vitro binding affinity for target DNA. Longer spacers also preserved the in vivo ability of Cascade to repress target gene expression and to recruit the Cas3 endonuclease for target degradation. Lastly, longer spacers exhibited enhanced silencing at particular target locations and were sensitive to mismatches within the extended region. These findings demonstrate the flexibility of the Type I-E CRISPR machinery and suggest that spacer length can be modified to fine-tune Cascade activity.« less

Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads.

PubMed

Nakada, Takashi; Masuda, Takeshi; Naito, Hiroyuki; Yoshida, Masao; Ashida, Shinji; Morita, Koji; Miyazaki, Hideki; Kasuya, Yuji; Ogitani, Yusuke; Yamaguchi, Junko; Abe, Yuki; Honda, Takeshi

2016-03-15

Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bispecific small molecule-antibody conjugate targeting prostate cancer.

PubMed

Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

2013-10-29

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

Bispecific small molecule–antibody conjugate targeting prostate cancer

PubMed Central

Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

2013-01-01

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

Predicting the impact of feed spacer modification on biofouling by hydraulic characterization and biofouling studies in membrane fouling simulators.

PubMed

Siddiqui, A; Lehmann, S; Bucs, Sz S; Fresquet, M; Fel, L; Prest, E I E C; Ogier, J; Schellenberg, C; van Loosdrecht, M C M; Kruithof, J C; Vrouwenvelder, J S

2017-03-01

Feed spacers are an essential part of spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane modules. Geometric modification of feed spacers is a potential option to reduce the impact of biofouling on the performance of membrane systems. The objective of this study was to evaluate the biofouling potential of two commercially available reference feed spacers and four modified feed spacers. The spacers were compared on hydraulic characterization and in biofouling studies with membrane fouling simulators (MFSs). The virgin feed spacer was characterized hydraulically by their resistance, measured in terms of feed channel pressure drop, performed by operating MFSs at varying feed water flow rates. Short-term (9 days) biofouling studies were carried out with nutrient dosage to the MFS feed water to accelerate the biofouling rate. Long-term (96 days) biofouling studies were done without nutrient dosage to the MFS feed water. Feed channel pressure drop was monitored and accumulation of active biomass was quantified by adenosine tri phosphate (ATP) determination. The six feed spacers were ranked on pressure drop (hydraulic characterization) and on biofouling impact (biofouling studies). Significantly different trends in hydraulic resistance and biofouling impact for the six feed spacers were observed. The same ranking for biofouling impact on the feed spacers was found for the (i) short-term biofouling study with nutrient dosage and the (ii) long-term biofouling study without nutrient dosage. The ranking for hydraulic resistance for six virgin feed spacers differed significantly from the ranking of the biofouling impact, indicating that hydraulic resistance of clean feed spacers does not predict the hydraulic resistance of biofouled feed spacers. Better geometric design of feed spacers can be a suitable approach to minimize impact of biofouling in spiral wound membrane systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polydiacetylene chromism towards toxic chemical detection via molecular size-dependent selectivity

NASA Astrophysics Data System (ADS)

Seo, Donghwan

Polydiacetylene (PDA) is a pi-conjugated polymer that has unique optical properties. PDA changes color from blue to red when subjected to various stimuli such as mechanical stress, heat, photoirradiation, pH change, and binding of specific ligands. The steric effect induced by those stimuli on PDA headgroup has been investigated to understand the mechanism of PDA chromism and to apply those optical properties to the development of various sensors. In this work, pH chromism of PDA was examined in terms of the effects of the molecular size and acidity of acid analytes with the consideration of the molecular design aspect of diacetylene lipids. The pH level is an important parameter, since a low pH will produce a charge on the amine headgroup of PDA, but this does not necessarily result in PDA chromatic transition from 'blue phase' to 'red phase.' The molecular size of the counter anion was identified as another determinant condition to ensure the perturbation of the ene-yne conjugated backbone of PDA, which produces the chromatic transition. In the molecular design of the sensory diacetylene lipids, the alkyl spacer length between the amine as a receptor and the amide linker was found to strongly affect the degree of PDA chromatic transition. The longer alkyl spacer showed the less chromatic transition. The length of alkyl spacer seems to promote the flexibility of the molecule diminishing the extent of the transfer of the steric effect at PDA headgroup to the conjugated backbone. Finally, PDA chromism dependent on the molecular size of acid analytes was applied to develop the colorimetric detection of diethyl phosphate (DEP), a degraded nerve agent simulant. PDA liposome sensors successfully showed selective chromatic transition with fluorescent emission upon binding of DEP compared to other acid analytes. The molecular size and acidity of acid analytes, and alkyl spacer length have proven to be correlated with PDA chromism. These new findings provide further

Toward efficient Zn(II)-based artificial nucleases.

PubMed

Boseggia, Elisa; Gatos, Maddalena; Lucatello, Lorena; Mancin, Fabrizio; Moro, Stefano; Palumbo, Manlio; Sissi, Claudia; Tecilla, Paolo; Tonellato, Umberto; Zagotto, Giuseppe

2004-04-14

A series of cis-cis-triaminocyclohexane Zn(II) complex-anthraquinone intercalator conjugates, designed in such a way to allow their easy synthesis and modification, have been investigated as hydrolytic cleaving agents for plasmid DNA. The ligand structure comprises a triaminocyclohexane platform linked by means of alkyl spacers of different length (from C(4) to C(8)) to the anthraquinone group which may intercalate the DNA. At a concentration of 5 microM, the complex of the derivative with a C(8) alkyl spacer induces the hydrolytic stand scission of supercoiled DNA with a rate of 4.6 x 10(-6) s(-1) at pH 7 and 37 degrees C. The conjugation of the metal complex with the anthraquinone group leads to a 15-fold increase of the cleavage efficiency when compared with the anthraquinone lacking Zn-triaminocyclohexane complex. The straightforward synthetic procedure employed, allowing a systematic change of the spacer length, made possible to gain more insight on the role of the intercalating group in determining the reactivity of the systems. Comparison of the reactivity of the different complexes shows a remarkable increase of the DNA cleaving efficiency with the length of the spacer. In the case of too-short spacers, the advantages due to the increased DNA affinity are canceled due to the incorrect positioning of the reactive group, thus leading to cleavage inhibition.

Dark current of organic heterostructure devices with insulating spacer layers

NASA Astrophysics Data System (ADS)

Yin, Sun; Nie, Wanyi; Mohite, Aditya D.; Saxena, Avadh; Smith, Darryl L.; Ruden, P. Paul

2015-03-01

The dark current density at fixed voltage bias in donor/acceptor organic planar heterostructure devices can either increase or decrease when an insulating spacer layer is added between the donor and acceptor layers. The dominant current flow process in these systems involves the formation and subsequent recombination of an interfacial exciplex state. If the exciplex formation rate limits current flow, the insulating interface layer can increase dark current whereas, if the exciplex recombination rate limits current flow, the insulating interface layer decreases dark current. We present a device model to describe this behavior and illustrate it experimentally for various donor/acceptor systems, e.g. P3HT/LiF/C60.

Less is More: A Comparison of Antibody-Gold Nanoparticle Conjugates of Different Ratios.

PubMed

Byzova, Nadezhda A; Safenkova, Irina V; Slutskaya, Elvira S; Zherdev, Anatoly V; Dzantiev, Boris B

2017-11-15

This comprehensive study is related to gold nanoparticles (GNPs) conjugated with antibodies. The goal of the study is to determine the minimal concentration of antibodies for conjugate synthesis when the conjugates have high antigen-capturing activity. Two systems were studied: gold nanoparticles conjugated with monoclonal antibodies (mAb-GNP) specific to Helicobacter pylori and gold nanoparticles conjugated with polyclonal antibodies (pAb-GNP) specific to mouse immunoglobulins. Several conjugates were synthesized with different GNP-to-antibody molar ratios (from 1:1 to 1:245) through nondirectional and noncovalent immobilization on a surface of GNPs with a diameter of 25.3 ± 4.6 nm. The maximal antigen-capturing activities and equilibrium constants of the conjugates correlate with the formation of a constant hydrodynamic radius of the conjugates for mAb-GNP (GNP to antibody molar ratio 1:58) and with the stabilizing concentration by flocculation curves for pAb-GNP (GNP to antibody molar ratio 1:116). The application of the conjugates to the lateral flow immunoassay shows that the antibody concentrations used for the conjugation can be reduced (below the stabilizing concentration) without losing activity for the mAb-GNP conjugates. The findings highlight that the optimal concentration of antibodies immobilized on the surface of GNPs is not always equal to the stabilizing concentration determined by the flocculation curve.

Electro-optical properties of zigzag and armchair boron nitride nanotubes under a transverse electric field: Tight binding calculations

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2012-02-01

The electro-optical properties of zigzag and armchair BNNTs in a uniform transverse electric field are investigated within tight binding approximation. It is found that the electric field modifies the band structure and splits band degeneracy where these effects reflect in the DOS and JDOS spectra. A decrease in the band gap, as a function of the electric field, is observed. This gap reduction increases with the diameter and it is independent of chirality. An analytic function to estimate the electric field needed for band gap closing is proposed which is in good agreement with DFT results. In additional, we show that the larger diameter tubes are more sensitive than small ones. Number and position of peaks in DOS and JDOS spectra for armchair and zigzag tubes with similar radius are dependent on electric field strength.

Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery

PubMed Central

Kim, Hyun Ah; Nam, Kihoon; Kim, Sung Wan

2014-01-01

Targeted delivery of therapeutic genes to the tumor site is critical for successful and safe cancer gene therapy. The arginine grafted bio-reducible poly (cystamine bisacrylamide-diaminohexane, CBA-DAH) polymer (ABP) conjugated poly (amido amine) (PAMAM), PAM-ABP (PA) was designed previously as an efficient gene delivery carrier. To achieve high efficacy in cancer selective delivery, we developed the tumor targeting bio-reducible polymer, PA-PEG1k-RGD, by conjugating cyclic RGDfC (RGD) peptides, which bind αvβ3/5 integrins, to the PAM-ABP using polyethylene glycol (PEG,1kDa) as a spacer. Physical characterization showed nanocomplex formation with bio-reducible properties between PA-PEG1k-RGD and plasmid DNA (pDNA). In transfection assays, PA-PEG1k-RGD showed significantly higher transfection efficiency in comparison with PAM-ABP or PA-PEG1k-RGD in αvβ3/5 positive MCF7 breast cancer and PANC-1 pancreatic cancer cells. The targeting ability of PA-PEG1k-RGD was further established using a competition assay. To confirm the therapeutic effect, the VEGF siRNA expressing plasmid was constructed and then delivered into cancer cells using PA-PEG1k-RGD. PA-PEG1k-RGD showed 20-59% higher cellular uptake rate into MCF7 and PANC-1 than that of non-targeted polymers. In addition, MCF7 and PANC-1 cancer cells transfected with PA-PEG1k-RGD/pshVEGF complexes had significantly decreased VEGF gene expression (51-71%) and cancer cell viability (35-43%) compared with control. These results demonstrate that a tumor targeting bio-reducible polymer with an anti-angiogenic therapeutic gene could be used for efficient and safe cancer gene therapy. PMID:24894645

The use of the Artelon CMC Spacer for osteoarthritis of the basal joint of the thumb.

PubMed

Richard, Marc J; Lunich, Julie A; Correll, Gretchen R

2014-01-01

Favorable clinical outcomes have been reported with the Artelon CMC Spacer, however, several studies have documented complications with the device. The purpose of this study is to review a single surgeon's experience with the Artelon CMC Spacer for the treatment of basal joint arthritis of the thumb. Five thumbs in 6 patients with symptomatic osteoarthritis of the thumb carpometacarpal (CMC) joint were treated with the Artelon CMC Spacer. The mean age of the patients was 60.8 years old. Patients were followed for a mean of 39.3 months (6-63) post-operatively. Complications occurred in 4 of the 6 thumbs and half of the thumbs required at least one secondary operative procedure. A documented foreign-body reaction was present in 2 of the 6 thumbs. The Artelon CMC Spacer is an interposition material that acts as a biologic spacer for arthritic joints while maintaining mechanical strength. Due to an unacceptably high complication rate, we no longer use the Artelon CMC Spacer for the management of basal joint arthritis of the thumb. 4. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Shape memory alloy smart knee spacer to enhance knee functionality: model design and finite element analysis.

PubMed

Gautam, Arvind; Rani, A Bhargavi; Callejas, Miguel A; Acharyya, Swati Ghosh; Acharyya, Amit; Biswas, Dwaipayan; Bhandari, Vasundhra; Sharma, Paresh; Naik, Ganesh R

2016-08-01

In this paper we introduce Shape Memory Alloy (SMA) for designing the tibial part of Total Knee Arthroplasty (TKA) by exploiting the shape-memory and pseudo-elasticity property of the SMA (e.g. NiTi). This would eliminate the drawbacks of the state-of-the art PMMA based knee-spacer including fracture, sustainability, dislocation, tilting, translation and subluxation for tackling the Osteoarthritis especially for the aged people of 45-plus or the athletes. In this paper a Computer Aided Design (CAD) model using SolidWorks for the knee-spacer is presented based on the proposed SMA adopting the state-of-the art industry-standard geometry that is used in the PMMA based spacer design. Subsequently Ansys based Finite Element Analysis is carried out to measure and compare the performance between the proposed SMA based model with the state-of-the art PMMA ones. 81% more bending is noticed in the PMMA based spacer compared to the proposed SMA that would eventually cause fracture and tilting or translation of spacer. Permanent shape deformation of approximately 58.75% in PMMA based spacer is observed compared to recoverable 11% deformation in SMA when same load is applied on both separately.

Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant protein as carrier.

PubMed

Guirola, María; Urquiza, Dioslaida; Alvarez, Anabel; Cannan-Haden, Leonardo; Caballero, Evelin; Guillén, Gerardo

2006-03-01

In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.

Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.

PubMed

Robertson, C F; Norden, M A; Fitzgerald, D A; Connor, F L; Van Asperen, P P; Cooper, P J; Francis, P W; Allen, H D

1998-04-01

To compare the efficacy of salbutamol delivered by jet nebuliser (JN) with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume spacer (Volumatic) for management of acute asthma. A total of 160 children aged from 4 to 12 years presenting to an Emergency Department with acute asthma. The study was of multicentre (n=5) randomised, double blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5 mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI. Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and 15, 30, 45 and 60 mins post administration. The improvement from baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI (P=0.001). Administration of salbutamol via a PMDI and a large volume spacer device provides effective relief in the management of acute asthma in children, but to a lesser extent than a jet nebuliser. This difference may represent a dose response effect.

Organic light-emitting diodes with a spacer enhanced exciplex emission

NASA Astrophysics Data System (ADS)

Yan, Fei; Chen, Rui; Sun, Handong; Wei Sun, Xiao

2014-04-01

By introducing a spacer molecule into the blended exciplex emissive layer, the performance of the bulk heterojunction exciplex organic light-emitting diodes (OLEDs) was improved dramatically; the maximum luminous efficiency was enhanced by about 22% from 7.9 cd/A to 9.7 cd/A, and the luminous efficiency drop was reduced by 28% at 400 mA/cm2. Besides the suppressed annihilation of exciton, the time-resolved photoluminescence measurements indicated that the spacer enhanced the delayed fluorescence through increasing the backward intersystem crossing rate from the triplet to singlet exciplex state. This method is useful for developing high performance exciplex OLEDs.

Unified model for singlet fission within a non-conjugated covalent pentacene dimer

DOE PAGES

Basel, Bettina S.; Zirzlmeier, Johannes; Hetzer, Constantin; ...

2017-05-18

When molecular dimers, crystalline films or molecular aggregates absorb a photon to produce a singlet exciton, spin-allowed singlet fission may produce two triplet excitons that can be used to generate two electron–hole pairs, leading to a predicted B50% enhancement in maximum solar cell performance. The singlet fission mechanism is still not well understood. Here we report on the use of time-resolved optical and electron paramagnetic resonance spectroscopy to probe singlet fission in a pentacene dimer linked by a non-conjugated spacer. We observe the key intermediates in the singlet fission process, including the formation and decay of a quintet state thatmore » precedes formation of the pentacene triplet excitons. In conclusion, using these combined data, we develop a single kinetic model that describes the data over seven temporal orders of magnitude both at room and cryogenic temperatures.« less

Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate).

PubMed

Suksiriworapong, Jiraphong; Taresco, Vincenzo; Ivanov, Delyan P; Styliari, Ioanna D; Sakchaisri, Krisada; Junyaprasert, Varaporn Buraphacheep; Garnett, Martin C

2018-07-01

Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5-9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthetically programmable nanoparticle superlattices using a hollow three-dimensional spacer approach.

PubMed

Auyeung, Evelyn; Cutler, Joshua I; Macfarlane, Robert J; Jones, Matthew R; Wu, Jinsong; Liu, George; Zhang, Ke; Osberg, Kyle D; Mirkin, Chad A

2011-12-11

Crystalline nanoparticle arrays and superlattices with well-defined geometries can be synthesized by using appropriate electrostatic, hydrogen-bonding or biological recognition interactions. Although superlattices with many distinct geometries can be produced using these approaches, the library of achievable lattices could be increased by developing a strategy that allows some of the nanoparticles within a binary lattice to be replaced with 'spacer' entities that are constructed to mimic the behaviour of the nanoparticles they replace, even though they do not contain an inorganic core. The inclusion of these spacer entities within a known binary superlattice would effectively delete one set of nanoparticles without affecting the positions of the other set. Here, we show how hollow DNA nanostructures can be used as 'three-dimensional spacers' within nanoparticle superlattices assembled through programmable DNA interactions. We show that this strategy can be used to form superlattices with five distinct symmetries, including one that has never before been observed in any crystalline material.

Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran-cysteine conjugate.

PubMed

Shahnaz, G; Perera, G; Sakloetsakun, D; Rahmat, D; Bernkop-Schnürch, A

2010-05-21

This study was aimed at improving the mucoadhesive properties of carboxymethyl dextran by the covalent attachment of cysteine. Mediated by a carbodiimide, l-cysteine was covalently attached to the polymer. The resulting CMD-cysteine conjugate (CMD-(273) conjugate) displayed 273+/-20 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). Within 2h the viscosity of an aqueous mucus/CMD-(273) conjugate mixture pH 7.4 increased at 37 degrees C by more than 85% compared to a mucus/carboxymethyl dextran mixture indicating enlarged interactions between the mucus and the thiolated polymer. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (p<0.05). In aqueous solutions the CMD-(273) conjugate was capable of forming inter- and/or intramolecular disulfide bonds. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 15 min, whereas tablets of the CMD-(273) conjugate remained stable for 160 min (means+/-S.D.; n=3). Results from LDH and MTT assays on Caco-2 cells revealed 4.96+/-0.98% cytotoxicity and 94.1+/-0.9% cell viability for the CMD-(273) conjugate, respectively. Controlled release of model compound from CMD-(273) conjugate tablets was observed over 6h. These findings suggest that CMD-(273) conjugate is a promising novel polymer for drug delivery systems providing improved mucoadhesive and cohesive properties, greater stability and biocompatibility. Copyright 2010 Elsevier B.V. All rights reserved.

Effects of electric and magnetic fields on the electronic properties of zigzag carbon and boron nitride nanotubes

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh; Ahmadi, Eghbal

2012-04-01

We have investigated the electronic properties of zigzag CNTs and BNNTs under the external transverse electric field and axial magnetic field, using tight binding approximation. It was found that after switching on the electric and magnetic fields, the band modification such as distortion of the degeneracy, change in energy dispersion, subband spacing and band gap size reduction occurs. The band gap of zigzag BNNTs decreases linearly with increasing the electric field strength but the band gap variation for CNTs increases first and later decreases (Metallic) or first hold constant and then decreases (semiconductor). For type (II) CNTs, at a weak magnetic field, by increasing the electric field strength, the band gap remains constant first and then decreases and in a stronger magnetic field the band gap reduction becomes parabolic. For type (III) CNTs, in any magnetic field, the band gap increases slowly until reaches a maximum value and then decreases linearly. Unlike to CNTs, the magnetic field has less effects on the BNNTs band gap variation.

Antenna Effect on the Organic Spacer-Modified Eu-Doped Layered Gadolinium Hydroxide for the Detection of Vanadate Ions over a Wide pH Range.

PubMed

Jeong, Heejin; Lee, Byung-Il; Byeon, Song-Ho

2016-05-04

The excitation of the adsorbed vanadate group led to the red emission arising from the efficient energy transfer to Eu-doped layered gadolinium hydroxide (LGdH:Eu). This light-harvesting antenna effect allowed LGdH:Eu to detect selectively a vanadate in aqueous solution at different pHs. Because vanadate exists in various forms by extensive oligomerization and protonation reactions in aqueous solution depending on pH, it is important to detect a vanadate regardless of its form over a wide pH range. In particular, spacer molecules with long alkyl chains greatly facilitated access of a vanadate antenna into the interlayer surface of LGdH:Eu. The concomitant increase in adsorption capacity of LGdH:Eu achieved a strong antenna effect of vanadate on the red emission from Eu(3+). When a suspension containing LGdH:Eu nanosheets (1.0 g/L) was used, the vanadate concentration down to 1 × 10(-5) M could even be visually monitored, and the detection limit based on the (5)D0 → (7)F2 emission intensity could reach 4.5 × 10(-8) M.

Investigating the edge state of graphene nanoribbons by a chemical approach: Synthesis and magnetic properties of zigzag-edged nanographene molecules

NASA Astrophysics Data System (ADS)

Konishi, Akihito; Hirao, Yasukazu; Kurata, Hiroyuki; Kubo, Takashi

2013-12-01

The edge state, which is a peculiar magnetic state in zigzag-edged graphene nanoribbons (GNRs) originating from an electron-electron correlation in an edge-localized π-state, has promising applications for magnetic and spintronics devices and has attracted much attention of physicists, chemists, and engineers. For deeper understanding the edge state, precise fabrication of edge structures in GNRs has been highly demanded. We focus on [a.b]periacene, which are polycyclic aromatic hydrocarbons (PAHs) that have zigzag and armchair edges on molecular periphery, as a model compound for the understanding and actually prepare and characterize them. This review summarizes our recent studies on the origin of the edge state by investigating [a.b]periacene in terms of the relationship between the molecular structure and spin-localizing character.

Experimental study and modeling of atomic-scale friction in zigzag and armchair lattice orientations of MoS2

PubMed Central

Li, Meng; Shi, Jialin; Liu, Lianqing; Yu, Peng; Xi, Ning; Wang, Yuechao

2016-01-01

Abstract Physical properties of two-dimensional materials, such as graphene, black phosphorus, molybdenum disulfide (MoS2) and tungsten disulfide, exhibit significant dependence on their lattice orientations, especially for zigzag and armchair lattice orientations. Understanding of the atomic probe motion on surfaces with different orientations helps in the study of anisotropic materials. Unfortunately, there is no comprehensive model that can describe the probe motion mechanism. In this paper, we report a tribological study of MoS2 in zigzag and armchair orientations. We observed a characteristic power spectrum and friction force values. To explain our results, we developed a modified, two-dimensional, stick-slip Tomlinson model that allows simulation of the probe motion on MoS2 surfaces by combining the motion in the Mo layer and S layer. Our model fits well with the experimental data and provides a theoretical basis for tribological studies of two-dimensional materials. PMID:27877869

Experimental study and modeling of atomic-scale friction in zigzag and armchair lattice orientations of MoS2.

PubMed

Li, Meng; Shi, Jialin; Liu, Lianqing; Yu, Peng; Xi, Ning; Wang, Yuechao

2016-01-01

Physical properties of two-dimensional materials, such as graphene, black phosphorus, molybdenum disulfide (MoS 2 ) and tungsten disulfide, exhibit significant dependence on their lattice orientations, especially for zigzag and armchair lattice orientations. Understanding of the atomic probe motion on surfaces with different orientations helps in the study of anisotropic materials. Unfortunately, there is no comprehensive model that can describe the probe motion mechanism. In this paper, we report a tribological study of MoS 2 in zigzag and armchair orientations. We observed a characteristic power spectrum and friction force values. To explain our results, we developed a modified, two-dimensional, stick-slip Tomlinson model that allows simulation of the probe motion on MoS 2 surfaces by combining the motion in the Mo layer and S layer. Our model fits well with the experimental data and provides a theoretical basis for tribological studies of two-dimensional materials.

Study on the Electronic Transport Properties of Zigzag GaN Nanotubes

NASA Astrophysics Data System (ADS)

Li, Enling; Wang, Xiqiang; Hou, Liping; Zhao, Danna; Dai, Yuanbin; Wang, Xuewen

2011-02-01

The electronic transport properties of zigzag GaN nanotubes (n, 0) (4 <= n <= 9) have been calculated using the density functional theory and non-equilibrium Green's functions method. Firstly, the density functional theory (DFT) is used to optimize and calculate the electronic structure of GaNNTs (n, 0) (4<=n<=9). Secondly, DFT and non-equilibrium Green function (NEGF) method are also used to predict the electronic transport properties of GaNNTs two-probe system. The results showed: there is a corresponding relation between the electronic transport properties and the valley of state density of each GaNNT. In addition, the volt-ampere curve of GaNNT is approximately linear.

Armchair and zigzag nanoribbons of gold and silver: A DFT study

NASA Astrophysics Data System (ADS)

Kapoor, Pooja; Sharma, Munish; Kumar, Ashok; Ahluwalia, P. K.

2018-04-01

This paper presents the results from a DFT-based computational study of structural and electronic properties of zigzag and armchair edge shaped nanoribbons of gold and silver in hexagonal phase. The cohesive energy of the considered nanoribbons are found to be more than the corresponding 2D counterpart, thereby, suggesting Au and Ag nanoribbons to be more stable in 1D as compared to 2D. All nanoribbons are found to be metallic with a modulation in quantum ballistic conductance with length and edge type of the nanoribbon. Au nanoribbons are found to have higher conductance than Ag nanoribbon. There is increase in conductance with increase in length of nanoribbon.

Research notes : the pH of water in contact with fresh concrete.

DOT National Transportation Integrated Search

2003-02-01

Fresh concrete can significantly change the pH of water. To study the impacts, the pH of a few drilled shaft pours on Bear Creek near Zigzag (US Highway 26, MP 42.6) were monitored in order to aid discussion on future similar work. The concrete was p...

A high-performance channel engineered charge-plasma-based MOSFET with high-κ spacer

NASA Astrophysics Data System (ADS)

Shan, Chan; Wang, Ying; Luo, Xin; Bao, Meng-tian; Yu, Cheng-hao; Cao, Fei

2017-12-01

In this paper, the performance of graded channel double-gate MOSFET (GC-DGFET) that utilizes the charge-plasma concept and a high-κ spacer is investigated through 2-D device simulations. The results demonstrate that GC-DGFET with high-κ spacer can effectively improve the ON-state driving current (ION) and reduce the OFF-leakage current (IOFF). We find that reduction of the initial energy barrier between the source and channel is the origin of this ION enhancement. The reason for the IOFF reduction is identified to be the extension of the effective channel length owing to the fringing field via high-κ spacers. Consequently, these devices offer enhanced performance by reducing the total gate-to-gate capacitance (Cgg) and decreasing the intrinsic delay (τ).

Molecular cloning and analysis of Schizosaccharomyces pombe Reb1p: sequence-specific recognition of two sites in the far upstream rDNA intergenic spacer.

PubMed Central

Zhao, A; Guo, A; Liu, Z; Pape, L

1997-01-01

The coding sequences for a Schizosaccharomyces pombe sequence-specific DNA binding protein, Reb1p, have been cloned. The predicted S. pombe Reb1p is 24-29% identical to mouse TTF-1 (transcription termination factor-1) and Saccharomyces cerevisiae REB1 protein, both of which direct termination of RNA polymerase I catalyzed transcripts. The S.pombe Reb1 cDNA encodes a predicted polypeptide of 504 amino acids with a predicted molecular weight of 58.4 kDa. The S. pombe Reb1p is unusual in that the bipartite DNA binding motif identified originally in S.cerevisiae and Klyveromyces lactis REB1 proteins is uninterrupted and thus S.pombe Reb1p may contain the smallest natural REB1 homologous DNA binding domain. Its genomic coding sequences were shown to be interrupted by two introns. A recombinant histidine-tagged Reb1 protein bearing the rDNA binding domain has two homologous, sequence-specific binding sites in the S. pomber DNA intergenic spacer, located between 289 and 480 nt downstream of the end of the approximately 25S rRNA coding sequences. Each binding site is 13-14 bp downstream of two of the three proposed in vivo termination sites. The core of this 17 bp site, AGGTAAGGGTAATGCAC, is specifically protected by Reb1p in footprinting analysis. PMID:9016645

Shape-memory-alloy-based smart knee spacer for total knee arthroplasty: 3D CAD modelling and a computational study.

PubMed

Gautam, Arvind; Callejas, Miguel A; Acharyya, Amit; Acharyya, Swati Ghosh

2018-05-01

This study introduced a shape memory alloy (SMA)-based smart knee spacer for total knee arthroplasty (TKA). Subsequently, a 3D CAD model of a smart tibial component of TKA was designed in Solidworks software, and verified using a finite element analysis in ANSYS Workbench. The two major properties of the SMA (NiTi), the pseudoelasticity (PE) and shape memory effect (SME), were exploited, modelled, and analysed for a TKA application. The effectiveness of the proposed model was verified in ANSYS Workbench through the finite element analysis (FEA) of the maximum deformation and equivalent (von Mises) stress distribution. The proposed model was also compared with a polymethylmethacrylate (PMMA)-based spacer for the upper portion of the tibial component for three subjects with body mass index (BMI) of 23.88, 31.09, and 38.39. The proposed SMA -based smart knee spacer contained 96.66978% less deformation with a standard deviation of 0.01738 than that of the corresponding PMMA based counterpart for the same load and flexion angle. Based on the maximum deformation analysis, the PMMA-based spacer had 30 times more permanent deformation than that of the proposed SMA-based spacer for the same load and flexion angle. The SME property of the lower portion of the tibial component for fixation of the spacer at its position was verified by an FEA in ANSYS. Wherein, a strain life-based fatigue analysis was performed and tested for the PE and SME built spacers through the FEA. Therefore, the SMA-based smart knee spacer eliminated the drawbacks of the PMMA-based spacer, including spacer fracture, loosening, dislocation, tilting or translation, and knee subluxation. Copyright © 2018. Published by Elsevier Ltd.

D4Z - a new renumbering for iterative solution of ground-water flow and solute- transport equations

USGS Publications Warehouse

Kipp, K.L.; Russell, T.F.; Otto, J.S.

1992-01-01

D4 zig-zag (D4Z) is a new renumbering scheme for producing a reduced matrix to be solved by an incomplete LU preconditioned, restarted conjugate-gradient iterative solver. By renumbering alternate diagonals in a zig-zag fashion, a very low sensitivity of convergence rate to renumbering direction is obtained. For two demonstration problems involving groundwater flow and solute transport, iteration counts are related to condition numbers and spectra of the reduced matrices.

Immobilization of pectinase on silica-based supports: Impacts of particle size and spacer arm on the activity.

PubMed

Alagöz, Dilek; Tükel, S Seyhan; Yildirim, Deniz

2016-06-01

The pectinase was separately immobilized onto Florisil and nano silica supports through both glutaraldehyde and 3-glyoxypropyltrietoxysilane spacer arms. The effects of spacer arm, particle size of support and ionic liquids on the activities of pectinase preparations were investigated. The immobilization of pectinase onto Florisil and nano silica through 3-glyoxypropyltrietoxysilane spacer arm completely led to inactivation of enzyme; however, 10 and 75% pectinase activity were retained when it was immobilized through glutaraldehyde spacer arm onto Florisil and nano silica, respectively. The pectinase immobilized onto nano silica through glutaraldehyde spacer arm showed 6.3-fold higher catalytic efficiency than that of the pectinase immobilized onto Florisil through same spacer arm. A 2.3-fold increase in thermal stability of pectinase was provided upon immobilization onto nano silica at 35°C. The effects of IL/buffer mixture and volume ratio of IL/buffer mixture on the catalytic activities of free and immobilized pectinase preparations were also tested. All the pectinase preparations showed highest activity in 10% (v/v) 1-butyl-3-methylimidazolium hexafluorophosphate containing medium and their activities significantly affected from the concentration of 1-butyl-3-methylimidazolium hexafluorophosphate. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

NASA Astrophysics Data System (ADS)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin

NASA Astrophysics Data System (ADS)

Wei, Lulu; Lu, Beibei; Cui, Lin; Peng, Xueying; Wu, Jianning; Li, Deqiang; Liu, Zhiyong; Guo, Xuhong

2017-12-01

A novel type of amphiphilic pH-responsive folate-poly(ɛ-caprolactone)- block-poly(2-hydroxyethylmethacrylate)- co-poly(2-(dimethylamino)-ethylmethacrylate) (FA-PCL- b-P(HEMA- co-DMAEMA)) (MFP) block copolymers were designed and synthesized via atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) techniques. The molecular structures of the copolymers were confirmed with 1H NMR, FTIR and GPC measurements. The critical micelle concentration (CMC) of MFP in aqueous solution was extremely low (about 6.54 mg/L). The in vitro release behavior of DOX-loaded micelles was significantly accelerated when the pH value of solution decreased from 7.4 to 5.0. In vitro antitumor efficiency was evaluated by incubating DOX-loaded micelles with Hela cells. The results demonstrated that this copolymer possessed excellent biocompatibility, and FA-decorated micelles MFP showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated biodegradable micelles are highly promising for targeted cancer chemothe-rapy.

P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.

PubMed

Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza

2014-12-01

Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Selected Heat-Sensitive Antibiotics Are Not Inactivated During Polymethylmethacrylate Curing and Can Be Used in Cement Spacers for Periprosthetic Joint Infection.

