Designing cooperatively folded abiotic uni- and multimolecular helix bundles

NASA Astrophysics Data System (ADS)

de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

Kinetically controlled transition from disordered aggregates to ordered lattices of a computationally designed peptide sequence.

NASA Astrophysics Data System (ADS)

Tian, Yu; Zhang, Huixi; Kiick, Kristi; Saven, Jeffrey; Pochan, Darrin

Peptides with well-defined secondary-structures have the ability to exhibit specific, local shapes, which enables the design of complex nanostructures through intermolecular assembly. Our computationally designed coiled-coil homotetrameric peptide building block can self-assemble into 2-D nanomaterial lattices with predetermined symmetries by control of the coiled-coil bundle exterior amino acid residues. And the assemblies can be controlled kinetically. Firstly, the solution pH influences the assembly by affecting the external charged state of peptide bundles which can lead the bundles to be either repulsive or attractive to each other. At room temperature when peptides are under the least charged pH conditions, disordered aggregates are formed that slowly transformed into the desired 2-D lattice structures over long periods of time (weeks). Around neutral pH, even subtle charge differences that come from small pH changes can have an influence on the thickness of afterwards formed plates. Secondly, the solution temperature can largely eliminate the formation of disordered aggregates and accelerate the assembling of matured, desired nanomaterial plates by providing extra energy for the organization process of assembly building blocks. The ability to control the assembly process kinetically makes our peptide plate assemblies very promising templates for further applications to develop inorganic-organic hybrid materials. Funding acknowledged from NSF DMREF program under awards DMR-1234161 and DMR-1235084.

Mechanism of Interaction Between the General Anesthetic Halothane and a Model Ion Channel Protein, I: Structural Investigations via X-Ray Reflectivity from Langmuir Monolayers

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

Strzalka, J.; Liu, J; Tronin, A

2009-01-01

We previously reported the synthesis and structural characterization of a model membrane protein comprised of an amphiphilic 4-helix bundle peptide with a hydrophobic domain based on a synthetic ion channel and a hydrophilic domain with designed cavities for binding the general anesthetic halothane. In this work, we synthesized an improved version of this halothane-binding amphiphilic peptide with only a single cavity and an otherwise identical control peptide with no such cavity, and applied x-ray reflectivity to monolayers of these peptides to probe the distribution of halothane along the length of the core of the 4-helix bundle as a function ofmore » the concentration of halothane. At the moderate concentrations achieved in this study, approximately three molecules of halothane were found to be localized within a broad symmetric unimodal distribution centered about the designed cavity. At the lowest concentration achieved, of approximately one molecule per bundle, the halothane distribution became narrower and more peaked due to a component of {approx}19Angstroms width centered about the designed cavity. At higher concentrations, approximately six to seven molecules were found to be uniformly distributed along the length of the bundle, corresponding to approximately one molecule per heptad. Monolayers of the control peptide showed only the latter behavior, namely a uniform distribution along the length of the bundle irrespective of the halothane concentration over this range. The results provide insight into the nature of such weak binding when the dissociation constant is in the mM regime, relevant for clinical applications of anesthesia. They also demonstrate the suitability of both the model system and the experimental technique for additional work on the mechanism of general anesthesia, some of it presented in the companion parts II and III under this title.« less

2-d and 1-d Nanomaterials Construction through Peptide Computational Design and Solution Assembly

NASA Astrophysics Data System (ADS)

Pochan, Darrin

Self-assembly of molecules is an attractive materials construction strategy due to its simplicity in application. By considering peptidic molecules in the bottom-up materials self-assembly design process, one can take advantage of inherently biomolecular attributes; intramolecular folding events, secondary structure, and electrostatic/H-bonding/hydrophobic interactions to define hierarchical material structure and consequent properties. Importantly, while biomimicry has been a successful strategy for the design of new peptide molecules for intermolecular assembly, computational tools have been developed to de novo design peptide molecules required for construction of pre-determined, desired nanostructures and materials. A new system comprised of coiled coil bundle motifs theoretically designed to assemble into designed, one and two-dimensional nanostructures will be introduced. The strategy provides the opportunity for arbitrary nanostructure formation, i.e. structures not observed in nature, with peptide molecules. Importantly, the desired nanostructure was chosen first while the peptides needed for coiled coil formation and subsequent nanomaterial formation were determined computationally. Different interbundle, two-dimensional nanostructures are stabilized by differences in amino acid composition exposed on the exterior of the coiled coil bundles. Computation was able to determine molecules required for different interbundle symmetries within two-dimensional sheets stabilized by subtle differences in amino acid composition of the inherent peptides. Finally, polymers were also created through covalent interactions between bundles that allowed formation of architectures spanning flexible network forming chains to ultra-stiff polymers, all with the same building block peptides. The success of the computational design strategy is manifested in the nanomaterial results as characterized by electron microscopy, scattering methods, and biophysical techniques. Support from NSF DMREF program under awards DMR-1234161 and DMR-1235084.

Trimeric, Coiled-coil Extension on Peptide Fusion Inhibitor of HIV-1 Influences Selection of Resistance Pathways*

PubMed Central

Zhuang, Min; Wang, Wei; De Feo, Christopher J.; Vassell, Russell; Weiss, Carol D.

2012-01-01

Peptides corresponding to N- and C-terminal heptad repeat regions (HR1 and HR2, respectively) of viral fusion proteins can block infection of viruses in a dominant negative manner by interfering with refolding of the viral HR1 and HR2 to form a six-helix bundle (6HB) that drives fusion between viral and host cell membranes. The 6HB of the HIV gp41 (endogenous bundle) consists of an HR1 coiled-coil trimer with grooves lined by antiparallel HR2 helices. HR1 peptides form coiled-coil oligomers that may bind to gp41 HR2 as trimers to form a heterologous 6HB (inhibitor bundle) or to gp41 HR1 as monomers or dimers to form a heterologous coiled coil. To gain insights into mechanisms of Env entry and inhibition by HR1 peptides, we compared resistance to a peptide corresponding to 36 residues in gp41 HR1 (N36) and the same peptide with a coiled-coil trimerization domain fused to its N terminus (IZN36) that stabilizes the trimer and increases inhibitor potency (Eckert, D. M., and Kim, P. S. (2001) Proc. Nat. Acad. Sci. U.S.A. 98, 11187–11192). Whereas N36 selected two genetic pathways with equal probability, each defined by an early mutation in either HR1 or HR2, IZN36 preferentially selected the HR1 pathway. Both pathways conferred cross-resistance to both peptides. Each HR mutation enhanced the thermostability of the endogenous 6HB, potentially allowing the virus to simultaneously escape inhibitors targeting either gp41 HR1 or HR2. These findings inform inhibitor design and identify regions of plasticity in the highly conserved gp41 that modulate virus entry and escape from HR1 peptide inhibitors. PMID:22235115

Role of the Simian Virus 5 Fusion Protein N-Terminal Coiled-Coil Domain in Folding and Promotion of Membrane Fusion

PubMed Central

West, Dava S.; Sheehan, Michael S.; Segeleon, Patrick K.; Dutch, Rebecca Ellis

2005-01-01

Formation of a six-helix bundle comprised of three C-terminal heptad repeat regions in antiparallel orientation in the grooves of an N-terminal coiled-coil is critical for promotion of membrane fusion by paramyxovirus fusion (F) proteins. We have examined the effect of mutations in four residues of the N-terminal heptad repeat in the simian virus 5 (SV5) F protein on protein folding, transport, and fusogenic activity. The residues chosen have previously been shown from study of isolated peptides to have differing effects on stability of the N-terminal coiled-coil and six-helix bundle (R. E. Dutch, G. P. Leser, and R. A. Lamb, Virology 254:147-159, 1999). The mutant V154M showed reduced proteolytic cleavage and surface expression, indicating a defect in intracellular transport, though this mutation had no effect when studied in isolated peptides. The mutation I137M, previously shown to lower thermostability of the six-helix bundle, resulted in an F protein which was properly processed and transported to the cell surface but which had reduced fusogenic activity. Finally, mutations at L140M and L161M, previously shown to disrupt α-helix formation of isolated N-1 peptides but not to affect six-helix bundle formation, resulted in F proteins that were properly processed. Interestingly, the L161M mutant showed increased syncytium formation and promoted fusion at lower temperatures than the wild-type F protein. These results indicate that interactions separate from formation of an N-terminal coiled-coil or six-helix bundle are important in the initial folding and transport of the SV5 F protein and that mutations that destabilize the N-terminal coiled-coil can result in stimulation of membrane fusion. PMID:15650180

Bis-polymer lipid-peptide conjugates and nanoparticles thereof

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

Xu, Ting; Dong, He; Shu, Jessica

The present invention provides bis-polymer lipid-peptide conjugates containing a hydrophobic block and headgroup containing a helical peptide and two polymer blocks. The conjugates can self-assemble to form helix bundle subunits, which in turn assemble to provide micellar nanocarriers for drug cargos and other agents. Particles containing the conjugates and methods for forming the particles are also disclosed.

PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments.

PubMed

Terada, Y; Tomita, K; Nonoguchi, H; Yang, T; Marumo, F

1994-08-01

The present study was undertaken to investigate the presence of C-type natriuretic peptide (CNP) mRNA and its receptor, natriuretic peptide B-type receptor (ANPR-B) mRNA, in rat renal structures. The microlocalization of mRNAs coding for CNP and ANPR-B was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments, glomeruli, vasa recta bundle, and arcuate arteries. The PCR signal for CNP was detected in glomerulus, vasa recta bundle, and arcuate artery. The PCR product of ANPR-B was widely present in renal structures. Relatively large amounts of ANPR-B PCR product were detected in glomerulus, vasa recta bundle, arcuate artery, and distal nephron segments. A relatively high concentration of CNP (10(-7) M) stimulated guanosine 3',5'-cyclic monophosphate accumulation in glomerulus, medullary thick ascending limb, cortical collecting duct, and inner medullary collecting duct. Our data demonstrate that CNP can be produced locally in the glomerulus and renal vascular system and that ANPR-B is widely distributed in renal structures. Thus CNP may influence renal function and act in autocrine and paracrine fashions in the kidney.

Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

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

Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine

2010-01-20

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by themore » fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of RSV F-mediated membrane fusion and have important implications for the identification of therapeutic strategies and vaccines targeting RSV F protein conformational changes.« less

Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

PubMed

Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

2008-02-01

We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

48 CFR 908.7110 - Coal.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Coal. 908.7110 Section 908... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7110 Coal. DOE offices and authorized contractors may participate in the Defense Fuel Supply Center (DFSC) coal contracting program for...

48 CFR 908.7110 - Coal.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Coal. 908.7110 Section 908... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7110 Coal. DOE offices and authorized contractors may participate in the Defense Fuel Supply Center (DFSC) coal contracting program for...

48 CFR 908.7110 - Coal.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Coal. 908.7110 Section 908... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7110 Coal. DOE offices and authorized contractors may participate in the Defense Fuel Supply Center (DFSC) coal contracting program for...

48 CFR 908.7110 - Coal.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Coal. 908.7110 Section 908... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7110 Coal. DOE offices and authorized contractors may participate in the Defense Fuel Supply Center (DFSC) coal contracting program for...

48 CFR 908.7110 - Coal.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Coal. 908.7110 Section 908... REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Special Items 908.7110 Coal. DOE offices and authorized contractors may participate in the Defense Fuel Supply Center (DFSC) coal contracting program for...

The pH sensibility of actin-bundling LIM proteins is governed by the acidic properties of their C-terminal domain.

PubMed

Moes, Danièle; Hoffmann, Céline; Dieterle, Monika; Moreau, Flora; Neumann, Katrin; Papuga, Jessica; Furtado, Angela Tavares; Steinmetz, André; Thomas, Clément

2015-08-19

Actin-bundling Arabidopsis LIM proteins are subdivided into two subfamilies differing in their pH sensitivity. Widely-expressed WLIMs are active under low and high physiologically-relevant pH conditions, whereas pollen-enriched PLIMs are inactivated by pH values above 6.8. By a domain swapping approach we identified the C-terminal (Ct) domain of PLIMs as the domain responsible for pH responsiveness. Remarkably, this domain conferred pH sensitivity to LIM proteins, when provided "in trans" (i.e., as a single, independent, peptide), indicating that it operates through the interaction with another domain. An acidic 6xc-Myc peptide functionally mimicked the Ct domain of PLIMs and efficiently inhibited LIM actin bundling activity under high pH conditions. Together, our data suggest a model where PLIMs are regulated by an intermolecular interaction between their acidic Ct domain and another, yet unidentified, domain. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation.

PubMed

Kawabata, Mihoko; Goya, Masahiko; Takagi, Takamitsu; Yamashita, Shu; Iwai, Shinsuke; Suzuki, Masahito; Takamiya, Tomomasa; Nakamura, Tomofumi; Hayashi, Tatsuya; Yagishita, Atsuhiko; Sasaki, Takeshi; Takahashi, Yoshihide; Ono, Yuhichi; Hachiya, Hitoshi; Yamauchi, Yasuteru; Otomo, Kenichiro; Nitta, Junichi; Okishige, Kaoru; Nishizaki, Mitsuhiro; Iesaka, Yoshito; Isobe, Mitsuaki; Hirao, Kenzo

2016-12-01

Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. This retrospective multicenter study included 96 patients (56±15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p=0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age ≥60 years, left atrial dimension ≥38mm, B-type natriuretic peptide (BNP) ≥40pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP ≥40pg/ml remained as an independent predictive factor (HR=17.1 and CI: 2.3-128.2; p=0.006). Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

41 CFR 101-26.602-2 - Procurement of packaged petroleum products.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., from the Commander, Defense Logistics Services Center, Attn: DLSC-T, Battle Creek, Mich. 49016... (FPMR 101-26.2) to the Defense General Supply Center (DGSC), Richmond, Va. 23297, using routing... Center (DFSC) procurements under the provisions of § 101-26.602-1 may be submitted to DGSC. DGSC will...

41 CFR 101-26.602-2 - Procurement of packaged petroleum products.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., from the Commander, Defense Logistics Services Center, Attn: DLSC-T, Battle Creek, Mich. 49016... (FPMR 101-26.2) to the Defense General Supply Center (DGSC), Richmond, Va. 23297, using routing... Center (DFSC) procurements under the provisions of § 101-26.602-1 may be submitted to DGSC. DGSC will...

41 CFR 101-26.602-2 - Procurement of packaged petroleum products.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., from the Commander, Defense Logistics Services Center, Attn: DLSC-T, Battle Creek, Mich. 49016... (FPMR 101-26.2) to the Defense General Supply Center (DGSC), Richmond, Va. 23297, using routing... Center (DFSC) procurements under the provisions of § 101-26.602-1 may be submitted to DGSC. DGSC will...

41 CFR 101-26.602-2 - Procurement of packaged petroleum products.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., from the Commander, Defense Logistics Services Center, Attn: DLSC-T, Battle Creek, Mich. 49016... (FPMR 101-26.2) to the Defense General Supply Center (DGSC), Richmond, Va. 23297, using routing... Center (DFSC) procurements under the provisions of § 101-26.602-1 may be submitted to DGSC. DGSC will...

41 CFR 101-26.602-2 - Procurement of packaged petroleum products.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., from the Commander, Defense Logistics Services Center, Attn: DLSC-T, Battle Creek, Mich. 49016... (FPMR 101-26.2) to the Defense General Supply Center (DGSC), Richmond, Va. 23297, using routing... Center (DFSC) procurements under the provisions of § 101-26.602-1 may be submitted to DGSC. DGSC will...

Piecing Together an Integrated Approach to Drug-Free Schools. 1992-93 Final Report.

ERIC Educational Resources Information Center

Wiehe, James A.

The federal Drug-Free Schools and Communities (DFSC) Act of 1986 provides funding to school districts to help eliminate drug and alcohol use on their campuses. In 1992-93, the Austin Independent School District (AISD) received $467,362 from the act. The funds supported a wide assortment of preventative and educational programs regarding the…

Should the Defense Fuel Supply Center Trade in the Futures Market?

DTIC Science & Technology

1993-12-01

reform, and Federal and State Law. 4 Over 30 hours of personal interviews were conducted with people from DFSC, the Department of Energy (DOE), the...Management, Finance and Accounting, and Personal Staff. (Defense Logistics Agency Command Support Office, 1993) Of particular interest is the Office of...member can beat the market price, attract hungry customers, improve personal market share, and thereby improve total revenue and profits. In effect

The distal C-terminal region of the KcsA potassium channel is a pH-dependent tetramerization domain.

PubMed

Kamnesky, Guy; Shaked, Hadassa; Chill, Jordan H

2012-05-04

The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is a 40-residue-long segment that natively adopts a helical bundle conformation with 4-fold symmetry. A hallmark of KcsA behavior is pH-induced conformational change, which leads to the opening of the channel at acidic pH. Previous studies have reached conflicting conclusions as to the role of the CTD in this transition. Here, we investigate the involvement of this domain in pH-mediated channel opening by NMR using a soluble peptide corresponding to residues 128-160 of the CTD (CTD34). At neutral pH, CTD34 exhibits concentration-dependent spectral changes consistent with oligomer formation. We prove this slowly tumbling species to be a tetramer with a dissociation constant of (2.0±0.5)×10(-)(11) M(3) by NMR and sedimentation equilibrium experiments. Whereas monomeric CTD34 is only mildly helical, secondary chemical shifts prove that the tetrameric species adopts a tight native-like helical bundle conformation. The tetrameric species undergoes pH-dependent dissociation, and CTD34 is fully monomeric below pH 5.0. The structural basis for this phenomenon is the destabilization of the tetrameric CTD34 by protonation of residue H145 in the monomeric form of the peptide. We conclude that (i) the CTD34 peptide is independently capable of forming a tetrameric helical bundle, and (ii) this structurally significant conformational shift is modulated by the effects of solution pH on residue H145. Therefore, the involvement of this domain in the pH gating of the channel is strongly suggested. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modification of β-Sheet Forming Peptide Hydrophobic Face: Effect on Self-Assembly and Gelation

PubMed Central

2016-01-01

β-Sheet forming peptides have attracted significant interest for the design of hydrogels for biomedical applications. One of the main challenges is the control and understanding of the correlations between peptide molecular structure, the morphology, and topology of the fiber and network formed as well as the macroscopic properties of the hydrogel obtained. In this work, we have investigated the effect that functionalizing these peptides through their hydrophobic face has on their self-assembly and gelation. Our results show that the modification of the hydrophobic face results in a partial loss of the extended β-sheet conformation of the peptide and a significant change in fiber morphology from straight to kinked. As a consequence, the ability of these fibers to associate along their length and form large bundles is reduced. These structural changes (fiber structure and network topology) significantly affect the mechanical properties of the hydrogels (shear modulus and elasticity). PMID:27089379

Final Environmental Impact Statement. Second KC-135R Air Refueling Squadron, Malmstrom Air Force Base, Montana

DTIC Science & Technology

1989-07-01

commercial center in the area. Those two counties are Cascade and Lewis & Clark. Population and Demographics. The ROI for this element includes areas...commercial trade, finance, III-2 II transportation, and service sectors of the area ( originating primarily in Great Falls) serve north-central Montana and...Malmstrom AFB through contracts with local and regional distributors that are filled through the Defense Fuels Supply Center I (DFSC). The fuel is

Kinetics of nucleation and crystallization in poly(e-caprolactone) (PCL)

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

Zhuravlev, Evgeny; Schmelzer, Jurn; Wunderlich, Bernhard

2011-01-01

The recently developed differential fast scanning calorimetry (DFSC) is used for a new look at the crystal growth of poly(3-caprolactone) (PCL) from 185 K, below the glass transition temperature, to 330 K, close to the equilibrium melting temperature. The DFSC allows temperature control of the sample and determination of its heat capacity using heating rates from 50 to 50,000 K/s. The crystal nucleation and crystallization halftimes were determined simultaneously. The obtained halftimes cover a range from 3 102 s (nucleation at 215 K) to 3 109 s (crystallization at 185 K). After attempting to analyze the experiments with the classicalmore » nucleation and growth model, developed for systems consisting of small molecules, a new methodology is described which addresses the specific problems of crystallization of flexible linear macromolecules. The key problems which are attempted to be resolved concern the differences between the structures of the various entities identified and their specific role in the mechanism of growth. The structures range from configurations having practically unmeasurable latent heats of ordering (nuclei) to being clearly-recognizable, ordered species with rather sharp disordering endotherms in the temperature range from the glass transition to equilibrium melting for increasingly perfect and larger crystals. The mechanisms and kinetics of growth involve also a detailed understanding of the interaction with the surrounding rigid-amorphous fraction (RAF) in dependence of crystal size and perfection.« less

Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia

PubMed Central

Hieke, Cathleen; Kriebel, Katja; Engelmann, Robby; Müller-Hilke, Brigitte; Lang, Hermann; Kreikemeyer, Bernd

2016-01-01

Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens. PMID:27974831

Folliculosebaceous cystic hamartoma with a neural component: an immunohistochemical study.

PubMed

Toyoda, M; Morohashi, M

1997-07-01

We present a case of follicular cystic hamartoma, a distinctive cutaneous malformation characterized by marked overgrowth of folliculosebaceous units accompanied by appreciable mesenchymal alterations, including fibroplasia, increased vascular components, and numerous adipocytes. A conspicuous feature of our case is an aggregation of thick trespassing nerve bundles in the deep portion of the neoplasm. An immunohistochemical study revealed the nerve bundles were immunoreactive for the general neuronal marker protein gene product 9.5. The nerves, however, stained negatively with antibodies against neuropeptides such as calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide, and neuropeptide Y, all of which are known to be contained in normal cutaneous nerves. The presence of these aberrant nerve bundles devoid of the normal expression of neuropeptides supports the concept that folliculosebaceous cystic hamartoma is a true, tumor-like malformation characterized by abnormal overgrowth of normal components of the skin.

Enzyme-mediated self-assembly of highly ordered structures from disordered proteins

NASA Astrophysics Data System (ADS)

Athamneh, Ahmad I.; Barone, Justin R.

2009-10-01

Wheat gluten is an amorphous storage protein. Trypsin hydrolysis of wheat gluten produced glutamine-rich peptides. Some peptides were able to self-assemble into fibrous structures extrinsic to native wheat gluten. The final material was an in situ formed peptide composite of highly ordered nanometer-sized fibrils and micron-sized fibers embedded in an unassembled peptide matrix. Fourier transform infrared spectroscopic and x-ray diffraction data suggested that the new structures resembled that of cross- β fibrils found in some insect silk and implicated in prion diseases. The largest self-assembled fibers were about 10 µm in diameter with right-handed helicity and appeared to be bundles of smaller nanometer-sized fibrils. Results demonstrated the potential for utilizing natural mechanisms of protein self-assembly to design advanced materials that can provide a wide range of structural and chemical functionality.

Anionic poly(amino acid)s dissolve F-actin and DNA bundles, enhance DNase activity, and reduce the viscosity of cystic fibrosis sputum.

PubMed

Tang, Jay X; Wen, Qi; Bennett, Andrew; Kim, Brian; Sheils, Catherine A; Bucki, Robert; Janmey, Paul A

2005-10-01

Bundles of F-actin and DNA present in the sputum of cystic fibrosis (CF) patients but absent from normal airway fluid contribute to the altered viscoelastic properties of sputum that inhibit clearance of infected airway fluid and exacerbate the pathology of CF. Previous strategies to remove these filamentous aggregates have focused on DNase to enzymatically depolymerize DNA to constituent monomers and gelsolin to sever F-actin to small fragments. The high densities of negative surface charge on DNA and F-actin suggest that the bundles of these filaments, which alone exhibit a strong electrostatic repulsion, may be stabilized by multivalent cations such as histones, antimicrobial peptides, and other positively charged molecules prevalent in airway fluid. This study reports that bundles of DNA or F-actin formed after addition of histone H1 or lysozyme are efficiently dissolved by soluble multivalent anions such as polymeric aspartate or glutamate. Addition of poly-aspartate or poly-glutamate also disperses DNA and actin-containing bundles in CF sputum and lowers the elastic moduli of these samples to levels comparable to those obtained after treatment with DNase I or gelsolin. Addition of poly-aspartic acid also increased DNase activity when added to samples containing DNA bundles formed with histone H1. When added to CF sputum, poly-aspartic acid significantly reduced the growth of bacteria, suggesting activation of endogenous antibacterial factors. These findings suggest that soluble multivalent anions have potential alone or in combination with other mucolytic agents to selectively dissociate the large bundles of charged biopolymers that form in CF sputum.

Comparison of Shear Shredder with Hammermill for Size Reduction of Navy Solid Waste

DTIC Science & Technology

1986-03-01

IVY CASE) IS. $1,249,650 $1,002,420 11" MAJOR EQUIPMENT ,EPL-..EMENT COST $ $737,660 $499,100 144 115 KAXINL’ PRACTICAL PROJECT LIfE YEARS 20 20 116...DC DEFFUELSUPPCEN DFSC-OWE, Alexandria VA DLSIE Army Logistics Mgt Center, Fort Lee . VA DOE Whid’Ocean Tech Div. Tobacco. ’AD ENVIRONMENTAL PROTECHION...UNIVERSITY W.B. Ledbetter . College Station. TX UNIVERSITY OF CALIFORNIA Energy Engineer, Davis CA; Prof E.A. Pearson. Berkeley, CA; CE Dept (Mitchell

The Militarily Useful Clean Product Tanker: Sealift Component of the DoD Petroleum Distribution System.

DTIC Science & Technology

1983-12-01

dentlfIr by block numbher) Clean product tanker Defense Fuel Supply Center (DFSC) Handy Size Tanker (HST) Petroleum, Lubricants, and Oils (POL) Military...ccnsumer representing approximately 81 percent of tha " total. The majority of DOD energy is in the form of petro- leum, oil and lubricants (POL) with...annual consumption equating to 250 million barrels of oil . it h over five percent of *he DOD budget devoted to energy expnadiu::es, it is reasonable to

The crystal structure of the calcium-bound con-G[Q6A] peptide reveals a novel metal-dependent helical trimer

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

Cnudde, Sara E.; Prorok, Mary; Jia, Xaofei

2012-02-15

The ability to form and control both secondary structure and oligomerization in short peptides has proven to be challenging owing to the structural instability of such peptides. The conantokin peptides are a family of {gamma}-carboxyglutamic acid containing peptides produced in the venoms of predatory sea snails of the Conus family. They are examples of short peptides that form stable helical structures, especially in the presence of divalent cations. Both monomeric and dimeric conantokin peptides have been identified and represent a new mechanism of helix association, 'the metallozipper motif' that is devoid of a hydrophobic interface between monomers. In the presentmore » study, a parallel/antiparallel three-helix bundle was identified and its crystal structure determined at high resolution. The three helices are almost perfectly parallel and represent a novel helix-helix association. The trimer interface is dominated by metal chelation between the three helices, and contains no interfacial hydrophobic interactions. It is now possible to produce stable monomeric, dimeric, or trimeric metallozippers depending on the peptide sequence and metal ion. Such structures have important applications in protein design.« less

Self-assembly of coiled coil peptides into nanoparticles vs 2-d plates: effects of assembly pathway

NASA Astrophysics Data System (ADS)

Kim, Kyunghee; Pochan, Darrin

Molecular solution assembly, or self-assembly, is a process by which ordered nanostructures or patterns are formed by non-covalent interactions during assembly. Biomimicry, the use of bioinspired molecules or biologically relevant materials, is an important area of self-assembly research with peptides serving a critical role as molecular tools. The morphology of peptide assemblies can be controlled by adjusting solution conditions such as the concentration of peptides, the temperature, and pH. Herein, spherical nanostructures, which have potential for creating an encapsulation system, are formed by self-assembly when coiled coil peptides are combined in solution. These peptides are homotrimeric and heterodimeric coiled-coil bundles and the homotrimer is connected with each of heterodimer through their external surfaces via disulfide bonds. The resultant covalent constructs could co-assemble into complementary trimeric hubs, respectively. The two peptide constructs are directly mixed and assembled in solution in order to produce either spherical particles or 2-d plates depending on the solution conditions and kinetic pathway of assembly. In particular, structural changes of the self-assembled peptides are explored by control of the thermal history of the assembly solution.