PubMed

Carli, Alberto V; Sethuraman, Arvinth S; Bhimani, Samrath J; Ross, Frederick P; Bostrom, Mathias P G

2018-06-01

Antibiotic use in polymethylmethacrylate (PMMA) spacers has historically been limited to those which are "heat-stable" and thus retain their antimicrobial properties after exposure to the high temperatures which occur during PMMA curing. This study examines the requirement of "heat stability" by measuring temperatures of Palacos and Simplex PMMA as they cure inside commercial silicone molds of the distal femur and proximal tibia. Temperature probes attached to thermocouples were placed at various depths inside the molds and temperatures were recorded for 20 minutes after PMMA introduced and a temperature curve for each PMMA product was determined. A "heat-stable" antibiotic, vancomycin, and a "heat-sensitive" antibiotic, ceftazidime, were placed in a programmable thermocycler and exposed to the same profile of PMMA curing temperatures. Antimicrobial activity against Staphylococcus aureus was compared for heat-treated antibiotics vs room temperature controls. Peak PMMA temperatures were significantly higher in tibial (115.2°C) vs femoral (85.1°C; P < .001) spacers. In the hottest spacers, temperatures exceeded 100°C for 3 minutes. Simplex PMMA produced significantly higher temperatures (P < .05) compared with Palacos. Vancomycin bioactivity did not change against S aureus with heat exposure. Ceftazidime bioactivity did not change when exposed to femoral temperature profiles and was reduced only 2-fold with tibial profiles. The curing temperatures of PMMA in knee spacers are not high enough or maintained long enough to significantly affect the antimicrobial efficacy of ceftazidime, a known "heat-sensitive" antibiotic. Future studies should investigate if more "heat-sensitive" antibiotics could be used clinically in PMMA spacers. Copyright © 2018 Elsevier Inc. All rights reserved.

Decitabine Nano-conjugate Sensitizing Human Glioblastoma Cells to Temozolomide

PubMed Central

Cui, Yi; Naz, Asia; Thompson, David H.; Irudayaraj, Joseph

2015-01-01

In this study we developed and characterized a delivery system for the epigenetic demethylating drug, decitabine, to sensitize temozolomide-resistant human glioblastoma multiforme (GBM) cells to alkylating chemotherapy. A poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) based nano-conjugate was fabricated to encapsulate decitabine and achieved a better therapeutic response in GBM cells. After synthesis, the highly efficient uptake process and intracellular dynamics of this nano-conjugate was monitored by single-molecule fluorescence tools. Our experiments demonstrated that, under an acidic pH due to active glycolysis in cancer cells, the PLGA-PEG nano-vector could release the conjugated decitabine at a faster rate, after which the hydrolyzed lactic acid and glycolic acid would further acidify the intracellular microenvironment, thus providing a “positive feedback” to increase the effective drug concentration and realize growth inhibition. In temozolomide-resistant GBM cells, decitabine can potentiate the cytotoxic DNA alkylation by counteracting cytosine methylation and reactivating tumor suppressor genes, such as p53 and p21. Owing to excellent internalization and endo-lysosomal escape enabled by the PLGA-PEG backbone, the encapsulated decitabine exhibited a better anti-GBM potential than free drug molecules. Hence, the synthesized nano-conjugate and temozolomide could act in synergy to deliver a more potent and long-term anti-proliferation effect against malignant GBM cells. PMID:25751281

Frustrated quantum magnetism in the Kondo lattice on the zigzag ladder

NASA Astrophysics Data System (ADS)

Peschke, Matthias; Rausch, Roman; Potthoff, Michael

2018-03-01

The interplay between the Kondo effect, indirect magnetic interaction, and geometrical frustration is studied in the Kondo lattice on the one-dimensional zigzag ladder. Using the density-matrix renormalization group, the ground-state and various short- and long-range spin- and density-correlation functions are calculated for the model at half filling as a function of the antiferromagnetic Kondo interaction down to J =0.3 t , where t is the nearest-neighbor hopping on the zigzag ladder. Geometrical frustration is shown to lead to at least two critical points: Starting from the strong-J limit, where almost local Kondo screening dominates and where the system is a nonmagnetic Kondo insulator, antiferromagnetic correlations between nearest-neighbor and next-nearest-neighbor local spins become stronger and stronger, until at Jcdim≈0.89 t frustration is alleviated by a spontaneous breaking of translational symmetry and a corresponding transition to a dimerized state. This is characterized by antiferromagnetic correlations along the legs and by alternating antiferro- and ferromagnetic correlations on the rungs of the ladder. A mechanism of partial Kondo screening that has been suggested for the Kondo lattice on the two-dimensional triangular lattice is not realized in the one-dimensional case. Furthermore, within the symmetry-broken dimerized state, there is a magnetic transition to a 90∘ quantum spin spiral with quasi-long-range order at Jcmag≈0.84 t . The quantum-critical point is characterized by a closure of the spin gap (with decreasing J ) and a divergence of the spin-correlation length and of the spin-structure factor S (q ) at wave vector q =π /2 . This is opposed to the model on the one-dimensional bipartite chain, which is known to have a finite spin gap for all J >0 at half filling.

Preparation and characterization of a dextran-amylase conjugate.

PubMed

Marshall, J J

1976-07-01

Bacillus amyloliquefaciens alpha-amylase was attached to dextran after activation of the polysaccharide by using a modification of the cyanogen bromide method. The soluble dextran-amylase conjugate was purified by molecular-sieve chromatography. The conjugated enzyme has greater stability than the unmodified enzyme at low pH values, during heat treatment, and on removal of calcium ions with a chelating agent. Attachment of dextran to alpha-amylase did not alter the Michaelis constant of the enzyme acting on starch. The polysaccharide-enzyme conjugate probably consists of a cross-linked aggregate of many dextran and many enzyme molecules, in which a proportion of the enzyme molecules, although not inactivated, are unable to express their activity, except after dextranase treatment.

Diagnosis Of Persistent Infection In Prosthetic Two-Stage Exchange: PCR analysis of Sonication fluid From Bone Cement Spacers.

PubMed

Mariaux, Sandrine; Tafin, Ulrika Furustrand; Borens, Olivier

2017-01-01

Introduction: When treating periprosthetic joint infections with a two-stage procedure, antibiotic-impregnated spacers are used in the interval between removal of prosthesis and reimplantation. According to our experience, cultures of sonicated spacers are most often negative. The objective of our study was to investigate whether PCR analysis would improve the detection of bacteria in the spacer sonication fluid. Methods: A prospective monocentric study was performed from September 2014 to January 2016. Inclusion criteria were two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Beside tissues samples and sonication, broad range bacterial PCRs, specific S. aureus PCRs and Unyvero-multiplex PCRs were performed on the sonicated spacer fluid. Results: 30 patients were identified (15 hip, 14 knee and 1 ankle replacements). At reimplantation, cultures of tissue samples and spacer sonication fluid were all negative. Broad range PCRs were all negative. Specific S. aureus PCRs were positive in 5 cases. We had two persistent infections and four cases of infection recurrence were observed, with bacteria different than for the initial infection in three cases. Conclusion: The three different types of PCRs did not detect any bacteria in spacer sonication fluid that was culture-negative. In our study, PCR did not improve the bacterial detection and did not help to predict whether the patient will present a persistent or recurrent infection. Prosthetic 2-stage exchange with short interval and antibiotic-impregnated spacer is an efficient treatment to eradicate infection as both culture- and molecular-based methods were unable to detect bacteria in spacer sonication fluid after reimplantation.

Spacer-length DNA intermediates are associated with Cas1 in cells undergoing primed CRISPR adaptation.

PubMed

Musharova, Olga; Klimuk, Evgeny; Datsenko, Kirill A; Metlitskaya, Anastasia; Logacheva, Maria; Semenova, Ekaterina; Severinov, Konstantin; Savitskaya, Ekaterina

2017-04-07

During primed CRISPR adaptation spacers are preferentially selected from DNA recognized by CRISPR interference machinery, which in the case of Type I CRISPR-Cas systems consists of CRISPR RNA (crRNA) bound effector Cascade complex that locates complementary targets, and Cas3 executor nuclease/helicase. A complex of Cas1 and Cas2 proteins is capable of inserting new spacers in the CRISPR array. Here, we show that in Escherichia coli cells undergoing primed adaptation, spacer-sized fragments of foreign DNA are associated with Cas1. Based on sensitivity to digestion with nucleases, the associated DNA is not in a standard double-stranded state. Spacer-sized fragments are cut from one strand of foreign DNA in Cas1- and Cas3-dependent manner. These fragments are generated from much longer S1-nuclease sensitive fragments of foreign DNA that require Cas3 for their production. We propose that in the course of CRISPR interference Cas3 generates fragments of foreign DNA that are recognized by the Cas1-Cas2 adaptation complex, which excises spacer-sized fragments and channels them for insertion into CRISPR array. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

SPACER: server for predicting allosteric communication and effects of regulation

PubMed Central

Goncearenco, Alexander; Mitternacht, Simon; Yong, Taipang; Eisenhaber, Birgit; Eisenhaber, Frank; Berezovsky, Igor N.

2013-01-01

The SPACER server provides an interactive framework for exploring allosteric communication in proteins with different sizes, degrees of oligomerization and function. SPACER uses recently developed theoretical concepts based on the thermodynamic view of allostery. It proposes easily tractable and meaningful measures that allow users to analyze the effect of ligand binding on the intrinsic protein dynamics. The server shows potential allosteric sites and allows users to explore communication between the regulatory and functional sites. It is possible to explore, for instance, potential effector binding sites in a given structure as targets for allosteric drugs. As input, the server only requires a single structure. The server is freely available at http://allostery.bii.a-star.edu.sg/. PMID:23737445

Effect of edge modification on the zigzag BC2N nanoribbons

NASA Astrophysics Data System (ADS)

Xiao, Xiang; Li, Hong; Tie, Jun; Lu, Jing

2016-08-01

We use first principles calculations to investigate the effects of edge modification with nonmetal species on zigzag-edged BC2N nanoribbons (ZBC2NNRs). These ZBC2NNRs show either semiconducting or metallic behaviors depending on the edge modifications and ribbon widths. We find that the O-modification induces a ferromagnetic ground state with a metallic behavior for all the ribbon widths investigated. And when the ribbon width is more than 3.32 nm (NZ ⩾ 16), an antiferromagnetic ground state with a half-metallic behavior is realized in the H-passivated ZBC2NNRs. These versatile electronic properties render the ZBC2NNRs a promising candidate material in nanoelectronics and nanospintronics.

Geometric effects on mixing performance in a novel passive micromixer with trapezoidal-zigzag channels

NASA Astrophysics Data System (ADS)

Le The, Hai; Ta, Bao Quoc; Le Thanh, Hoa; Dong, Tao; Nguyen Thoi, Trung; Karlsen, Frank

2015-09-01

A novel passive micromixer, called a trapezoidal-zigzag micromixer (TZM), is reported. A TZM is composed of trapezoidal channels in a zigzag and split-recombine arrangement that enables multiple mixing mechanisms, including splitting-recombining, twisting, transversal flows, vortices, and chaotic advection. The effects of geometric parameters of the TZM on mixing performance are systematically investigated by the Taguchi method and numerical simulations in COMSOL Multiphysics. The number of mixing units, the slope angle of the trapezoidal channel, the height of the constriction element, and the width ratio between the middle-trapezoidal channel and the side-trapezoidal channel are the four parameters under study. The mixing performance of the TZM is investigated at three different Reynolds number (Re) values of 0.5, 5, and 50. The results showed that a TZM with six mixing units, a trapezoidal slope angle of 75°, a constricting height of 100 µm, and a width ratio of 0.5 has the highest mixing efficiency. This optimal TZM has a mixing efficiency greater than 85% for Re values from 0.1 to 80. In particular, for Re  ⩽  0.9 and Re  ⩾  20, the mixing efficiency of the optimal TZM is greater than 90%. The proposed TZM has a higher mixing efficiency and a smaller footprint than previously reported micromixers.

Improved nuclear fuel assembly grid spacer

DOEpatents

Marshall, John; Kaplan, Samuel

1977-01-01

An improved fuel assembly grid spacer and method of retaining the basic fuel rod support elements in position within the fuel assembly containment channel. The improvement involves attachment of the grids to the hexagonal channel and of forming the basic fuel rod support element into a grid structure, which provides a design which is insensitive to potential channel distortion (ballooning) at high fluence levels. In addition the improved method eliminates problems associated with component fabrication and assembly.

Negative differential resistance and magnetoresistance in zigzag borophene nanoribbons

NASA Astrophysics Data System (ADS)

Liu, Jiayi; Wu, Jiaxin; Chen, Changpeng; Han, Lu; Zhu, Ziqing; Wu, Jinping

2018-02-01

Since borophene has been grown experimentally, its extraordinary characteristics have attracted more and more attentions. In this paper, we construct pristine zigzag-edged borophene nanoribbons (ZBNRs) of different widths to study the transport properties, using the first-principles calculations. The differences of the quantum transport properties are discussed, where even-N ZBNRs and odd-N ZBNRs have different current-voltage relationships. Especially, the negative differential resistance (NDR) can be observed within certain bias range in 5-ZBNR and 7-ZBNR, while 6-ZBNR behaves like a metal whose current rises with the increase of the voltage. Moreover, borophene nanoribbon shows interesting magnetic transport properties. The spin-filtering effect can be revealed when the two electrodes have opposite magnetization directions. Besides, the magnetoresistance effect appears to exist in even-N ZBNRs and the maximum value can reach 70%. The mechanisms of these phenomena are proposed in detail.

How type II CRISPR-Cas establish immunity through Cas1-Cas2-mediated spacer integration.

PubMed

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-10-05

CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby Cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical. The conserved Cas1 and Cas2 proteins form an integrase complex consisting of two distal Cas1 dimers bridged by a Cas2 dimer. The prespacer is bound by Cas1-Cas2 as a dual-forked DNA, and the terminal 3'-OH of each 3' overhang serves as an attacking nucleophile during integration. The prespacer is preferentially integrated into the leader-proximal region of the CRISPR array, guided by the leader sequence and a pair of inverted repeats inside the CRISPR repeat. Spacer integration in the well-studied Escherichia coli type I-E CRISPR system also relies on the bacterial integration host factor. In type II-A CRISPR, however, Cas1-Cas2 alone integrates spacers efficiently in vitro; other Cas proteins (such as Cas9 and Csn2) have accessory roles in the biogenesis phase of prespacers. Here we present four structural snapshots from the type II-A system of Enterococcus faecalis Cas1 and Cas2 during spacer integration. Enterococcus faecalis Cas1-Cas2 selectively binds to a splayed 30-base-pair prespacer bearing 4-nucleotide 3' overhangs. Three molecular events take place upon encountering a target: first, the Cas1-Cas2-prespacer complex searches for half-sites stochastically, then it preferentially interacts with the leader-side CRISPR repeat, and finally, it catalyses a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3' overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework to explain the stepwise spacer

Highly Efficient White Organic Light-Emitting Diodes with Ultrathin Emissive Layers and a Spacer-Free Structure

PubMed Central

Wu, Shengfan; Li, Sihua; Sun, Qi; Huang, Chenchao; Fung, Man-Keung

2016-01-01

Ultrathin emissive layers (UEMLs) of phosphorescent materials with a layer thickness of less than 0.3 nm were introduced for high-efficiency organic light-emitting diodes (OLEDs). All the UEMLs for white OLEDs can be prepared without the use of interlayers or spacers. Compared with devices fabricated with interlayers inserted in-between the UEMLs, our spacer-free structure not only significantly improves device efficiency, but also simplifies the fabrication process, thus it has a great potential in lowering the cost of OLED panels. In addition, its spacer-free structure decreases the number of interfaces which often introduce unnecessary energy barriers in these devices. In the present work, UEMLs of red, green and blue-emitting phosphorescent materials and yellow and blue phosphorescent emitters are utilized for the demonstration of spacer-free white OLEDs. Upon optimization of the device structure, we demonstrated spacer-free and simple-structured white-emitting OLEDs with a good device performance. The current and power efficiencies of our white-emitting devices are as high as 56.0 cd/A and 55.5 lm/W, respectively. These efficiencies are the highest ever reported for OLEDs fabricated with the UEML approach. PMID:27170543

Highly Efficient White Organic Light-Emitting Diodes with Ultrathin Emissive Layers and a Spacer-Free Structure.

PubMed

Wu, Shengfan; Li, Sihua; Sun, Qi; Huang, Chenchao; Fung, Man-Keung

2016-05-12

Ultrathin emissive layers (UEMLs) of phosphorescent materials with a layer thickness of less than 0.3 nm were introduced for high-efficiency organic light-emitting diodes (OLEDs). All the UEMLs for white OLEDs can be prepared without the use of interlayers or spacers. Compared with devices fabricated with interlayers inserted in-between the UEMLs, our spacer-free structure not only significantly improves device efficiency, but also simplifies the fabrication process, thus it has a great potential in lowering the cost of OLED panels. In addition, its spacer-free structure decreases the number of interfaces which often introduce unnecessary energy barriers in these devices. In the present work, UEMLs of red, green and blue-emitting phosphorescent materials and yellow and blue phosphorescent emitters are utilized for the demonstration of spacer-free white OLEDs. Upon optimization of the device structure, we demonstrated spacer-free and simple-structured white-emitting OLEDs with a good device performance. The current and power efficiencies of our white-emitting devices are as high as 56.0 cd/A and 55.5 lm/W, respectively. These efficiencies are the highest ever reported for OLEDs fabricated with the UEML approach.