Short peptides derived from the BAG-1 C-terminus inhibit the interaction between BAG-1 and HSC70 and decrease breast cancer cell growth.

PubMed

Sharp, Adam; Cutress, Ramsey I; Johnson, Peter W M; Packham, Graham; Townsend, Paul A

2009-11-03

BAG-1, a multifunctional protein, interacts with a plethora of cellular targets where the interaction with HSC70 and HSP70, is considered vital. Structural studies have demonstrated the C-terminal of BAG-1 forms a bundle of three alpha-helices of which helices 2 and 3 are directly involved in binding to the chaperones. Here we found peptides derived from helices 2 and 3 of BAG-1 interfered with BAG-1:HSC70 binding. We confirmed that a 12 amino-acid peptide from helix 2 directly interacted with HSC70 and when introduced into MCF-7 and ZR-75-1 cells, these peptides inhibited their growth. In conclusion, we have identified a small domain within BAG-1 which appears to play a critical role in the interaction with HSC70.

A peptide hormone required for Casparian strip diffusion barrier formation in Arabidopsis roots.

PubMed

Nakayama, Takuya; Shinohara, Hidefumi; Tanaka, Mina; Baba, Koki; Ogawa-Ohnishi, Mari; Matsubayashi, Yoshikatsu

2017-01-20

Plants achieve mineral ion homeostasis by means of a hydrophobic barrier on endodermal cells called the Casparian strip, which restricts lateral diffusion of ions between the root vascular bundles and the soil. We identified a family of sulfated peptides required for contiguous Casparian strip formation in Arabidopsis roots. These peptide hormones, which we named Casparian strip integrity factor 1 (CIF1) and CIF2, are expressed in the root stele and specifically bind the endodermis-expressed leucine-rich repeat receptor kinase GASSHO1 (GSO1)/SCHENGEN3 and its homolog, GSO2. A mutant devoid of CIF peptides is defective in ion homeostasis in the xylem. CIF genes are environmentally responsive. Casparian strip regulation is not merely a passive process driven by root developmental cues; it also serves as an active strategy to cope with adverse soil conditions. Copyright © 2017, American Association for the Advancement of Science.

Effect of heterocyclic capping groups on the self-assembly of a dipeptide hydrogel.

PubMed

Martin, Adam D; Wojciechowski, Jonathan P; Warren, Holly; in het Panhuis, Marc; Thordarson, Pall

2016-03-14

The mechanism and design rules associated with the self-assembly of short peptides into hydrogels is currently not well understood. In this work, four diphenylalanine-based peptides have been synthesised, bearing heterocyclic capping groups which have different degrees of hydrogen bonding potential and nitrogen substitution. For these four peptides, zeta potential and electrical impedance spectroscopy measurements were undertaken to monitor gelation, with the impedance data showing different gelation times for each peptide hydrogel. Through a combination of atomic force microscopy and rheological measurmeents, including dynamic strain and frequency sweeps, and thixotropic tests, the relationship between the mechanism of self-assembly in these hydrogels and their macroscopic behaviour can be established. It is observed that the degree of nitrogen substitution affects the self-assembly mechanisms of the hydrogels and as such, that there is an interplay between branching and bundling self-assembly pathways that are responsible for the final properties of each hydrogel.

Structure and Dynamics of Helical Protein Fragments Investigated by Theory and Experiment

NASA Astrophysics Data System (ADS)

Karimi, Afshin

This work addresses the conformation and dynamics of model peptides using spectroscopy and molecular dynamics simulations. Experimentally, we investigate the structure and dynamics of peptide fragments taken from coiled coil and three helical bundle motifs of bacterial coat proteins. Theoretically, we use molecular dynamics simulations of isolated helices with explicit water molecules to derive trajectories which reveal features about picosecond dynamics and local unfolding events. The assignment of the ^1H, ^{15}N, and ^ {13}C resonances, secondary structure, backbone dynamics, hydration and other biophysical parameters of a 30 residue recombinant peptide corresponding to an immunogenic site on the coiled coil region of Streptococcus pyogenes 24M protein are reported. Our results suggest that this peptide is a symmetric parallel dimeric alpha-helical coiled coil with local defects within the helix and fraying at the termini. The ^1H and ^ {15}N assignments, the hydration, the overall fold, and other biophysical parameters of a recombinant B domain of Staphylococcal protein A (FB) are reported. Our results indicate FB is a highly stable monomeric three helical bundle. A symmetric two domain construct was used to probe the modular assembly of two B domains. Here, spectroscopic results suggest weak interactions between the two domains. The folding pathway of FB was investigated using amide exchange data of the native protein and peptide models. We propose that the helical hairpin consisting of helices II and III is an on-pathway intermediate in the folding of FB. Two 1 ns molecular dynamics simulations (MD) on two mainly helical peptides--an 18 residue peptide corresponding to a portion of the H helix of myoglobin (MBH) and a 14 residue analogue of the C-peptide of ribonuclease A (CRNA) --were carried out in water using the united atom AMBER/OPLS force-field. In the case of MBH, the initial helical conformation progressively frays to a more disordered structure. A common motif in the unfolding mechanism involves the formation of transient turn structures involving several water molecules. In contrast to the MBH simulation, the CRNA trajectory was characterized by the presence of fairly stable i ... i+4 (alpha-helical) hydrogen bonds throughout the simulation, except at the N-terminus where some fraying was observed.

Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold

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

Checco, James W.; Kreitler, Dale F.; Thomas, Nicole C.

Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. In this paper, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold. We show that α/β-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding α/β-peptide inhibits the VEGF 165-induced proliferation of human umbilical vein endothelialmore » cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain–mimetic α/β-peptides that bind to two other protein partners, IgG and tumor necrosis factor-α. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable α/β-peptides that bind tightly and specifically to diverse targets of biomedical interest. Finally, such reagents would be useful for diagnostic and therapeutic applications.« less

Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold

DOE PAGES

Checco, James W.; Kreitler, Dale F.; Thomas, Nicole C.; ...

2015-03-30

Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. In this paper, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold. We show that α/β-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding α/β-peptide inhibits the VEGF 165-induced proliferation of human umbilical vein endothelialmore » cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain–mimetic α/β-peptides that bind to two other protein partners, IgG and tumor necrosis factor-α. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable α/β-peptides that bind tightly and specifically to diverse targets of biomedical interest. Finally, such reagents would be useful for diagnostic and therapeutic applications.« less

Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

PubMed

Porotto, Matteo; Rockx, Barry; Yokoyama, Christine C; Talekar, Aparna; Devito, Ilaria; Palermo, Laura M; Liu, Jie; Cortese, Riccardo; Lu, Min; Feldmann, Heinz; Pessi, Antonello; Moscona, Anne

2010-10-28

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

The M-T Hook Structure Is Critical for Design of HIV-1 Fusion Inhibitors*

PubMed Central

Chong, Huihui; Yao, Xue; Sun, Jianping; Qiu, Zonglin; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian

2012-01-01

CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. PMID:22879603

Structure based computational assessment of channel properties of assembled ORF-8a from SARS-CoV.

PubMed

Hsu, Hao-Jen; Lin, Meng-Han; Schindler, Christina; Fischer, Wolfgang B

2015-02-01

ORF 8a is a short 39 amino acid bitopic membrane protein encoded by severe acute respiratory syndrome causing corona virus (SARS-CoV). It has been identified to increase permeability of the lipid membrane for cations. Permeability is suggested to occur due to the assembly of helical bundles. Computational models of a pentameric assembly of 8a peptides are generated using the first 22 amino acids, which include the transmembrane domain. Low energy structures reveal a hydrophilic pore mantled by residues Thr-8, and -18, Ser-11, Cys-13, and Arg-22. Potential of mean force (PMF) profiles for mono (Na(+) , K(+) , Cl(-) ) and divalent (Ca(2+) ) ions along the pore are calculated. The data support experimental findings of a weak cation selectivity of the channel. Calculations on 8a are compared to data derived for a pentameric bundle consisting of the M2 helices of the bacterial pentameric ligand gated ion channel GLIC (3EHZ). PMF curves of both, bundles 8a and M2, show sigmoidal shaped profiles. In comparison to the data for the M2-GLIC model, data of the 8a bundle show lower amplitude of the PMF values between maximum and minimum and less discrimination amongst ions. © 2014 Wiley Periodicals, Inc.

Inhibition of Nipah Virus Infectin In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

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

M Porotto; B Rockx; C Yokoyama

2011-12-31

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viralmore » and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.« less

Peptides at Membrane Surfaces and their Role in the Origin of Life

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Wilson, Michael A.; DeVincenzi, D. (Technical Monitor)

2002-01-01

All ancestors of contemporary cells (protocells) had to transport ions and organic matter across membranous walls, capture and utilize energy and transduce environmental signals. In modern organisms, all these functions are preformed by membrane proteins. We make the parsimonious assumption that in the protobiological milieu the same functions were carried out by their simple analogs - peptides. This, however, required that simple peptides could self-organize into ordered, functional structures. In a series of detailed, molecular-level computer simulations we demonstrated how this is possible. One example is the peptide (LSLLLSL)3 which forms a trameric bundle capable of transporting protons across membranes. Another example is the transmembrane pore of the influenza M2 protein. This aggregate of four identical alpha-helices, each built of 25 amino acids, forms an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism in this channel. The channel can be re-engineered into a simple proton pump.

A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin

PubMed Central

Raimondo, Domenico; Andreotti, Giuseppina; Saint, Nathalie; Amodeo, Pietro; Renzone, Giovanni; Sanseverino, Marina; Zocchi, Ivana; Molle, Gerard; Motta, Andrea; Scaloni, Andrea

2005-01-01

Many bioactive peptides, presenting an unstructured conformation in aqueous solution, are made resistant to degradation by posttranslational modifications. Here, we describe how molecular oligomerization in aqueous solution can generate a still unknown transport form for amphipathic peptides, which is more compact and resistant to proteases than forms related to any possible monomer. This phenomenon emerged from 3D structure, function, and degradation properties of distinctin, a heterodimeric antimicrobial compound consisting of two peptide chains linked by a disulfide bond. After homodimerization in water, this peptide exhibited a fold consisting of a symmetrical full-parallel four-helix bundle, with a well secluded hydrophobic core and exposed basic residues. This fold significantly stabilizes distinctin against proteases compared with other linear amphipathic peptides, without affecting its antimicrobial, hemolytic, and ion-channel formation properties after membrane interaction. This full-parallel helical orientation represents a perfect compromise between formation of a stable structure in water and requirement of a drastic structural rearrangement in membranes to elicit antimicrobial potential. Thus, distinctin can be claimed as a prototype of a previously unrecognized class of antimicrobial derivatives. These results suggest a critical revision of the role of peptide oligomerization whenever solubility or resistance to proteases is known to affect biological properties. PMID:15840728

Discovery of Critical Residues for Viral Entry and Inhibition through Structural Insight of HIV-1 Fusion Inhibitor CP621–652*

PubMed Central

Chong, Huihui; Yao, Xue; Qiu, Zonglin; Qin, Bo; Han, Ruiyun; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian

2012-01-01

The core structure of HIV-1 gp41 is a stable six-helix bundle (6-HB) folded by its trimeric N- and C-terminal heptad repeats (NHR and CHR). We previously identified that the 621QIWNNMT627 motif located at the upstream region of gp41 CHR plays critical roles for the stabilization of the 6-HB core and peptide CP621–652 containing this motif is a potent HIV-1 fusion inhibitor, however, the molecular determinants underlying the stability and anti-HIV activity remained elusive. In this study, we determined the high-resolution crystal structure of CP621–652 complexed by T21. We find that the 621QIWNNMT627 motif does not maintain the α-helical conformation. Instead, residues Met626 and Thr627 form a unique hook-like structure (denoted as M-T hook), in which Thr627 redirects the peptide chain to position Met626 above the left side of the hydrophobic pocket on the NHR trimer. The side chain of Met626 caps the hydrophobic pocket, stabilizing the interaction between the pocket and the pocket-binding domain. Our mutagenesis studies demonstrate that mutations of the M-T hook residues could completely abolish HIV-1 Env-mediated cell fusion and virus entry, and significantly destabilize the interaction of NHR and CHR peptides and reduce the anti-HIV activity of CP621–652. Our results identify an unusual structural feature that stabilizes the six-helix bundle, providing novel insights into the mechanisms of HIV-1 fusion and inhibition. PMID:22511760

LOGMARS (Logistics Applications of Automated Marking and Reading Symbols) Clearinghouse. Applications Directory.

DTIC Science & Technology

1985-09-01

iD- A1t62 3 ? LOOM S (LOGISTICS APPLIC TIONS OF UTO NTED M ARING 1/2 WARND READING SYMBOLS) C EARINGHOUSE APPLICATIONS DIRECTORY(U) DEFENSE GENERAL...Rubin Patterson, SC, USN, DLA DMECSO, (AV) 695-4787. 1 Encl T. R. WILD Captain, SC, U. S . Navy Chief, DLA Depot Mechanization Support Office cc; . DLA-OW...DIc.-TRIBUTrION: DLA-L DLA-Z DLA-ZS DLA- S DLA-WS DGSC-T * DPSC-C DCSC-T DFSC-W DESC-L - DESC-Q * DISC-LO * DDOU-T DDt4P--T - - DDTC-T DDMT-T DRMS DSAC

F5-peptide induces aspermatogenesis by disrupting organization of actin- and microtubule-based cytoskeletons in the testis

PubMed Central

Gao, Ying; Mruk, Dolores D.; Lui, Wing-yee; Lee, Will M.; Cheng, C. Yan

2016-01-01

During the release of sperm at spermiation, a biologically active F5-peptide, which can disrupt the Sertoli cell tight junction (TJ) permeability barrier, is produced at the site of the degenerating apical ES (ectoplasmic specialization). This peptide coordinates the events of spermiation and blood-testis barrier (BTB) remodeling at stage VIII of the epithelial cycle, creating a local apical ES-BTB axis to coordinate cellular events across the epithelium. The mechanism(s) by which F5-peptide perturbs BTB restructuring, and its involvement in apical ES dynamics remain unknown. F5-peptide, besides perturbing BTB integrity, was shown to induce germ cell release from the epithelium following its efficient in vivo overexpression in the testis. Overexpression of F5-peptide caused disorganization of actin- and microtubule (MT)-based cytoskeletons, mediated by altering the spatiotemporal expression of actin binding/regulatory proteins in the seminiferous epithelium. F5-peptide perturbed the ability of actin microfilaments and/or MTs from converting between their bundled and unbundled/defragmented configuration, thereby perturbing adhesion between spermatids and Sertoli cells. Since apical ES and basal ES/BTB are interconnected through the underlying cytoskeletal networks, this thus provides an efficient and novel mechanism to coordinate different cellular events across the epithelium during spermatogenesis through changes in the organization of actin microfilaments and MTs. These findings also illustrate the potential of F5-peptide being a male contraceptive peptide for men. PMID:27611949

Elastic deformation and failure in protein filament bundles: Atomistic simulations and coarse-grained modeling.

PubMed

Hammond, Nathan A; Kamm, Roger D

2008-07-01

The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long beta-sheets that pair together to form filaments; filaments form bundles approximately 30-60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two beta-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials.

An Experimental and Theoretical Evaluation of Multi-site Cadmium(II) Exchange in Designed Three-Stranded Coiled Coil Peptides

PubMed Central

Chakraborty, Saumen; Iranzo, Olga; Zuiderweg, Erik R.P.; Pecoraro, Vincent L.

2012-01-01

An important factor that defines the toxicity of elements such as cadmium(II), mercury(II), and lead(II) with biological macromolecules is metal ion exchange dynamics. Intriguingly, little is known about the fundamental rates and mechanisms of metal ion exchange into proteins, especially helical bundles. Herein, we investigate the exchange kinetics of cadmium(II) using de novo designed three-stranded coiled coil peptides that contain metal complexing cysteine thiolates as a model for the incorporation of this ion into trimeric, parallel helical bundles. Peptides were designed containing both single cadmium(II) binding site, GrandL12AL16C [Grand=AcG-(LKALEEK)5-GNH2], GrandL26AL30C, and GrandL26AE28QL30C, as well as GrandL12AL16CL26AL30C with two cadmium(II) binding sites. The binding of cadmium(II) to any of these sites is of high affinity (KA > 3×107 M−1). Using 113Cd NMR spectroscopy, cadmium(II) binding to these designed peptides was monitored. While the cadmium(II) binding is in extreme slow exchange without showing any chemical shift changes, incremental line broadening for the bound 113cadmium(II) signal is observed when excess 113cadmium(II) is titrated into the peptides. Most dramatically, for one site, L26AL30C, all 113cadmium(II) NMR signals disappear once a 1.7:1 ratio of cadmium(II)/(peptide)3 is reached. The observed processes are not compatible with simple “free-bound” two-site exchange kinetics at any time regime. The experimental results can, however, be simulated in detail with a multi-site binding model, which features additional cadmium(II) binding site(s) which, once occupied, perturb the primary binding site. This model is expanded into differential equations for five-site NMR chemical exchange. The numerical integration of these equations exhibits progressive loss of the primary site NMR signal without a chemical shift change and with limited line broadening, in good agreement with the observed experimental data. The mathematical model is interpreted in molecular terms as representing binding of excess cadmium(II) to surface Glu residues located at the helical interfaces. In the absence of cadmium(II), the Glu residues stabilize the three-helical structure though salt bridge interactions with surface Lys residues. We hypothesize that cadmium(II) interferes with these surface ion pairs, destabilizing the helical structure, and perturbing the primary cadmium(II) binding site. This hypothesis is supported by the observation that the cadmium(II)-excess line broadening is attenuated in GrandL26AE28QL30C where a surface Glu(28), close to the metal binding site, was changed to Gln. The external binding site may function as an entry pathway for cadmium(II) to find its internal binding site following a molecular rearrangement which may serve as a basis for our understanding of metal complexation, transport and exchange in complex native systems containing α-helical bundles. PMID:22394049

High-resolution protein design with backbone freedom.

PubMed

Harbury, P B; Plecs, J J; Tidor, B; Alber, T; Kim, P S

1998-11-20

Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form alpha-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.

Structures of the transmembrane helices of the G-protein coupled receptor, rhodopsin.

PubMed

Katragadda, M; Chopra, A; Bennett, M; Alderfer, J L; Yeagle, P L; Albert, A D

2001-07-01

An hypothesis is tested that individual peptides corresponding to the transmembrane helices of the membrane protein, rhodopsin, would form helices in solution similar to those in the native protein. Peptides containing the sequences of helices 1, 4 and 5 of rhodopsin were synthesized. Two peptides, with overlapping sequences at their termini, were synthesized to cover each of the helices. The peptides from helix 1 and helix 4 were helical throughout most of their length. The N- and C-termini of all the peptides were disordered and proline caused opening of the helical structure in both helix 1 and helix 4. The peptides from helix 5 were helical in the middle segment of each peptide, with larger disordered regions in the N- and C-termini than for helices 1 and 4. These observations show that there is a strong helical propensity in the amino acid sequences corresponding to the transmembrane domain of this G-protein coupled receptor. In the case of the peptides from helix 4, it was possible to superimpose the structures of the overlapping sequences to produce a construct covering the whole of the sequence of helix 4 of rhodopsin. As similar superposition for the peptides from helix 1 also produced a construct, but somewhat less successfully because of the disordering in the region of sequence overlap. This latter problem was more severe for helix 5 and therefore a single peptide was synthesized for the entire sequence of this helix, and its structure determined. It proved to be helical throughout. Comparison of all these structures with the recent crystal structure of rhodopsin revealed that the peptide structures mimicked the structures seen in the whole protein. Thus similar studies of peptides may provide useful information on the secondary structure of other transmembrane proteins built around helical bundles.

Redesigning Channel-Forming Peptides: Amino Acid Substitutions that Enhance Rates of Supramolecular Self-Assembly and Raise Ion Transport Activity

PubMed Central

Shank, Lalida P.; Broughman, James R.; Takeguchi, Wade; Cook, Gabriel; Robbins, Ashley S.; Hahn, Lindsey; Radke, Gary; Iwamoto, Takeo; Schultz, Bruce D.; Tomich, John M.

2006-01-01

Three series of 22-residue peptides derived from the transmembrane M2 segment of the glycine receptor α1-subunit (M2GlyR) have been designed, synthesized, and tested to determine the plasticity of a channel-forming sequence and to define whether channel pores with enhanced conductive properties could be created. Sixteen sequences were examined for aqueous solubility, solution-association tendency, secondary structure, and half-maximal concentration for supramolecular assembly, channel activity, and ion transport properties across epithelial monolayers. All peptides interact strongly with membranes: associating with, inserting across, and assembling to form homooligomeric bundles when in micromolar concentrations. Single and double amino acid replacements involving arginine and/or aromatic amino acids within the final five C-terminal residues of the peptide cause dramatic effects on the concentration dependence, yielding a range of K1/2 values from 36 ± 5 to 390 ± 220 μM for transport activity. New water/lipid interfacial boundaries were established for the transmembrane segment using charged or aromatic amino acids, thus limiting the peptides' ability to move perpendicularly to the plane of the bilayer. Formation of discrete water/lipid interfacial boundaries appears to be necessary for efficient supramolecular assembly and high anion transport activity. A peptide sequence is identified that may show efficacy in channel replacement therapy for channelopathies such as cystic fibrosis. PMID:16387776

Sequence dependent aggregation of peptides and fibril formation

NASA Astrophysics Data System (ADS)

Hung, Nguyen Ba; Le, Duy-Manh; Hoang, Trinh X.

2017-09-01

Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.

Immunohistochemical evidence suggests intrinsic regulatory activity of human eccrine sweat glands

PubMed Central

ZANCANARO, CARLO; MERIGO, FLAVIA; CRESCIMANNO, CATERINA; ORLANDINI, SIMONETTA; OSCULATI, ANTONIO

1999-01-01

Immunohistochemistry of normal eccrine sweat glands was performed on paraffin sections of human skin. Immunoreactivity (ir) for neuron specific enolase, S100 protein (S100), regulatory peptides, nitric oxide synthase type I (NOS-I) and choline-acetyltransferase (ChAT) was found in small nerve bundles close to sweat glands. In the glands, secretory cells were labelled with anticytokeratin antibody. Using antibodies to S100, calcitonin gene-related peptide (CGRP) and substance P (SP) a specific distribution pattern was found in secretory cells. Granulated (dark) and parietal (clear) cells were immunopositive for CGRP, and S100 and SP, respectively. Immunoreactivity was diffuse in the cytoplasm for CGRP and S100, and peripheral for SP. Myoepithelial cells were not labelled. Electron microscopy revealed electron dense granules, probably containing peptide, in granulated cells. Using antibodies to NOS-I and ChAT, ir was exclusively found in myoepithelial cells. Immunoreactivity for the atrial natriuretic peptide was absent in sweat glands. These results provide evidence for the presence of both regulatory peptides involved in vasodilation and key enzymes for the synthesis of nitric oxide and acetylcholine in the secretory coil of human sweat glands. It is suggested that human sweat glands are capable of some intrinsic regulation in addition to that carried out by their nerve supply. PMID:10386780

Solid-State Nuclear Magnetic Resonance Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain.

PubMed

Yao, Hongwei; Lee, Myungwoon; Liao, Shu-Yu; Hong, Mei

2016-12-13

The fusion peptide (FP) and transmembrane domain (TMD) of viral fusion proteins play important roles during virus-cell membrane fusion, by inducing membrane curvature and transient dehydration. The structure of the water-soluble ectodomain of viral fusion proteins has been extensively studied crystallographically, but the structures of the FP and TMD bound to phospholipid membranes are not well understood. We recently investigated the conformations and lipid interactions of the separate FP and TMD peptides of parainfluenza virus 5 (PIV5) fusion protein F using solid-state nuclear magnetic resonance. These studies provide structural information about the two domains when they are spatially well separated in the fusion process. To investigate how these two domains are structured relative to each other in the postfusion state, when the ectodomain forms a six-helix bundle that is thought to force the FP and TMD together in the membrane, we have now expressed and purified a chimera of the FP and TMD, connected by a Gly-Lys linker, and measured the chemical shifts and interdomain contacts of the protein in several lipid membranes. The FP-TMD chimera exhibits α-helical chemical shifts in all the membranes examined and does not cause strong curvature of lamellar membranes or membranes with negative spontaneous curvature. These properties differ qualitatively from those of the separate peptides, indicating that the FP and TMD interact with each other in the lipid membrane. However, no 13 C- 13 C cross peaks are observed in two-dimensional correlation spectra, suggesting that the two helices are not tightly associated. These results suggest that the ectodomain six-helix bundle does not propagate into the membrane to the two hydrophobic termini. However, the loosely associated FP and TMD helices are found to generate significant negative Gaussian curvature to membranes that possess spontaneous positive curvature, consistent with the notion that the FP-TMD assembly may facilitate the transition of the membrane from hemifusion intermediates to the fusion pore.

Vaccine and Monoclonal Antibody That Enhance Mouse Resistance to Candidiasis ▿

PubMed Central

Xin, Hong; Cutler, Jim E.

2011-01-01

Previously we showed that antibodies specific for the glycan β-1,2-mannotriose [β-(Man)3] on the cell surface of Candida albicans protect mice against disseminated candidiasis (H. Xin, S. Dziadek, D. R. Bundle, and J. E. Cutler, Proc. Natl. Acad. Sci. U. S. A. 105:13526–13531, 2008). Furthermore, six 14-mer peptides that are within the N-terminal portion of C. albicans wall proteins were conjugated to the glycan in an attempt to create immunogenic glycopeptide conjugates. By a dendritic cell (DC)-based immunization approach, all were immunogenic and three of the six conjugates induced a high degree of protection in mice. Interestingly, whereas all six peptides induced antibody responses when used alone to pulse DCs for subsequent immunizations, three peptides induced protection, and one in particular, peptide Fba (derived from fructose-bisphosphate aldolase), induced robust protective responses and is the focus of the current work. Fba peptide is not restricted by the major histocompatibility complex class II (MHC-II), as it induced anti-Fba antibodies in mice of different H-2 haplotypes and in rabbits. Furthermore, the peptide induced protection against disease caused by different C. albicans strains. Partial protection was achieved when alum was used in place of DCs for Fba immunizations. The passive transfer of immune sera from Fba-vaccinated mice, but not immune serum preabsorbed with fungal cells, conferred protection in naïve mice. This result, along with our finding that a monoclonal antibody specific for the peptide, E2-9 (IgM), protected mice against candidiasis, provide strong evidence that antibodies contribute to protection. Our work demonstrates the utility of cell wall peptides alone or as glycopeptides in vaccines designed for the induction of immunity against candidiasis and monoclonal antibodies as a rapid immunoprotective approach against the disease. PMID:21832099

Tuning the entropic spring to dictate order and functionality in polymer conjugated peptide biomaterials

NASA Astrophysics Data System (ADS)

Keten, Sinan

Hybrid peptide-polymer conjugates have the potential to combine the advantages of natural proteins and synthetic polymers, resulting in biomaterials with improved stability, controlled assembly, and tailored functionalities. However, the effect of polymer conjugation on peptide structural organization and functionality, along with the behavior of polymers at the interface with biomolecules remain to be fully understood. This talk will summarize our recent efforts towards establishing a modeling framework to design entropic forces in helix-polymer conjugates and polymer-conjugated peptide nanotubes to achieve hierarchical self-assembling systems with predictable order. The first part of the talk will discuss how self-assembly principles found in biology, combined with polymer physics concepts can be used to create artificial membranes that mimic certain features of ion channels. Thermodynamics and kinetics aspects of self-assembly and how it governs the growth and stacking sequences of peptide nanotubes will be discussed, along with its implications for nanoscale transport. The second part of the talk will review advances related to modeling polymer conjugated coiled coils at relevant length and time scales. Atomistic simulations combined with sampling techniques will be presented to discuss the energy landscapes governing coiled-coil stability, revealing cascades of events governing disassembly. This will be followed by a discussion of mechanisms through which polymers can stabilize small proteins, such as shielding of solvents, and how specific peptide sequences can reciprocate by altering polymer conformations. Correlations between mechanical and thermal stability of peptides will be discussed. Finally, coarse-grained simulations will provide insight into how the location of polymer attachment changes entropic forces and higher-level organization in helix bundle assemblies. Our findings set the stage for a materials-by-design capability towards dictating complex topologies of polymer-peptide conjugate systems.

Interactions of histatin-3 and histatin-5 with actin.

PubMed

Blotnick, Edna; Sol, Asaf; Bachrach, Gilad; Muhlrad, Andras

2017-03-06

Histatins are histidine rich polypeptides produced in the parotid and submandibular gland and secreted into the saliva. Histatin-3 and -5 are the most important polycationic histatins. They possess antimicrobial activity against fungi such as Candida albicans. Histatin-5 has a higher antifungal activity than histatin-3 while histatin-3 is mostly involved in wound healing in the oral cavity. We found that these histatins, like other polycationic peptides and proteins, such as LL-37, lysozyme and histones, interact with extracellular actin. Histatin-3 and -5 polymerize globular actin (G-actin) to filamentous actin (F-actin) and bundle F-actin filaments. Both actin polymerization and bundling by histatins is pH sensitive due to the high histidine content of histatins. In spite of the equal number of net positive charges and histidine residues in histatin-3 and -5, less histatin-3 is needed than histatin-5 for polymerization and bundling of actin. The efficiency of actin polymerization and bundling by histatins greatly increases with decreasing pH. Histatin-3 and -5 induced actin bundles are dissociated by 100 and 50 mM NaCl, respectively. The relatively low NaCl concentration required to dissociate histatin-induced bundles implies that the actin-histatin filaments bind to each other mainly by electrostatic forces. The binding of histatin-3 to F-actin is stronger than that of histatin-5 showing that hydrophobic forces have also some role in histatin-3- actin interaction. Histatins affect the fluorescence of probes attached to the D-loop of G-actin indicating histatin induced changes in actin structure. Transglutaminase cross-links histatins to actin. Competition and limited proteolysis experiments indicate that the main histatin cross-linking site on actin is glutamine-49 on the D-loop of actin. Both histatin-3 and -5 interacts with actin, however, histatin 3 binds stronger to actin and affects actin structure at lower concentration than histatin-5 due to the extra 8 amino acid sequence at the C-terminus of histatin-3. Extracellular actin might regulate histatin activity in the oral cavity, which should be the subject of further investigation.

De novo design, synthesis and characterisation of MP3, a new catalytic four-helix bundle hemeprotein.

PubMed

Faiella, Marina; Maglio, Ornella; Nastri, Flavia; Lombardi, Angela; Lista, Liliana; Hagen, Wilfred R; Pavone, Vincenzo

2012-12-07

A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the excellent structural properties of four-helix bundle protein scaffolds with the activity of natural peroxidases, was synthesised and characterised. This new hemeprotein model was developed by covalently linking the deuteroporphyrin to two peptide chains of different compositions to obtain an asymmetric helix-loop-helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant distal site that is able to accommodate exogenous ligands or substrates; and 3) an Arg residue in the distal site that should assist in hydrogen peroxide activation to give an HRP-like catalytic process. MP3 was synthesised and characterised as its iron complex. CD measurements revealed the high helix-forming propensity of the peptide, confirming the appropriateness of the model procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)-MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the possibility of mimicking the functional features of natural enzymes. The synergistic application of de novo design methods, synthetic procedures, and spectroscopic characterisation, described herein, demonstrates a method by which to implement and optimise catalytic activity for an enzyme mimetic. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations.

PubMed

Zhu, Yun; Su, Shan; Qin, Lili; Wang, Qian; Shi, Lei; Ma, Zhenxuan; Tang, Jianchao; Jiang, Shibo; Lu, Lu; Ye, Sheng; Zhang, Rongguang

2016-09-26

Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.

The three lives of viral fusion peptides

PubMed Central

Apellániz, Beatriz; Huarte, Nerea; Largo, Eneko; Nieva, José L.

2014-01-01

Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention. PMID:24704587

Crystal structure of an HIV assembly and maturation switch

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

Wagner, Jonathan M.; Zadrozny, Kaneil K.; Chrustowicz, Jakub

Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysismore » during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.« less

Phase 1 Development Report for the SESSA Toolkit.

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

Knowlton, Robert G.; Melton, Brad J; Anderson, Robert J.

The Site Exploitation System for Situational Awareness ( SESSA ) tool kit , developed by Sandia National Laboratories (SNL) , is a comprehensive de cision support system for crime scene data acquisition and Sensitive Site Exploitation (SSE). SESSA is an outgrowth of another SNL developed decision support system , the Building R estoration Operations Optimization Model (BROOM), a hardware/software solution for data acquisition, data management, and data analysis. SESSA was designed to meet forensic crime scene needs as defined by the DoD's Military Criminal Investigation Organiza tion (MCIO) . SESSA is a very comprehensive toolki t with a considerable amountmore » of database information managed through a Microsoft SQL (Structured Query Language) database engine, a Geographical Information System (GIS) engine that provides comprehensive m apping capabilities, as well as a an intuitive Graphical User Interface (GUI) . An electronic sketch pad module is included. The system also has the ability to efficiently generate necessary forms for forensic crime scene investigations (e.g., evidence submittal, laboratory requests, and scene notes). SESSA allows the user to capture photos on site, and can read and generate ba rcode labels that limit transcription errors. SESSA runs on PC computers running Windows 7, but is optimized for touch - screen tablet computers running Windows for ease of use at crime scenes and on SSE deployments. A prototype system for 3 - dimensional (3 D) mapping and measur e ments was also developed to complement the SESSA software. The mapping system employs a visual/ depth sensor that captures data to create 3D visualizations of an interior space and to make distance measurements with centimeter - level a ccuracy. Output of this 3D Model Builder module provides a virtual 3D %22walk - through%22 of a crime scene. The 3D mapping system is much less expensive and easier to use than competitive systems. This document covers the basic installation and operation of th e SESSA tool kit in order to give the user enough information to start using the tool kit . SESSA is currently a prototype system and this documentation covers the initial release of the tool kit . Funding for SESSA was provided by the Department of Defense (D oD), Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) Rapid Fielding (RF) organization. The project was managed by the Defense Forensic Science Center (DFSC) , formerly known as the U.S. Army Criminal Investigation Laboratory (USACIL) . ACKNOWLEDGEMENTS The authors wish to acknowledge the funding support for the development of the Site Exploitation System for Situational Awareness (SESSA) toolkit from the Department of Defense (DoD), Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) Rapid Fielding (RF) organization. The project was managed by the Defense Forensic Science Center (DFSC) , formerly known as the U.S. Army Criminal Investigation Laboratory (USACIL). Special thanks to Mr. Garold Warner, of DFSC, who served as the Project Manager. Individuals that worked on the design, functional attributes, algorithm development, system arc hitecture, and software programming include: Robert Knowlton, Brad Melton, Robert Anderson, and Wendy Amai.« less

Two M-T hook residues greatly improve the antiviral activity and resistance profile of the HIV-1 fusion inhibitor SC29EK

PubMed Central

2014-01-01

Background Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We have recently found that two N-terminal residues (Met115 and Thr116) of CHR peptides form a unique M-T hook structure that can greatly enhance the binding and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent anti-HIV activity. Results The resulting peptide MT-SC29EK showed a dramatically increased binding affinity and could block the six-helical bundle (6-HB) formation more efficiently. As expected, MT-SC29EK potently inhibited HIV-1 entry and infection, especially against those T20- and SC29EK-resistant HIV-1 variants. More importantly, MT-SC29EK and its short form (MT-SC22EK) suffered from the difficulty to induce HIV-1 resistance during the in vitro selection, suggesting their high genetic barriers to the development of resistance. Conclusions Our studies have verified the M-T hook structure as a vital strategy to design novel HIV-1 fusion inhibitors and offered an ideal candidate for clinical development. PMID:24884671

Mutation of charged residues to neutral ones accelerates urea denaturation of HP-35.

PubMed

Wei, Haiyan; Yang, Lijiang; Gao, Yi Qin

2010-09-16

Following the studies of urea denaturation of β-hairpins using molecular dynamics, in this paper, molecular dynamics simulations of two peptides, a 35 residue three helix bundle villin headpiece protein HP-35 and its doubly norleucine-substituent mutant (Lys24Nle/Lys29Nle) HP-35 NleNle, were undertaken in urea solutions to understand the molecular mechanism of urea denaturation of α-helices. The mutant HP-35 NleNle was found to denature more easily than the wild type. During the expansion of the small hydrophobic core, water penetration occurs first, followed by that of urea molecules. It was also found that the initial hydration of the peptide backbone is achieved through water hydrogen bonding with the backbone CO groups during the denaturation of both polypeptides. The mutation of the two charged lysine residues to apolar norleucine enhances the accumulation of urea near the hydrophobic core and facilitates the denaturation process. Urea also interacts directly with the peptide backbone as well as side chains, thereby stabilizing nonnative conformations. The mechanism revealed here is consistent with the previous study on secondary structure of β-hairpin polypeptide, GB1, PEPTIDE 1, and TRPZIP4, suggesting that there is a general mechanism in the denaturation of protein backbone hydrogen bonds by urea.

Inhibition of hair follicle growth by a laminin-1 G-domain peptide, RKRLQVQLSIRT, in an organ culture of isolated vibrissa rudiment.

PubMed

Hayashi, Kazuhiro; Mochizuki, Mayumi; Nomizu, Motoyoshi; Uchinuma, Eijyu; Yamashina, Shohei; Kadoya, Yuichi

2002-04-01

We established a serum-free organ culture system of isolated single vibrissa rudiments taken from embryonic day 13 mice. This system allowed us to test more than 30 laminin-derived cell adhesive peptides to determine their roles on the growth and differentiation of vibrissa hair follicles. We found that the RKRLQVQLSIRT sequence (designated AG-73), which mapped to the LG-4 module of the laminin-alpha1 chain carboxyl-terminal G domain, perturbed the growth of hair follicles in vitro. AG-73 is one of the cell-binding peptides identified from more than 600 systematically synthesized 12 amino acid peptides covering the whole amino acid sequence of the laminin-alpha1, -beta1, and -gamma1 chains, by cell adhesion assay. Other cell-adhesive laminin peptides and a control scrambled peptide, LQQRRSVLRTKI, however, failed to show any significant effects on the growth of hair follicles. The AG-73 peptide binds to syndecan-1, a transmembrane heparan-sulfate proteoglycan. Syndecan-1 was expressed in both the mesenchymal condensation and the epithelial hair peg of developing vibrissa, suggesting that AG-73 binding to the cell surface syndecan-1 perturbed the epithelial-mesenchymal interactions of developing vibrissa. The formation of hair bulbs was aberrant in the explants treated with AG-73. In addition, impaired basement membrane formation, an abnormal cytoplasmic bleb formation, and an unusual basal formation of actin bundles were noted in the AG-73-treated-hair matrix epithelium, indicating that AG-73 binding perturbs various steps of epithelial morphogenesis, including the basement membrane remodeling. We also found a region-specific loss of the laminin-alpha1 chain in the basement membrane at the distal region of the invading hair follicle epithelium, indicating that laminins play a part in hair morphogenesis.

Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide

NASA Astrophysics Data System (ADS)

Wang, Yukun; Chen, Charles H.; Hu, Dan; Ulmschneider, Martin B.; Ulmschneider, Jakob P.

2016-11-01

Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures--formed by a single sequence--may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.

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

Chang, C.; Coggill, P.; Bateman, A.

Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. Wemore » have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.« less

Peptidergic control in a fruit crop pest: The spotted-wing drosophila, Drosophila suzukii

PubMed Central

Gough, Caroline S.; Fairlamb, Grace M.; Bell, Petra; Nachman, Ronald J.; Audsley, Neil

2017-01-01

Neuropeptides play an important role in the regulation of feeding in insects and offer potential targets for the development of new chemicals to control insect pests. A pest that has attracted much recent attention is the highly invasive Drosophila suzukii, a polyphagous pest that can cause serious economic damage to soft fruits. Previously we showed by mass spectrometry the presence of the neuropeptide myosuppressin (TDVDHVFLRFamide) in the nerve bundle suggesting that this peptide is involved in regulating the function of the crop, which in adult dipteran insects has important roles in the processing of food, the storage of carbohydrates and the movement of food into the midgut for digestion. In the present study antibodies that recognise the C-terminal RFamide epitope of myosuppressin stain axons in the crop nerve bundle and reveal peptidergic fibres covering the surface of the crop. We also show using an in vitro bioassay that the neuropeptide is a potent inhibitor (EC50 of 2.3 nM) of crop contractions and that this inhibition is mimicked by the non-peptide myosuppressin agonist, benzethonium chloride (Bztc). Myosuppressin also inhibited the peristaltic contractions of the adult midgut, but was a much weaker agonist (EC50 = 5.7 μM). The oral administration of Bztc (5 mM) in a sucrose diet to adult female D. suzukii over 4 hours resulted in less feeding and longer exposure to dietary Bztc led to early mortality. We therefore suggest that myosuppressin and its cognate receptors are potential targets for disrupting feeding behaviour of adult D. suzukii. PMID:29125862

Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein

PubMed Central

Torres, Jaume; Maheswari, Uma; Parthasarathy, Krupakar; Ng, Lifang; Liu, Ding Xiang; Gong, Xiandi

2007-01-01

The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM α-helical bundle. We have shown previously that the topology of the α-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM α-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric α-helical bundle model. PMID:17766393

Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex

PubMed Central

Zhang, Xinming; Rebane, Aleksander A.; Ma, Lu; Li, Feng; Jiao, Junyi; Qu, Hong; Pincet, Frederic; Rothman, James E.

2016-01-01

Synaptic soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex on the target plasma membrane, which then zippers with the vesicle (v)-SNARE on the vesicle to drive membrane fusion. However, the t-SNARE complex readily misfolds, and its structure, stability, and dynamics are elusive. Using single-molecule force spectroscopy, we modeled the synaptic t-SNARE complex as a parallel three-helix bundle with a small frayed C terminus. The helical bundle sequentially folded in an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a central ionic layer, with total unfolding energy of ∼17 kBT, where kB is the Boltzmann constant and T is 300 K. Peptide binding to the CTD activated the t-SNARE complex to initiate NTD zippering with the v-SNARE, a mechanism likely shared by the mammalian uncoordinated-18-1 protein (Munc18-1). The NTD zippering then dramatically stabilized the CTD, facilitating further SNARE zippering. The subtle bidirectional t-SNARE conformational switch was mediated by the ionic layer. Thus, the t-SNARE complex acted as a switch to enable fast and controlled SNARE zippering required for synaptic vesicle fusion and neurotransmission. PMID:27911771

Selection of a platinum-binding sequence in a loop of a four-helix bundle protein.

PubMed

Yagi, Sota; Akanuma, Satoshi; Kaji, Asumi; Niiro, Hiroya; Akiyama, Hayato; Uchida, Tatsuya; Yamagishi, Akihiko

2018-02-01

Protein-metal hybrids are functional materials with various industrial applications. For example, a redox enzyme immobilized on a platinum electrode is a key component of some biofuel cells and biosensors. To create these hybrid materials, protein molecules are bound to metal surfaces. Here, we report the selection of a novel platinum-binding sequence in a loop of a four-helix bundle protein, the Lac repressor four-helix protein (LARFH), an artificial protein in which four identical α-helices are connected via three identical loops. We created a genetic library in which the Ser-Gly-Gln-Gly-Gly-Ser sequence within the first inter-helical loop of LARFH was semi-randomly mutated. The library was then subjected to selection for platinum-binding affinity by using the T7 phage display method. The majority of the selected variants contained the Tyr-Lys-Arg-Gly-Tyr-Lys (YKRGYK) sequence in their randomized segment. We characterized the platinum-binding properties of mutant LARFH by using quartz crystal microbalance analysis. Mutant LARFH seemed to interact with platinum through its loop containing the YKRGYK sequence, as judged by the estimated exclusive area occupied by a single molecule. Furthermore, a 10-residue peptide containing the YKRGYK sequence bound to platinum with reasonably high affinity and basic side chains in the peptide were crucial in mediating this interaction. In conclusion, we have identified an amino acid sequence, YKRGYK, in the loop of a helix-loop-helix motif that shows high platinum-binding affinity. This sequence could be grafted into loops of other polypeptides as an approach to immobilize proteins on platinum electrodes for use as biosensors among other applications. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Structural characterization of Mumps virus fusion protein core

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

Liu Yueyong; Xu Yanhui; Lou Zhiyong

2006-09-29

The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus,more » forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins.« less

Identification of novel targets for HIV-1: Molecular dynamics simulation and binding energy calculations

NASA Astrophysics Data System (ADS)

Pandey, Vishnudatt; Tiwari, Gargi; Mall, Vijaya Shri; Tiwari, Rakesh Kumar; Ojha, R. P.

2018-05-01

HIV-1 envelope glycoprotein-mediated fusion is managed by the concerted coalescence of the HIV-1 gp41 N- and C- helical regions, which is a product in the formation of 6-helix bundles. These two regions are considered prime targets for peptides and antibodies that inhibit HIV-1 entry. There are so many rational method aimed to attach a rationally designed artificial tail to the C-terminus of HIV-1 fusion inhibitors to increase their antiviral potency. Here M. D. simulation was performed to go insight for study of C-terminal tail of Ile-Asp-Leu (IDL).

Using the peptide BP100 as a cell-penetrating tool for the chemical engineering of actin filaments within living plant cells.

PubMed

Eggenberger, Kai; Mink, Christian; Wadhwani, Parvesh; Ulrich, Anne S; Nick, Peter

2011-01-03

The delivery of externally applied macromolecules or nanoparticles into living cells still represents a critically limiting step before the full capabilities of chemical engineering can be explored. Molecular transporters such as cell-penetrating peptides, peptoids, and other mimetics can be used to carry cargo across the cellular membrane, but it is still difficult to find suitable sequences that operate efficiently for any particular type of cell. Here we report that BP100 (KKLFKKILKYL-amide), originally designed as an antimicrobial peptide against plant pathogens, can be employed as a fast and efficient cell-penetrating agent to transport fluorescent test cargoes into the cytosol of walled plant cells. The uptake of BP100 proceeds slightly more slowly than the endocytosis of fluorescent dextranes, but BP100 accumulates more efficiently and to much higher levels (by an order of magnitude). The entry of BP100 can be efficiently blocked by latrunculin B; this suggests that actin filaments are essential to the uptake mechanism. To test whether this novel transporter can also be used to deliver functional cargoes, we designed a fusion construct of BP100 with the actin-binding Lifeact peptide (MGVADLIKKFESISKEE). We demonstrated that the short BP100 could transport the attached 17-residue sequence quickly and efficiently into tobacco cells. The Lifeact construct retained its functionality as it successfully labeled the actin bundles that tether the nucleus in the cell center.

The Earliest Ion Channels in Protocellular Membranes

NASA Technical Reports Server (NTRS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

2010-01-01

Cellular membranes with their hydrophobic interior are virtually impermeable to ions. Bulk of ion transport through them is enabled through ion channels. Ion channels of contemporary cells are complex protein molecules which span the membrane creating a cylindrical pore filled with water. Protocells, which are widely regarded as precursors to modern cells, had similarly impermeable membranes, but the set of proteins in their disposal was much simpler and more limited. We have been, therefore, exploring an idea that the first ion channels in protocellular membranes were formed by much smaller peptide molecules that could spontaneously selfassemble into short-lived cylindrical bundles in a membrane. Earlier studies have shown that a group of peptides known as peptaibols is capable of forming ion channels in lipid bilayers when they are exposed to an electric field. Peptaibols are small, non-genetically encoded peptides produced by some fungi as a part of their system of defense against bacteria. They are usually only 14-20 residues long, which is just enough to span the membrane. Their sequence is characterized by the presence of non-standard amino acids which, interestingly, are also expected to have existed on the early earth. In particular, the presence of 2-aminoisobutyric acid (AIB) gives peptaibols strong helix forming propensities. Association of the helices inside membranes leads to the formation of cylindrical bundles, typically containing 4 to 10 monomers. Although peptaibols are excellent candidates for models of the earliest ion channels their structures, which are stabilized only by van der Waals forces and occasional hydrogen bonds between neighboring helices, are not very stable. Although it might properly reflect protobiological reality, it is also a major obstacle in studying channel behavior. For this reason we focused on two members of the peptaibol family, trichotoxin and antiamoebin, which are characterized by a single conductance level. This indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, alpha-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

The earliest ion channels in protocellular membranes

NASA Astrophysics Data System (ADS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

Cellular membranes with their hydrophobic interior are virtually impermeable to ions. Bulk of ion transport through them is enabled through ion channels. Ion channels of contemporary cells are complex protein molecules which span the membrane creating a cylindrical pore filled with water. Protocells, which are widely regarded as precursors to modern cells, had similarly impermeable membranes, but the set of proteins in their disposal was much simpler and more limited. We have been, therefore, exploring an idea that the first ion channels in protocellular membranes were formed by much smaller peptide molecules that could spontaneously self-assemble into short-lived cylindrical bundles in a membrane. Earlier studies have shown that a group of peptides known as peptaibols is capable of forming ion channels in lipid bilayers when they are exposed to an electric field. Peptaibols are small, non-genetically encoded peptides produced by some fungi as a part of their system of defense against bacteria. They are usually only 14-20 residues long, which is just enough to span the membrane. Their sequence is characterized by the presence of non-standard amino acids which, interestingly, are also expected to have existed on the early earth. In particular, the presence of 2-aminoisobutyric acid (AIB) gives peptaibols strong helix forming propensities. Association of the helices inside membranes leads to the formation of cylindrical bundles, typically containing 4 to 10 monomers. Although peptaibols are excellent candidates for models of the earliest ion channels their struc-tures, which are stabilized only by van der Waals forces and occasional hydrogen bonds between neighboring helices, are not very stable. Although it might properly reflect protobiological real-ity, it is also a major obstacle in studying channel behavior. For this reason we focused on two members of the peptaibol family, trichotoxin and antiamoebin, which are characterized by a single conductance level. This indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, α-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Leucine-rich amelogenin peptide (LRAP) as a surface primer for biomimetic remineralization of superficial enamel defects: An in vitro study.

PubMed

Shafiei, Farhad; Hossein, Bagheri G; Farajollahi, Mohammad M; Fathollah, Moztarzadeh; Marjan, Behroozibakhsh; Tahereh, Jafarzadeh Kashi

2015-01-01

This study was carried out to obtain more information about the assembly of hydroxyapatite bundles formed in the presence of Leucine-Rich Amelogenin Peptide (LRAP) and to evaluate its effect on the remineralization of enamel defects through a biomimetic approach. One or 2 mg/mL LRAP solutions containing 2.5 mM of Ca(+2) and 1.5 mM phosphate were prepared (pH = 7.2) and stored at 37 °C for 24 h. The products of the reaction were studied using atomic force microscopy (AFM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). Vickers surface microhardness recovery (SMR%) of acid-etched bovine enamel, with or without LRAP surface treatment, were calculated to evaluate the influence of peptide on the lesion remineralization. Distilled water and 1 or 2 mg/mL LRAP solution (pH = 7.2) were applied on the lesions and the specimens were incubated in mineralization solution (2.5mM Ca(+2) , 1.5mM PO4 (-3) , pH = 7.2) for 24 h. One-way ANOVA and Tukey's multi-comparison tests were used for statistical analysis. The pattern of enamel surface repair was studied using FE-SEM. AFM showed the formation of highly organized hierarchical structures, composed of hydroxyapatite (HA) crystals, similar to the dental enamel microstructure. ANOVA procedure showed significant effect of peptide treatment on the calculated SMR% (p < 0.001). Tukey's test revealed that peptide treated groups had significantly higher values of SMR%. In conclusion, LRAP is able to regulate the formation of HA and enhances the remineralization of acid-etched enamel as a surface treatment agent. © Wiley Periodicals, Inc.

A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.

PubMed

Watanabe, Masahiro; Hashimoto, Koichi; Abe, Yusaku; Kodama, Eiichi N; Nabika, Ryota; Oishi, Shinya; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Fujii, Nobutaka; Hosoya, Mitsuaki

2016-01-01

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.

A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo

PubMed Central

Watanabe, Masahiro; Hashimoto, Koichi; Abe, Yusaku; Kodama, Eiichi N.; Nabika, Ryota; Oishi, Shinya; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Fujii, Nobutaka; Hosoya, Mitsuaki

2016-01-01

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model. PMID:27612283

Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells

PubMed Central

Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Changyaleket, Benjarat; Whitlon, Donna S.; Mugnaini, Enrico; Bartles, James R.