Highly Efficient White Organic Light-Emitting Diodes with Ultrathin Emissive Layers and a Spacer-Free Structure

NASA Astrophysics Data System (ADS)

Wu, Shengfan; Li, Sihua; Sun, Qi; Huang, Chenchao; Fung, Man-Keung

2016-05-01

Ultrathin emissive layers (UEMLs) of phosphorescent materials with a layer thickness of less than 0.3 nm were introduced for high-efficiency organic light-emitting diodes (OLEDs). All the UEMLs for white OLEDs can be prepared without the use of interlayers or spacers. Compared with devices fabricated with interlayers inserted in-between the UEMLs, our spacer-free structure not only significantly improves device efficiency, but also simplifies the fabrication process, thus it has a great potential in lowering the cost of OLED panels. In addition, its spacer-free structure decreases the number of interfaces which often introduce unnecessary energy barriers in these devices. In the present work, UEMLs of red, green and blue-emitting phosphorescent materials and yellow and blue phosphorescent emitters are utilized for the demonstration of spacer-free white OLEDs. Upon optimization of the device structure, we demonstrated spacer-free and simple-structured white-emitting OLEDs with a good device performance. The current and power efficiencies of our white-emitting devices are as high as 56.0 cd/A and 55.5 lm/W, respectively. These efficiencies are the highest ever reported for OLEDs fabricated with the UEML approach.

Custom-made hinged spacers in revision knee surgery for patients with infection, bone loss and instability.

PubMed

Macmull, S; Bartlett, W; Miles, J; Blunn, G W; Pollock, R C; Carrington, R W J; Skinner, J A; Cannon, S R; Briggs, T W R

2010-12-01

Polymethyl methacrylate spacers are commonly used during staged revision knee arthroplasty for infection. In cases with extensive bone loss and ligament instability, such spacers may not preserve limb length, joint stability and motion. We report a retrospective case series of 19 consecutive patients using a custom-made cobalt chrome hinged spacer with antibiotic-loaded cement. The "SMILES spacer" was used at first-stage revision knee arthroplasty for chronic infection associated with a significant bone loss due to failed revision total knee replacement in 11 patients (58%), tumour endoprosthesis in four patients (21%), primary knee replacement in two patients (11%) and infected metalwork following fracture or osteotomy in a further two patients (11%). Mean follow-up was 38 months (range 24-70). In 12 (63%) patients, infection was eradicated, three patients (16%) had persistent infection and four (21%) developed further infection after initially successful second-stage surgery. Above knee amputation for persistent infection was performed in two patients. In this particularly difficult to treat population, the SMILES spacer two-stage technique has demonstrated encouraging results and presents an attractive alternative to arthrodesis or amputation. Copyright © 2009 Elsevier B.V. All rights reserved.

Spacer Facial Artery Musculomucosal Flap: Simultaneous Closure of Oronasal Fistulas and Palatal Lengthening.

PubMed

Lee, Jonathan Y; Alizadeh, Kaveh

2016-01-01

In this series, the authors describe a modification of the facial artery musculomucosal flap for oronasal fistula repair. The spacer facial artery musculomucosal flap technique is characterized by a pedicle inset into the retromolar trigone and palate, obviating a second operative stage. This was performed in 14 patients with a 5.2-cm mean fistula size. Average follow-up was 4.3 years, with one partial flap necrosis but no recurrent oronasal fistula. There was a mean decrease of 18 percent in the distance between the velum and the posterior pharyngeal wall. The spacer facial artery musculomucosal flap provides a single-stage reconstruction of oronasal fistula while lengthening the palate through a pushback mechanism. Although further study of velopharyngeal function is needed, the spacer facial artery musculomucosal flap may be beneficial for patients with a short velum and an oronasal fistula. Therapeutic, IV.

Accurate pKa calculation of the conjugate acids of alkanolamines, alkaloids and nucleotide bases by quantum chemical methods.

PubMed

Gangarapu, Satesh; Marcelis, Antonius T M; Zuilhof, Han

2013-04-02

The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum model (CPCM) and universal solvation models (SMD, SM8). G3, SCS-MP2 and M11-L methods coupled with SMD and SM8 solvation models perform well for alkanolamines with mean unsigned errors below 0.20 pKa units, in all cases. Extending this method to the pKa calculation of 35 nitrogen-containing compounds spanning 12 pKa units showed an excellent correlation between experimental and computational pKa values of these 35 amines with the computationally low-cost SM8/M11-L density functional approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conjugate and method for forming aminomethyl phosphorus conjugates

DOEpatents

Katti, Kattesh V.; Berning, Douglas E.; Volkert, Wynn A.; Ketring, Alan R.; Churchill, Robert

1999-01-01

A method of forming phosphine-amine conjugates includes reacting a hydroxymethyl phosphine group of an amine-free first molecule with at least one free amine group of a second molecule to covalently bond the first molecule with the second molecule through an aminomethyl phosphorus linkage and the conjugates formed thereby.

Comparison of Hydrazone Heterobifunctional Crosslinking Agents for Reversible Conjugation of Thiol-Containing Chemistry

PubMed Central

Christie, R. James; Anderson, Diana J.; Grainger, David W.

2010-01-01

Reversible covalent conjugation chemistries that allow site- and condition-specific coupling and uncoupling reactions are attractive components in nanotechnologies, bioconjugation methods, imaging and drug delivery systems. Here, we compare three heterobifunctional crosslinkers, containing both thiol- and amine- reactive chemistry, to form pH-labile hydrazones with hydrazide derivatives of the known and often published water-soluble polymer, poly[N-(2-hydroxypropyl methacrylamide)] (pHPMA), while subsequently coupling thiol-containing molecules to the crosslinker via maleimide addition. Two novel crosslinkers were prepared from the popular heterobifunctional crosslinking agent, succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), modified to contain either terminal aldehyde groups (i.e., 1-(N-3-propanal)-4-(N-maleimidomethyl) cyclohexane carboxamide, PMCA) or methylketone groups (i.e., 1-(N-3-butanone)-4-(N-maleimidomethyl) cyclohexane carboxamide, BMCA). A third crosslinking agent was the commercially available N-4-acetylphenyl maleimide (APM). PMCA and BMCA exhibited excellent reactivity towards hydrazide-derivatized pHPMA with essentially complete hydrazone conjugation to polymer reactive sites, while APM coupled only ~ 60% of available reactive sites on the polymer despite a 3-fold molar excess relative to polymer hydrazide groups. All polymer hydrazone conjugates bearing these bifunctional agents were then further reacted with thiol-modified tetramethylrhodamine dye, confirming crosslinker maleimide reactivity after initial hydrazone polymer conjugation. Incubation of dye-labeled polymer conjugates in phosphate buffered saline at 37°C showed that hydrazone coupling resulting from APM exhibited the greatest difference in stability between pH 7.4 and 5.0, with hydrolysis and dye release increased at pH 5.0 over a 24hr incubation period. Polymer conjugates bearing hydrazones formed from crosslinker BMCA exhibited intermediate stability with

The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5

PubMed Central

Lopez-Abarrategui, Carlos; Figueroa-Espi, Viviana; Lugo-Alvarez, Maria B; Pereira, Caroline D; Garay, Hilda; Barbosa, João ARG; Falcão, Rosana; Jiménez-Hernández, Linnavel; Estévez-Hernández, Osvaldo; Reguera, Edilso; Franco, Octavio L; Dias, Simoni C; Otero-Gonzalez, Anselmo J

2016-01-01

Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid-modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 µg/mL. However, the nanoparticles were not capable of inhibiting Gram-negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 µg/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity. PMID:27563243

Atomistic full-quantum transport model for zigzag graphene nanoribbon-based structures: Complex energy-band method

NASA Astrophysics Data System (ADS)

Chen, Chun-Nan; Luo, Win-Jet; Shyu, Feng-Lin; Chung, Hsien-Ching; Lin, Chiun-Yan; Wu, Jhao-Ying

2018-01-01

Using a non-equilibrium Green’s function framework in combination with the complex energy-band method, an atomistic full-quantum model for solving quantum transport problems for a zigzag-edge graphene nanoribbon (zGNR) structure is proposed. For transport calculations, the mathematical expressions from the theory for zGNR-based device structures are derived in detail. The transport properties of zGNR-based devices are calculated and studied in detail using the proposed method.

[Conjugated vaccines].

PubMed

Fritzell, Bernard

2005-01-01

Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.

PubMed

Bromberg, Lev; Raduyk, Svetlana; Hatton, T Alan; Concheiro, Angel; Rodriguez-Valencia, Cosme; Silva, Maite; Alvarez-Lorenzo, Carmen

2009-05-20

Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.

Effects of spacer orientations on the cake formation during membrane fouling: Quantitative analysis based on 3D OCT imaging.

PubMed

Liu, Xin; Li, Weiyi; Chong, Tzyy Haur; Fane, Anthony G

2017-03-01

Spacer design plays an important role in improving the performance of membrane processes for water/wastewater treatment. This work focused on a fundamental issue of spacer design, i.e., investigating the effects of spacer orientations on the fouling behavior during a membrane process. A series of fouling experiments with different spacer orientation were carried out to in situ characterize the formation of a cake layer in a spacer unit cell via 3D optical coherence tomography (OCT) imaging. The cake layers formed at different times were digitalized for quantitatively analyzing the variation in the cake morphology as a function of time. In particular, the local deposition rates were evaluated to determine the active regions where the instantaneous changes in deposit thickness were significant. The characterization results indicate that varying the spacer orientation could substantially change the evolution of membrane fouling by particulate foulants and thereby result in a cake layer with various morphologies; the competition between growth and erosion at different locations would instantaneously respond to the micro-hydrodynamic environment that might change with time. This work confirms that the OCT-based characterization method is a powerful tool for exploring novel spacer design. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative differential resistance in oxidized zigzag graphene nanoribbons.

PubMed

Wang, Min; Li, Chang Ming

2011-01-28

A theoretical study of zigzag graphene nanoribbons (ZGNRs) with an epoxy-pair chain (ZGO) is performed. The electronic transport properties are mainly evaluated by non-equilibrium Green's functions using the TRANSIESTA package. The results indicate that the graphene oxide can have a negative differential resistance (NDR) phenomenon, supported by bias-dependent transmission curves of different spin orientations. Applying non-zero bias voltages makes the density of states (DOS) of the right electrodes shift down. Due to an energy gap between the LUMO and LUMO+1 in ZGOs, with a certain bias, the conduction band of the right electrode cannot match the LUMO of the scattering region, then NDR occurs. With a larger bias, NDR ends when the second conduction band of the right electrode's DOS covers the LUMO of the scattering region. Since most of proposed ZGO systems possess such a gap between the LUMO and LUMO+1, NDR can be widely observed and this discovery may provide great potential applications in NDR-based nanoelectronics by using modified graphene materials.

Anticancer activity of drug conjugates in head and neck cancer cells.

PubMed

Majumdar, Debatosh; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Shin, Dong M

2016-06-01

Sexually transmitted oral cancer/head and neck cancer is increasing rapidly. Human papilloma virus (HPV) is playing a role in the pathogenesis of a subset of squamous cell carcinoma of head and neck (SCCHN). Paclitaxel is a widely used anticancer drug for breast, ovarian, testicular, cervical, non-small cell lung, head and neck cancer. However, it is water insoluble and orally inactive. We report the synthesis of water soluble nanosize conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide by employing native chemical ligation. We performed a native chemical ligation between the N-hydroxy succinimide (NHS) ester of paclitaxel succinate and cysteine at pH 6.5 to give the cysteine-conjugated paclitaxel derivative. The thiol functionality of cysteine was activated and subsequently conjugated to multiarm thiol-PEG to obtain the paclitaxel branched PEG conjugate. Finally, we conjugated an EGFR-targeting peptide to obtain conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide. These conjugates show anticancer activity against squamous cell carcinoma of head and neck cells (SCCHN, Tu212).

Discovery of a Conjugative Megaplasmid in Bifidobacterium breve

PubMed Central

Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco

2014-01-01

Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. PMID:25326305

On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires.

PubMed

Silas, Sukrit; Makarova, Kira S; Shmakov, Sergey; Páez-Espino, David; Mohr, Georg; Liu, Yi; Davison, Michelle; Roux, Simon; Krishnamurthy, Siddharth R; Fu, Becky Xu Hua; Hansen, Loren L; Wang, David; Sullivan, Matthew B; Millard, Andrew; Clokie, Martha R; Bhaya, Devaki; Lambowitz, Alan M; Kyrpides, Nikos C; Koonin, Eugene V; Fire, Andrew Z

2017-07-11

Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium- Arthrospira platensis Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown. IMPORTANCE While the majority of CRISPR-Cas immune systems adapt to foreign genetic elements by capturing segments of invasive DNA, some systems carry reverse transcriptases (RTs) that enable adaptation to RNA molecules. From

Filter holder assembly having extended collar spacer ring

DOEpatents

Alvin, Mary Anne; Bruck, Gerald J.

2002-01-01

A filter holder assembly is provided that utilizes a fail-safe regenerator unit with an annular spacer ring having an extended metal collar for containment and positioning of a compliant ceramic gasket used in the assembly. The filter holder assembly is disclosed for use with advanced composite, filament wound, and metal candle filters.

LISA telescope spacer design investigations

NASA Astrophysics Data System (ADS)

Sanjuan, Josep; Mueller, Guido; Livas, Jeffrey; Preston, Alix; Arsenovic, Petar; Castellucci, Kevin; Generie, Joseph; Howard, Joseph; Stebbins, Robin

The Laser Interferometer Space Antenna (LISA) is a space-based gravitational wave observa-tory with the goal of observing Gravitational Waves (GWs) from astronomical sources in a frequency range from 30 µHz to 0.1 Hz. The detection of GWs at such low frequency requires measurements of distances at the pico-meter level between bodies separated by 5 million kilo-meters. The LISA mission consists of three identical spacecraft (SC) separated by 5 × 106 km forming an equilateral triangle. Each SC contains two optical assemblies and two vacuum en-closures housing one proof mass (PM) in geodesic (free fall) motion each. The two assemblies on one SC are each pointing towards an identical assembly on each of the other two SC to form a non-equal arm interferometer. The measurement of the GW strain is done by measuring the change in the length of the optical path between the PMs of one arm relative to the other arms caused by the pass of a GW. An important element of the Interferometric Measurement System (IMS) is the telescope which, on one hand, gathers the light coming from the far SC (˜100 pW) and, on the other hand, expands and collimates the small outgoing beam ( 1 W) and sends it to the far SC. Due to the very demanding sensitivity requirements care must be taken in the design and validation of the telescope not to degrade the IMS performance. For instance, the diameter of the telescope sets the the shot noise of the IMS and depends critically on the diameter of the primary and the divergence angle of the outgoing beam. As the telescope is rather fast telescope, the divergence angle is a critical function of the overall separation between the primary and secondary. Any long term changes of the distance of more than a a few micro-meter would be detrimental to the LISA mission. Similarly challenging are the requirements on the in-band path-length noise for the telescope which has to be kept below 1 pm Hz-1/2 in the LISA band. Different configurations (on-axis/off axis

Quenching of fluorescence of conjugated poly(p-phenylene) polymers by benzil and dimethylaminobenzil molecules

NASA Astrophysics Data System (ADS)

Bagnich, S. A.; Knyukshto, V. N.

2006-11-01

We have studied the mechanisms for quenching of the fluorescence of conjugated poly(p-phenylene) polymers by benzil and dimethylaminobenzil molecules. We have shown that molecules in the diketone series are quenching agents for the fluorescence of the indicated polymers, and can serve as singlet-triplet converters capable of populating the triplet state of the polymer. We have observed that the efficiency of quenching of the fluorescence of the studied polymers depends considerably on the presence of bulky side groups in the polymer or in the activator molecules. Based on analysis of the data obtained, we conclude that in the case of a rigid planar structure for the polymer, a significant contribution to quenching of its fluorescence comes from not only singlet-singlet energy transfer but also charge transfer, leading to formation of intermolecular complexes (exciplexes).

MO-AB-BRA-02: Modeling Nanoparticle-Eluting Spacer Degradation During Brachytherapy Application with in Situ Dose-Painting

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

Boateng, F; Ngwa, W; Harvard Medical School, Boston, MA

Purpose: Brachytherapy application with in situ dose-painting using gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers has been proposed as an innovative approach to increase therapeutic efficacy during brachytherapy. This work investigates the dosimetric impact of slow versus burst release of GNP from next generation biodegradable spacers. Methods: Mathematical models were developed based on experimental data to study the release of GNP from a spacer designed with FDA approved poly(lactic-co-glycolic acid) (PLGA) polymer. The diffusion controlled released process and PLGA polymer degradation kinetics was incorporated in the calculations for the first time. An in vivo determined diffusion coefficient was usedmore » for determining the concentration profiles and corresponding dose enhancement based on initial GNP-loading concentrations of 7 mg/g. Results: The results showed that there is significant delay before the concentration profile of GNP diffusion in the tumor is similar to that when burst release is assumed as in previous studies. For example, in the case of burst release after spacer administration, it took up to 25 days for all the GNP to be released from the spacer using diffusion controlled release process only. However, it took up to 45 days when a combined model for both diffusion and polymer degradation processes was used. Based on the tumor concentration profiles, a significant dose enhancement factor (DEF >20%), could be attained at a tumor distances of 5 mm from a spacer loaded with 10 nm GNP sizes. Conclusion: The results highlight the need to take the slow release of GNP from spacers and factors such as biodegradation of polymers into account in research development of GNP-eluting spacers for brachytherapy applications with in-situ dose-painting using gold nanoparticles. The findings suggest that I-125 may be the more appropriate for such applications given the relatively longer half-live compared to other radioisotopes

Altered stoichiometry Escherichia coli Cascade complexes with shortened CRISPR RNA spacers are capable of interference and primed adaptation

DOE PAGES

Kuznedelov, Konstantin; Mekler, Vladimir; Lemak, Sofia; ...