2010-01-01

Espins are associated with the parallel actin bundles of hair cell stereocilia and are the target of mutations that cause deafness and vestibular dysfunction in mice and humans. Here, we report that espins are also concentrated in the microvilli of a number of other sensory cells: vomeronasal organ sensory neurons, solitary chemoreceptor cells, taste cells and Merkel cells. Moreover, we show that hair cells and these other sensory cells contain novel espin isoforms that arise from a different transcriptional start site and differ significantly from other espin isoforms in their complement of ligand-binding activities and their effects on actin polymerization. The novel espin isoforms of sensory cells bundled actin filaments with high affinity in a Ca2+-resistant fashion, bound actin monomer via a WASP homology 2 domain, bound profilin via a single proline-rich peptide, and caused a dramatic elongation of microvillus-type parallel actin bundles in transfected epithelial cells. In addition, the novel espin isoforms of sensory cells differed from other espin isoforms in that they potently inhibited actin polymerization in vitro, did not bind the Src homology 3 domain of the adapter protein insulin receptor substrate p53 and did not bind the acidic, signaling phospholipid phosphatidylinositol 4,5- bisphosphate. Thus, the espins constitute a family of multifunctional actin cytoskeletal regulatory proteins with the potential to differentially influence the organization, dimensions, dynamics and signaling capabilities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in a variety of mechanosensory and chemosensory cells. PMID:15190118

Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

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

Palomo, Concepción; Mas, Vicente; Vázquez, Mónica

Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to exploremore » the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.« less

Electron Transfer Activity of a de Novo Designed Copper Center in a Three-Helix Bundle Fold

PubMed Central

Plegaria, Jefferson S.; Herrero, Christian; Quaranta, Annamaria; Pecoraro, Vincent L.

2017-01-01

In this work, we characterized the intermolecular ET property of a de novo designed metallopeptide using laser-flash photolysis. α3D-CH3 is three-helix bundle peptide that was designed to contain a copper ET site found in the β-barrel fold of native cupredoxins. The ET activity of Cuα3D-CH3 was determined using five different photosensitizers. By exhibiting a complete depletion of the photo-oxidant and the successive formation of a Cu(II) species at 400 nm, the transient and generated spectra demonstrated an ET transfer reaction between the photo-oxidant and Cu(I)α3D-CH3. This observation illustrated our success in integrating an ET center within a de novo designed scaffold. From the kinetic traces at 400 nm, first-order and bimolecular rate constants of 105 s−1 and 108 M−1 s−1 were derived. Moreover, a Marcus equation analysis on the rate versus driving force study produced a reorganization energy of 1.1 eV, demonstrating that the helical fold of α3D requires further structural optimization to efficiently perform ET. PMID:26427552

Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

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

Boggiano, Cesar; Jiang Shibo; Lu Hong

2006-09-08

Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide DC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While DC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonalmore » antibody and chemokine SDF-1{alpha} to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of DC13 implies additional mode(s) of action. These results suggest that DC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors.« less

Mitochondria-targeting nanomedicine: An effective and potent strategy against aminoglycosides-induced ototoxicity.

PubMed

Zhou, Shuang; Sun, Yanhui; Kuang, Xiao; Hou, Shanshan; Yang, YinXian; Wang, Zhenjie; Liu, Hongzhuo

2018-04-21

We report a proof-of-concept for the development of mitochondria-targeting nanoparticles (NPs) loaded with geranylgeranylacetone (GGA) to protect against a wide range of gentamicin-induced ototoxicity symptoms in a zebrafish model. The polymeric NPs were functionalized with a mitochondrial-homing peptide (d‑Arg‑Dmt‑Orn‑Phe‑NH 2 ) and exhibited greater mitochondrial uptake and lower gentamicin uptake in hair cells via mechanotransduction (MET) channels and tuned machinery in the hair bundle than the ordinary NPs did. Blockade of MET channels rapidly reversed this effect, indicating the reversible responses of hair cells to the targeting NPs were mediated by MET channels. Pretreatment of hair cells with mitochondria-targeting GGA-loaded NPs exhibited a superior acute or chronic protective efficacy against subsequent exposure to gentamicin compared with unmodified formulations. Mitochondrial delivery regulating the death pathway of hair cells appeared to cause the therapeutic failure of untargeted NPs. Thus, peptide-directed mitochondria-targeting NPs may represent a novel therapeutic strategy for mitochondrial dysfunction-linked diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

De Novo Design of Protein Mimics of B-DNA

PubMed Central

Yüksel, Deniz; Bianco, Piero R.; Kumar, Krishna

2015-01-01

Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr – the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B–DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem. PMID:26568416

Deletion of fusion peptide or destabilization of fusion core of HIV gp41 enhances antigenicity and immunogenicity of 4E10 epitope

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

Li Jing; Beijing Key Laboratory for Protein Therapeutics, Beijing 100084; Chen Xi

2008-11-07

The human monoclonal antibody 4E10 against the membrane-proximal external region (MPER) of HIV-1 gp41 demonstrates broad neutralizing activity across various strains, and makes its epitope an attractive target for HIV-1 vaccine development. Although the contiguous epitope of 4E10 has been identified, attempts to re-elicit 4E10-like antibodies have failed, possibly due to the lack of proper conformation of the 4E10 epitope. Here we used pIg-tail expression system to construct a panel of eukaryotic cell-surface expression plasmids encoding the extracellular domain of gp41 with deletion of fusion peptide and/or introduction of L568P mutation that may disrupt the gp41 six-helix bundle core conformationmore » as DNA vaccines for immunization of mice. We found that these changes resulted in significant increase of the antigenicity and immunogenicity of 4E10 epitope. This information is thus useful for rational design of vaccines targeting the HIV-1 gp41 MPER.« less

Cell shape acquisition and maintenance in rodlike bacteria

NASA Astrophysics Data System (ADS)

van Teeffelen, Sven; Wingreen, Ned; Gitai, Zemer

2010-03-01

The shape of rodlike bacteria such as Escherichia coli is mainly governed by the expansion and reorganization of the peptidoglycan cell wall. The cell wall is a huge, mostly single-layered molecule of stiff glycan strands that typically run perpendicular to the long axis and are crosslinked by short peptides. The wall resists the excess pressure from inside the cell. Although much is known about the enzymes that synthesize the wall, the mechanisms by which the cell maintains a constant rod diameter and uniform glycan strand orientation during growth remain unknown. Here we present quantitative results on the structure and dynamics of two essential proteins, which are believed to play an important role in cell wall synthesis. In particular, we have focused on the filament-forming protein MreB, an actin homolog that forms a long helical bundle along the inner membrane of the cell, and penicillin-binding protein 2, an essential protein for peptide bond formation in the periplasm. Based on their interplay we discuss the possibility of MreB serving as a guide and ruler for cell wall synthesis.

Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

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

Duan, Liangwei; Du, Jiansen; Wang, Xuefeng

Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesismore » of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.« less

Hierarchical self-assembly of di-, tri- and tetraphenylalanine peptides capped with two fluorenyl functionalities: from polymorphs to dendrites.

PubMed

Mayans, Enric; Ballano, Gema; Casanovas, Jordi; Del Valle, Luis J; Pérez-Madrigal, Maria M; Estrany, Francesc; Jiménez, Ana I; Puiggalí, Jordi; Cativiela, Carlos; Alemán, Carlos

2016-06-28

Homopeptides with 2, 3 and 4 phenylalanine (Phe) residues and capped with fluorenylmethoxycarbonyl and fluorenylmethyl esters at the N-terminus and C-terminus, respectively, have been synthesized to examine their self-assembly capabilities. Depending on the conditions, the di- and triphenylalanine derivatives self-organize into a wide variety of stable polymorphic structures, which have been characterized: stacked braids, doughnut-like shapes, bundled arrays of nanotubes, corkscrew-like shapes and spherulitic microstructures. These highly aromatic Phe-based peptides also form incipient branched dendritic microstructures, even though they are highly unstable, making their manipulation very difficult. Conversely, the tetraphenylalanine derivative spontaneously self-assembles into stable dendritic microarchitectures made of branches growing from nucleated primary frameworks. The fractal dimension of these microstructures is ∼1.70, which provides evidence for self-similarity and two-dimensional diffusion controlled growth. DFT calculations at the M06L/6-31G(d) level have been carried out on model β-sheets since this is the most elementary building block of Phe-based peptide polymorphs. The results indicate that the antiparallel β-sheet is more stable than the parallel one, with the difference between them growing with the number of Phe residues. Thus, the cooperative effects associated with the antiparallel disposition become more favorable when the number of Phe residues increases from 2 to 4, while those of the parallel disposition remained practically constant.

Changes in neuroendocrine elements in bronchial mucosa in chronic lung disease in adults.

PubMed

Pilmane, M; Luts, A; Sundler, F

1995-05-01

It is not clear whether there is any association between metaplasia of the bronchial epithelium and changes in the distribution of neuroendocrine cells. This study examined, by immunohistological techniques, the distribution of neuroendocrine cells and juxtamucoscal nerve fibres in bronchial biopsies showing metaplastic changes. Bronchial biopsies from 12 subjects with epithelial metaplasia associated with bronchiectasis and diffuse pulmonary fibrosis were examined by conventional light microscopy and immunohistological techniques for protein gene product 9.5 (PGP), chromogranin A and B (CAB), serotonin, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), calcitonin (CT), and gastrin releasing peptide (GRP). Regions of non-metaplastic epithelium contained numerous PGP and serotonin immunoreactive cells. Sub-populations of these cells displayed CAB, CGRP, CT, and GRP immunoreactivity. Metaplastic epithelium contained only a few weakly stained PGP, serotonin, CAB, GRP, CT and CGRP immunoreactive cells in six cases. Metaplastic epithelium was characterised by a high number of CAB-containing cells in six cases and in these biopsies prominent PGP-containing nerve bundles were seen in the subepithelial layer beneath the metaplastic epithelium. The distribution patterns of neuroendocrine cells and neuronal elements vary between areas of normal and metaplastic epithelium and within areas of metaplastic epithelium. Neuronal hyperplasia was associated with an increase in the number of CAB-containing cells within the metaplastic epithelium.

Changes in neuroendocrine elements in bronchial mucosa in chronic lung disease in adults.

PubMed Central

Pilmane, M.; Luts, A.; Sundler, F.

1995-01-01

BACKGROUND--It is not clear whether there is any association between metaplasia of the bronchial epithelium and changes in the distribution of neuroendocrine cells. This study examined, by immunohistological techniques, the distribution of neuroendocrine cells and juxtamucoscal nerve fibres in bronchial biopsies showing metaplastic changes. METHODS--Bronchial biopsies from 12 subjects with epithelial metaplasia associated with bronchiectasis and diffuse pulmonary fibrosis were examined by conventional light microscopy and immunohistological techniques for protein gene product 9.5 (PGP), chromogranin A and B (CAB), serotonin, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), calcitonin (CT), and gastrin releasing peptide (GRP). RESULTS--Regions of non-metaplastic epithelium contained numerous PGP and serotonin immunoreactive cells. Sub-populations of these cells displayed CAB, CGRP, CT, and GRP immunoreactivity. Metaplastic epithelium contained only a few weakly stained PGP, serotonin, CAB, GRP, CT and CGRP immunoreactive cells in six cases. Metaplastic epithelium was characterised by a high number of CAB-containing cells in six cases and in these biopsies prominent PGP-containing nerve bundles were seen in the subepithelial layer beneath the metaplastic epithelium. CONCLUSIONS--The distribution patterns of neuroendocrine cells and neuronal elements vary between areas of normal and metaplastic epithelium and within areas of metaplastic epithelium. Neuronal hyperplasia was associated with an increase in the number of CAB-containing cells within the metaplastic epithelium. Images PMID:7541167

Postnatal development of autonomic and sensory innervation of thoracic hairy skin in the rat. A histochemical, immunocytochemical, and radioenzymatic study.

PubMed

Schotzinger, R J; Landis, S C

1990-05-01

Histochemical, immunocytochemical, and radioenzymatic techniques were used to examine the neurotransmitter-related properties of the innervation of thoracic hairy skin in rats during adulthood and postnatal development. In the adult, catecholamine-containing fibers were associated with blood vessels and piloerector muscles, and ran in nerve bundles throughout the dermis. The distribution of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers was identical. Neuronal fibers displaying neuropeptide Y (NPY) immunoreactivity were seen in association with blood vessels. Double-labeling studies suggested that most, if not all, NPY-IR fibers were also TH-IR and likewise most, if not all, vessel-associated TH-IR fibers were also NPY-IR. Calcitonin gene-related peptide (CGRP)-IR fibers were observed near and penetrating into the epidermis, in close association with hair follicles and blood vessels, and in nerve bundles. A similar distribution of substance P (SP)-IR fibers was evident. In adult animals treated as neonates with the sympathetic neurotoxin 6-hydroxydopamine, a virtual absence of TH-IR and NPY-IR fibers was observed, whereas the distribution of CGRP-IR and SP-IR fibers appeared unaltered. During postnatal development, a generalized increase in the number, fluorescence intensity, and varicose morphology of neuronal fibers displaying catecholamine fluorescence, NPY-IR, CGRP-IR, and SP-IR was observed. By postnatal day 21, the distribution of the above fibers had reached essentially adult levels, although the density of epidermal-associated CGRP-IR and SP-IR fibers was significantly greater than in the adult. The following were not evident in thoracic hairy skin at any timepoint examined: choline acetyltransferase activity, acetylcholinesterase histochemical staining or immunoreactivity, fibers displaying immunoreactivity to vasoactive intestinal peptide, cholecystokinin, or leucine-enkephalin. The present study demonstrates that the thoracic hairy skin in developing and adult rats receives an abundant sympathetic catecholaminergic and sensory innervation, but not a cholinergic innervation.

Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography

PubMed Central

Han, Shen; Kollmer, Marius; Markx, Daniel; Claus, Stephanie; Walther, Paul; Fändrich, Marcus

2017-01-01

The deposition of amyloid fibrils as plaques is a key feature of several neurodegenerative diseases including in particular Alzheimer’s. This disease is characterized, if not provoked, by amyloid aggregates formed from Aβ peptide that deposit inside the brain or are toxic to neuronal cells. We here used scanning transmission electron microscopy (STEM) to determine the fibril network structure and interactions of Aβ fibrils within a cell culture model of Alzheimer’s disease. STEM images taken from the formed Aβ amyloid deposits revealed three main types of fibril network structures, termed amorphous meshwork, fibril bundle and amyloid star. All three were infiltrated by different types of lipid inclusions from small-sized exosome-like structures (50–100 nm diameter) to large-sized extracellular vesicles (up to 300 nm). The fibrils also presented strong interactions with the surrounding cells such that fibril bundles extended into tubular invaginations of the plasma membrane. Amyloid formation in the cell model was previously found to have an intracellular origin and we show here that it functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage. These data provide a mechanistic link to explain why intracellular fibril formation is toxic to the cell. PMID:28240273

Biochemistry and Biophysics of HIV-1 gp41 – membrane interactions

PubMed Central

Cai, Lifeng; Gochin, Miriam; Liu, Keliang

2011-01-01

Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein – mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), N-terminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors. PMID:22044229

Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

PubMed

Cai, Lifeng; Gochin, Miriam; Liu, Keliang

2011-12-01

Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Recognition of white matter bundles using local and global streamline-based registration and clustering.

PubMed

Garyfallidis, Eleftherios; Côté, Marc-Alexandre; Rheault, Francois; Sidhu, Jasmeen; Hau, Janice; Petit, Laurent; Fortin, David; Cunanne, Stephen; Descoteaux, Maxime

2018-04-15

Virtual dissection of diffusion MRI tractograms is cumbersome and needs extensive knowledge of white matter anatomy. This virtual dissection often requires several inclusion and exclusion regions-of-interest that make it a process that is very hard to reproduce across experts. Having automated tools that can extract white matter bundles for tract-based studies of large numbers of people is of great interest for neuroscience and neurosurgical planning. The purpose of our proposed method, named RecoBundles, is to segment white matter bundles and make virtual dissection easier to perform. This can help explore large tractograms from multiple persons directly in their native space. RecoBundles leverages latest state-of-the-art streamline-based registration and clustering to recognize and extract bundles using prior bundle models. RecoBundles uses bundle models as shape priors for detecting similar streamlines and bundles in tractograms. RecoBundles is 100% streamline-based, is efficient to work with millions of streamlines and, most importantly, is robust and adaptive to incomplete data and bundles with missing components. It is also robust to pathological brains with tumors and deformations. We evaluated our results using multiple bundles and showed that RecoBundles is in good agreement with the neuroanatomical experts and generally produced more dense bundles. Across all the different experiments reported in this paper, RecoBundles was able to identify the core parts of the bundles, independently from tractography type (deterministic or probabilistic) or size. Thus, RecoBundles can be a valuable method for exploring tractograms and facilitating tractometry studies. Copyright © 2017 Elsevier Inc. All rights reserved.

On the concept of a filtered bundle

NASA Astrophysics Data System (ADS)

Bruce, Andrew James; Grabowska, Katarzyna; Grabowski, Janusz

We present the notion of a filtered bundle as a generalization of a graded bundle. In particular, we weaken the necessity of the transformation laws for local coordinates to exactly respect the weight of the coordinates by allowing more general polynomial transformation laws. The key examples of such bundles include affine bundles and various jet bundles, both of which play fundamental roles in geometric mechanics and classical field theory. We also present the notion of double filtered bundles which provide natural generalizations of double vector bundles and double affine bundles. Furthermore, we show that the linearization of a filtered bundle — which can be seen as a partial polarization of the admissible changes of local coordinates — is well defined.

Anatomy of the anterior cruciate ligament with regard to its two bundles.

PubMed

Petersen, Wolf; Zantop, Thore

2007-01-01

The anterior cruciate ligament (ACL) consists of two major fiber bundles, namely the anteromedial and posterolateral bundle. When the knee is extended, the posterolateral bundle (PL) is tight and the anteromedial (AM) bundle is moderately lax. As the knee is flexed, the femoral attachment of the ACL becomes a more horizontal orientation; causing the AM bundle to tighten and the PL bundle to relax. There is some degree of variability for the femoral origin of the anterome-dial and posterolateral bundle. The anteromedial bundle is located proximal and anterior in the femoral ACL origin (high and deep in the notch when the knee is flexed at 90 degrees ); the posterolateral bundle starts in the distal and posterior aspect of the femoral ACL origin (shallow and low when the knee is flexed at 90 degrees ). In the frontal plane the anteromedial bundle origin is in the 10:30 clock position and the postero-lateral bundle origin in the 9:30 clock position. At the tibial insertion the ACL fans out to form the foot region. The anteromedial bundle insertion is in the anterior part of the tibial ACL footprint, the posterolateral bundle in the posterior part. While the anteromedial bundle is the primary restraint against anterior tibial translation, the posterolateral bundle tends to stabilize the knee near full extension, particularly against rotatory loads.

Selection of peptides for binding semiconductor and magnetic materials for the purpose of organizing nanoscaled materials

NASA Astrophysics Data System (ADS)

Whaley, Sandra Renee

A peptide combinatorial approach, also known as phage display, was used to isolate peptides with the ability to bind semiconductor (GaAs, GaN, and InP) and magnetic (Fe2O3 and Fe3O4) materials. The commercially available combinatorial libraries contain randomized peptides either twelve (Ph.D-12(TM)) or seven (Ph.D-C7C(TM)) amino acids in length. The peptides are displayed on the pIII protein of M13 bacteriophage, which have been imaged by atomic force microscopy and transmission electron microscopy. After seven rounds of phage selection with a constrained seven amino acid sequence library (Ph.D-C7C(TM)), two sequences were isolated for binding Fe3O4 (MG-127 and MG-78). The haematite surface was screened with the same library and four unique sequences were isolated after six rounds of selection (HM-95, HM-101, HM-103, and HM-111). According to binding experiments (MG-78 v. MG-127 on Fe3O 4, MG-127 v. HM-95 on Fe3O4 and Fe2O 3, and MG-127 v. HM-95 on gamma-Fe2O3), the MG-127 clone had the highest affinity for iron oxide surfaces (magnetite, haematite, and maghemite) among the clones tested. The Fe3O 4 clone MG-127 displayed the ability to organize Fe3O 4 nanoparticles along bundles of phage. The synthetic peptide analog of this clone was used in the organization of nanoparticles onto the surface of latex beads. The surfaces of the III-V semiconductors were studied using x-ray photoelectron spectroscopy to determine their reactivity in the aqueous conditions used for phage selection. The GaN surface was shown to oxidize the least under these conditions, aiding in the ability to isolate a consensus amino acid sequence responsible for binding to this surface. The G1-3 clone isolated for binding the GaAs (100) surface displayed preferential binding to the GaAs (100) surface over Si (100), GaAs (111) A, GaAs (111) B, and AlGaAs. The synthetic peptide analog of the G12-3 clone was found to preferentially bind to GaAs (100) over either GaAs (111) surfaces or InP (100). This peptide was used to immobilize 10 nm gold particles onto the surface of GaAs within ten minutes. From these results we have shown that it is possible to isolate peptides with high affinities for binding technologically relevant materials, even those not found in nature. These peptides can be used for the organization of pre-formed nanoparticles in solution and on the surface of semiconductor materials.

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed

Jen, P Y; Dixon, J S

1995-08-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between helix stability and binding affinities: molecular dynamics simulations of Bfl-1/A1-binding pro-apoptotic BH3 peptide helices in explicit solvent.

PubMed

Modi, Vivek; Lama, Dilraj; Sankararamakrishnan, Ramasubbu

2013-01-01

The anti-apoptotic protein Bfl-1, also known as A1, belongs to the Bcl-2 family of proteins and interacts with pro-apoptotic Bcl-2 counterparts to regulate programmed cell death. As demonstrated for other anti-apoptotic Bcl-2 proteins, Bfl-1/A1 has also been shown to be overexpressed in various human cancers and hence they are attractive targets for anticancer drugs. Peptides derived from the BH3 region of pro-apoptotic Bcl-2 proteins have been shown to elicit similar biological response as that of parent proteins. BH3 peptides from different pro-apoptotic proteins have wide range of affinities for Bfl-1/A1. Experimentally determined complex structures show that the hydrophobic side of amphipathic BH3 peptides binds to the hydrophobic groove formed by the α-helical bundle of Bfl-1/A1 protein. Apart from the length and amino acid composition, a BH3 peptide's ability to form a stable helical structure has been suggested to be important for its high binding affinity. Molecular dynamics simulations of three BH3 peptides derived from the pro-apoptotic proteins Bak, Bid, and Bmf were carried out each for a period of at least 100 ns after 2 ns equilibration run. The length of simulated BH3 peptides varied from 22 to 24 residues and their binding affinities for Bfl-1/A1 varied from 1 to 180 nM. Our results show that the hydrophobic residues from the hydrophobic face of BH3 peptides tend to cluster together quickly to avoid being exposed to the solvent. This resulted in either reduction of helix length or complete loss of helical character. Bak and Bid BH3 peptides with high affinities for Bf1-1/A1 have stable helical segments in the N-terminal region. The highly conserved Leu residue lies just outside the helical region at the C-terminal end. Capping interactions arising out of N-cap residues seem to be extremely important to maintain the helical stability. Favorable hydrophilic interactions between residues also give further stability to the helix fragment and at least one of the interacting residues resides within the helical region. Bmf BH3 peptide with a weaker binding affinity for Bmf-1/A1 completely lost its helical character at the end of 100 ns production run and a further 50 ns simulation showed that the Bmf peptide continues to remain in random conformation. The present study clearly establishes a link between a BH3 peptide's ability to form a stable helical segment and its high binding affinity for an anti-apoptotic protein. To further test this hypothesis, we simulated a mutant Bmf peptide for 100 ns in which two residues R129 and H146 were substituted by Asn in silico in the wild-type peptide. Introduction of N-terminal Asn clearly enabled the formation of capping interactions at the N-terminus and resulted in a stable N-terminal helical segment. This demonstrates that the knowledge of interactions that help to maintain stable helical segments in a high-affinity BH3 peptide will help in designing highly specific peptide-based drugs/inhibitors. Such molecules will have the ability to bind a particular anti-apoptotic protein with high affinity.

Structure, Function, Self-Assembly and Origin of Simple Membrane Proteins

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2003-01-01

Integral membrane proteins perform such essential cellular functions as transport of ions, nutrients and waste products across cell walls, transduction of environmental signals, regulation of cell fusion, recognition of other cells, energy capture and its conversion into high-energy compounds. In fact, 30-40% of genes in modem organisms codes for membrane proteins. Although contemporary membrane proteins or their functional assemblies can be quite complex, their transmembrane fragments are usually remarkably simple. The most common structural motif for these fragments is a bundle of alpha-helices, but occasionally it could be a beta-barrel. In a series of molecular dynamics computer simulations we investigated self-organizing properties of simple membrane proteins based on these structural motifs. Specifically, we studied folding and insertion into membranes of short, nonpolar or amphiphatic peptides. We also investigated glycophorin A, a peptide that forms sequence-specific dimers, and a transmembrane aggregate of four identical alpha-helices that forms an efficient and selective voltage-gated proton channel was investigated. Many peptides are attracted to water-membrane interfaces. Once at the interface, nonpolar peptides spontaneously fold to a-helices. Whenever the sequence permits, peptides that contain both polar and nonpolar amino also adopt helical structures, in which polar and nonpolar amino acid side chains are immersed in water and membrane, respectively. Specific identity of side chains is less important. Helical peptides at the interface could insert into the membrane and adopt a transmembrane conformation. However, insertion of a single helix is unfavorable because polar groups in the peptide become completely dehydrated upon insertion. The unfavorable free energy of insertion can be regained by spontaneous association of peptides in the membrane. The first step in this process is the formation of dimers, although the most common are aggregates of 4-7 helices. The helices could arrange themselves such that they formed pores capable of transporting ions and small molecules across membranes. Stability of transmembrane aggregates of simple proteins is often only marginal and, therefore, it can be regulated by environmental signals or small sequence modifications in the region of interhelical interactions. A key step in the earliest evolution of membrane proteins was the emergence of selectivity for specific substrates. Many channels could become selective if one or only a few properly chosen amino acids are properly placed along the channel, acting as filters or gates. This is a convenient evolutionary solution because it does not require imposing conditions on the whole sequence.

Verification of the FBR fuel bundle-duct interaction analysis code BAMBOO by the out-of-pile bundle compression test with large diameter pins

NASA Astrophysics Data System (ADS)

Uwaba, Tomoyuki; Ito, Masahiro; Nemoto, Junichi; Ichikawa, Shoichi; Katsuyama, Kozo

2014-09-01

The BAMBOO computer code was verified by results for the out-of-pile bundle compression test with large diameter pin bundle deformation under the bundle-duct interaction (BDI) condition. The pin diameters of the examined test bundles were 8.5 mm and 10.4 mm, which are targeted as preliminary fuel pin diameters for the upgraded core of the prototype fast breeder reactor (FBR) and for demonstration and commercial FBRs studied in the FaCT project. In the bundle compression test, bundle cross-sectional views were obtained from X-ray computer tomography (CT) images and local parameters of bundle deformation such as pin-to-duct and pin-to-pin clearances were measured by CT image analyses. In the verification, calculation results of bundle deformation obtained by the BAMBOO code analyses were compared with the experimental results from the CT image analyses. The comparison showed that the BAMBOO code reasonably predicts deformation of large diameter pin bundles under the BDI condition by assuming that pin bowing and cladding oval distortion are the major deformation mechanisms, the same as in the case of small diameter pin bundles. In addition, the BAMBOO analysis results confirmed that cladding oval distortion effectively suppresses BDI in large diameter pin bundles as well as in small diameter pin bundles.

Signal detection by active, noisy hair bundles

NASA Astrophysics Data System (ADS)

O'Maoiléidigh, Dáibhid; Salvi, Joshua D.; Hudspeth, A. J.

2018-05-01

Vertebrate ears employ hair bundles to transduce mechanical movements into electrical signals, but their performance is limited by noise. Hair bundles are substantially more sensitive to periodic stimulation when they are mechanically active, however, than when they are passive. We developed a model of active hair-bundle mechanics that predicts the conditions under which a bundle is most sensitive to periodic stimulation. The model relies only on the existence of mechanotransduction channels and an active adaptation mechanism that recloses the channels. For a frequency-detuned stimulus, a noisy hair bundle's phase-locked response and degree of entrainment as well as its detection bandwidth are maximized when the bundle exhibits low-amplitude spontaneous oscillations. The phase-locked response and entrainment of a bundle are predicted to peak as functions of the noise level. We confirmed several of these predictions experimentally by periodically forcing hair bundles held near the onset of self-oscillation. A hair bundle's active process amplifies the stimulus preferentially over the noise, allowing the bundle to detect periodic forces less than 1 pN in amplitude. Moreover, the addition of noise can improve a bundle's ability to detect the stimulus. Although, mechanical activity has not yet been observed in mammalian hair bundles, a related model predicts that active but quiescent bundles can oscillate spontaneously when they are loaded by a sufficiently massive object such as the tectorial membrane. Overall, this work indicates that auditory systems rely on active elements, composed of hair cells and their mechanical environment, that operate on the brink of self-oscillation.

Crossed Module Bundle Gerbes; Classification, String Group and Differential Geometry

NASA Astrophysics Data System (ADS)

Jurčo, Branislav

We discuss nonabelian bundle gerbes and their differential geometry using simplicial methods. Associated to any crossed module there is a simplicial group NC, the nerve of the 1-category defined by the crossed module and its geometric realization |NC|. Equivalence classes of principal bundles with structure group |NC| are shown to be one-to-one with stable equivalence classes of what we call crossed module gerbes bundle gerbes. We can also associate to a crossed module a 2-category C'. Then there are two equivalent ways how to view classifying spaces of NC-bundles and hence of |NC|-bundles and crossed module bundle gerbes. We can either apply the W-construction to NC or take the nerve of the 2-category C'. We discuss the string group and string structures from this point of view. Also a simplicial principal bundle can be equipped with a simplicial connection and a B-field. It is shown how in the case of a simplicial principal NC-bundle these simplicial objects give the bundle gerbe connection and the bundle gerbe B-field.

Anatomical approach to permanent His bundle pacing: Optimizing His bundle capture.

PubMed

Vijayaraman, Pugazhendhi; Dandamudi, Gopi

2016-01-01

Permanent His bundle pacing is a physiological alternative to right ventricular pacing. In this article we describe our approach to His bundle pacing in patients with AV nodal and intra-Hisian conduction disease. It is essential for the implanters to understand the anatomic variations of the His bundle course and its effect on the type of His bundle pacing achieved. We describe several case examples to illustrate our anatomical approach to permanent His bundle pacing in this article. Copyright © 2016 Elsevier Inc. All rights reserved.

NMR structure of the viral peptide linked to the genome (VPg) of poliovirus

PubMed Central

Schein, Catherine H.; Oezguen, Numan; Volk, David E.; Garimella, Ravindranath; Paul, Aniko; Braun, Werner

2006-01-01

VPgs are essential for replication of picornaviruses, which cause diseases such as poliomyelitis, foot and mouth disease, and the common cold. VPg in infected cells is covalently linked to the 5' end of the viral RNA, or, in a uridylylated form, free in the cytoplasm. We show here the first solution structure for a picornaviral VPg, that of the 22-residue peptide from poliovirus serotype 1. VPg in buffer is inherently flexible, but a single conformer was obtained by adding trimethylamine N-oxide (TMAO). TMAO had only minor effects on the TOCSY spectrum. However, it increased the amount of structured peptide, as indicated by more peaks in the NOESY spectrum and an up to 300% increase in the ratio of normalized NOE crosspeak intensities to that in buffer. The data for VPg in TMAO yielded a well defined structure bundle with 0.6Å RMSD (vs. 6.6 Å in buffer alone), with 10–30 unambiguous constraints per residue. The structure consists of a large loop region from residues 1–14, from which the reactive tyrosinate projects outward, and a C-terminal helix from residues 18–21 that aligns the sidechains of conserved residues on one face. The structure has a stable docking position at an area on the poliovirus polymerase crystal structure identified as a VPg binding site by mutagenesis studies. Further, UTP and ATP dock in a base-specific manner to the reactive face of VPg, held in place by residues conserved in all picornavirus VPgs. PMID:16540201

Refinement of glucagon-like peptide 1 docking to its intact receptor using mid-region photolabile probes and molecular modeling.

PubMed

Miller, Laurence J; Chen, Quan; Lam, Polo C-H; Pinon, Delia I; Sexton, Patrick M; Abagyan, Ruben; Dong, Maoqing

2011-05-06

The glucagon-like peptide 1 (GLP1) receptor is an important drug target within the B family of G protein-coupled receptors. Its natural agonist ligand, GLP1, has incretin-like actions and the receptor is a recognized target for management of type 2 diabetes mellitus. Despite recent solution of the structure of the amino terminus of the GLP1 receptor and several close family members, the molecular basis for GLP1 binding to and activation of the intact receptor remains unclear. We previously demonstrated molecular approximations between amino- and carboxyl-terminal residues of GLP1 and its receptor. In this work, we study spatial approximations with the mid-region of this peptide to gain insights into the orientation of the intact receptor and the ligand-receptor complex. We have prepared two new photolabile probes incorporating a p-benzoyl-l-phenylalanine into positions 16 and 20 of GLP1(7-36). Both probes bound to the GLP1 receptor specifically and with high affinity. These were each fully efficacious agonists, stimulating cAMP accumulation in receptor-bearing CHO cells in a concentration-dependent manner. Each probe specifically labeled a single receptor site. Protease cleavage and radiochemical sequencing identified receptor residue Leu(141) above transmembrane segment one as its site of labeling for the position 16 probe, whereas the position 20 probe labeled receptor residue Trp(297) within the second extracellular loop. Establishing ligand residue approximation with this loop region is unique among family members and may help to orient the receptor amino-terminal domain relative to its helical bundle region.

Warps, grids and curvature in triple vector bundles

NASA Astrophysics Data System (ADS)

Flari, Magdalini K.; Mackenzie, Kirill

2018-06-01

A triple vector bundle is a cube of vector bundle structures which commute in the (strict) categorical sense. A grid in a triple vector bundle is a collection of sections of each bundle structure with certain linearity properties. A grid provides two routes around each face of the triple vector bundle, and six routes from the base manifold to the total manifold; the warps measure the lack of commutativity of these routes. In this paper we first prove that the sum of the warps in a triple vector bundle is zero. The proof we give is intrinsic and, we believe, clearer than the proof using decompositions given earlier by one of us. We apply this result to the triple tangent bundle T^3M of a manifold and deduce (as earlier) the Jacobi identity. We further apply the result to the triple vector bundle T^2A for a vector bundle A using a connection in A to define a grid in T^2A . In this case the curvature emerges from the warp theorem.

Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure.

PubMed

Spoon, Corrie; Moravec, W J; Rowe, M H; Grant, J W; Peterson, E H

2011-12-01

Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics.

Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure

PubMed Central

Spoon, Corrie; Moravec, W. J.; Rowe, M. H.; Grant, J. W.

2011-01-01

Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics. PMID:21918003

Double-bundle anterior cruciate ligament reconstruction is superior to single-bundle reconstruction in terms of revision frequency: a study of 22,460 patients from the Swedish National Knee Ligament Register.

PubMed

Svantesson, Eleonor; Sundemo, David; Hamrin Senorski, Eric; Alentorn-Geli, Eduard; Musahl, Volker; Fu, Freddie H; Desai, Neel; Stålman, Anders; Samuelsson, Kristian

2017-12-01

Studies comparing single- and double-bundle anterior cruciate ligament (ACL) reconstructions often include a combined analysis of anatomic and non-anatomic techniques. The purpose of this study was to compare the revision rates between single- and double-bundle ACL reconstructions in the Swedish National Knee Ligament Register with regard to surgical variables as determined by the anatomic ACL reconstruction scoring checklist (AARSC). Patients from the Swedish National Knee Ligament Register who underwent either single- or double-bundle ACL reconstruction with hamstring tendon autograft during the period 2007-2014 were included. The follow-up period started with primary ACL reconstruction, and the outcome measure was set as revision surgery. An online questionnaire based on the items of the AARSC was used to determine the surgical technique implemented in the single-bundle procedures. These were organized into subgroups based on surgical variables, and the revision rates were compared with the double-bundle ACL reconstruction. Hazard ratios (HR) with 95% confidence interval (CI) was calculated and adjusted for confounders by Cox regression. A total of 22,460 patients were included in the study, of which 21,846 were single-bundle and 614 were double-bundle ACL reconstruction. Double-bundle ACL reconstruction had a revision frequency of 2.0% (n = 12) and single-bundle 3.2% (n = 689). Single-bundle reconstruction had an increased risk of revision surgery compared with double-bundle [adjusted HR 1.98 (95% CI 1.12-3.51), p = 0.019]. The subgroup analysis showed a significantly increased risk of revision surgery in patients undergoing single-bundle with anatomic technique using transportal drilling [adjusted HR 2.51 (95% CI 1.39-4.54), p = 0.002] compared with double-bundle ACL reconstruction. Utilizing a more complete anatomic technique according to the AARSC lowered the hazard rate considerably when transportal drilling was performed but still resulted in significantly increased risk of revision surgery compared with double-bundle ACL reconstruction [adjusted HR 1.87 (95% CI 1.04-3.38), p = 0.037]. Double-bundle ACL reconstruction is associated with a lower risk of revision surgery than single-bundle ACL reconstruction. Single-bundle procedures performed using transportal femoral drilling technique had significantly higher risk of revision surgery compared with double-bundle. However, a reference reconstruction with transportal drilling defined as a more complete anatomic reconstruction reduces the risk of revision surgery considerably. III.

Side-chain conformation of the M2 transmembrane peptide proton channel of influenza a virus from 19F solid-state NMR.

PubMed

Luo, Wenbin; Mani, Rajeswari; Hong, Mei

2007-09-13

The M2 transmembrane peptide (M2TMP) of the influenza A virus forms a tetrameric helical bundle that acts as a proton-selective channel important in the viral life cycle. The side-chain conformation of the peptide is largely unknown and is important for elucidating the proton-conducting mechanism and the channel stability. Using a 19F spin diffusion NMR technique called CODEX, we have measured the oligomeric states and interhelical side chain-side chain 19F-19F distances at several residues using singly fluorinated M2TMP bound to DMPC bilayers. 19F CODEX data at a key residue of the proton channel, Trp41, confirm the tetrameric state of the peptide and yield a nearest-neighbor interhelical distance of approximately 11 A under both neutral and acidic pH. Since the helix orientation is precisely known from previous 15N NMR experiments and the backbone channel diameter has a narrow allowed range, this 19F distance constrains the Trp41 side-chain conformation to t90 (chi1 approximately 180 degrees , chi2 approximately 90 degrees ). This Trp41 rotamer, combined with a previously measured 15N-13C distance between His37 and Trp411, suggests that the His37 rotamer is t-160. The implication of the proposed (His37, Trp41) rotamers to the gating mechanism of the M2 proton channel is discussed. Binding of the antiviral drug amantadine to the peptide does not affect the F-F distance at Trp41. Interhelical 19F-19F distances are also measured at residues 27 and 38, each mutated to 4-19F-Phe. For V27F-M2TMP, the 19F-19F distances suggest a mixture of dimers and tetramers, whereas the L38F-M2TMP data indicate two tetramers of different sizes, suggesting side chain conformational heterogeneity at this lipid-facing residue. This work shows that 19F spin diffusion NMR is a valuable tool for determining long-range intermolecular distances that shed light on the mechanism of action and conformational heterogeneity of membrane protein oligomers.

Moisture separator reheater with round tube bundle

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

Byerley, W. M.

1984-11-27

A moisture separator reheater having a central chamber with cylindrical wall protions and a generally round tube bundle, the tube bundle having arcuate plates disposed on each side of the bundle which form a wrapper on each side of the bundle and having a tongue and groove juncture between the wrapper and cylindrical wall portions to provide a seal therebetween and a track for installing and removing the tube bundle from the central chamber.

["Habitual" left branch block alternating with 2 "disguised" bracnch block].

PubMed

Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

1976-10-01

Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

Characterization of active hair-bundle motility by a mechanical-load clamp

NASA Astrophysics Data System (ADS)

Salvi, Joshua D.; Maoiléidigh, Dáibhid Ó.; Fabella, Brian A.; Tobin, Mélanie; Hudspeth, A. J.

2015-12-01

Active hair-bundle motility endows hair cells with several traits that augment auditory stimuli. The activity of a hair bundle might be controlled by adjusting its mechanical properties. Indeed, the mechanical properties of bundles vary between different organisms and along the tonotopic axis of a single auditory organ. Motivated by these biological differences and a dynamical model of hair-bundle motility, we explore how adjusting the mass, drag, stiffness, and offset force applied to a bundle control its dynamics and response to external perturbations. Utilizing a mechanical-load clamp, we systematically mapped the two-dimensional state diagram of a hair bundle. The clamp system used a real-time processor to tightly control each of the virtual mechanical elements. Increasing the stiffness of a hair bundle advances its operating point from a spontaneously oscillating regime into a quiescent regime. As predicted by a dynamical model of hair-bundle mechanics, this boundary constitutes a Hopf bifurcation.

Bundled payments in orthopedic surgery.

PubMed

Bushnell, Brandon D

2015-02-01

As a result of reading this article, physicians should be able to: 1. Describe the concept of bundled payments and the potential applications of bundled payments in orthopedic surgery. 2. For specific situations, outline a clinical episode of care, determine the participants in a bundling situation, and define care protocols and pathways. 3. Recognize the importance of resource utilization management, quality outcome measurement, and combined economic-clinical value in determining the value of bundled payment arrangements. 4. Identify the implications of bundled payments for practicing orthopedists, as well as the legal issues and potential future directions of this increasingly popular alternative payment method. Bundled payments, the idea of paying a single price for a bundle of goods and services, is a financial concept familiar to most American consumers because examples appear in many industries. The idea of bundled payments has recently gained significant momentum as a financial model with the potential to decrease the significant current costs of health care. Orthopedic surgery as a field of medicine is uniquely positioned for success in an environment of bundled payments. This article reviews the history, logistics, and implications of the bundled payment model relative to orthopedic surgery. Copyright 2015, SLACK Incorporated.

Human Antimicrobial Peptides and Proteins

PubMed Central

Wang, Guangshun

2014-01-01

As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs. PMID:24828484

Quantitative study of bundle size effect on thermal conductivity of single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Feng, Ya; Inoue, Taiki; An, Hua; Xiang, Rong; Chiashi, Shohei; Maruyama, Shigeo

2018-05-01

Compared with isolated single-walled carbon nanotubes (SWNTs), thermal conductivity is greatly impeded in SWNT bundles; however, the measurement of the bundle size effect is difficult. In this study, the number of SWNTs in a bundle was determined based on the transferred horizontally aligned SWNTs on a suspended micro-thermometer to quantitatively study the effect of the bundle size on thermal conductivity. Increasing the bundle size significantly degraded the thermal conductivity. For isolated SWNTs, thermal conductivity was approximately 5000 ± 1000 W m-1 K-1 at room temperature, three times larger than that of the four-SWNT bundle. The logarithmical deterioration of thermal conductivity resulting from the increased bundle size can be attributed to the increased scattering rate with neighboring SWNTs based on the kinetic theory.

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Spinal surgery: variations in health care costs and implications for episode-based bundled payments.

PubMed

Ugiliweneza, Beatrice; Kong, Maiying; Nosova, Kristin; Huang, Kevin T; Babu, Ranjith; Lad, Shivanand P; Boakye, Maxwell

2014-07-01

Retrospective, observational. To simulate what episodes of care in spinal surgery might look like in a bundled payment system and to evaluate the associated costs and characteristics. Episode-based payment bundling has received considerable attention as a potential method to help curb the rise in health care spending and is being investigated as a new payment model as part of the Affordable Care Act. Although earlier studies investigated bundled payments in a number of surgical settings, very few focused on spine surgery, specifically. We analyzed data from MarketScan. Patients were included in the study if they underwent cervical or lumbar spinal surgery during 2000-2009, had at least 2-year preoperative and 90-day postoperative follow-up data. Patients were grouped on the basis of their diagnosis-related group (DRG) and then tracked in simulated episodes-of-care/payment bundles that lasted for the duration of 30, 60, and 90 days after the discharge from the index-surgical hospitalization. The total cost associated with each episode-of-care duration was measured and characterized. A total of 196,918 patients met our inclusion criteria. Significant variation existed between DRGs, ranging from $11,180 (30-day bundle, DRG 491) to $107,642 (30-day bundle, DRG 456). There were significant cost variations within each individual DRG. Postdischarge care accounted for a relatively small portion of overall bundle costs (range, 4%-8% in 90-day bundles). Total bundle costs remained relatively flat as bundle-length increased (total average cost of 30-day bundle: $33,522 vs. $35,165 for 90-day bundle). Payments to hospitals accounted for the largest portion of bundle costs (76%). There exists significant variation in total health care costs for patients who undergo spinal surgery, even within a given DRG. Better characterization of impacts of a bundled payment system in spine surgery is important for understanding the costs of index procedure hospital, physician services, and postoperative care on potential future health care policy decision making. N/A.

Nurses' perceptions of a pressure ulcer prevention care bundle: a qualitative descriptive study.

PubMed

Roberts, Shelley; McInnes, Elizabeth; Wallis, Marianne; Bucknall, Tracey; Banks, Merrilyn; Chaboyer, Wendy

2016-01-01

Pressure ulcer prevention is a critical patient safety indicator for acute care hospitals. An innovative pressure ulcer prevention care bundle targeting patient participation in their care was recently tested in a cluster randomised trial in eight Australian hospitals. Understanding nurses' perspectives of such an intervention is imperative when interpreting results and translating evidence into practice. As part of a process evaluation for the main trial, this study assessed nurses' perceptions of the usefulness and impact of a pressure ulcer prevention care bundle intervention on clinical practice. This qualitative descriptive study involved semi-structured interviews with nursing staff at four Australian hospitals that were intervention sites for a cluster randomised trial testing a pressure ulcer prevention care bundle. Four to five participants were purposively sampled at each site. A trained interviewer used a semi-structured interview guide to question participants about their perceptions of the care bundle. Interviews were digitally recorded, transcribed and analysed using thematic analysis. Eighteen nurses from four hospitals participated in the study. Nurses' perceptions of the intervention are described in five themes: 1) Awareness of the pressure ulcer prevention care bundle and its similarity to current practice; 2) Improving awareness, communication and participation with the pressure ulcer prevention care bundle; 3) Appreciating the positive aspects of patient participation in care; 4) Perceived barriers to engaging patients in the pressure ulcer prevention care bundle; and 5) Partnering with nursing staff to facilitate pressure ulcer prevention care bundle implementation. Overall, nurses found the care bundle feasible and acceptable. They identified a number of benefits from the bundle, including improved communication, awareness and participation in pressure ulcer prevention care among patients and staff. However, nurses thought the care bundle was not appropriate or effective for all patients, such as those who were cognitively impaired. Perceived enablers to implementation of the bundle included facilitation through effective communication and dissemination of evidence about the care bundle; strong leadership and ability to influence staff behaviour; and simplicity of the care bundle.

MOX fuel assembly design

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

Reese, A.P.; Crowther, R.L. Jr.

1992-02-18

This patent describes improvement in a boiling water reactor core having a plurality of vertically upstanding fuel bundles; each fuel bundle containing longitudinally extending sealed rods with fissile material therein; the improvement comprises the fissile material including a mixture of uranium and recovered plutonium in rods of the fuel bundle at locations other than the corners of the fuel bundle; and, neutron absorbing material being located in rods of the fuel bundle at rod locations adjacent the corners of the fuel bundles whereby the neutron absorbing material has decreased shielding from the plutonium and maximum exposure to thermal neutrons formore » shaping the cold reactivity shutdown zone in the fuel bundle.« less

Polycation induced actin bundles.

PubMed

Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

2011-04-01

Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

Post-natal molecular adaptations in anteromedial and posterolateral bundles of the ovine anterior cruciate ligament: one structure with two parts or two distinct ligaments?

PubMed

Huebner, Kyla D; O'Brien, Etienne J O; Heard, Bryan J; Chung, May; Achari, Yamini; Shrive, Nigel G; Frank, Cyril B

2012-01-01

The human anterior cruciate ligament (ACL) is a composite structure of two anatomically distinct bundles: an anteromedial (AM) and posterolateral (PL) bundles. Tendons are often used as autografts for surgical reconstruction of ACL following severe injury. However, despite successful surgical reconstruction, some people experience re-rupture and later development of osteoarthritis. Understanding the structure and molecular makeup of normal ACL is essential for its optimal replacement. Reportedly the two bundles display different tensions throughout joint motion and may be fundamentally different. This study assessed the similarities and differences in ultrastructure and molecular composition of the AM and PL bundles to test the hypothesis that the two bundles of the ACL develop unique characteristics with maturation. ACLs from nine mature and six immature sheep were compared. The bundles were examined for mRNA and protein levels of collagen types I, III, V, and VI, and two proteoglycans. The fibril diameter composition of the two bundles was examined with transmission electron microscopy. Maturation does alter the molecular and structural composition of the two bundles of ACL. Although the PL band appears to mature slower than the AM band, no significant differences were detected between the bundles in the mature animals. We thus reject our hypothesis that the two ACL bundles are distinct. The two anatomically distinct bundles of the sheep ACL can be considered as two parts of one structure at maturity and material that would result in a structure of similar functionality can be used to replace each ACL bundle in the sheep.

Nonabelian Bundle Gerbes, Their Differential Geometry and Gauge Theory

NASA Astrophysics Data System (ADS)

Aschieri, Paolo; Cantini, Luigi; Jurčo, Branislav

2005-03-01

Bundle gerbes are a higher version of line bundles, we present nonabelian bundle gerbes as a higher version of principal bundles. Connection, curving, curvature and gauge transformations are studied both in a global coordinate independent formalism and in local coordinates. These are the gauge fields needed for the construction of Yang-Mills theories with 2-form gauge potential.

Bundled payment fails to gain a foothold In California: the experience of the IHA bundled payment demonstration.

PubMed

Ridgely, M Susan; de Vries, David; Bozic, Kevin J; Hussey, Peter S

2014-08-01

To determine whether bundled payment could be an effective payment model for California, the Integrated Healthcare Association convened a group of stakeholders (health plans, hospitals, ambulatory surgery centers, physician organizations, and vendors) to develop, through a consensus process, the methods and means of implementing bundled payment. In spite of a high level of enthusiasm and effort, the pilot did not succeed in its goal to implement bundled payment for orthopedic procedures across multiple payers and hospital-physician partners. An evaluation of the pilot documented a number of barriers, such as administrative burden, state regulatory uncertainty, and disagreements about bundle definition and assumption of risk. Ultimately, few contracts were signed, which resulted in insufficient volume to test hypotheses about the impact of bundled payment on quality and costs. Although bundled payment failed to gain a foothold in California, the evaluation provides lessons for future bundled payment initiatives. Project HOPE—The People-to-People Health Foundation, Inc.

Double-bundle ACL reconstruction can improve rotational stability.

PubMed

Yagi, Masayoshi; Kuroda, Ryosuke; Nagamune, Kouki; Yoshiya, Shinichi; Kurosaka, Masahiro

2007-01-01

Double-bundle anterior cruciate ligament (ACL) reconstruction reproduces anteromedial and posterolateral bundles, and thus has theoretical advantages over conventional single-bundle reconstruction in controlling rotational torque in vitro. However, its superiority in clinical practice has not been proven. We analyzed rotational stability with three reconstruction techniques in 60 consecutive patients who were randomly divided into three groups (double-bundle, anteromedial single-bundle, posterolateral single-bundle). In the reconstructive procedure, the hamstring tendon was harvested and used as a free tendon graft. Followup examinations were performed 1 year after surgery. Anteroposterior laxity of the knee was examined with a KT-1000 arthrometer, whereas rotatory instability, as elicited by the pivot shift test, was assessed using a new measurement system incorporating three-dimensional electromagnetic sensors. Routine clinical evaluations, including KT examination, demonstrated no differences among the three groups. However, using the new measurement system, patients with double-bundle ACL reconstruction showed better pivot shift control of complex instability than patients with anteromedial and posterolateral single-bundle reconstruction.

Risk of Revision Was Not Reduced by a Double-bundle ACL Reconstruction Technique: Results From the Scandinavian Registers.

PubMed

Aga, Cathrine; Kartus, Jüri-Tomas; Lind, Martin; Lygre, Stein Håkon Låstad; Granan, Lars-Petter; Engebretsen, Lars

2017-10-01

Double-bundle anterior cruciate ligament (ACL) reconstruction has demonstrated improved biomechanical properties and moderately better objective outcomes compared with single-bundle reconstructions. This could make an impact on the rerupture rate and reduce the risk of revisions in patients undergoing double-bundle ACL reconstruction compared with patients reconstructed with a traditional single-bundle technique. The National Knee Ligament Registers in Scandinavia provide information that can be used to evaluate the revision outcome after ACL reconstructions. The purposes of the study were (1) to compare the risk of revision between double-bundle and single-bundle reconstructions, reconstructed with autologous hamstring tendon grafts; (2) to compare the risk of revision between double-bundle hamstring tendon and single-bundle bone-patellar tendon-bone autografts; and (3) to compare the hazard ratios for the same two research questions after Cox regression analysis was performed. Data collection of primary ACL reconstructions from the National Knee Ligament Registers in Denmark, Norway, and Sweden from July 1, 2005, to December 31, 2014, was retrospectively analyzed. A total of 60,775 patients were included in the study; 994 patients were reconstructed with double-bundle hamstring tendon grafts, 51,991 with single-bundle hamstring tendon grafts, and 7790 with single-bundle bone-patellar tendon-bone grafts. The double-bundle ACL-reconstructed patients were compared with the two other groups. The risk of revision for each research question was detected by the risk ratio, hazard ratio, and the corresponding 95% confidence intervals. Kaplan-Meier analysis was used to estimate survival at 1, 2, and 5 years for the three different groups. Furthermore, a Cox proportional hazard regression model was applied and the hazard ratios were adjusted for country, age, sex, meniscal or chondral injury, and utilized fixation devices on the femoral and tibial sides. There were no differences in the crude risk of revision between the patients undergoing the double-bundle technique and the two other groups. A total of 3.7% patients were revised in the double-bundle group (37 of 994 patients) versus 3.8% in the single-bundle hamstring tendon group (1952 of 51,991; risk ratio, 1.01; 95% confidence interval (CI), 0.73-1.39; p = 0.96), and 2.8% of the patients were revised in the bone-patellar tendon-bone group (219 of the 7790 bone-patellar tendon-bone patients; risk ratio, 0.76; 95% CI, 0.54-1.06; p = 0.11). Cox regression analysis with adjustment for country, age, sex, menisci or cartilage injury, and utilized fixation device on the femoral and tibial sides, did not reveal any further difference in the risk of revision between the single-bundle hamstring tendon and double-bundle hamstring tendon groups (hazard ratio, 1.18; 95% CI, 0.85-1.62; p = 0.33), but the adjusted hazard ratio showed a lower risk of revision in the single-bundle bone-patellar tendon-bone group compared with the double-bundle group (hazard ratio, 0.62; 95% CI, 0.43-0.90; p = 0.01). Comparisons of the graft revision rates reported separately for each country revealed that double-bundle hamstring tendon reconstructions in Sweden had a lower hazard ratio compared with the single-bundle hamstring tendon reconstructions (hazard ratio, 1.00 versus 1.89; 95% CI, 1.09-3.29; p = 0.02). Survival at 5 years after index surgery was 96.0% for the double-bundle group, 95.4% for the single-bundle hamstring tendon group, and 97.0% for the single-bundle bone-patellar tendon-bone group. Based on the data from all three national registers, the risk of revision was not influenced by the reconstruction technique in terms of using single- or double-bundle hamstring tendons, although national differences in survival existed. Using bone-patellar tendon-bone grafts lowered the risk of revision compared with double-bundle hamstring tendon grafts. These findings should be considered when deciding what reconstruction technique to use in ACL-deficient knees. Future studies identifying the reasons for graft rerupture in single- and double-bundle reconstructions would be of interest to understand the findings of the present study. Level III, therapeutic study.