2016-10-13

The Escherichia coli type I-E CRISPR-Cas system Cascade effector is a multisubunit complex that binds CRISPR RNA (crRNA). Through its 32-nucleotide spacer sequence, Cascade-bound crRNA recognizes protospacers in foreign DNA, causing its destruction during CRISPR interference or acquisition of additional spacers in CRISPR array during primed CRISPR adaptation. Within Cascade, the crRNA spacer interacts with a hexamer of Cas7 subunits. We show that crRNAs with a spacer length reduced to 14 nucleotides cause primed adaptation, while crRNAs with spacer lengths of more than 20 nucleotides cause both primed adaptation and target interference in vivo. Shortened crRNAs assemble into altered-stoichiometry Cascademore » effector complexes containing less than the normal amount of Cas7 subunits. The results show that Cascade assembly is driven by crRNA and suggest that multi-subunit type I CRISPR effectors may have evolved from much simpler ancestral complexes.« less

Altered stoichiometry Escherichia coli Cascade complexes with shortened CRISPR RNA spacers are capable of interference and primed adaptation

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

Kuznedelov, Konstantin; Mekler, Vladimir; Lemak, Sofia

The Escherichia coli type I-E CRISPR-Cas system Cascade effector is a multisubunit complex that binds CRISPR RNA (crRNA). Through its 32-nucleotide spacer sequence, Cascade-bound crRNA recognizes protospacers in foreign DNA, causing its destruction during CRISPR interference or acquisition of additional spacers in CRISPR array during primed CRISPR adaptation. Within Cascade, the crRNA spacer interacts with a hexamer of Cas7 subunits. We show that crRNAs with a spacer length reduced to 14 nucleotides cause primed adaptation, while crRNAs with spacer lengths of more than 20 nucleotides cause both primed adaptation and target interference in vivo. Shortened crRNAs assemble into altered-stoichiometry Cascademore » effector complexes containing less than the normal amount of Cas7 subunits. The results show that Cascade assembly is driven by crRNA and suggest that multi-subunit type I CRISPR effectors may have evolved from much simpler ancestral complexes.« less

Lower Eyelid Retraction Surgery Without Internal Spacer Graft.

PubMed

Taban, Mehryar Ray

2017-02-01

Internal eyelid spacer graft is routinely placed during lower eyelid retraction surgery, which may be unnecessary. To evaluate the efficacy of lower eyelid retraction surgery without internal graft in select cases. Retrospective analysis of patients undergoing reconstructive lower eyelid retraction surgery without internal graft, by one surgeon from 2013 to 2015. Surgical technique included transconjunctival lower eyelid retractor lysis, canthoplasty, and temporary tarsorrhaphy, with or without subperiosteal midface-sub oribularis oculi fat (SOOF) lifting and scar lysis. Eyelids with true lower eyelid middle-lamella shortage were excluded. Analysis included 17 surgeries (11 patients). Eight of 11 patients had undergone at least one previous lower eyelid surgery with resultant lower eyelid retraction and sclera show. Preoperative and postoperative photographs at longest follow-up visit were analyzed with standardized measurements. Patient satisfaction was recorded using questionnaire. Etiologies of lower eyelid retraction included prior lower blepharoplasty, thyroid eye disease, and chronic facial palsy. All 11 patients (17 procedures) demonstrated improvement of lower eyelid position. The mean improvement of marginal reflex distance was 2.2 mm (range, 1.6-2.8 mm). There was one case of mild overcorrection. The average follow-up was 7 months (range, 6 months-2 years). Midface lift was performed for 14 of 17 eyelids. This study demonstrates improvement of lower lid position after lower eyelid retraction surgery without internal eyelid spacer graft in select patients. Most patients in our study had undergone previous lower eyelid blepharoplasty and required midface-SOOF lifting. The author proposes that "routine" placement of lower eyelid internal spacer/graft may not be necessary during lower eyelid retraction surgery. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

The effect of anterior longitudinal ligament resection on lordosis correction during minimally invasive lateral lumbar interbody fusion: Biomechanical and radiographic feasibility of an integrated spacer/plate interbody reconstruction device.

PubMed

Kim, Choll; Harris, Jonathan A; Muzumdar, Aditya; Khalil, Saif; Sclafani, Joseph A; Raiszadeh, Kamshad; Bucklen, Brandon S

2017-03-01

Lateral lumbar interbody fusion is powerful for correcting degenerative conditions, yet sagittal correction remains limited by anterior longitudinal ligament tethering. Although lordosis has been restored via ligament release, biomechanical consequences remain unknown. Investigators examined radiographic and biomechanical of ligament release for restoration of lumbar lordosis. Six fresh-frozen human cadaveric spines (L3-S1) were tested: (Miller et al., 1988) intact; (Battie et al., 1995) 8mm spacer with intact anterior longitudinal ligament; (Cho et al., 2013) 8mm spacer without intact ligament following ligament resection; (Galbusera et al., 2013) 13mm lateral lumbar interbody fusion; (Goldstein et al., 2001) integrated 13mm spacer. Focal lordosis and range of motion were assessed by applying pure moments in flexion-extension, lateral bending, and axial rotation. Cadaveric radiographs showed significant improvement in lordosis correction following ligament resection (P<0.05). The 8mm spacer with ligament construct provided greatest stability relative to intact (P>0.05) but did little to restore lordosis. Ligament release significantly destabilized the spine relative to intact in all modes and 8mm with ligament in lateral bending and axial rotation (P<0.05). Integrated lateral lumbar interbody fusion following ligament resection did not significantly differ from intact or from 8mm with ligament in all testing modes (P>0.05). Lordosis corrected by lateral lumbar interbody fusion can be improved by anterior longitudinal ligament resection, but significant construct instability and potential implant migration/dislodgment may result. This study shows that an added integrated lateral fixation system can significantly improve construct stability. Long-term multicenter studies are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles

NASA Astrophysics Data System (ADS)

Czylkowski, R.; Karolak-Wojciechowska, J.; Mrozek, A.; Yalçin, I.; Aki-Şener, E.

2001-12-01

The mutual position of two pharmacophoric elements in flexible biologically active molecules depends on the spacer conformation. This is true even for a two-atomic chain put to use as a spacer. It was established for 2-substituted-benzoxazoles containing two aromatic centres joined by -CH2-X- (X=S or O). From crystallographic studies of four molecules it was found that the role of heteroatom is essential for the whole molecule conformation. The spacer with X=S adopts the (-)synclinal conformation while for X=O the (+)antiperiplanar one. Such preferences were also found in the statistical data from Cambridge Structural Database (CSD).

(R-X-R)4 -Motif Peptides Containing Conformationally Constrained Cyclohexane-Derived Spacers: Effect on Cellular Uptake.

PubMed

Bhosle, Govind S; Fernandes, Moneesha

2017-11-08

Arginine-rich peptides having the (R-X-R) n motif are among the most effective cell-penetrating peptides (CPPs). Herein we report a several-fold increase in the efficacy of such CPPs if the linear flexible spacer (-X-) in the (R-X-R) motif is replaced by constrained cyclic 1,4-substituted-cyclohexane-derived spacers. Internalization of these oligomers in mammalian cell lines was found to be an energy-dependent process. Incorporation of these constrained, non-proteinogenic amino acid spacers in the CPPs is shown to enhance their proteolytic stability. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

RISSC: a novel database for ribosomal 16S–23S RNA genes spacer regions

PubMed Central

García-Martínez, Jesús; Bescós, Ignacio; Rodríguez-Sala, Jesús Javier; Rodríguez-Valera, Francisco

2001-01-01

A novel database, under the acronym RISSC (Ribosomal Intergenic Spacer Sequence Collection), has been created. It compiles more than 1600 entries of edited DNA sequence data from the 16S–23S ribosomal spacers present in most prokaryotes and organelles (e.g. mitochondria and chloroplasts) and is accessible through the Internet (http://ulises.umh.es/RISSC), where systematic searches for specific words can be conducted, as well as BLAST-type sequence searches. Additionally, a characteristic feature of this region, the presence/absence and nature of tRNA genes within the spacer, is included in all the entries, even when not previously indicated in the original database. All these combined features could provide a useful documen­tation tool for studies on evolution, identification, typing and strain characterization, among others. PMID:11125084

Width-Tuned Magnetic Order Oscillation on Zigzag Edges of Honeycomb Nanoribbons.

PubMed

Chen, Wen-Chao; Zhou, Yuan; Yu, Shun-Li; Yin, Wei-Guo; Gong, Chang-De

2017-07-12

Quantum confinement and interference often generate exotic properties in nanostructures. One recent highlight is the experimental indication of a magnetic phase transition in zigzag-edged graphene nanoribbons at the critical ribbon width of about 7 nm [ Magda , G. Z. et al. Nature 2014 , 514 , 608 ]. Here we show theoretically that with further increase in the ribbon width, the magnetic correlation of the two edges can exhibit an intriguing oscillatory behavior between antiferromagnetic and ferromagnetic, driven by acquiring the positive coherence between the two edges to lower the free energy. The oscillation effect is readily tunable in applied magnetic fields. These novel properties suggest new experimental manifestation of the edge magnetic orders in graphene nanoribbons and enhance the hopes of graphene-like spintronic nanodevices functioning at room temperature.

Potential of a cyclone prototype spacer to improve in vitro dry powder delivery.

PubMed

Parisini, Irene; Cheng, Sean J; Symons, Digby D; Murnane, Darragh

2014-05-01

Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin−1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51% at 30 Lmin−1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.

How Type II CRISPR-Cas establish immunity through Cas1-Cas2 mediated spacer integration

PubMed Central

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-01-01

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the nearby cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes1–5. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer6–9. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical7–9. The conserved Cas1 and Cas2 proteins form an integrase complex consisting two distal Cas1 dimers bridged by a Cas2 dimer in the middle6,10. The prespacer is bound by Cas1-Cas2 as a dual forked DNA, and the terminal 3′-OH of each 3′-overhang serves as an attacking nucleophile during integration11–14. Importantly, the prespacer is preferentially integrated into the leader-proximal region of the CRISPR array1,7,10,15, guided by the leader sequence and a pair of inverted repeats (IRs) inside the CRISPR repeat7,15–20. Spacer integration in the most well-studied Escherichia coli Type I-E CRISPR system further relies on the bacterial Integration Host Factor (IHF)21,22. In Type II-A CRISPR, however, Cas1-Cas2 alone integrates spacer efficiently in vitro18; other Cas proteins (Cas9 and Csn2) play accessory roles in prespacer biogenesis17,23. Focusing on the Enterococcus faecalis Type II-A system24, here we report four structure snapshots of Cas1-Cas2 during spacer integration. EfaCas1-Cas2 selectively binds to a splayed 30-bp prespacer bearing 4-nt 3′-overhangs. Three molecular events take place upon encountering a target: Cas1-Cas2/prespacer first searches for half-sites stochastically, then preferentially interacts with the leader-side CRISPR repeat and catalyzes a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3′-overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework explaining

Discovery of a conjugative megaplasmid in Bifidobacterium breve.

PubMed

Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco; van Sinderen, Douwe

2015-01-01

Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Silibinin phosphodiester glyco-conjugates: Synthesis, redox behaviour and biological investigations.

PubMed

Romanucci, Valeria; Agarwal, Chapla; Agarwal, Rajesh; Pannecouque, Christophe; Iuliano, Mauro; De Tommaso, Gaetano; Caruso, Tonino; Di Fabio, Giovanni; Zarrelli, Armando

2018-04-01

New silibinin phosphodiester glyco-conjugates were synthesized by efficient phosphoramidite chemistry and were fully characterized by 2D-NMR. A wide-ranging study focused on the determination of their pKa and E° values as well as on their radical scavenging activities by different assays (DPPH, ABTS + and HRSA) was conducted. The new glyco-conjugates are more water-soluble than silibinin, and their radical scavenging activities are higher than those of silibinin. The conjugation therefore improves both the water solubilities and antioxidant activities of the flavonolignan moieties. The serum stability was evaluated under physiological conditions, and the glyco-conjugates degraded with half-lives of 40-70 h, making them useful in pro-drug approaches. We started by treating androgen-dependent prostate cancer (PCa) LNCaP cells and then expanded our studies to androgen-independent PCa PC3 and DU145 cells. In most cases, the new derivatives significantly reduced both total and live cell numbers, albeit at different levels. Anti-HIV activities were evaluated and the glucosamine-phosphate silibinin derivative showed higher activity (IC 50  = 73 μM) than silibinin. Copyright © 2018 Elsevier Inc. All rights reserved.

Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs.

PubMed

Nguyen, Thi Tram Chau; Nguyen, Cuu Khoa; Nguyen, Thi Hiep; Tran, Ngoc Quyen

2017-01-01

In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, 1 H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

[Two-stage revision of infected total knee arthroplasty using antibiotic-impregnated articulating cement spacer].

PubMed

Cai, Pengde; Hu, Yihe; Xie, Lie; Wang, Long

2012-10-01

To investigate the effectiveness of two-stage revision of infected total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement spacer. The clinical data were analyzed from 23 patients (23 knees) undergoing two-stage revision for late infection after primary TKA between January 2007 and December 2009. There were 15 males and 8 females, aged from 43 to 75 years (mean, 65.2 years). Infection occurred at 13-52 months (mean, 17.3 months) after TKA. The time interval between infection and admission ranged from 15 days to 7 months (mean, 2.1 months). One-stage operation included surgical debridement and removal of all knee prosthesis and cement, then an antibiotic-impregnated articulating cement spacer was implanted. The re-implantation of prosthesis was performed after 8-10 weeks when infections were controlled. The American Hospital for Special Surgery (HSS) score and Knee Society Score (KSS) were used to compare the function of the knee between pre- and post-revision. The rate of infection control and complication were analyzed. All incisions healed primarily. Re-infection occurred in 2 cases after two-stage revision, and infection was controlled in the other 21 cases, with an infection control rate of 91.3%. The patients were followed up 2-5 years (mean, 3.6 years). The HSS score was increased from 60.6 +/- 9.8 at pre-revision to 82.3 +/- 7.4 at last follow-up, the KSS score was increased from 110.7 +/- 9.6 at pre-revision to 134.0 +/- 10.5 at last follow-up, all showing significant differences (P < 0.01). Radiographs showed that prosthesis had good position with no loosening, fracture, or periprosthetic radiolucent. Two-stage revision using an antibiotic-impregnated articulating cement spacer is an effective method to control infected TKA and to restore the function of affected knee.

Development of a new multi-layer insulation blanket with non-interlayer-contact spacer for space cryogenic mission

NASA Astrophysics Data System (ADS)

Miyakita, Takeshi; Hatakenaka, Ryuta; Sugita, Hiroyuki; Saitoh, Masanori; Hirai, Tomoyuki

2014-11-01

For conventional Multi-Layer Insulation (MLI) blankets, it is difficult to control the layer density and the thermal insulation performance degrades due to the increase in conductive heat leak through interlayer contacts. At low temperatures, the proportion of conductive heat transfer through MLI blankets is large compared to that of radiative heat transfer, hence the decline in thermal insulation performance is significant. A new type of MLI blanket using new spacers; the Non-Interlayer-Contact Spacer MLI (NICS MLI) has been developed. This new MLI blanket uses small discrete spacers and can exclude uncertain interlayer contact between films. It is made of polyetheretherketone (PEEK) making it suitable for space use. The cross-sectional area to length ratio of the spacer is 1.0 × 10-5 m with a 10 mm diameter and 4 mm height. The insulation performance is measured with a boil-off calorimeter. Because the NICS MLI blanket can exclude uncertain interlayer contact, the test results showed good agreement with estimations. Furthermore, the NICS MLI blanket shows significantly good insulation performance (effective emissivity is 0.0046 at ordinary temperature), particularly at low temperatures, due to the high thermal resistance of this spacer.

Crosslinked polymer nanoparticles containing single conjugated polymer chains

NASA Astrophysics Data System (ADS)

Ponzio, Rodrigo A.; Marcato, Yésica L.; Gómez, María L.; Waiman, Carolina V.; Chesta, Carlos A.; Palacios, Rodrigo E.

2017-06-01

Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.

Oxygen vacancy effect on dielectric and hysteretic properties of zigzag ferroelectric iron dioxide nanoribbon

NASA Astrophysics Data System (ADS)

Zriouel, S.; Taychour, B.; Yahyaoui, F. El; Drissi, L. B.

2017-07-01

Zigzag FeO2 nanoribbon defected by the removal of oxygen atoms is simulated using Monte Carlo simulations. All possible arrangements of positions and number of oxygen vacancy are investigated. Temperature dependence of polarization, dielectric susceptibility, internal energy, specific heat and dielectric hysteresis loops are all studied. Results show the presence of second order phase transition and Q - type behavior. Dielectric properties dependence on ribbon's edge, positions and number of oxygen vacancy are discussed in detail. Moreover, single and square hysteresis loops are observed whatever the number of oxygen vacancy in the system.