Heat Transfer Analysis in Wire Bundles for Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Rickman, S. L.; Iamello, C. J.

2016-01-01

Design of wiring for aerospace vehicles relies on an understanding of "ampacity" which refers to the current carrying capacity of wires, either, individually or in wire bundles. Designers rely on standards to derate allowable current flow to prevent exceedance of wire temperature limits due to resistive heat dissipation within the wires or wire bundles. These standards often add considerable margin and are based on empirical data. Commercial providers are taking an aggressive approach to wire sizing which challenges the conventional wisdom of the established standards. Thermal modelling of wire bundles may offer significant mass reduction in a system if the technique can be generalized to produce reliable temperature predictions for arbitrary bundle configurations. Thermal analysis has been applied to the problem of wire bundles wherein any or all of the wires within the bundle may carry current. Wire bundles present analytical challenges because the heat transfer path from conductors internal to the bundle is tortuous, relying on internal radiation and thermal interface conductance to move the heat from within the bundle to the external jacket where it can be carried away by convective and radiative heat transfer. The problem is further complicated by the dependence of wire electrical resistivity on temperature. Reduced heat transfer out of the bundle leads to higher conductor temperatures and, hence, increased resistive heat dissipation. Development of a generalized wire bundle thermal model is presented and compared with test data. The steady state heat balance for a single wire is derived and extended to the bundle configuration. The generalized model includes the effects of temperature varying resistance, internal radiation and thermal interface conductance, external radiation and temperature varying convective relief from the free surface. The sensitivity of the response to uncertainties in key model parameters is explored using Monte Carlo analysis.

78 FR 76987 - Adjustment of Determination of Compulsory License Rates for Mechanical and Digital Phonorecords

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... service bundles, music bundles, paid locker services, and purchased content locker services. The technical... downloads, limited offerings, mixed service bundles, music bundles, paid locker services, and purchased...

Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus

PubMed Central

Sun, Yaping; Zhang, Huaidong; Shi, Jian; Zhang, Zhe; Gong, Rui

2017-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent. PMID:28906430

Targeted sections in either XY or XZ plane with dual-axes confocal endomicroscope (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Gaoming; Li, Haijun; Duan, Xiyu; Zhou, Quan; Zhou, Juan; Oldham, Kenn R.; Wang, Thomas D.

2017-02-01

We demonstrate a dual axes confocal architecture, which can be used to collect horizontal(XY-plane) or vertical cross-sectional(XZ-plane) images for tissue. This scanner head is 5.5mm in outer diameter(OD), and integrates a 3D MEMS scanner with a compact chip size of 3.2×2.9mm2. To realize the miniaturization, there are some obstacles of the small size of 3D MEMS scanner, MEMS wire bundle, the air pressure effect for MEMS motion, the processing of parabolic mirror, and optical alignment to come over. In our probe, separation mechanical structure for optical alignment was adopted and a step shape MEMS holder was designed to deal with the difficult of MEMS wire bundle. Peptides have been demonstrated tremendous potential for in vivo use to detect colonic dysplasia. This class of in vivo molecular probe can be labeled with near-infrared (NIR) dyes for visualizing the full depth of the epithelium in small animals. To confirm our probe performance, we take use of USAF 1951 resolution target to test its lateral and axial resolution. It has lateral and axial resolution of 2.49um and 4.98um, respectively. When we collect the fluorescence imaging of colon, it shows that the field of view are 1000um×1000um (horizontal) and 1000um×430um (vertical). The horizontal and vertical cross-sectional images of fresh mouse colonic mucosa demonstrate imaging performance with this miniature instrument.

Cost-Effectiveness of a Central Venous Catheter Care Bundle

PubMed Central

Halton, Kate A.; Cook, David; Paterson, David L.; Safdar, Nasia; Graves, Nicholas

2010-01-01

Background A bundled approach to central venous catheter care is currently being promoted as an effective way of preventing catheter-related bloodstream infection (CR-BSI). Consumables used in the bundled approach are relatively inexpensive which may lead to the conclusion that the bundle is cost-effective. However, this fails to consider the nontrivial costs of the monitoring and education activities required to implement the bundle, or that alternative strategies are available to prevent CR-BSI. We evaluated the cost-effectiveness of a bundle to prevent CR-BSI in Australian intensive care patients. Methods and Findings A Markov decision model was used to evaluate the cost-effectiveness of the bundle relative to remaining with current practice (a non-bundled approach to catheter care and uncoated catheters), or use of antimicrobial catheters. We assumed the bundle reduced relative risk of CR-BSI to 0.34. Given uncertainty about the cost of the bundle, threshold analyses were used to determine the maximum cost at which the bundle remained cost-effective relative to the other approaches to infection control. Sensitivity analyses explored how this threshold alters under different assumptions about the economic value placed on bed-days and health benefits gained by preventing infection. If clinicians are prepared to use antimicrobial catheters, the bundle is cost-effective if national 18-month implementation costs are below $1.1 million. If antimicrobial catheters are not an option the bundle must cost less than $4.3 million. If decision makers are only interested in obtaining cash-savings for the unit, and place no economic value on either the bed-days or the health benefits gained through preventing infection, these cost thresholds are reduced by two-thirds. Conclusions A catheter care bundle has the potential to be cost-effective in the Australian intensive care setting. Rather than anticipating cash-savings from this intervention, decision makers must be prepared to invest resources in infection control to see efficiency improvements. PMID:20862246

Cost-effectiveness of a central venous catheter care bundle.

PubMed

Halton, Kate A; Cook, David; Paterson, David L; Safdar, Nasia; Graves, Nicholas

2010-09-17

A bundled approach to central venous catheter care is currently being promoted as an effective way of preventing catheter-related bloodstream infection (CR-BSI). Consumables used in the bundled approach are relatively inexpensive which may lead to the conclusion that the bundle is cost-effective. However, this fails to consider the nontrivial costs of the monitoring and education activities required to implement the bundle, or that alternative strategies are available to prevent CR-BSI. We evaluated the cost-effectiveness of a bundle to prevent CR-BSI in Australian intensive care patients. A Markov decision model was used to evaluate the cost-effectiveness of the bundle relative to remaining with current practice (a non-bundled approach to catheter care and uncoated catheters), or use of antimicrobial catheters. We assumed the bundle reduced relative risk of CR-BSI to 0.34. Given uncertainty about the cost of the bundle, threshold analyses were used to determine the maximum cost at which the bundle remained cost-effective relative to the other approaches to infection control. Sensitivity analyses explored how this threshold alters under different assumptions about the economic value placed on bed-days and health benefits gained by preventing infection. If clinicians are prepared to use antimicrobial catheters, the bundle is cost-effective if national 18-month implementation costs are below $1.1 million. If antimicrobial catheters are not an option the bundle must cost less than $4.3 million. If decision makers are only interested in obtaining cash-savings for the unit, and place no economic value on either the bed-days or the health benefits gained through preventing infection, these cost thresholds are reduced by two-thirds. A catheter care bundle has the potential to be cost-effective in the Australian intensive care setting. Rather than anticipating cash-savings from this intervention, decision makers must be prepared to invest resources in infection control to see efficiency improvements.

Adhering to a national surgical care bundle reduces the risk of surgical site infections

PubMed Central

Hopmans, Titia E. M.; Soetens, Loes C.; Wille, Jan C.; Geerlings, Suzanne E.; Vos, Margreet C.; van Benthem, Birgit H. B.; de Greeff, Sabine C.

2017-01-01

Background In 2008, a bundle of care to prevent Surgical Site Infections (SSIs) was introduced in the Netherlands. The bundle consisted of four elements: antibiotic prophylaxis according to local guidelines, no hair removal, normothermia and ‘hygiene discipline’ in the operating room (i.e. number of door movements). Dutch hospitals were advised to implement the bundle and to measure the outcome. This study’s goal was to assess how effective the bundle was in reducing SSI risk. Methods Hospitals assessed whether their staff complied with each of the bundle elements and voluntary reported compliance data to the national SSI surveillance network (PREZIES). From PREZIES data, we selected data from 2009 to 2014 relating to 13 types of surgical procedures. We excluded surgeries with missing (non)compliance data, and calculated for each remaining surgery with reported (non)compliance data the level of compliance with the bundle (that is, being compliant with 0, 1, 2, 3, or 4 of the elements). Subsequently, we used this level of compliance to assess the effect of bundle compliance on the SSI risk, using multilevel logistic regression techniques. Results 217 489 surgeries were included, of which 62 486 surgeries (29%) had complete bundle reporting. Within this group, the SSI risk was significantly lower for surgeries with complete bundle compliance compared to surgeries with lower compliance levels. Odds ratios ranged from 0.63 to 0.86 (risk reduction of 14% to 37%), while a 13% risk reduction was demonstrated for each point increase in compliance-level. Sensitivity analysis indicated that due to analysing reported bundles only, we probably underestimated the total effect of implementing the bundle. Conclusions This study demonstrated that adhering to a surgical care bundle significantly reduced the risk of SSIs. Reporting of and compliance with the bundle compliance can, however, still be improved. Therefore an even greater effect might be achieved. PMID:28877223

Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

PubMed

Wahle, P; Meyer, G

1989-04-08

The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of descending axonal bundles and the density of the layer VI plexus is reduced, but the latter is maintained during adulthood by the two persisting cell types. Two further cell types belong to the first population: The transient bipolar cells of layers IV, V, and VI have long dendrites which extend through the entire cortical width. Their axons always descend, leave the gray matter, and apparently terminate in the upper white matter. The neurons differentiate concurrently with the pseudohorsetail cells at P 4, are very frequent during the following weeks, and eventually disappear at P 30.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed Central

Jen, P Y; Dixon, J S

1995-01-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:7591978

Ab initio density functional theory investigation of electronic properties of semiconducting single-walled carbon nanotube bundles

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Behzad, Somayeh; Azadi, Sam

2008-09-01

By using ab initio density functional theory we investigated the structural and electronic properties of semiconducting (7, 0), (8, 0) and (10, 0) carbon nanotube bundles. The energetic and electronic evolutions of nanotubes in the bundling process are also studied. The effects of inter-tube coupling on the electronic dispersions of semiconducting carbon nanotube bundles are demonstrated. Our results show that the inter-tube coupling decreases the energy gap in semiconducting nanotubes. We found that bundles of (7, 0) and (8, 0) carbon nanotubes have metallic feature, while (10, 0) bundle is a semiconductor with an energy gap of 0.22 eV. To clarify our results the band structures of isolated and bundled nanotubes are compared.

Lexical bundles in an advanced INTOCSU writing class and engineering texts: A functional analysis

NASA Astrophysics Data System (ADS)

Alquraishi, Mohammed Abdulrahman

The purpose of this study is to investigate the functions of lexical bundles in two corpora: a corpus of engineering academic texts and a corpus of IEP advanced writing class texts. This study is concerned with the nature of formulaic language in Pathway IEPs and engineering texts, and whether those types of texts show similar or distinctive formulaic functions. Moreover, the study looked into lexical bundles found in an engineering 1.26 million-word corpus and an ESL 65000-word corpus using a concordancing program. The study then analyzed the functions of those lexical bundles and compared them statistically using chi-square tests. Additionally, the results of this investigation showed 236 unique frequent lexical bundles in the engineering corpus and 37 bundles in the pathway corpus. Also, the study identified several differences between the density and functions of lexical bundles in the two corpora. These differences were evident in the distribution of functions of lexical bundles and the minimal overlap of lexical bundles found in the two corpora. The results of this study call for more attention to formulaic language at ESP and EAP programs.

Biological natural retting for determining the hierarchical structuration of banana fibers.

PubMed

Gañán, Piedad; Zuluaga, Robin; Velez, Juan Manuel; Mondragon, Iñaki

2004-10-20

Extraction processes of natural fibers can be performed by different procedures that include mechanical, chemical and biological methods. Each method presents different advantages or drawbacks according to the amount of fiber produced or the quality and properties of fiber bundles obtained. In this study, biological natural retting was satisfactorily used for obtaining banana fibers from plant bunches. However, the most important contribution of this work refers to the description of the hierarchical microstructural ordering present in banana fiber bundles in both bundle surface and inner region. The chemical composition of banana fiber bundles has been evaluated by FTIR spectroscopy. Through exposure time, the fiber bundle configuration presents small variations in composition. The main changes are related to hemicellulose and pectins as they conform the outer walls of the bundle. Hierarchical helicoidal ordering in the bundle surface as well as orientation on the longitudinal axis of the bundle were observed by optical microscopy (OM) and scanning electron microscopy (SEM) for 3-4 microm surface fibers and 10-15 microm inner elementary fibers, respectively. With increasing exposure time, fiber bundle walls lose integrity, as reflected in their mechanical behavior.

Stimulation of hair cells with ultraviolet light

NASA Astrophysics Data System (ADS)

Azimzadeh, Julien B.; Fabella, Brian A.; Hudspeth, A. J.

2018-05-01

Hair bundles are specialized organelles that transduce mechanical inputs into electrical outputs. To activate hair cells, physiologists have resorted to mechanical methods of hair-bundle stimulation. Here we describe a new method of hair-bundle stimulation, irradiation with ultraviolet light. A hair bundle illuminated by ultraviolet light rapidly moves towards its tall edge, a motion typically associated with excitatory stimulation. The motion disappears upon tip-link rupture and is associated with the opening of mechanotransduction channels. Hair bundles can be induced to move sinusoidally with oscillatory modulation of the stimulation power. We discuss the implications of ultraviolet stimulation as a novel hair-bundle stimulus.

Formation and structural organization of the egg-sperm bundle of the scleractinian coral Montipora capitata

NASA Astrophysics Data System (ADS)

Padilla-Gamiño, J. L.; Weatherby, T. M.; Waller, R. G.; Gates, R. D.

2011-06-01

The majority of scleractinian corals are hermaphrodites that broadcast spawn their gametes separately or packaged as egg-sperm bundles during spawning events that are timed to the lunar cycle. The egg-sperm bundle is an efficient way of transporting gametes to the ocean surface where fertilization takes place, while minimizing sperm dilution and maximizing the opportunity for gamete encounters during a spawning event. To date, there are few studies that focus on the formation and structure of egg-sperm bundle. This study explores formation, ultrastructure, and longevity of the egg-sperm bundle in Montipora capitata, a major reef building coral in Hawai`i. Our results show that the egg-sperm bundle is formed by a mucus layer secreted by the oocytes. The sperm package is located at the center of each bundle, possibly reflecting the development of male and female gametes in different mesenteries. Once the egg-sperm bundle has reached the ocean surface, it breaks open within 10-35 min, depending on the environmental conditions (i.e., wind, water turbulence). Although the bundle has an ephemeral life span, the formation of an egg-sperm bundle is a fundamental part of the reproductive process that could be strongly influenced by climate change and deterioration of water quality (due to anthropogenic effects) and thus requires further investigation.

Robust Mapping of Incoherent Fiber-Optic Bundles

NASA Technical Reports Server (NTRS)

Roberts, Harry E.; Deason, Brent E.; DePlachett, Charles P.; Pilgrim, Robert A.; Sanford, Harold S.

2007-01-01

A method and apparatus for mapping between the positions of fibers at opposite ends of incoherent fiber-optic bundles have been invented to enable the use of such bundles to transmit images in visible or infrared light. The method is robust in the sense that it provides useful mapping even for a bundle that contains thousands of narrow, irregularly packed fibers, some of which may be defective. In a coherent fiber-optic bundle, the input and output ends of each fiber lie at identical positions in the input and output planes; therefore, the bundle can be used to transmit images without further modification. Unfortunately, the fabrication of coherent fiber-optic bundles is too labor-intensive and expensive for many applications. An incoherent fiber-optic bundle can be fabricated more easily and at lower cost, but it produces a scrambled image because the position of the end of each fiber in the input plane is generally different from the end of the same fiber in the output plane. However, the image transmitted by an incoherent fiber-optic bundle can be unscrambled (or, from a different perspective, decoded) by digital processing of the output image if the mapping between the input and output fiber-end positions is known. Thus, the present invention enables the use of relatively inexpensive fiber-optic bundles to transmit images.

A compressed sensing approach for resolution improvement in fiber-bundle based endomicroscopy

NASA Astrophysics Data System (ADS)

Dumas, John P.; Lodhi, Muhammad A.; Bajwa, Waheed U.; Pierce, Mark C.

2018-02-01

Endomicroscopy techniques such as confocal, multi-photon, and wide-field imaging have all been demonstrated using coherent fiber-optic imaging bundles. While the narrow diameter and flexibility of fiber bundles is clinically advantageous, the number of resolvable points in an image is conventionally limited to the number of individual fibers within the bundle. We are introducing concepts from the compressed sensing (CS) field to fiber bundle based endomicroscopy, to allow images to be recovered with more resolvable points than fibers in the bundle. The distal face of the fiber bundle is treated as a low-resolution sensor with circular pixels (fibers) arranged in a hexagonal lattice. A spatial light modulator is located conjugate to the object and distal face, applying multiple high resolution masks to the intermediate image prior to propagation through the bundle. We acquire images of the proximal end of the bundle for each (known) mask pattern and then apply CS inversion algorithms to recover a single high-resolution image. We first developed a theoretical forward model describing image formation through the mask and fiber bundle. We then imaged objects through a rigid fiber bundle and demonstrate that our CS endomicroscopy architecture can recover intra-fiber details while filling inter-fiber regions with interpolation. Finally, we examine the relationship between reconstruction quality and the ratio of the number of mask elements to the number of fiber cores, finding that images could be generated with approximately 28,900 resolvable points for a 1,000 fiber region in our platform.

Understanding nurses' views on a pressure ulcer prevention care bundle: a first step towards successful implementation.

PubMed

Chaboyer, Wendy; Gillespie, Brigid M

2014-12-01

To explore nurses' views of the barriers and facilitators to the use of a newly devised patient-centred pressure ulcer prevention care bundle. Given pressure ulcer prevention strategies are not implemented consistently, the use of a pressure ulcer care bundle may improve implementation given bundles generally assist in standardising care. A quality improvement project was undertaken after a pressure ulcer prevention care bundle was developed and pilot-tested. Short, conversational interviews with nurse explored their views of a patient-centred pressure ulcer care bundle. Interviews were audio-taped and transcribed. Inductive content analysis was used to analyse the transcripts. A total of 20 nurses were interviewed. Five categories with corresponding subcategories emerged from the analysis. They were increasing awareness of pressure ulcer prevention, prompting pressure ulcer prevention activities, promoting active patient participation, barriers to using a pressure ulcer prevention care bundle and enabling integration of the pressure ulcer prevention care bundle into routine practice. Benefits of using a patient-centred pressure ulcer prevention care bundle may include prompting patients and staff to implement prevention strategies and promote active patient participation in care. The success of the care bundle relied on both patients' willingness to participate and nurses' willingness to incorporate it into their routine work. A patient-centred pressure ulcer prevention care bundle may facilitate more consistent implementation of pressure ulcer prevention strategies and active patient participation in care. © 2014 John Wiley & Sons Ltd.

Swell Gels to Dumbbell Micelles: Construction of Materials and Nanostructure with Self-assembly

NASA Astrophysics Data System (ADS)

Pochan, Darrin

2007-03-01

Bionanotechnology, the emerging field of using biomolecular and biotechnological tools for nanostructure or nanotecnology development, provides exceptional opportunity in the design of new materials. Self-assembly of molecules is an attractive materials construction strategy due to its simplicity in application. By considering peptidic or charged synthetic polymer molecules in the bottom-up materials self-assembly design process, one can take advantage of inherently biomolecular attributes; intramolecular folding events, secondary structure, and electrostatic interactions; in addition to more traditional self-assembling molecular attributes such as amphiphilicty, to define hierarchical material structure and consequent properties. Several molecular systems will be discussed. Synthetic block copolymers with charged corona blocks can be assembled in dilute solution containing multivalent organic counterions to produce micelle structures such as toroids. These ring-like micelles are similar to the toroidal bundling of charged semiflexible biopolymers like DNA in the presence of multivalent counterions. Micelle structure can be tuned between toroids, cylinders, and disks simply by using different concentrations or molecular volumes of organic counterion. In addition, these charged blocks can consist of amino acids as monomers producing block copolypeptides. In addition to the above attributes, block copolypeptides provide the control of block secondary structure to further control self-assembly. Design strategies based on small (less than 24 amino acids) beta-hairpin peptides will be discussed. Self-assembly of the peptides is predicated on an intramolecular folding event caused by desired solution properties. Importantly, the intramolecular folding event impart a molecular-level mechanism for environmental responsiveness at the material level (e.g. infinite change in viscosity of a solution to a gel with changes in pH, ionic strength, temperature).

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion.

PubMed

Mahajan, Mukesh; Chatterjee, Deepak; Bhuvaneswari, Kannaian; Pillay, Shubhadra; Bhattacharjya, Surajit

2018-02-01

The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15 N{ 1 H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanical Overstimulation of Hair Bundles: Suppression and Recovery of Active Motility

PubMed Central

Kao, Albert; Meenderink, Sebastiaan W. F.; Bozovic, Dolores

2013-01-01

We explore the effects of high-amplitude mechanical stimuli on hair bundles of the bullfrog sacculus. Under in vitro conditions, these bundles exhibit spontaneous limit cycle oscillations. Prolonged deflection exerted two effects. First, it induced an offset in the position of the bundle. Recovery to the original position displayed two distinct time scales, suggesting the existence of two adaptive mechanisms. Second, the stimulus suppressed spontaneous oscillations, indicating a change in the hair bundle’s dynamic state. After cessation of the stimulus, active bundle motility recovered with time. Both effects were dependent on the duration of the imposed stimulus. External calcium concentration also affected the recovery to the oscillatory state. Our results indicate that both offset in the bundle position and calcium concentration control the dynamic state of the bundle. PMID:23505461

Influence of knee flexion angle and transverse drill angle on creation of femoral tunnels in double-bundle anterior cruciate ligament reconstruction using the transportal technique: Three-dimensional computed tomography simulation analysis.

PubMed

Choi, Chong Hyuk; Kim, Sung-Jae; Chun, Yong-Min; Kim, Sung-Hwan; Lee, Su-Keon; Eom, Nam-Kyu; Jung, Min

2018-01-01

The purpose of this study was to find appropriate flexion angle and transverse drill angle for optimal femoral tunnels of anteromedial (AM) bundle and posterolateral (PL) bundle in double-bundle ACL reconstruction using transportal technique. Thirty three-dimensional knee models were reconstructed. Knee flexion angles were altered from 100° to 130° at intervals of 10°. Maximum transverse drill angle (MTA), MTA minus 10° and 20° were set up. Twelve different tunnels were determined by four flexion angles and three transverse drill angles for each bundle. Tunnel length, wall breakage, inter-tunnel communication and graft-bending angle were assessed. Mean tunnel length of AM bundle was >30mm at 120° and 130° of flexion in all transverse drill angles. Mean tunnel length of PL bundle was >30mm during every condition. There were ≥1 cases of wall breakage except at 120° and 130° of flexion with MTA for AM bundle. There was no case of wall breakage for PL bundle. Considering inter-tunnel gap of >2mm without communication and obtuse graft-bending angle, 120° of flexion and MTA could be recommended as optimal condition for femoral tunnels of AM and PL bundles. Flexion angle and transverse drill angle had combined effect on femoral tunnel in double-bundle ACL reconstruction using transportal technique. Achieving flexion angle of 120° and transverse drill angle close to the medial femoral condyle could be recommended as optimal condition for femoral tunnels of AM and PL bundles to avoid insufficient tunnel length, wall breakage, inter-tunnel communication and acute graft-bending angle. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Hughes, Michael John; McConnaughhay, Johnie Franklin

A combustor includes a tube bundle that extends radially across at least a portion of the combustor. The tube bundle includes an upstream surface axially separated from a downstream surface, and a plurality of tubes extend from the upstream surface through the downstream surface to provide fluid communication through the tube bundle. A barrier extends radially inside the tube bundle between the upstream and downstream surfaces, and a baffle extends axially inside the tube bundle between the upstream surface and the barrier.

Sampling system and method

DOEpatents

Decker, David L; Lyles, Brad F; Purcell, Richard G; Hershey, Ronald Lee

2014-05-20

An apparatus and method for supporting a tubing bundle during installation or removal. The apparatus includes a clamp for securing the tubing bundle to an external wireline. The method includes deploying the tubing bundle and wireline together, The tubing bundle is periodically secured to the wireline using a clamp.

Fiber-bundle-basis sparse reconstruction for high resolution wide-field microendoscopy.

PubMed

Mekhail, Simon Peter; Abudukeyoumu, Nilupaer; Ward, Jonathan; Arbuthnott, Gordon; Chormaic, Síle Nic

2018-04-01

In order to observe deep regions of the brain, we propose the use of a fiber bundle for microendoscopy. Fiber bundles allow for the excitation and collection of fluorescence as well as wide field imaging while remaining largely impervious to image distortions brought on by bending. Furthermore, their thin diameter, from 200-500 µ m, means their impact on living tissue, though not absent, is minimal. Although wide field imaging with a bundle allows for a high temporal resolution since no scanning is involved, the largest criticism of bundle imaging is the drastically lowered spatial resolution. In this paper, we make use of sparsity in the object being imaged to up sample the low resolution images from the fiber bundle with compressive sensing. We take each image in a single shot by using a measurement basis dictated by the quasi-crystalline arrangement of the bundle's cores. We find that this technique allows us to increase the resolution of a typical image taken through a fiber bundle.