The Packing of Helical and Zigzag Chains and Distribution of Interstitial Voids in Expanded Liquid Se near the Semiconductor to Metal Transition

NASA Astrophysics Data System (ADS)

Maruyama, Kenji; Hiroi (Sato), Satoshi; Endo, Hirohisa; Hoshino, Hideoki; Odagaki, Takashi; Hensel, Friedrich

2017-08-01

The reverse Monte Carlo (RMC) and Voronoi-Delaunay (VD) void analyses were applied to study the modification of chain geometries near the semiconductor (SC) to metal (M) transition in expanded liquid Se along the isochore of d = 3.4 g/cm3. Fluctuations of dihedral angles with increasing temperature and pressure cause modification of the helical (H) chain to the planar zigzag (Z) chain conformations. The distribution of voids size (rV ) supported by chain segments and distances to the 4th 6th neighbor atoms on the chain segments provide information on the stacking of planar zigzag chains compensated by empty space (L-voids, rV 3.6 Å) which leads to the formation of metallic domains. Near SC-M transition region the number fraction NZ/NH for Z and H chain segments increases.

Intercalation of XR5944 with the estrogen response element is modulated by the tri-nucleotide spacer sequence between half-sites

PubMed Central

Sidell, Neil; Mathad, Raveendra I.; Shu, Feng-jue; Zhang, Zhenjiang; Kallen, Caleb B.; Yang, Danzhou

2011-01-01

DNA-intercalating molecules can impair DNA replication, DNA repair, and gene transcription. We previously demonstrated that XR5944, a DNA bis-intercalator, specifically blocks binding of estrogen receptor-α (ERα) to the consensus estrogen response element (ERE). The consensus ERE sequence is AGGTCAnnnTGACCT, where nnn is known as the tri-nucleotide spacer. Recent work has shown that the tri-nucleotide spacer can modulate ERα-ERE binding affinity and ligand-mediated transcriptional responses. To further understand the mechanism by which XR5944 inhibits ERα-ERE binding, we tested its ability to interact with consensus EREs with variable tri-nucleotide spacer sequences and with natural but non-consensus ERE sequences using one dimensional nuclear magnetic resonance (1D 1H NMR) titration studies. We found that the tri-nucleotide spacer sequence significantly modulates the binding of XR5944 to EREs. Of the sequences that were tested, EREs with CGG and AGG spacers showed the best binding specificity with XR5944, while those spaced with TTT demonstrated the least specific binding. The binding stoichiometry of XR5944 with EREs was 2:1, which can explain why the spacer influences the drug-DNA interaction; each XR5944 spans four nucleotides (including portions of the spacer) when intercalating with DNA. To validate our NMR results, we conducted functional studies using reporter constructs containing consensus EREs with tri-nucleotide spacers CGG, CTG, and TTT. Results of reporter assays in MCF-7 cells indicated that XR5944 was significantly more potent in inhibiting the activity of CGG- than TTT-spaced EREs, consistent with our NMR results. Taken together, these findings predict that the anti-estrogenic effects of XR5944 will depend not only on ERE half-site composition but also on the tri-nucleotide spacer sequence of EREs located in the promoters of estrogen-responsive genes. PMID:21333738

Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability.

PubMed

Manju, S; Sreenivasan, K

2011-07-01

Polymer-drug conjugates have gained much attention largely to circumvent lower drug solubility and to enhance drug stability. Curcumin is widely known for its medicinal properties including its anticancer efficacy. One of the serious drawbacks of curcumin is its poor water solubility which leads to reduced bioavailability. With a view to address these issues, we synthesized hyaluronic acid-curcumin (HA-Cur) conjugate. The drug conjugate was characterized using FT-IR, NMR, Dynamic light scattering and TEM techniques. The conjugates, interestingly found to assembles as micelles in aqueous phase. The formation of micelles seems to improve the stability of the drug in physiological pH. We also assessed cytotoxicity of the conjugate using L929 fibroblast cells and quantified by MTT assay. Copyright © 2011 Elsevier Inc. All rights reserved.

Localized surface plasmon-enhanced ultraviolet electroluminescence from n-ZnO/i-ZnO/p-GaN heterojunction light-emitting diodes via optimizing the thickness of MgO spacer layer

NASA Astrophysics Data System (ADS)

Liu, W. Z.; Xu, H. Y.; Zhang, L. X.; Zhang, C.; Ma, J. G.; Wang, J. N.; Liu, Y. C.

2012-10-01

Localized surface plasmon (LSP)-enhanced ultraviolet light-emitting diodes were manufactured by introducing Ag nanoparticles and MgO spacer layer into n-ZnO/i-ZnO/p-GaN heterostructures. By optimizing the MgO thickness, which can suppress the undesired charge transfer and nonradiative Förster resonant energy transfer between Ag and ZnO, a 7-fold electroluminescence enhancement was achieved. Time-resolved and temperature-dependent photoluminescence measurements reveal that both spontaneous emission rate and internal quantum efficiency are increased as a result of coupling between ZnO excitons and Ag LSPs, and simple calculations, based on experimental data, also indicate that most of LSP's energy can be converted into the photon energy.

Commercially available trabecular metal ankle interpositional spacer for tibiotalocalcaneal arthrodesis secondary to severe bone loss of the ankle.

PubMed

Horisberger, Monika; Paul, Jochen; Wiewiorski, Martin; Henninger, Heath B; Khalifa, Muhammad S; Barg, Alexej; Valderrabano, Victor

2014-01-01

Retrograde tibiotalocalcaneal nailing arthrodesis has proved to be a viable salvage procedure; however, extended bone loss around the ankle has been associated with high rates of nonunion and considerable shortening of the hindfoot. We present the surgical technique and the first 2 cases in which a trabecular metal™ interpositional spacer, specifically designed for tibiotalocalcaneal nailing arthrodesis, was used. The spacer can be implanted using either an anterior or a lateral approach. An integrated hole in the spacer allows a retrograde nail to be inserted, which provides excellent primary stability of the construct. Trabecular metal™ is a well-established and well-described material used to supplement deficient bone stock in surgery of the spine, hip, and knee. It has shown excellent incorporation and reduces the need for auto- and allografts. The trabecular metal™ interpositional ankle spacer is the first trabecular metal spacer designed specifically for ankle surgery. Its shape and variable size will make it a valuable tool for reconstructing bone loss in tibiotalocalcaneal nailing arthrodesis. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine conjugates.

PubMed

Bernkop-Schnürch, A; Clausen, A E; Hnatyszyn, M

2001-09-11

The purpose of the present study was to synthesize and characterize novel thiolated polymers. Mediated by a carbodiimide cysteamine was covalently linked to sodium carboxymethylcellulose (CMC) and polycarbophil (PCP). The resulting CMC-cysteamine conjugates displayed 77.9+/-6.7 and 365.1+/-8.7 micromol thiol groups per gram of polymer, whereas the PCP-cysteamine conjugates showed 26.3+/-1.9 and 122.7+/-3.8 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). In aqueous solutions above pH 5.0 both modified polymers were capable of forming inter- and/or intra-molecular disulfide bonds. The reaction velocity of this oxidation process was accelerated with a decrease in the proton concentration. The oxidation proceeded more rapidly within thiolated CMC than within thiolated PCP. Permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs utilizing sodium fluorescein as model drug for the paracellular uptake revealed an enhancement ratio (R=P(app) (conjugate)/P(app) (control)) of 1.15 and 1.41 (mean+/-S.D.; n=3) for the higher thiolated CMC-cysteamine (0.5%; m/v) and PCP-cysteamine conjugate (1.0%; m/v), respectively. The decrease in the transepithelial electrical resistance values was in good correlation with the enhancement ratios. Due to a high crosslinking tendency by the formation of disulfide bonds stabilizing drug carrier systems based on thiolated polymers and a permeation enhancing effect, CMC- and PCP-cysteamine conjugates represent promising excipients for the development of novel drug delivery systems.

In Vitro Targeted Photodynamic Therapy with a Pyropheophorbide-a Conjugated Inhibitor of Prostate Specific Membrane Antigen

PubMed Central

Liu, Tiancheng; Wu, Lisa Y.; Choi, Joseph K.; Berkman, Clifford E.

2009-01-01

BACKROUND The lack of specific delivery of photosensitizers (PSs), represents a significant limitation of photodynamic therapy (PDT) of cancer. The biomarker prostate-specific membrane antigen (PSMA) has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. Although recent efforts have been made to conjugate inhibitors of PSMA with imaging agents, there have been no reports on photosensitizer-conjugated PSMA inhibitors for targeted PDT of prostate cancer. The present study focuses on the use of a PSMA inhibitor-conjugate of pyropheophorbide-a (Ppa-conjugate 2) for targeted PDT to achieve apoptosis in PSMA+ LNCaP cells. METHODS Confocal laser scanning microscopy with a combination of nuclear staining and immunofluorescence methods were employed to monitor the specific imaging and PDT-mediated apoptotic effects on PSMA-positive LNCaP and PSMA-negative (PC-3) cells. RESULTS Our results demonstrated that PDT-mediated effects by Ppa-conjugate 2 were specific to LNCaP cells, but not PC-3 cells. Cell permeability was detected as early as 2 h by HOE33342/PI double-staining, becoming more intense by 4 h. Evidence for the apoptotic caspase cascade being activated was based on the appearance of PARP p85 fragment. TUNEL assay detected DNA fragmentation 16 h post-PDT, confirming apoptotic events. CONCLUSIONS Cell permeability by HOE33342/PI double-staining as well as PARP p85 fragment and TUNEL assays confirm cellular apoptosis in PSMA+ cells when treated with PS-inhibitor conjugate 2 and subsequently irradiated. It is expected that the PSMA targeting small-molecule of this conjugate can serve as a delivery vehicle for PDT and other therapeutic applications for prostate cancer. PMID:19142895

[Cervical adaptation of complete cast crowns of various metal alloys, with and without die spacers].

PubMed

Stephano, C B; Roselino, R F; Roselino, R B; Campos, G M

1989-01-01

A metallic replica from a dental preparation for crown was used to make 8 class-IV stone dies. The wax patterns for the casting of the crowns were obtained in two conditions: a) from the stone die with no spacer; and b) from the stone die with an acrylic spacer. Thus, 64 metallic crowns were casted, using 4 different alloys: DURACAST (Cu-Al), NICROCAST (Ni-Cr) and DURABOND (Ni-Cr), and gold. The casted crowns were fitted in the metallic replica and measured as to the cervical discrepance of fitting. The results showed that the use of die spacers decreases the clinical discrepancies of fitting of the casted crowns (in a statistically significant level), no matter the metallic alloy employed.

Comparison of Efficacy and Complications Among Various Spacer Grafts in the Treatment of Lower Eyelid Retraction: A Systematic Review.

PubMed

Park, Eugene; Lewis, Kevin; Alghoul, Mohammed S

2017-07-01

Lower eyelid retraction is a difficult problem to treat, but it is a prevalent condition and a common complication of blepharoplasty. The use of spacer grafts to increase eyelid height and improve symptoms has been described for a long time, but the optimal choice of spacer graft material is unknown. The authors reviewed the currently available evidence to determine the best available spacer graft material in terms of efficacy and complications. A systematic review of all available literature published between 1985 and the present was performed using the Pubmed, Ovid MEDLINE, and Cochrane library databases. Inclusion criteria were that the studies contain original content assessing the treatment of lower eyelid retraction in humans using a spacer graft and provide quantitative outcomes data. One hundred and twelve articles were reviewed following an initial screen using titles, and 19 articles were chosen for inclusion in this systematic review. Analysis of these articles revealed no spacer graft material that is clearly superior to others. Due to a lack of high quality evidence, this review did not reveal one spacer graft material that is clearly superior to others. However, a narrative summary of the available evidence reveals unique sets of advantages and disadvantages associated with the various materials currently available. Further research in the form of well-designed studies will be necessary to further clarify advantages of certain spacer graft materials over others. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.

PubMed

Srinivasan, Supriya; Bhardwaj, Vinay; Nagasetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J

2016-12-01

This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.

Porosity of spacer-filled channels in spiral-wound membrane systems: Quantification methods and impact on hydraulic characterization.

PubMed

Siddiqui, A; Lehmann, S; Haaksman, V; Ogier, J; Schellenberg, C; van Loosdrecht, M C M; Kruithof, J C; Vrouwenvelder, J S

2017-08-01

The porosity of spacer-filled feed channels influences the hydrodynamics of spiral-wound membrane systems and impacts the overall performance of the system. Therefore, an exact measurement and a detailed understanding of the impact of the feed channel porosity is required to understand and improve the hydrodynamics of spiral-wound membrane systems applied for desalination and wastewater reuse. The objectives of this study were to assess the accuracy of porosity measurement techniques for feed spacers differing in geometry and thickness and the consequences of using an inaccurate method on hydrodynamic predictions, which may affect permeate production. Six techniques were applied to measure the porosity namely, three volumetric techniques based on spacer strand count together with a cuboidal (SC), cylindrical (VCC) and ellipsoidal volume calculation (VCE) and three independent techniques based on volume displacement (VD), weight and density (WD) and computed tomography (CT) scanning. The CT method was introduced as an alternative for the other five already existing and applied methods in practice. Six feed spacers used for the porosity measurement differed in filament thickness, angle between the filaments and mesh-size. The results of the studies showed differences between the porosities, measured by the six methods. The results of the microscopic techniques SC, VCC and VCE deviated significantly from measurements by VD, WD and CT, which showed similar porosity values for all spacer types. Depending on the maximum deviation of the porosity measurement techniques from -6% to +6%, (i) the linear velocity deviations were -5.6% and +6.4% respectively and (ii) the pressure drop deviations were -31% and +43% respectively, illustrating the importance of an accurate porosity measurement. Because of the accuracy and standard deviation, the VD and WD method should be applied for the porosity determination of spacer-filled channels, while the CT method is recommended

Light-activated nanotube-porphyrin conjugates as effective antiviral agents

NASA Astrophysics Data System (ADS)

Banerjee, Indrani; Douaisi, Marc P.; Mondal, Dhananjoy; Kane, Ravi S.

2012-03-01

Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents.

Peri-Prosthetic Knee Infection Management: Spacers Loaded with Two or Three Antibiotic Agents.

PubMed

Ortola, David Joaquin; Fenga, Domenico; Marcellino, Sandra; Rosi, Massimiliano; Centofanti, Francesco; Rosa, Michele Attilio

2017-07-01

The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction. A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score. With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%. Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections.

Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications.

PubMed

Correa, D S; Medeiros, E S; Oliveira, J E; Paterno, L G; Mattoso, Luiz C

2014-09-01

Conjugated polymers are organic materials endowed with a π-electron conjugation along the polymer backbone that present appealing electrical and optical properties for technological applications. By using conjugated polymeric materials in the nanoscale, such properties can be further enhanced. In addition, the use of nanostructured materials makes possible miniaturize devices at the micro/nano scale. The applications of conjugated nanostructured polymers include sensors, actuators, flexible displays, discrete electronic devices, and smart fabric, to name a few. In particular, the use of conjugated polymers in chemical and biological sensors is made feasible owning to their sensitivity to the physicochemical conditions of its surrounding environment, such as chemical composition, pH, dielectric constant, humidity or even temperature. Subtle changes in these conditions bring about variations on the electrical (resistivity and capacitance), optical (absorptivity, luminescence, etc.), and mechanical properties of the conjugated polymer, which can be precisely measured by different experimental methods and ultimately associated with a specific analyte and its concentration. The present review article highlights the main features of conjugated polymers that make them suitable for chemical sensors. An especial emphasis is given to nanostructured sensors systems, which present high sensitivity and selectivity, and find application in beverage and food quality control, pharmaceutical industries, medical diagnosis, environmental monitoring, and homeland security, and other applications as discussed throughout this review.

Rhenium and technetium tricarbonyl complexes of 1,4-Substituted pyridyl-1,2,3-triazole bidentate 'click' ligands conjugated to a targeting RGD peptide.

PubMed

Connell, Timothy U; Hayne, David J; Ackermann, Uwe; Tochon-Danguy, Henri J; White, Jonathan M; Donnelly, Paul S

2014-04-01

New 1,4-substituted pyridyl-1,2,3-triazole ligands with pendent phenyl isothiocyanate functional groups linked to the heterocycle through a short methylene or longer polyethylene glycol spacers were prepared and conjugated to a peptide containing the arginine-glycine-aspartic acid peptide motif. Rhenium and technetium carbonyl complexes, [M(CO)3 L(x) (py)](+) (where M = Re(I) or (99m) Tc(I) ; L(x)  = 1,4-substituted pyridyl-1,2,3-triazole ligands and py = pyridine) were prepared. One rhenium complex has been characterized by X-ray crystallography, and the luminescent properties of [M(CO)3 L(x) (py)](+) are reported. Copyright © 2013 John Wiley & Sons, Ltd.

Origin of spin polarization in an edge boron doped zigzag graphene nanoribbon: a potential spin filter.