Equilibrium polyelectrolyte bundles with different multivalent counterion concentrations

NASA Astrophysics Data System (ADS)

Sayar, Mehmet; Holm, Christian

2010-09-01

We present the results of molecular-dynamics simulations on the salt concentration dependence of the formation of polyelectrolyte bundles in thermodynamic equilibrium. Extending our results on salt-free systems we investigate here deficiency or excess of trivalent counterions in solution. Our results reveal that the trivalent counterion concentration significantly alters the bundle size and size distribution. The onset of bundle formation takes place at earlier Bjerrum length values with increasing trivalent counterion concentration. For the cases of 80%, 95%, and 100% charge compensation via trivalent counterions, the net charge of the bundles decreases with increasing size. We suggest that competition among two different mechanisms, counterion condensation and merger of bundles, leads to a nonmonotonic change in line-charge density with increasing Bjerrum length. The investigated case of having an abundance of trivalent counterions by 200% prohibits such a behavior. In this case, we find that the difference in effective line-charge density of different size bundles diminishes. In fact, the system displays an isoelectric point, where all bundles become charge neutral.

Overhead electric power transmission line jumpering system for bundles of five or more subconductors

DOEpatents

Winkelman, Paul F.

1982-01-01

Jumpering of electric power transmission lines at a dead end tower. Two transmission line conductor bundles each contain five or more spaced apart subconductors (5) arranged in the shape of a cylinder having a circular cross section. The ends of each bundle of subconductors are attached with insulators to a dead end tower (1). Jumpering allows the electric current to flow between the two bundles of subconductors using jumper buses, internal jumper conductors, and external jumper conductors. One or more current collecting jumper buses (37) are located inside each bundle of subconductors with each jumper bus being attached to the end of a subconductor. Small-diameter internal jumper conductors (33) are located in the inherently electrically shielded area inside each bundle of subconductors with each subconductor (except ones having an attached jumper bus) having one internal jumper conductor connected between that subconductor's end and a jumper bus. Large-diameter external jumper conductors (9) are located outside each bundle of subconductors with one or more external jumper conductors being connected between the jumper buses in one bundle of subconductors and the jumper buses in the other bundle.

Comparison of computational results of the SABRE LMFBR pin bundle blockage code with data from well-instrumented out-of-pile test bundles (THORS bundles 3A and 5A)

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

Dearing, J.F.

The Subchannel Analysis of Blockages in Reactor Elements (SABRE) computer code, developed by the United Kingdom Atomic Energy Authority, is currently the only practical tool available for performing detailed analyses of velocity and temperature fields in the recirculating flow regions downstream of blockages in liquid-metal fast breeder reactor (LMFBR) pin bundles. SABRE is a subchannel analysis code; that is, it accurately represents the complex geometry of nuclear fuel pins arranged on a triangular lattice. The results of SABRE computational models are compared here with temperature data from two out-of-pile 19-pin test bundles from the Thermal-Hydraulic Out-of-Reactor Safety (THORS) Facility atmore » Oak Ridge National Laboratory. One of these bundles has a small central flow blockage (bundle 3A), while the other has a large edge blockage (bundle 5A). Values that give best agreement with experiment for the empirical thermal mixing correlation factor, FMIX, in SABRE are suggested. These values of FMIX are Reynolds-number dependent, however, indicating that the coded turbulent mixing correlation is not appropriate for wire-wrap pin bundles.« less

Characterization of midrib vascular bundles of selected medicinal species in Rubiaceae

NASA Astrophysics Data System (ADS)

Nurul-Syahirah, M.; Noraini, T.; Latiff, A.

2016-11-01

An anatomical study was carried out on mature leaves of five selected medicinal species of Rubiaceae from Peninsular Malaysia. The chosen medicinal species were Aidia densiflora, Aidia racemosa, Chasallia chartacea, Hedyotis auricularia and Ixora grandifolia. The objective of this study is to determine the taxonomic value of midrib anatomical characteristics. Leaves samples were collected from Taman Paku Pakis, Universiti Kebangsaan Malaysia, Bangi, Selangor and Kledang Saiong Forest Reserve, Perak, Malaysia. Leaves samples then were fixed in spirit and acetic acid (3:1), the midrib parts then were sectioned using sliding microtome, cleared using Clorox, stained in Safranin and Alcian blue, mounted in Euparal and were observed under light microscope. Findings in this study have shown all species have collateral bundles. The midrib vascular bundles characteristics that can be used as tool to differentiate between species or genus are vascular bundles system (opened or closed), shape and arrangement of main vascular bundles, presence of both additional and medullary vascular bundles, position of additional vascular bundles, shape of medullary vascular bundles, presence of sclerenchyma cells ensheathed the vascular bundles. As a conclusion, midrib anatomical characteristics can be used to identify and discriminate medicinal plants species studied in the Rubiaceae.

Biomimetic virus-based colourimetric sensors.

PubMed

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

Biomimetic virus-based colourimetric sensors

NASA Astrophysics Data System (ADS)

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

Gating Topology of the Proton-Coupled Oligopeptide Symporters

PubMed Central

Fowler, Philip W.; Orwick-Rydmark, Marcella; Radestock, Sebastian; Solcan, Nicolae; Dijkman, Patricia M.; Lyons, Joseph A.; Kwok, Jane; Caffrey, Martin; Watts, Anthony; Forrest, Lucy R.; Newstead, Simon

2015-01-01

Summary Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. Recent crystal structures suggest the MFS fold facilitates transport through rearrangement of their two six-helix bundles around a central ligand binding site; how this is achieved, however, is poorly understood. Using modeling, molecular dynamics, crystallography, functional assays, and site-directed spin labeling combined with double electron-electron resonance (DEER) spectroscopy, we present a detailed study of the transport dynamics of two bacterial oligopeptide transporters, PepTSo and PepTSt. Our results identify several salt bridges that stabilize outward-facing conformations and we show that, for all the current structures of MFS transporters, the first two helices of each of the four inverted-topology repeat units form half of either the periplasmic or cytoplasmic gate and that these function cooperatively in a scissor-like motion to control access to the peptide binding site during transport. PMID:25651061

Evidence for two populations of hair bundles in the sea anemone, Nematostella vectensis.

PubMed

Menard, Shelcie S; Watson, Glen M

2017-06-01

Cytochalasin D (CD) was employed to disrupt F-actin within stereocilia of anemone hair bundles. CD treatment decreases the abundance of hair bundles (by 85%) while significantly impairing predation. The remaining hair bundles are 'CD-resistant.' Surprisingly, the morphology and F-actin content of resistant hair bundles are comparable to those of untreated controls. However, the resistant hair bundles fail to respond normally to the N-acetylated sugar, NANA, by elongating. Instead, they remain at resting length. Immediately after CD treatment, when only CD-resistant hair bundles are present, nematocyst discharge is normal into targets touched to tentacles in the absence of vibrations (i.e., baseline) but fails to increase normally in the presence of nearby vibrations at 56Hz, a key frequency. After CD treatment, the abundance of hair bundles recovers to control levels within three hours. At 2h after CD treatment, when CD-resistant and CD-sensitive hair bundles are both present, but a full-recovery is not yet complete, somewhat enhanced discharge of nematocysts occurs into targets touched to tentacles in the presence of nearby vibrations at 56Hz (at least as compared to the response of CD-treated animals to contact with test probes in the absence of vibrations). Additionally, at 2h after CD-treatment, prey capture recovers to normal. Thus, two populations of hair bundles may be present on tentacles of sea anemones: those that are CD-resistant and those that are CD-sensitive. The functions of these hair bundles may be distinct. Copyright © 2017 Elsevier Inc. All rights reserved.

Translating Pressure Ulcer Prevention Into Intensive Care Nursing Practice: Overlaying a Care Bundle Approach With a Model for Research Implementation.

PubMed

Tayyib, Nahla; Coyer, Fiona

This article reports on the development and implementation process used to integrate a care bundle approach (a pressure ulcer [PU] prevention bundle to improve patients' skin integrity in intensive care) and the Ottawa Model of Research Use (OMRU). The PU prevention care bundle demonstrated significant reduction in PU incidence, with the OMRU model providing a consolidated framework for the implementation of bundled evidence in an effective and consistent manner into daily clinical nursing practice.

Localized Statistics for DW-MRI Fiber Bundle Segmentation

PubMed Central

Lankton, Shawn; Melonakos, John; Malcolm, James; Dambreville, Samuel; Tannenbaum, Allen

2013-01-01

We describe a method for segmenting neural fiber bundles in diffusion-weighted magnetic resonance images (DWMRI). As these bundles traverse the brain to connect regions, their local orientation of diffusion changes drastically, hence a constant global model is inaccurate. We propose a method to compute localized statistics on orientation information and use it to drive a variational active contour segmentation that accurately models the non-homogeneous orientation information present along the bundle. Initialized from a single fiber path, the proposed method proceeds to capture the entire bundle. We demonstrate results using the technique to segment the cingulum bundle and describe several extensions making the technique applicable to a wide range of tissues. PMID:23652079

Field Emission Study of Carbon Nanotubes: High Current Density from Nanotube Bundle Arrays

NASA Technical Reports Server (NTRS)

Bronikowski, Micheal J.; Manohara, Harish M.; Siegel, Peter H.; Hunt, Brian D.

2004-01-01

We have investigated the field emission behavior of lithographically patterned bundles of multiwalled carbon nanotubes arranged in a variety of array geometries. Such arrays of nanotube bundles are found to perform significantly better in field emission than arrays of isolated nanotubes or dense, continuous mats of nanotubes, with the field emission performance depending on the bundle diameter and inter-bundle spacing. Arrays of 2-micrometers diameter nanotube bundles spaced 5 micrometers apart (edge-to-edge spacing) produced the largest emission densities, routinely giving 1.5 to 1.8 A/cm(sup 2) at approximately 4 V/micrometer electric field, and greater than 6 A/cm(sup 2) at 20 V/micrometers.

National Partnership for Maternal Safety: Consensus Bundle on Safe Reduction of Primary Cesarean Births-Supporting Intended Vaginal Births.

PubMed

Lagrew, David C; Low, Lisa Kane; Brennan, Rita; Corry, Maureen P; Edmonds, Joyce K; Gilpin, Brian G; Frost, Jennifer; Pinger, Whitney; Reisner, Dale P; Jaffer, Sara

2018-03-01

Cesarean births and associated morbidity and mortality have reached near epidemic proportions. The National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care responded by developing a patient safety bundle to reduce the number of primary cesarean births. Safety bundles outline critical practices to implement in every maternity unit. This National Partnership for Maternity Safety bundle, as with other bundles, is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Bundle components may be adapted to individual facilities, but standardization within an institution is advised. Evidence-based resources and recommendations are provided to assist implementation.

Matrix remodeling between cells and cellular interactions with collagen bundle

NASA Astrophysics Data System (ADS)

Kim, Jihan; Sun, Bo

When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction With a Free Quadriceps Tendon Autograft.

PubMed

Caterev, Sergiu; Nistor, Dan Viorel; Todor, Adrian

2016-10-01

Anatomic double-bundle anterior cruciate ligament (ACL) reconstruction aims to restore the 2 functional bundles of the ACL in an attempt to better reproduce the native biomechanics of the injured knee and promote long-term knee health. However, this concept is not fully accepted and is not performed on a standard basis. In addition, the superiority of this technique over the conventional single-bundle technique has been questioned, especially the long-term clinical results. One of the down sides of the double-bundle reconstruction is the complexity of the procedure, with increased risks, operative time, and costs compared with the single-bundle procedure. Also, the revision procedure, if necessary, is more challenging. We propose a technique that has some advantages over the traditional double-bundle procedure, using a single femoral tunnel, 2 tibial tunnels, and a free quadriceps tendon autograft.

Synchronization of Spontaneous Active Motility of Hair Cell Bundles

PubMed Central

Zhang, Tracy-Ying; Ji, Seung; Bozovic, Dolores

2015-01-01

Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID:26540409

Exploring Differential Bundle Functioning in Mathematics by Gender: The Effect of Hierarchical Modelling

ERIC Educational Resources Information Center

Ong, Yoke Mooi; Williams, Julian; Lamprianou, Iasonas

2013-01-01

Researchers interested in exploring substantive group differences are increasingly attending to bundles of items (or testlets): the aim is to understand how gender differences, for instance, are explained by differential performances on different types or bundles of items, hence differential bundle functioning (DBF). Some previous work has…

Universal fiber-optic C.I.E. colorimeter

DOEpatents

Kronberg, James W.

1992-01-01

Apparatus for color measurements according to the C.I.E. system comprises a first fiber optic cable for receiving and linearizing light from a light source, a lens system for spectrally displaying the linearized light and focusing the light on one end of a trifurcated fiber optic assembly that integrates and separates the light according to the three C.I.E. tristimulus functions. The separated light is received by three photodiodes and electronically evaluated to determine the magnitude of the light corresponding to the tristimulus functions. The fiber optic assembly is made by forming, at one end, a bundle of optic fibers to match the contours of one of the tristimulus functions, encapsulating that bundle, adding a second bundle that, together with the first bundle, will match the contours of the first plus one other tristimulus function, encapsulating that second bundle, then adding a third bundle which together with the first and second bundles, has contours matching the sum of all three tristimulus functions. At the other end of the assembly the three bundles are separated and aligned with their respective photodiodes.

Implementing a Daily Maintenance Care Bundle to Prevent Central Line-Associated Bloodstream Infections in Pediatric Oncology Patients.

PubMed

Duffy, Elizabeth A; Rodgers, Cheryl C; Shever, Leah L; Hockenberry, Marilyn J

2015-01-01

Eliminating central line-associated bloodstream infection (CLABSI) is a national priority. Central venous catheter (CVC) care bundles are composed of a series of interventions that, when used together, are effective in preventing CLABSI. A CVC daily maintenance care bundle includes procedural guidelines for hygiene, dressing changes, and access as well as specific timeframes. Failure to complete one of the components of the care bundle predisposes the patient to a bloodstream infection. A nurse-led multidisciplinary team implemented and, for six months, sustained a daily maintenance care bundle for pediatric oncology patients. This quality improvement project focused on nursing staffs' implementation of the daily maintenance care bundle and the sustainment of the intervention. The project used a pre-post program design to evaluate outcomes of CVC daily maintenance care bundle compliancy and CLABSI. A statistically significant increase between the pre- and post-assessments of the compliance was noted with the CVC daily maintenance care bundle. CLABSI infection rates decreased during the intervention. Strategies to implement practice change and promote sustainability are discussed. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period.

PubMed

Bernstein, Peter S; Martin, James N; Barton, John R; Shields, Laurence E; Druzin, Maurice L; Scavone, Barbara M; Frost, Jennifer; Morton, Christine H; Ruhl, Catherine; Slager, Joan; Tsigas, Eleni Z; Jaffer, Sara; Menard, M Kathryn

2017-08-01

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

Microtubule bundling plays a role in ethylene-mediated cortical microtubule reorientation in etiolated Arabidopsis hypocotyls.

PubMed

Ma, Qianqian; Sun, Jingbo; Mao, Tonglin

2016-05-15

The gaseous hormone ethylene is known to regulate plant growth under etiolated conditions (the 'triple response'). Although organization of cortical microtubules is essential for cell elongation, the underlying mechanisms that regulate microtubule organization by hormone signaling, including ethylene, are ambiguous. In the present study, we demonstrate that ethylene signaling participates in regulation of cortical microtubule reorientation. In particular, regulation of microtubule bundling is important for this process in etiolated hypocotyls. Time-lapse analysis indicated that selective stabilization of microtubule-bundling structures formed in various arrays is related to ethylene-mediated microtubule orientation. Bundling events and bundle growth lifetimes were significantly increased in oblique and longitudinal arrays, but decreased in transverse arrays in wild-type cells in response to ethylene. However, the effects of ethylene on microtubule bundling were partially suppressed in a microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests that modulation of microtubule bundles that have formed in certain orientations plays a role in reorienting microtubule arrays in response to ethylene-mediated etiolated hypocotyl cell elongation. © 2016. Published by The Company of Biologists Ltd.

Abnormal Q waves in right sided chest leads provoked by onset of right bundle-branch block in patients with anteroseptal infarction.

PubMed Central

Rosenbaum, M B; Girotti, L A; Lázzari, J O; Halpern, M S; Elizari, M V

1982-01-01

In five cases of anteroseptal myocardial infarction complicated by intermittent right bundle-branch block, the onset of right bundle-branch block provoked the appearance of abnormal Q waves in leads V1 and V2, whereas a small initial R wave was present in the same leads during normal conduction. The intermittency of the conduction disturbance indicated that the Q waves were "right bundle-branch block dependent". It was also apparent that right bundle-branch block shifted the electrical location of the infarct towards the right, and made it look much larger. Right bundle-branch block dependent Q waves may arise during the acute stage of an anterior infarct suggesting, fallaciously, that an acute extension has occurred, or during the chronic stage, leading to the erroneous supposition that a new infarct had developed. The abnormal Q waves anteroseptal infarction complicated by fixed right bundle-branch block, though obviously related to the infarct, may be dependent on the right bundle-branch block. PMID:7059400

Actin-binding proteins sensitively mediate F-actin bundle stiffness

NASA Astrophysics Data System (ADS)

Claessens, Mireille M. A. E.; Bathe, Mark; Frey, Erwin; Bausch, Andreas R.

2006-09-01

Bundles of filamentous actin (F-actin) form primary structural components of a broad range of cytoskeletal processes including filopodia, sensory hair cell bristles and microvilli. Actin-binding proteins (ABPs) allow the cell to tailor the dimensions and mechanical properties of the bundles to suit specific biological functions. Therefore, it is important to obtain quantitative knowledge on the effect of ABPs on the mechanical properties of F-actin bundles. Here we measure the bending stiffness of F-actin bundles crosslinked by three ABPs that are ubiquitous in eukaryotes. We observe distinct regimes of bundle bending stiffness that differ by orders of magnitude depending on ABP type, concentration and bundle size. The behaviour observed experimentally is reproduced quantitatively by a molecular-based mechanical model in which ABP shearing competes with F-actin extension/compression. Our results shed new light on the biomechanical function of ABPs and demonstrate how single-molecule properties determine mesoscopic behaviour. The bending mechanics of F-actin fibre bundles are general and have implications for cytoskeletal mechanics and for the rational design of functional materials.

Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell.

PubMed

Martin, P; Mehta, A D; Hudspeth, A J

2000-10-24

Hearing and balance rely on the ability of hair cells in the inner ear to sense miniscule mechanical stimuli. In each cell, sound or acceleration deflects the mechanosensitive hair bundle, a tuft of rigid stereocilia protruding from the cell's apical surface. By altering the tension in gating springs linked to mechanically sensitive transduction channels, this deflection changes the channels' open probability and elicits an electrical response. To detect weak stimuli despite energy losses caused by viscous dissipation, a hair cell can use active hair-bundle movement to amplify its mechanical inputs. This amplificatory process also yields spontaneous bundle oscillations. Using a displacement-clamp system to measure the mechanical properties of individual hair bundles from the bullfrog's ear, we found that an oscillatory bundle displays negative slope stiffness at the heart of its region of mechanosensitivity. Offsetting the hair bundle's position activates an adaptation process that shifts the region of negative stiffness along the displacement axis. Modeling indicates that the interplay between negative bundle stiffness and the motor responsible for mechanical adaptation produces bundle oscillation similar to that observed. Just as the negative resistance of electrically excitable cells and of tunnel diodes can be embedded in a biasing circuit to amplify electrical signals, negative stiffness can be harnessed to amplify mechanical stimuli in the ear.

Influence of fiber packing structure on permeability

NASA Technical Reports Server (NTRS)

Cai, Zhong; Berdichevsky, Alexander L.

1993-01-01

The study on the permeability of an aligned fiber bundle is the key building block in modeling the permeability of advanced woven and braided preforms. Available results on the permeability of fiber bundles in the literature show that a substantial difference exists between numerical and analytical calculations on idealized fiber packing structures, such as square and hexagonal packing, and experimental measurements on practical fiber bundles. The present study focuses on the variation of the permeability of a fiber bundle under practical process conditions. Fiber bundles are considered as containing openings and fiber clusters within the bundle. Numerical simulations on the influence of various openings on the permeability were conducted. Idealized packing structures are used, but with introduced openings distributed in different patterns. Both longitudinal and transverse flow are considered. The results show that openings within the fiber bundle have substantial effect on the permeability. In the longitudinal flow case, the openings become the dominant flow path. In the transverse flow case, the fiber clusters reduce the gap sizes among fibers. Therefore the permeability is greatly influenced by these openings and clusters, respectively. In addition to the porosity or fiber volume fraction, which is commonly used in the permeability expression, another fiber bundle status parameter, the ultimate fiber volume fraction, is introduced to capture the disturbance within a fiber bundle.

Monoubiquitination Inhibits the Actin Bundling Activity of Fascin*

PubMed Central

Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

2016-01-01

Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys247 and Lys250, two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC50, delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. PMID:27879315

Accuracy of Shack-Hartmann wavefront sensor using a coherent wound fibre image bundle

NASA Astrophysics Data System (ADS)

Zheng, Jessica R.; Goodwin, Michael; Lawrence, Jon

2018-03-01

Shack-Hartmannwavefront sensors using wound fibre image bundles are desired for multi-object adaptive optical systems to provide large multiplex positioned by Starbugs. The use of a large-sized wound fibre image bundle provides the flexibility to use more sub-apertures wavefront sensor for ELTs. These compact wavefront sensors take advantage of large focal surfaces such as the Giant Magellan Telescope. The focus of this paper is to study the wound fibre image bundle structure defects effect on the centroid measurement accuracy of a Shack-Hartmann wavefront sensor. We use the first moment centroid method to estimate the centroid of a focused Gaussian beam sampled by a simulated bundle. Spot estimation accuracy with wound fibre image bundle and its structure impact on wavefront measurement accuracy statistics are addressed. Our results show that when the measurement signal-to-noise ratio is high, the centroid measurement accuracy is dominated by the wound fibre image bundle structure, e.g. tile angle and gap spacing. For the measurement with low signal-to-noise ratio, its accuracy is influenced by the read noise of the detector instead of the wound fibre image bundle structure defects. We demonstrate this both with simulation and experimentally. We provide a statistical model of the centroid and wavefront error of a wound fibre image bundle found through experiment.

Spatial confinement of active microtubule networks induces large-scale rotational cytoplasmic flow

PubMed Central

Suzuki, Kazuya; Miyazaki, Makito; Takagi, Jun; Itabashi, Takeshi; Ishiwata, Shin’ichi

2017-01-01

Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow. PMID:28265076

Reducing hospital-acquired pressure ulcers using bundle methodology in pediatric and neonatal patients receiving extracorporeal membrane oxygenation therapy: An integrative review and call to action.

PubMed

Courtwright, Suzanne E; Mastro, Kari A; Preuster, Christa; Dardashti, Navid; McGill, Sandra; Madelon, Myrlene; Johnson, Donna

2017-10-01

This review focuses on identifying (1) evidence of the effectiveness of care bundle methodology to reduce hospital-acquired pressure ulcers (HAPUs) in pediatric and neonatal patients receiving extracorporeal membrane oxygenation (ECMO) therapy and (2) barriers to implementing HAPU care bundles in this at-risk population. An integrative review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the scientific literature was performed. Studies included were published between January 2011 and February 2016. A total of seven articles met inclusion criteria. Data were extracted from each published article and analyzed to identify common themes, specifically bundle methodology and barriers to implementing HAPU bundles, in this population. There is limited research on effectiveness of care bundle methodology in reducing HAPUs in children, and no research specific to its effectiveness in pediatric or neonatal ECMO patients. No research was identified studying barriers to implementation of HAPU care bundles in this population. Nurses are well poised to test innovative strategies to prevent HAPUs. Nurses should consider implementing and testing bundle methodology to reduce HAPU in this at-risk population, and conduct research to identify any barriers to implementing this strategy. There is literature to support the use of nurses as unit-based skin care champions to facilitate teamwork and reliable use of the bundle, both critical components to the success of bundle methodology. © 2017 Wiley Periodicals, Inc.

[Substance P and/or calcitonin gene-related peptide immunoreactive neurons in dorsal root ganglia possibly involved in the transmission of nociception in rat penile frenulum].

PubMed

Wu, Zhong-Min; Ni, Jing-Jing; Ling, Shu-Cai

2007-12-01

To study the relationship between substance P (SP) and/or calcitonin gene-related peptide (CGRP) immunoreactive neurons in dorsal root ganglia (DRG) and the transmission of nociception in the penile frenulum of rats. The fluoro-gold (FG) retrograde tracing method was used to trace the origin of nerve terminals in the penile frenulum of rats. And SP and/or CGRP immunofluorescence labeling was employed to detect the distribution of SP and/or CGRP immunoreactive neurons in DRG. FG retrograde tracing showed that the FG retrolabeled neurons were localized in L6-DRG and S1-DRG. SP and/or CGRP immunofluorescence labeling indicated that a large number of DRG neurons were SP- and CGRP-immunoreactive, different in size, bright red and bright green respectively in color, and arranged in rows or spots among nerve bundles. All the FG/SP and FG/CGRP double-labeled neurons were medium or small-sized. One third of the FG-labeled neurons were SP-immunoreactive, and a half of them CGRP-immunoreactive in L6-DRG and S1-DRG respectively. The FG/SP/CGRP-labeled neurons accounted for one fifth of the FG retro labeled neurons. SP- and CGRP-immunoreactive neurons in L6-DRG and SI-DRG of rats may be involved in the transmission of nociception in rat penile frenulum.

Molecular determinants of tetramerization in the KcsA cytoplasmic domain.

PubMed

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-10-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. © 2014 The Protein Society.

Molecular determinants of tetramerization in the KcsA cytoplasmic domain

PubMed Central

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-01-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. PMID:25042120

Hsp70 in the atrial neuroendocrine units of the snail, Achatina fulica.

PubMed

Martynova, M G; Bystrova, O A; Shabelnikov, S V; Margulis, B A; Prokofjeva, D S

2007-04-01

Heat shock proteins (Hsps) are evolutionary conserved peptides well known as molecular chaperones and stress proteins. Elevated levels of extracellular Hsps in blood plasma have been observed during the stress responses and some diseases. Information on the cellular sources of extracellular Hsps and mechanisms regulating their release is still scanty. Here we showed the presence and localization of Hsp70 in the neuroendocrine system in the atrium of the snail, Achatina fulica. The occurrence of the peptide in snail atrium lysate was detected by Western blot analysis. Immunoperoxidase and immunogold staining demonstrated that Hsp70-immunoreactivity is mainly confined to the peculiar atrial neuroendocrine units which are formed by nerve fibers tightly contacted with large granular cells. Immunolabelling intensity differed in morphologically distinct types of secretory granules in the granular cells. The pictures of exocytosis of Hsp70-immunolabeled granules from the granular cells were observed. In nerve bundles, axon profiles with Hsp70-immunoreactive and those with non-immunoreactive neurosecretory granules were found. In addition, Hsp70-like material was also revealed in the granules of glia-interstitial cells that accompanied nerve fibers. Our findings provide an immuno-morphological basis for a role of Hsp70 in the functioning of the neuroendocrine system in the snail heart, and show that the atrial granular cells are a probable source of extracellular Hsp70 in the snail hemolymph.

Sustained Reduction of Ventilator-Associated Pneumonia Rates Using Real-Time Course Correction With a Ventilator Bundle Compliance Dashboard.