PubMed

Chakrabarty, Soubhik; Wasey, A H M Abdul; Thapa, Ranjit; Das, G P

2018-08-24

To realize a graphene based spintronic device, the prime challenge is to control the electronic structure of edges. In this work we find the origin of the spin filtering property in edge boron doped zigzag graphene nanoribbons (ZGNRs) and provide a guide to preparing a graphene based next-generation spin filter based device. Here, we unveil the role of orbitals (p-electron) to tune the electronic, magnetic and transport properties of edge B doped ZGNRs. When all the edge carbon atoms at one of the edges of ZGNRs are replaced by B (100% edge B doping), the system undergoes a semiconductor to metal transition. The role of passivation of the edge with single/double atomic hydrogen on the electronic properties and its relation with the p-electron is correlated in-depth. 50% edge B doped ZGNRs (50% of the edge C atoms at one of the edges are replaced by B) also show half-metallicity when the doped edge is left unpassivated. The half-metallic systems show 100% spin filtering efficiency for a wide range of bias voltages. Zero-bias transmission function of the other configurations shows asymmetric behavior for the up and down spin channels, thereby indicating their possible application potential in nano-spintronics.

Porous polyurethaneurea (Artelon) joint spacer compared to trapezium resection and ligament reconstruction.

PubMed

Blount, Andrew L; Armstrong, Shannon D; Yuan, Frank; Burgess, Scott D

2013-09-01

To examine outcomes and complications of the porous polyurethaneurea (Artelon; Small Bone Innovations, Morrisville, PA) spacer compared to traditional surgical treatment of trapeziectomy with ligament reconstruction and tendon interposition (LRTI). A retrospective chart review was undertaken of patients with carpometacarpal (CMC) arthritis who had either placement of an Artelon spacer or LRTI. Patients were brought back to clinic for interview and functional testing. Pain was graded using a visual analog scale. Grip and pinch strength, as well as range of motion at the first CMC joint, were measured. Nine-hole peg, Moberg pickup, and Jebson-Taylor tests were performed. Research and Development 36, Michigan Hand Outcomes, and Quick Disabilities of the Arm, Shoulder, and Hand questionnaires were administered. Thirty-eight patients received Artelon implants into the CMC joint, and 6 were lost to follow-up. Twelve of 32 patients (37%) required revision surgery with removal of implant and salvage arthroplasty. Twenty patients with nonrevised Artelon implants were compared with 10 patients who received 13 LRTI procedures. Patients with Artelon had significantly less pain improvement compared to those receiving the LRTI procedure. In addition, satisfaction was significantly decreased. There was no significant difference in any other functional or quality of life measures. In our practice, use of the Artelon joint spacer resulted in an explantation rate of 37%. Due to these findings, we have abandoned its use for treatment of basilar thumb osteoarthritis. In contrast to previous studies, pain and satisfaction are worse in patients with intact Artelon spacers than those who had received LRTI. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Multi-step high-throughput conjugation platform for the development of antibody-drug conjugates.

PubMed

Andris, Sebastian; Wendeler, Michaela; Wang, Xiangyang; Hubbuch, Jürgen

2018-07-20

Antibody-drug conjugates (ADCs) form a rapidly growing class of biopharmaceuticals which attracts a lot of attention throughout the industry due to its high potential for cancer therapy. They combine the specificity of a monoclonal antibody (mAb) and the cell-killing capacity of highly cytotoxic small molecule drugs. Site-specific conjugation approaches involve a multi-step process for covalent linkage of antibody and drug via a linker. Despite the range of parameters that have to be investigated, high-throughput methods are scarcely used so far in ADC development. In this work an automated high-throughput platform for a site-specific multi-step conjugation process on a liquid-handling station is presented by use of a model conjugation system. A high-throughput solid-phase buffer exchange was successfully incorporated for reagent removal by utilization of a batch cation exchange step. To ensure accurate screening of conjugation parameters, an intermediate UV/Vis-based concentration determination was established including feedback to the process. For conjugate characterization, a high-throughput compatible reversed-phase chromatography method with a runtime of 7 min and no sample preparation was developed. Two case studies illustrate the efficient use for mapping the operating space of a conjugation process. Due to the degree of automation and parallelization, the platform is capable of significantly reducing process development efforts and material demands and shorten development timelines for antibody-drug conjugates. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular survey of ITS1 spacer and Rickettsia infection in human flea, Pulex irritans.

PubMed

Ghavami, Mohammad Bagher; Mirzadeh, Habibeh; Mohammadi, Jamshid; Fazaeli, Asghar

2018-05-01

The human flea is an important ectoparasite causing serious public health problems worldwide. Planning and monitoring the control programs against this vector require the knowledge of population structure and vector competence. This study was carried out to identify molecular structure of internal transcribed spacer 1 (ITS1) of ribosomal gene and its capability in the survey of Pulex irritans populations as well as to investigate Rickettsia infection in these populations. Flea samples were collected via human baits from animal farms in two districts of Zanjan Province, northwest of Iran. The ITS1 region and the partial Rickettsia gltA gene were amplified from the samples of human flea, and 30 amplicons were sequenced. The 1136 collected fleas consisted of 1079 (94.98%) P. irritans, 36 (3.17%) Ctenocephalides canis, and 21 (1.85%) Ctenocephalides felis. Molecular investigation of 182 human fleas detected the infection of Rickettsia sp. in 4.9%. The ITS1 region covered 957 bp and contained three tandem units of 98-99 bp, starting at positions 145, 245, and 331. Multiple alignments of ITS1 sequences showed single-nucleotide polymorphism at position 798, which caused the substitution of cytosine for adenine in the novel haplotype. High frequency of P. irritans and its Rickettsia infection requires the application of vector control measures, and full characterization of Rickettsia sp. and its potential to cause disease in humans. Regarding the consistency of ITS1 region and its ability to differentiate insect communities, further investigations are recommended to identify the role of selective factors in maintenance of this spacer.

Experimental study on the use of spacer foils in two-step putty and wash impression procedures using silicone impression materials.

PubMed

Mann, Karsten; Davids, Andreas; Range, Ursula; Richter, Gert; Boening, Klaus; Reitemeier, Bernd

2015-04-01

The 2-step putty and wash impression technique is commonly used in fixed prosthodontics. However, cutting sluiceways to allow the light-body material to drain is time-consuming. A solution might be the use of a spacer foil. The purpose of this study was to evaluate the influence of spacer foil on the margin reproduction and dimensional accuracy of 2-step putty and wash impressions. Two methods of creating space for the wash material in a 2-step putty and wash impression were compared: the traditional cutout technique and a spacer foil. Eleven commercially available combinations of silicone impression materials were included in the study. The impressions and the cast production were carried out under standardized conditions. All casts were measured with a 3-dimensional (3D) coordinate measuring machine. Preparation margin reproduction and the diameters and spacing of the stone cast dies were measured (α=.05). The 2 methods showed significant differences (P<.05) in the reproduction of the preparation margins (complete reproduction cutout, 90% to 98%; foil, 74% to 91%). The use of a foil resulted in greater dimensional accuracy of the cast dies compared to the cutout technique. Cast dies from the cutout technique were significantly smaller than the metallic original cast (cutout median, 4.55 mm to 4.61 mm; foil median, 4.61 to 4.64). Spacing between the dies revealed only a few additional significant differences between the techniques. When spacer foils were used, dies were obtained that better corresponded to the original tooth. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

PubMed Central

Tebbe, David; Thull, Roger; Gbureck, Uwe

2007-01-01

Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS) are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide) surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl)-propylamine (APMS), N- [3-(Trimethoxysilyl)propyl]ethylenediamine (Diamino-APMS) and N1- [3-(Trimethoxy-silyl)-propyl]diethylenetriamine (Triamino-APMS). The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring) technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV) shifted into the positive range (> + 40 mV) after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug. Furthermore, the

Development and characterization of lysine-methotrexate conjugate for enhanced brain delivery.

PubMed

Singh, Vijay Kumar; Subudhi, Bharat Bhusan

2016-09-01

Methotrexate (MTX), an anticancer drug of choice, has poor permeability across blood-brain barrier (BBB) making it unsuitable for brain tumor application. Its brain availability and scope of application was improved by preparation of reversible conjugate with lysine by capitalizing the endogenous transport system of lysine at BBB. To enhance its delivery to brain, MTX was reversibly conjugated with l-Lysine by an amide linkage. It was characterized by advanced spectroscopy techniques including IR, NMR and MS. Furthermore, conjugate was assessed for stability, toxicity and drug release ability. In vivo distribution studies were done by radioscintigraphy study using 99m Tc radioisotope. The structure of prodrug was confirmed by 1 H-NMR, 13 C-NMR and Mass. The m/e (mass to charge ratio) fragment was found at [M + H] 711.32 in Mass spectra. Stability and metabolic studies suggested that conjugate was stable at physiological pH (in Phosphate buffer pH 7.4 t 1/2 is 70.25 ± 2.17 h and in plasma t 1/2 is 193.57 ± 2.03 min) and circulated adequately to release MTX slowly in brain. In vivo biodistribution study showed that prodrug significantly increased the level of MTX in brain when compared with pharmacokinetic parameter of parent drug. The brain permeability of MTX was enhanced significantly by this conjugate.

Heterogeneous Diversity of Spacers within CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

NASA Astrophysics Data System (ADS)

He, Jiankui; Deem, Michael W.

2010-09-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of antiviral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face.

Heterogeneous diversity of spacers within CRISPR (clustered regularly interspaced short palindromic repeats).

PubMed

He, Jiankui; Deem, Michael W

2010-09-17

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of antiviral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face.

Two-dimensional thermography image retrieval from zig-zag scanned data with TZ-SCAN

NASA Astrophysics Data System (ADS)

Okumura, Hiroshi; Yamasaki, Ryohei; Arai, Kohei

2008-10-01

TZ-SCAN is a simple and low cost thermal imaging device which consists of a single point radiation thermometer on a tripod with a pan-tilt rotator, a DC motor controller board with a USB interface, and a laptop computer for rotator control, data acquisition, and data processing. TZ-SCAN acquires a series of zig-zag scanned data and stores the data as CSV file. A 2-D thermal distribution image can be retrieved by using the second quefrency peak calculated from TZ-SCAN data. An experiment is conducted to confirm the validity of the thermal retrieval algorithm. The experimental result shows efficient accuracy for 2-D thermal distribution image retrieval.

Molecular engineering of phosphole-based conjugated materials

NASA Astrophysics Data System (ADS)

Ren, Yi

The work in this thesis focuses on the molecular engineering of phosphorus-based conjugated materials. In the first part (Chapters Two and Three), new phosphorus-based conjugated systems were designed and synthesized to study the effect of the heteroelement on the electronic properties of the π-conjugated systems. The second part (Chapters Four and Five) deals with the self-assembly features of specifically designed phosphorus-based conjugated systems. In Chapter Two, electron-poor and electron-rich aromatic substituents were introduced to the dithienophosphole core in order to balance the electron-accepting and electron-donating character of the systems. Furthermore, an intriguing intramolecular charge transfer process could be observed between two dithienophosphole cores in a bridged bisphosphole-system. In Chapter Three, a secondary heteroelement (Si, P, S) was incorporated in the phosphorus-based conjugated systems. Extensive structure-property studies revealed that the secondary heteroelement can effectively manipulate the communication in phosphinine-based systems. The study of a heterotetracene system allowed for selectively applying distinct heteroatom (S/P) chemistries, which offers a powerful tool for the modification of the electronic structure of the system. More importantly, the heteroatom-specific electronic nature (S/P) can be utilized to selectively control different photophysical aspects (energy gap and fluorescence quantum yield). Furthermore, additional molecular engineering of the heterotetracene provided access to well-defined 1D microstructures, which opened the door for designing multi-functional self-assembled phosphorus-based materials. In Chapter Four, the self-organizing phosphole-lipid system is introduced, which combines the features of phospholipids with the electronics of phospholes. Its amphiphilic nature induces intriguing self-assembly features - liquid crystal and soft crystal architectures, both exhibiting well

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2016-12-01

gastrocnemius muscles. 4. Place an interlocking intramedullary nail using a custom spacer to maintain 5-cm defect length. 5. Place a pre-molded 5 cm long x...2 cm diameter PMMA spacer around the nail in the defect. 6. Irrigate the wound with normal (0.9 %) saline and close the wound. The Treatment...PMMA spacer using a “bomb bay door opening”. 4. Remove the spacer without damaging the membrane or nail . 5. Collect appropriate IM samples as

In vitro targeted photodynamic therapy with a pyropheophorbide--a conjugated inhibitor of prostate-specific membrane antigen.

PubMed

Liu, Tiancheng; Wu, Lisa Y; Choi, Joseph K; Berkman, Clifford E

2009-05-01

The lack of specific delivery of photosensitizers (PSs), represents a significant limitation of photodynamic therapy (PDT) of cancer. The biomarker prostate-specific membrane antigen (PSMA) has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. Although recent efforts have been made to conjugate inhibitors of PSMA with imaging agents, there have been no reports on PS-conjugated PSMA inhibitors for targeted PDT of prostate cancer. The present study focuses on the use of a PSMA inhibitor-conjugate of pyropheophorbide-a (Ppa-conjugate 2) for targeted PDT to achieve apoptosis in PSMA+ LNCaP cells. Confocal laser scanning microscopy with a combination of nuclear staining and immunofluorescence methods were employed to monitor the specific imaging and PDT-mediated apoptotic effects on PSMA-positive LNCaP and PSMA-negative (PC-3) cells. Our results demonstrated that PDT-mediated effects by Ppa-conjugate 2 were specific to LNCaP cells, but not PC-3 cells. Cell permeability was detected as early as 2 hr by HOE33342/PI double staining, becoming more intense by 4 hr. Evidence for the apoptotic caspase cascade being activated was based on the appearance of poly-ADP-ribose polymerase (PARP) p85 fragment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay detected DNA fragmentation 16 hr post-PDT, confirming apoptotic events. Cell permeability by HOE33342/PI double staining as well as PARP p85 fragment and TUNEL assays confirm cellular apoptosis in PSMA+ cells when treated with PS-inhibitor conjugate 2 and subsequently irradiated. It is expected that the PSMA targeting small-molecule of this conjugate can serve as a delivery vehicle for PDT and other therapeutic applications for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Physicochemical properties and cell-based bioactivity of Pu'erh tea polysaccharide conjugates.

PubMed

Chen, Xiao-Qiang; Zhang, Zhi-Fa; Gao, Zhi-Ming; Huang, Yi; Wu, Zheng-Qi

2017-11-01

Polysaccharide conjugates were prepared from Pu'erh tea and fractionated by DEAE-cellulose DE-52 column chromatography to yield one unexplored polysaccharide-conjugate fraction termed TPC-P with a molecular weight of 251,200Da. DVS (dynamic vapour sorption) result discovered that the humidity condition of long-term preservation for TPC-P is below 70% RH. Although it contained proteins, TPC-P could not bind to the Coomassie Brilliant Blue dyes G250 and R250. The "shoulder-shaped" ultroviolet absorption peak in TPC-P UV-vis scanning spectum ascribe theabrownins that inevitably adsorbed the polysaccharide conjugate. Zeta potential results demonstrated TPC-P aqueous solution merely presented the negative charge properties of polysaccharides instead of acid-base property of its protein section, and had more stability in greater than pH 5.5. No precipitation or haze occurred in the three TPC-P/EGCG aqueous mixtures during their being stored for 12h. The phase separation was observed in aqueous mixtures of TPC-P and type B gelatin. TPC-P possessed the fine stability as a function of temperature heating and cooling between 0 and 55°C. It is proposed that some properties of the covalent binding protein of TPC-P were "shielded" by its polysaccharide chains. Copyright © 2017 Elsevier B.V. All rights reserved.

Electron doping effects on the electrical conductivity of zigzag carbon nanotubes and corresponding unzipped armchair graphene nanoribbons

NASA Astrophysics Data System (ADS)

Mousavi, Hamze; Jalilvand, Samira; Kurdestany, Jamshid Moradi; Grabowski, Marek

2017-10-01

The Kubo formula is used to extract the electrical conductivity (EC) of different diameters of doped zigzag carbon nanotubes and their corresponding unzipped armchair graphene nanoribbons, as a function of temperature and chemical potential, within the tight-binding Hamiltonian model and Green's functions approach. The results reveal more sensitivity to temperature for semiconducting systems in addition to a decrease in EC of all systems with increasing cross-sections.

Designing of spin-filtering devices in zigzag graphene nanoribbons heterojunctions by asymmetric hydrogenation and B-N doping

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

Zhang, Dan; Zhang, Xiaojiao; Ouyang, Fangping

2015-01-07

Using nonequilibrium Green's function in combination with the spin-polarized density functional theory, the spin-dependent transport properties of boron and nitrogen doped zigzag graphene nanoribbons (ZGNRs) heterojunctions with single or double edge-saturated hydrogen have been investigated. Our results show that the perfect spin-filtering effect (100%), rectifying behavior and negative differential resistance can be realized in the ZGNRs-based systems. And the corresponding physical analysis has been given.

Enhanced current-perpendicular-to-plane giant magnetoresistance effect in half-metallic NiMnSb based nanojunctions with multiple Ag spacers

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

Wen, Zhenchao; Yamamoto, Tatsuya; Kubota, Takahide

2016-06-06

Current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) heterostructure devices using half-metallic NiMnSb Heusler alloy electrodes with single, dual, and triple Ag spacers were fabricated. The NiMnSb alloy films and Ag spacers show (001) epitaxial growth in all CPP-GMR multilayer structures. The dual-spacer CPP-GMR nanojunction exhibited an enhanced CPP-GMR ratio of 11% (a change in the resistance-area product, ΔRA, of 3.9 mΩ μm{sup 2}) at room temperature, which is approximately twice (thrice) of 6% (1.3 mΩ μm{sup 2}) in the single-spacer device. The enhancement of the CPP-GMR effects in the dual-spacer devices could be attributed to improved interfacial spin asymmetry. Moreover, it was observedmore » that the CPP-GMR ratios increased monotonically as the temperatures decreased. At 4.2 K, a CPP-GMR ratio of 41% (ΔRA = 10.5 mΩ μm{sup 2}) was achieved in the dual-spacer CPP-GMR device. This work indicates that multispacer structures provide an efficient enhancement of CPP-GMR effects in half-metallic material-based CPP-GMR systems.« less

Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy.

PubMed

Ferguson, Elaine L; Alshame, Alshame M J; Thomas, David W

2010-12-15

Bioresponsive polymers may effectively be utilized to enhance the circulation time and stability of biologically active proteins and peptides, while reducing their immunogenicity and toxicity. Recently, dextrin-epidermal growth factor (EGF) conjugates, which make use of the Polymer-masked UnMasked Protein Therapy (PUMPT) concept, have been developed and shown potential as modulators of impaired wound healing. This study investigated the potential of PUMPT using hyaluronic acid (HA) conjugates to mask activity and enhance protein stability, while allowing restoration of biological activity following triggered degradation. HA fragments (Mw ∼90,000g/mol), obtained by acid hydrolysis of Rooster comb HA, were conjugated to trypsin as a model enzyme or to EGF as a model growth factor. Conjugates contained 2.45 and 0.98% (w/w) trypsin or EGF, respectively, and contained <5% free protein. HA conjugation did not significantly alter trypsin's activity. However, incubation of the conjugate with physiological concentrations of HAase increased its activity to ∼145% (p<0.001) that of the free enzyme. In contrast, when HA-EGF conjugates were tested in vitro, no effect on cell proliferation was seen, even in the presence of HAase. HA conjugates did not display typical masking/unmasking behavior, HA-trypsin conjugates exhibited ∼52% greater stability in the presence of elastase, compared to free trypsin, demonstrating the potential of HA conjugates for further development as modulators of tissue repair. Copyright © 2010 Elsevier B.V. All rights reserved.

Properties of acid gels made from sodium caseinate-maltodextrin conjugates prepared by a wet heating method.

PubMed

Zhang, Shuwen; Gong, Yuansheng; Khanal, Som; Lu, Yanjie; Lucey, John A

2017-11-01

Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions. The Md samples had dextrose equivalents of 4 to 7, 9 to 12, and 20 to 23 for Md40, Md100, and Md200, respectively. The conjugation reaction was performed in mixtures with 5% NaCN and 5% Md, which were heated at 90°C for 10 h. The degree of conjugation was estimated from the reduction in free amino groups as well as color changes. Sodium dodecyl sulfate-PAGE analysis was performed to confirm conjugation by employing staining of both protein and carbohydrate bands. The molar mass of samples was determined by size-exclusion chromatography coupled with multi-angle laser light scattering. After the conjugation reaction, samples were then gelled by the addition of 0.63% (wt/vol) glucono-δ-lactone at 30°C, such that samples reached pH 4.6 after about 13 h. The rheological properties of samples during acidification was monitored by small-strain dynamic oscillatory rheology. The microstructure of acid gels at pH 4.6 was examined by fluorescence microscopy. Conjugation resulted in a loss of 10.8, 8.8, and 11.9% of the available amino groups in the protein for the NaCN-Md40 conjugates (C40), NaCN-Md100 conjugates (C100), and NaCN-Md100 conjugates (C200), respectively. With a decrease in the size of the type of Md, an increase occurred in the molar mass of the resultant conjugate. The weight average molar masses of NaCN-Md samples were 340, 368, and 425 kDa for the conjugates C40, C100, and C200, respectively. Addition of Md to Na

Determination of glycation sites by tandem mass spectrometry in a synthetic lactose-bovine serum albumin conjugate, a vaccine model prepared by dialkyl squarate chemistry

PubMed Central

Jahouh, Farid; Hou, Shu-jie; Kováč, Pavol; Banoub, Joseph H.

2012-01-01

RATIONALE Neoglycoconjugate vaccines synthesized by the squaric acid spacer method allow single point attachment of the carbohydrate antigen to the protein carrier. However, the localization of the carbohydrate antigen sites of conjugation on the protein carrier has been an elusive task difficult to achieve. METHOD Covalent attachment of the lactose antigen to the bovine serum albumin (BSA) was prepared by the squaric acid method using a hapten:BSA ratio of 20:1. Different reaction times were used during the conjugation reaction and two different lactose-BSA glycoconjugate vaccines were obtained. The carbohydrate antigen hapten:BSA ratios of these lactose-BSA glycoconjugate vaccines were determined by MALDI-TOF/RTOF-MS and the glycation sites in the neoglycoconjugates were determined using nano-LC/ESI-QqTOF-MS/MS analysis of the trypsin and GluC V8 digests of the conjugates. RESULTS We have identified a total of 15 glycation sites located on the BSA lysine residues for the neoglycoconjugate vaccine formed with a hapten:BSA ratio of 5.1:1, However, the tryptic and GluC V8 digests of the hapten-BSA glycoconjugate with a hapten:BSA ratio of 19.0:1 allowed identification of 30 glycation sites located on the BSA. These last results seem to indicate that this conjugation results in formation of various glycoforms. CONCLUSIONS It was observed that the number of identified glycation sites increased when the hapten:BSA ratio of glycoconjugate formation increased, and that the location of the glycation sites appears to be mainly on the outer surface of the BSA carrier molecule which is in line with the assumption that the sterically more accessible lysine residues, namely those located on the outer surface of the BSA, would be conjugated preferentially. PMID:22368054

Improved conjugation and purification strategies for the preparation of protein-polysaccharide conjugates.

PubMed

Suárez, N; Massaldi, H; Franco Fraguas, L; Ferreira, F

2008-12-12

A glycoconjugate constituted by the Streptococcus pneumoniae serotype 14 capsular polysaccharide (CPS14) and bovine serum albumin (BSA) was prepared, and the unique properties of Sephadex LH-20 were used to separate the conjugate from the unconjugated material. The strength of this approach consists in its capacity to produce pure polysaccharide-protein conjugate in good yield and free from unconjugated material, a common residual contaminant of this type of immunobiologicals. The CPS14-BSA conjugate prepared via an improved 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP)-activation technique was characterized chemically and its immunogenicity was evaluated in mice. The purified conjugate, unlike the corresponding polysaccharide, produced a T-cell-dependent response in this species.

Comparison of Models for Spacer Grid Pressure Loss in Nuclear Fuel Bundles for One and Two-Phase Flows

NASA Astrophysics Data System (ADS)

Maskal, Alan B.

Spacer grids maintain the structural integrity of the fuel rods within fuel bundles of nuclear power plants. They can also improve flow characteristics within the nuclear reactor core. However, spacer grids add reactor coolant pressure losses, which require estimation and engineering into the design. Several mathematical models and computer codes were developed over decades to predict spacer grid pressure loss. Most models use generalized characteristics, measured by older, less precise equipment. The study of OECD/US-NRC BWR Full-Size Fine Mesh Bundle Tests (BFBT) provides updated and detailed experimental single and two-phase results, using technically advanced flow measurements for a wide range of boundary conditions. This thesis compares the predictions from the mathematical models to the BFBT experimental data by utilizing statistical formulae for accuracy and precision. This thesis also analyzes the effects of BFBT flow characteristics on spacer grids. No single model has been identified as valid for all flow conditions. However, some models' predictions perform better than others within a range of flow conditions, based on the accuracy and precision of the models' predictions. This study also demonstrates that pressure and flow quality have a significant effect on two-phase flow spacer grid models' biases.

Preclinical in vivo long-term evaluation of the novel Mitra-Spacer technology: experimental validation in the ovine model.

PubMed

Peppas, Athanasios; Furer, Ariel; Wilson, Jon; Yi, GengHua; Cheng, Yanping; Van Wygerden, Karl; Seguin, Christopher; Shibuya, Masahiko; Kaluza, Grzegorz L; Granada, Juan F

2017-06-20

The Mitra-Spacer (Cardiosolutions, Bridgewater, MA, USA) is designed to treat mitral regurgitation by introducing a dynamic spacer that constantly adapts to the changing haemodynamic conditions during the cardiac cycle. We aimed to evaluate the performance and safety of this device in the chronic ovine model. Eight sheep were enrolled in this study. Through a left thoracotomy, the Mitra-Spacer was inserted via the transapical approach and advanced into the left atrium (LA) under imaging guidance. Device performance and safety were evaluated up to 90 days using fluoroscopy, echocardiography and histopathology. The volume within the balloon spacer shifted during the cardiac cycle in all cases. Seven animals survived up to 90 days for terminal imaging and tissue harvest. Echocardiography showed no change in left ventricle (LV) ejection fraction from baseline to 90 days. There were no observations of changes in LV diastolic function, pulmonary vein inflow, or tricuspid valve function. Histological analysis demonstrated no significant injury to the mitral apparatus. In the healthy ovine model, Mitra-Spacer implantation was feasible and safe. At 90 days, no evidence of structural damage to the mitral apparatus or deterioration of cardiac performance was demonstrated.

Sequences in the intergenic spacer influence RNA Pol I transcription from the human rRNA promoter

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

Li, W.M.; Sylvester, J.E.

1994-09-01

In most eucaryotic species, ribosomal genes are tandemly repeated about 100-5000 times per haploid genome. The 43 Kb human rDNA repeat consists of a 13 Kb coding region for the 18S, 5.8S, 28S ribosomal RNAs (rRNAs) and transcribed spacers separated by a 30 Kb intergenic spacer. For species such as frog, mouse and rat, sequences in the intergenic spacer other than the gene promoter have been shown to modulate transcription of the ribosomal gene. These sequences are spacer promoters, enhancers and the terminator for spacer transcription. We are addressing whether the human ribosomal gene promoter is similarly influenced. In-vitro transcriptionmore » run-off assays have revealed that the 4.5 kb region (CBE), directly upstream of the gene promoter, has cis-stimulation and trans-competition properties. This suggests that the CBE fragment contains an enhancer(s) for ribosomal gene transcription. Further experiments have shown that a fragment ({approximately}1.6 kb) within the CBE fragment also has trans-competition function. Deletion subclones of this region are being tested to delineate the exact sequences responsible for these modulating activities. Previous sequence analysis and functional studies have revealed that CBE contains regions of DNA capable of adopting alternative structures such as bent DNA, Z-DNA, and triple-stranded DNA. Whether these structures are required for modulating transcription remains to be determined as does the specific DNA-protein interaction involved.« less

A computational NMR study on zigzag aluminum nitride nanotubes

NASA Astrophysics Data System (ADS)

Bodaghi, Ali; Mirzaei, Mahmoud; Seif, Ahmad; Giahi, Masoud

2008-12-01

A computational nuclear magnetic resonance (NMR) study is performed to investigate the electronic structure properties of the single-walled zigzag aluminum nitride nanotubes (AlNNTs). The chemical-shielding (CS) tensors are calculated at the sites of Al-27 and N-15 nuclei in three structural forms of AlNNT including H-saturated, Al-terminated, and N-terminated ones. The structural forms are firstly optimized and then the calculated CS tensors in the optimized structures are converted to chemical-shielding isotropic (CSI) and chemical-shielding anisotropic (CSA) parameters. The calculated parameters reveal that various Al-27 and N-15 nuclei are divided into some layers with equivalent electrostatic properties; furthermore, Al and N can act as Lewis base and acid, respectively. In the Al-terminated and N-terminated forms of AlNNT, in which one mouth of the nanotube is terminated by aluminum and nitrogen nuclei, respectively, just the CS tensors of the nearest nuclei to the mouth of the nanotube are significantly changed due to removal of saturating hydrogen atoms. Density functional theory (DFT) calculations are performed using GAUSSIAN 98 package of program.

Cellulose-ethylenediaminetetraacetic acid conjugates protect mammalian cells from bacterial cells.

PubMed

Luo, Jie; Lv, Wei; Deng, Ying; Sun, Yuyu

2013-04-08

Cellulose-ethylenediaminetetraacetic acid (EDTA) conjugates were synthesized by the esterification of cellulose with ethylenediaminetetraacetic dianhydride (EDTAD). The new materials provided potent antimicrobial activities against Staphylococcus aureus (S. aureus, Gram-positive bacteria) and Pseudomonas aeruginosa (P. aeruginosa, Gram-negative bacteria), and inhibited the formation of bacterial biofilms. The biocompatibility of the new cellulose-EDTA conjugates was evaluated with mouse skin fibroblasts for up to 14 days. SEM observation and DNA content analysis suggested that the new materials sustained the viability of fibroblast cells. Moreover, in mouse skin fibroblast-bacteria co-culture systems, the new cellulose-EDTA conjugates prevented bacterial biofilm formation and protected the mammalian cells from the bacterial cells for at least one day.

Negative differential resistance and rectification effects in zigzag graphene nanoribbon heterojunctions: Induced by edge oxidation and symmetry concept

NASA Astrophysics Data System (ADS)

Nazirfakhr, Maryam; Shahhoseini, Ali

2018-03-01

By applying non-equilibrium Green's functions (NEGF) in combination with tight-binding (TB) model, we investigate and compare the electronic transport properties of H-terminated zigzag graphene nanoribbon (H/ZGNR) and O-terminated ZGNR/H-terminated ZGNR (O/ZGNR-H/ZGNR) heterostructure under finite bias. Moreover, the effect of width and symmetry on the electronic transport properties of both models is also considered. The results reveal that asymmetric H/ZGNRs have linear I-V characteristics in whole bias range, but symmetric H-ZGNRs show negative differential resistance (NDR) behavior which is inversely proportional to the width of the H/ZGNR. It is also shown that the I-V characteristic of O/ZGNR-H/ZGNR heterostructure shows a rectification effect, whether the geometrical structure is symmetric or asymmetric. The fewer the number of zigzag chains, the bigger the rectification ratio. It should be mentioned that, the rectification ratios of symmetric heterostructures are much bigger than asymmetric one. Transmission spectrum, density of states (DOS), molecular projected self-consistent Hamiltonian (MPSH) and molecular eigenstates are analyzed subsequently to understand the electronic transport properties of these ZGNR devices. Our findings could be used in developing nanoscale rectifiers and NDR devices.

Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme~Ubiquitin Conjugate

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

Pruneda, Jonathan N.; Stoll, Kate E.; Bolton, Laura J.

2011-03-15

Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2~Ub conjugate. Therefore, full characterization of the structure and dynamics of E2~Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2~Ub conjugates of two human enzymes, UbcH5c~Ub and Ubc13~Ub,more » in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5c~Ub conjugate populates an array of extended conformations, and the population of Ubc13~Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. Finally, we propose that the varied conformations adopted by Ub represent available binding modes of the E2~Ub species and thus provide insight into the diverse E2~Ub protein interactome, particularly with regard to interaction with Ub ligases.« less

Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran.

PubMed

Parhizkar, Elahehnaz; Ahmadi, Fatemeh; Daneshamouz, Saeid; Mohammadi-Samani, Soliman; Sakhteman, Amirhossein; Parhizkar, Golnaz

2017-11-24

Cabazitaxel (CTX) is a second- generation taxane derivative, a class of potent anticancer drugs with very low water solubility. CTX is used in patients with resistant prostate cancer unresponsive to the first generation taxane, docetaxel. Currently marketed formulations of CTX contain high concentrations of surfactant and ethanol, which cause severe hypersensitivity reactions in patients. In order to increase its solubility, two hemiester analogs; CTX-succinate and CTX-glutarate were synthesized and characterized. To improve the solubility of hemiesters even more, dextran as a biocompatible polymer was also conjugated to hemiester analogs. MTT assay was performed on MCF-7 cell line to evaluate the cytotoxicity effect of hemiesters and conjugates. Based on the results, hemiester analogs increased water solubility of the drug up to about 3 and 8 fold. Conjugation to dextran enhanced the CTX solubility to more than 1500 fold. These conjugates released the conjugated CTX in less than 24 hours in a pH dependent manner and showed proper hemocompatibility characteristics. The hemiesters had approximately similar cytotoxicity in comparison with CTX and the dextran conjugates showed higher cytotoxicity effect on MCF-7 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of edge magnetism on the Kohn anomalies of zigzag graphene nanoribbons.

PubMed

Culchac, F J; Capaz, Rodrigo B

2016-02-12

The effects of edge magnetism on the Kohn anomaly (KA) of the G-band phonons of zigzag graphene nanoribbons (ZGNRs) are studied using a combination of the tight-binding and mean-field Hubbard models. We show that the opening of an energy gap, induced by magnetic ordering, significantly changes the KA effects, particularly for narrow ribbons in which the gap is larger than the phonon energy. Therefore, the G-band phonon frequency and lifetime are altered for a magnetically-ordered edge state with respect to an unpolarized edge state. The effects of temperature, ZGNR width, doping and transverse electric fields are systematically investigated. We propose using this effect to probe the magnetic order of edge states in graphene nanoribbons using Raman spectroscopy.