PubMed

Talbot, Thomas R; Carr, Devin; Parmley, C Lee; Martin, Barbara J; Gray, Barbara; Ambrose, Anna; Starmer, Jack

2015-11-01

The effectiveness of practice bundles on reducing ventilator-associated pneumonia (VAP) has been questioned. To implement a comprehensive program that included a real-time bundle compliance dashboard to improve compliance and reduce ventilator-associated complications. DESIGN Before-and-after quasi-experimental study with interrupted time-series analysis. SETTING Academic medical center. In 2007 a comprehensive institutional ventilator bundle program was developed. To assess bundle compliance and stimulate instant course correction of noncompliant parameters, a real-time computerized dashboard was developed. Program impact in 6 adult intensive care units (ICUs) was assessed. Bundle compliance was noted as an overall cumulative bundle adherence assessment, reflecting the percentage of time all elements were concurrently in compliance for all patients. The VAP rate in all ICUs combined decreased from 19.5 to 9.2 VAPs per 1,000 ventilator-days following program implementation (P<.001). Bundle compliance significantly increased (Z100 score of 23% in August 2007 to 83% in June 2011 [P<.001]). The implementation resulted in a significant monthly decrease in the overall ICU VAP rate of 3.28/1,000 ventilator-days (95% CI, 2.64-3.92/1,000 ventilator-days). Following the intervention, the VAP rate decreased significantly at a rate of 0.20/1,000 ventilator-days per month (95% CI, 0.14-0.30/1,000 ventilator-days per month). Among all adult ICUs combined, improved bundle compliance was moderately correlated with monthly VAP rate reductions (Pearson correlation coefficient, -0.32). A prevention program using a real-time bundle adherence dashboard was associated with significant sustained decreases in VAP rates and an increase in bundle compliance among adult ICU patients.

High-resolution imaging of the retinal nerve fiber layer in normal eyes using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Arakawa, Naoko; Oshima, Susumu; Shibata, Naohisa; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2012-01-01

To conduct high-resolution imaging of the retinal nerve fiber layer (RNFL) in normal eyes using adaptive optics scanning laser ophthalmoscopy (AO-SLO). AO-SLO images were obtained in 20 normal eyes at multiple locations in the posterior polar area and a circular path with a 3-4-mm diameter around the optic disc. For each eye, images focused on the RNFL were recorded and a montage of AO-SLO images was created. AO-SLO images for all eyes showed many hyperreflective bundles in the RNFL. Hyperreflective bundles above or below the fovea were seen in an arch from the temporal periphery on either side of a horizontal dividing line to the optic disc. The dark lines among the hyperreflective bundles were narrower around the optic disc compared with those in the temporal raphe. The hyperreflective bundles corresponded with the direction of the striations on SLO red-free images. The resolution and contrast of the bundles were much higher in AO-SLO images than in red-free fundus photography or SLO red-free images. The mean hyperreflective bundle width around the optic disc had a double-humped shape; the bundles at the temporal and nasal sides of the optic disc were narrower than those above and below the optic disc (P<0.001). RNFL thickness obtained by optical coherence tomography correlated with the hyperreflective bundle widths on AO-SLO (P<0.001) AO-SLO revealed hyperreflective bundles and dark lines in the RNFL, believed to be retinal nerve fiber bundles and Müller cell septa. The widths of the nerve fiber bundles appear to be proportional to the RNFL thickness at equivalent distances from the optic disc.

High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2013-05-01

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

Framework for shape analysis of white matter fiber bundles.

PubMed

Glozman, Tanya; Bruckert, Lisa; Pestilli, Franco; Yecies, Derek W; Guibas, Leonidas J; Yeom, Kristen W

2018-02-15

Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Implementation of a post-cardiac arrest care bundle including therapeutic hypothermia and hemodynamic optimization in comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest: a feasibility study.

PubMed

Walters, Elizabeth Lea; Morawski, Kyle; Dorotta, Ihab; Ramsingh, Davinder; Lumen, Kelly; Bland, David; Clem, Kathleen; Nguyen, H Bryant

2011-04-01

Patients who present to the emergency department (ED) with return of spontaneous circulation after cardiac arrest generally have poor outcomes. Guidelines for treatment can be complicated and difficult to implement. This study examined the feasibility of implementing a care bundle including therapeutic hypothermia (TH) and early hemodynamic optimization for comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. The study included patients over a 2-year period in the ED and intensive care unit of an academic tertiary-care medical center. The first year (prebundle) provided a historical control, followed by a prospective observational period of bundle implementation during the second year. The bundle elements included (a) TH initiated; (b) central venous pressure/central venous oxygen saturation monitoring in 2 h; (c) target temperature in 4 h; (d) central venous pressure greater than 12 mmHg in 6 h; (e) MAP greater than 65 mmHg in 6 h; (f) central venous oxygen saturation greater than 70% in 6 h; (g) TH maintained for 24 h; and (h) decreasing lactate in 24 h. Fifty-five patients were enrolled, 26 patients in the prebundle phase and 29 patients in the bundle phase. Seventy-seven percent of bundle elements were completed during the bundle phase. In-hospital mortality in bundle compared with prebundle patients was 55.2% vs. 69.2% (P = 0.29). In the bundle patients, those patients who received all elements of the care bundle had mortality 33.3% compared with 60.9% in those receiving some of the bundle elements (P = 0.22). Bundle patients tended to achieve good neurologic outcome compared with prebundle patients, Cerebral Performance Category 1 or 2 in 31 vs. 12% patients, respectively (P = 0.08). Our study demonstrated that a post-cardiac arrest care bundle that incorporates TH and early hemodynamic optimization can be implemented in the ED and intensive care unit collaboratively and can achieve similar clinical benefits compared with those observed in previous clinical trials.

[Screening for asymptomatic left ventricular systolic dysfunction in high-risk patients. Preliminary experience with a program based on the use of ECG and natriuretic peptide].

PubMed

Tarantini, Luigi; Cioffi, Giovanni; Di Lenarda, Andrea; Valle, Roberto; Pulignano, Giovanni; Del Sindaco, Donatella; Frigo, Gianfranco; Soravia, Giorgio; Tessier, Renato; Catania, Giuseppe

2008-12-01

Patients with asymptomatic left ventricular systolic dysfunction (ALVSD) have an increased risk of heart failure (HF) and a worse life expectancy. Since valuable therapies may prevent such dismal evolution, screening programs for ALVSD have recently been advocated to detect as early as possible such ominous condition. Echocardiography represents the gold standard for the assessment of ALVSD but its indiscriminate use in screening programs is impractical. Clinical multivariate risk assessment associated with ECG and serum brain natriuretic peptide (BNP) may be a feasible strategy to screen ALVSD. We prospectively sought to investigate the feasibility and effectiveness of a screening program for ALVSD based on ECG and BNP used in a hierarchical sequence in patients at high risk for HF. Patients > or =55 years old with > or =2 risk factors for HF or > or =70 years old with > or =1 risk factor for HF entered the study performing sequentially ECG, BNP and echocardiographic evaluation. ALVSD was defined as a left ventricular ejection fraction < or =50%. Thirty-three of 122 enrolled patients (27%) had ALVSD. They were older, presented more frequently a history of chemotherapy exposure, had often bundle branch block and higher BNP levels. No patient without any major abnormalities (atrial fibrillation, left ventricular hypertrophy, STT alterations of ischemic/strain origin, pathologic Q wave, bundle branch block) on ECG (n=31, 24.4%) had ALVSD. Among the 91 patients with abnormal ECG, ALVSD was observed in 33 (36%). The area under the receiver operating characteristic curve to detect ALVSD by BNP was 0.86 (confidence interval 0.79-0.94, p<0.0001) and BNP values of > or =43 pg/ml showed a sensitivity and a specificity of 94% and 57%, respectively. The proposed screening program was able to identify 95% (31/33) of patients with ALVSD saving 53% of echocardiographic examinations with a substantial reduction of the costs to diagnose ALVSD. Our prospective investigation confirms that ECG and BNP may be useful in detecting ALVSD in high-risk patients. A cost-effective screening program based on such simple and low-cost diagnostic tests might be employed for the prevention of HF in primary and secondary prevention programs in high-risk patients.

Turkish and Native English Academic Writers' Use of Lexical Bundles

ERIC Educational Resources Information Center

Öztürk, Yusuf; Köse, Gül Durmusoglu

2016-01-01

Lexical bundles such as "on the other hand" and "as a result of" are extremely common and important in academic discourse. The appropriate use of lexical bundles typical of a specific academic discipline is important for writers and the absence of such bundles may not sound fluent and native-like. Recent studies (e.g. Adel…

Bundles over nearly-Kahler homogeneous spaces in heterotic string theory

NASA Astrophysics Data System (ADS)

Klaput, Michael; Lukas, Andre; Matti, Cyril

2011-09-01

We construct heterotic vacua based on six-dimensional nearly-Kahler homogeneous manifolds and non-trivial vector bundles thereon. Our examples are based on three specific group coset spaces. It is shown how to construct line bundles over these spaces, compute their properties and build up vector bundles consistent with supersymmetry and anomaly cancelation. It turns out that the most interesting coset is SU(3)/U(1)2. This space supports a large number of vector bundles which lead to consistent heterotic vacua, some of them with three chiral families.

Coupling and Elastic Loading Affect the Active Response by the Inner Ear Hair Cell Bundles

PubMed Central

Strimbu, Clark Elliott; Fredrickson-Hemsing, Lea; Bozovic, Dolores

2012-01-01

Active hair bundle motility has been proposed to underlie the amplification mechanism in the auditory endorgans of non-mammals and in the vestibular systems of all vertebrates, and to constitute a crucial component of cochlear amplification in mammals. We used semi-intact in vitro preparations of the bullfrog sacculus to study the effects of elastic mechanical loading on both natively coupled and freely oscillating hair bundles. For the latter, we attached glass fibers of different stiffness to the stereocilia and observed the induced changes in the spontaneous bundle movement. When driven with sinusoidal deflections, hair bundles displayed phase-locked response indicative of an Arnold Tongue, with the frequency selectivity highest at low amplitudes and decreasing under stronger stimulation. A striking broadening of the mode-locked response was seen with increasing stiffness of the load, until approximate impedance matching, where the phase-locked response remained flat over the physiological range of frequencies. When the otolithic membrane was left intact atop the preparation, the natural loading of the bundles likewise decreased their frequency selectivity with respect to that observed in freely oscillating bundles. To probe for signatures of the active process under natural loading and coupling conditions, we applied transient mechanical stimuli to the otolithic membrane. Following the pulses, the underlying bundles displayed active movement in the opposite direction, analogous to the twitches observed in individual cells. Tracking features in the otolithic membrane indicated that it moved in phase with the bundles. Hence, synchronous active motility evoked in the system of coupled hair bundles by external input is sufficient to displace large overlying structures. PMID:22479461

Prevalence of Split Nerve Fiber Layer Bundles in Healthy People Imaged with Spectral Domain Optical Coherence Tomography.

PubMed

Gür Güngör, Sirel; Akman, Ahmet; Sarıgül Sezenöz, Almila; Tanrıaşıkı, Gülşah

2016-12-01

The presence of retinal nerve fiber layer (RNFL) split bundles was recently described in normal eyes scanned using scanning laser polarimetry and by histologic studies. Split bundles may resemble RNFL loss in healthy eyes. The aim of our study was to determine the prevalence of nerve fiber layer split bundles in healthy people. We imaged 718 eyes of 359 healthy persons with the spectral domain optical coherence tomography in this cross-sectional study. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). In our study, a bundle was defined as 'split' when there is localized defect not resembling a wedge defect in the RNFL deviation map with a symmetrically divided RNFL appearance on the RNFL thickness map. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. Inter-observer consensus was reached in all cases. Bilateral superior split bundles were seen in 19 cases (5.29%) and unilateral superior split was observed in 15 cases (4.16%). In 325 cases (90.52%) there was no split bundle. Split nerve fiber layer bundles, in contrast to single nerve fiber layer bundles, are not common findings in healthy eyes. In eyes with normal optic disc appearance, especially when a superior RNFL defect is observed in RNFL deviation map, the RNLF thickness map and graphs should also be examined for split nerve fiber layer bundles.

Computational imaging through a fiber-optic bundle

NASA Astrophysics Data System (ADS)

Lodhi, Muhammad A.; Dumas, John Paul; Pierce, Mark C.; Bajwa, Waheed U.

2017-05-01

Compressive sensing (CS) has proven to be a viable method for reconstructing high-resolution signals using low-resolution measurements. Integrating CS principles into an optical system allows for higher-resolution imaging using lower-resolution sensor arrays. In contrast to prior works on CS-based imaging, our focus in this paper is on imaging through fiber-optic bundles, in which manufacturing constraints limit individual fiber spacing to around 2 μm. This limitation essentially renders fiber-optic bundles as low-resolution sensors with relatively few resolvable points per unit area. These fiber bundles are often used in minimally invasive medical instruments for viewing tissue at macro and microscopic levels. While the compact nature and flexibility of fiber bundles allow for excellent tissue access in-vivo, imaging through fiber bundles does not provide the fine details of tissue features that is demanded in some medical situations. Our hypothesis is that adapting existing CS principles to fiber bundle-based optical systems will overcome the resolution limitation inherent in fiber-bundle imaging. In a previous paper we examined the practical challenges involved in implementing a highly parallel version of the single-pixel camera while focusing on synthetic objects. This paper extends the same architecture for fiber-bundle imaging under incoherent illumination and addresses some practical issues associated with imaging physical objects. Additionally, we model the optical non-idealities in the system to get lower modelling errors.

Monoubiquitination Inhibits the Actin Bundling Activity of Fascin.

PubMed

Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

2016-12-30

Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys 247 and Lys 250 , two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC 50 , delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

75 FR 51668 - Optional Mail Preparation Standards for Flat-Size Mailpieces in FSS Zones

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... bundles of six or more addressed pieces each, subject to these standards: * * * * * [Revise item b of 13.2... combination. Mailers will then prepare bundles of uniform size from the pieces in the pool. Bundles must be... this option may be applied to the top piece of each bundle, unless otherwise required to be placed on...

Recognizing asymmetry in pseudo-symmetry; structural insights into the interaction between amphipathic α-helices and X-bundle proteins.

PubMed

Haddad, John Faissal; Yang, Yidai; Yeung, Sylvain; Couture, Jean-François

2017-11-01

An α-helix bundle is a small and compact protein fold always composed of more than 2 α-helices that typically run nearly parallel or antiparallel to each other. The repertoire of arrangements of α-helix bundle is such that these domains bind to a myriad of molecular entities including DNA, RNA, proteins and small molecules. A special instance of α-helical bundle is the X-type in which the arrangement of two α-helices interact at 45° to form an X. Among those, some X-helix bundle proteins bind to the hydrophobic section of an amphipathic α-helix in a seemingly orientation and sequence specific manner. In this review, we will compare the binding mode of amphipathic α-helices to X-helix bundle and α-helical bundle proteins. From these structures, we will highlight potential regulatory paradigms that may control the specific interactions of X-helix bundle proteins to amphipathic α-helices. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Muscle architecture of the elongated nose in the Asian elephant (Elephas maximus).

PubMed

Endo, H; Hayashi, Y; Komiya, T; Narushima, E; Sasaki, M

2001-05-01

The architecture of the M. caninus in the elongated nose was examined in the Asian elephant (Elephas maximus). The following complicated musculature of the M. caninus was observed in the proximal and distal regions of the nose: (1) Proximal region: In the superficial layer, the longitudinal bundles are confirmed in the dorsal part, and the obliquely-oriented ones in the ventral part. In the middle layer, some bundles run ventro-distally, while other ones represent longitudinally-oriented running. The deep layer consists of complicated architecture of many bundles. Some muscle bundles run medio-laterally, while the others extend proximo-distally in this space. (2) Distal region: In the dorsal part of the M. caninus, the bundles run at deep-superficial direction, while in the ventral part the bundles are longitudinally arranged. The bundles run at lateral direction near the septum of the nasal conduits. The N. facialis and N. infraorbitalis send many branches in the lateral area of the M. caninus in the trunk. This muscle architecture of multi-oriented bundles and well-developed innervation to them suggest that they enable the elongated nose to act as a refined manipulator in the Asian elephant.

The impact of a ventilator bundle on preventing ventilator-associated pneumonia: a multicenter study.

PubMed

Eom, Joong Sik; Lee, Mi-Suk; Chun, Hee-Kyung; Choi, Hee Jung; Jung, Sun-Young; Kim, Yeon-Sook; Yoon, Seon Jin; Kwak, Yee Gyung; Oh, Gang-Bok; Jeon, Min-Hyok; Park, Sun-Young; Koo, Hyun-Sook; Ju, Young-Su; Lee, Jin Seo

2014-01-01

For prevention of ventilator-associated pneumonia (VAP), a bundle approach was applied to patients receiving mechanical ventilation in intensive care units. The incidence of VAP and the preventive efficacy of the VAP bundle were investigated. A quasi-experimental study was conducted in adult intensive care units of 6 university hospitals with similar VAP rates. We implemented the VAP bundle between March 2011 and June 2011, then compared the rate of VAP after implementation of the VAP bundle with the rate in the previous 8 months. Our ventilator bundle included head of bed elevation, peptic ulcer disease prophylaxis, deep venous thrombosis prophylaxis, and oral decontamination with chlorhexidine 0.12%. Continuous aspiration of subglottic secretions was an option. Implementation of the VAP bundle reduced the VAP rate from a mean of 4.08 cases per 1,000 ventilator-days to 1.16 cases per 1,000 ventilator-days. The incidence density ratio (rate) was 0.28 (95% confidence interval, 0.275-0.292). Implementing the appropriate VAP bundle significantly decreased the incidence of VAP in patients with mechanical ventilation. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Nanomechanics of Pectin-Linked β-Lactoglobulin Nanofibril Bundles.

PubMed

Loveday, Simon M; Gunning, A Patrick

2018-06-14

Nanofibrils of β-lactoglobulin can be assembled into bundles by site-specific noncovalent cross-linking with high-methoxyl pectin (Hettiarachchi et al. Soft Matter 2016, 12, 756). Here we characterized the nanomechanical properties of bundles using atomic force microscopy and force spectroscopy. Bundles had Gaussian cross sections and a mean height of 17.4 ± 1.4 nm. Persistence lengths were calculated using image analysis with the mean-squared end-to-end model. The relationship between the persistence length and the thickness had exponents of 1.69-2.30, which is consistent with previous reports for other fibril types. In force spectroscopy experiments, the bundles stretched in a qualitatively different manner to fibrils, and some of the force curves were consistent with peeling fibrils away from bundles. The flexibility of pectin-linked nanofibril bundles is likely to be tunable by modulating the stiffness and length of fibrils and the ratio of pectin to fibrils, giving rise to a wide range of structures and functionalities.

Tokyo Guidelines 2018: management bundles for acute cholangitis and cholecystitis.

PubMed

Mayumi, Toshihiko; Okamoto, Kohji; Takada, Tadahiro; Strasberg, Steven M; Solomkin, Joseph S; Schlossberg, David; Pitt, Henry A; Yoshida, Masahiro; Gomi, Harumi; Miura, Fumihiko; Garden, O James; Kiriyama, Seiki; Yokoe, Masamichi; Endo, Itaru; Asbun, Horacio J; Iwashita, Yukio; Hibi, Taizo; Umezawa, Akiko; Suzuki, Kenji; Itoi, Takao; Hata, Jiro; Han, Ho-Seong; Hwang, Tsann-Long; Dervenis, Christos; Asai, Koji; Mori, Yasuhisa; Huang, Wayne Shih-Wei; Belli, Giulio; Mukai, Shuntaro; Jagannath, Palepu; Cherqui, Daniel; Kozaka, Kazuto; Baron, Todd H; de Santibañes, Eduardo; Higuchi, Ryota; Wada, Keita; Gouma, Dirk J; Deziel, Daniel J; Liau, Kui-Hin; Wakabayashi, Go; Padbury, Robert; Jonas, Eduard; Supe, Avinash Nivritti; Singh, Harjit; Gabata, Toshifumi; Chan, Angus C W; Lau, Wan Yee; Fan, Sheung Tat; Chen, Miin-Fu; Ker, Chen-Guo; Yoon, Yoo-Seok; Choi, In-Seok; Kim, Myung-Hwan; Yoon, Dong-Sup; Kitano, Seigo; Inomata, Masafumi; Hirata, Koichi; Inui, Kazuo; Sumiyama, Yoshinobu; Yamamoto, Masakazu

2018-01-01

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Ab initio density functional theory investigation of structural and electronic properties of silicon carbide nanotube bundles

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2008-10-01

By using ab initio density functional theory the structural and electronic properties of isolated and bundled (8,0) and (6,6) silicon carbide nanotubes (SiCNTs) are investigated. Our results show that for such small diameter nanotubes the inter-tube interaction causes a very small radial deformation, while band splitting and reduction of the semiconducting energy band gap are significant. We compared the equilibrium interaction energy and inter-tube separation distance of (8,0) SiCNT bundle with (10,0) carbon nanotube (CNT) bundle where they have the same radius. We found that there is a larger inter-tube separation and weaker inter-tube interaction in the (8,0) SiCNT bundle with respect to (10,0) CNT bundle, although they have the same radius.

A collagen and elastic network in the wing of the bat.

PubMed

Holbrook, K A; Odland, G F

1978-05-01

Bundles of collagen fibrils, elastic fibres and fibroblasts are organized into a network that lies in the plane of a large portion of the bat wing. By ultrastructural (TEM and SEM) and biochemical analyses it was found that individual bundles of the net are similar to elastic ligaments. Although elastic fibres predominate, they are integrated and aligned in parallel with small bundles of collagen. A reticulum of fibroblasts, joined by focal junctions, forms a cellular framework throughout each bundle. Because of the unique features of the fibre bundles of the bat's wing, in particular their accessibility, and the parallel alignment of the collagen fibrils and elastic fibres in each easily isolatable fibre bundle, they should prove a most valuable model for connective tissue studies, particularly for the study of collagen-elastin interactions.

Analysis of the Proteome of Hair-Cell Stereocilia by Mass Spectrometry

PubMed Central

Krey, Jocelyn F.; Wilmarth, Philip A.; David, Larry L.; Barr-Gillespie, Peter G.

2017-01-01

Characterization of proteins that mediate mechanotransduction by hair cells, the sensory cells of the inner ear, is hampered by the scarcity of these cells and their sensory organelle, the hair bundle. Mass spectrometry, with its high sensitivity and identification precision, is the ideal method for determining which proteins are present in bundles and what proteins they interact with. We describe here the isolation of mouse hair bundles, as well as preparation of bundle-protein samples for mass spectrometry. We also describe protocols for data-dependent (shotgun) and parallel-reaction-monitoring (targeted) mass spectrometry that allow us to identify and quantify proteins of the hair bundle. These sensitive methods are particularly useful for comparing proteomes of wild-type and mice with deafness mutations affecting hair-bundle proteins. (120 words; maximum 250) PMID:28109437

PDS4 Bundle Creation Governance Using BPMN

NASA Astrophysics Data System (ADS)

Radulescu, C.; Levoe, S. R.; Algermissen, S. S.; Rye, E. D.; Hardman, S. H.

2015-06-01

The AMMOS-PDS Pipeline Service (APPS) provides a Bundle Builder tool, which governs the process of creating, and ultimately generates, PDS4 bundles incrementally, as science products are being generated.

Bundle Branch Block

MedlinePlus

... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

Deformation quantization with separation of variables of an endomorphism bundle

NASA Astrophysics Data System (ADS)

Karabegov, Alexander

2014-01-01

Given a holomorphic Hermitian vector bundle E and a star-product with separation of variables on a pseudo-Kähler manifold, we construct a star product on the sections of the endomorphism bundle of the dual bundle E∗ which also has the appropriately generalized property of separation of variables. For this star product we prove a generalization of Gammelgaard's graph-theoretic formula.

Effect of fabricated density and bamboo species on physical-mechanical properties of bamboo fiber bundle reinforced composites

Treesearch

Jiulong Xie; Jinqiu Qi; Tingxing Hu; Cornelis F. De Hoop; Chung Yun Hse; Todd F. Shupe

2016-01-01

Bamboo stems were subjected to a mechanical treatment process for the extraction of bamboo fiber bundles. The fiber bundles were used as reinforcement for the fabrication of high-performance composites with phenolic resins as matrix. The influence of fabricated density and bamboo species on physical–mechanical properties of bamboo fiber bundle reinforced composites (...

ACL double-bundle reconstruction with one tibial tunnel provides equal stability compared to two tibial tunnels.

PubMed

Drews, Björn Holger; Seitz, Andreas Martin; Huth, Jochen; Bauer, Gerhard; Ignatius, Anita; Dürselen, Lutz

2017-05-01

The purpose of this study was to investigate whether an anterior cruciate ligament (ACL) double-bundle reconstruction with one tibial tunnel displays the same in vitro stability as a conventional double-bundle reconstruction with two tibial tunnels when using the same tensioning protocol. In 11 fresh-frozen cadaveric knees, ACL double-bundle reconstruction with one and two tibial tunnels was performed. The two grafts were tightened using 80 N in different flexion angles (anteromedial-bundle at 60° and posterolateral-bundle at 15°). Anterior tibial translation (134 N) and translation with combined rotatory and valgus loads (10 Nm valgus stress and 4 Nm internal tibial torque) were determined at 0°, 30°, 60° and 90° flexion. Measurements were taken in intact ACL, resected ACL, three-tunnel reconstruction and four-tunnel reconstruction. Additionally, the tension on the grafts was determined. Student's t test was performed for statistical analysis of the related samples. Significance was set at p < 0.017 according to Bonferroni correction. The two reconstructive techniques displayed no significant differences in comparison with the intact ACL in anterior tibial translation at 0°, 60° and 90° of flexion. The same results were obtained for the anterior tibial translation with a combined rotatory load at 60° and 90°. When directly comparing both reconstructive techniques, there were no significant differences for the anterior tibial translation and combined rotatory load at all flexion angles. The measured tension on grafts displayed similar load sharing between both bundles. Except at full extension, both grafts displayed a significantly different tension increase under anterior tibial translation for both techniques (p = 0.0086). Tightening both bundles in ACL double-bundle reconstruction with one or two tibial tunnels in different flexion angles achieved comparable restoration of stability, although there was different load sharing on the bundles. With regard to individualized ACL reconstruction, the double-bundle technique with one tibial tunnel offers a possibility to address small tibial insertion sites without compromising the advantages of a double-bundle procedure.

Femoral tunnel placement in single-bundle anterior cruciate ligament reconstruction: a cadaveric study relating transtibial lateralized femoral tunnel position to the anteromedial and posterolateral bundle femoral origins of the anterior cruciate ligament.

PubMed

Rue, John-Paul H; Ghodadra, Neil; Bach, Bernard R

2008-01-01

There is controversy regarding the necessity of reconstructing both the posterolateral and anteromedial bundles of the anterior cruciate ligament. A laterally oriented transtibial drilled femoral tunnel replaces portions of the femoral footprints of the anteromedial and posterolateral bundles of the anterior cruciate ligament. Descriptive laboratory study. Footprints of the anteromedial and posterolateral bundles of the anterior cruciate ligament were preserved on 7 matched pairs (5 female, 2 male) of fresh-frozen human cadaveric femurs (14 femurs total). Each femur was anatomically oriented and secured in a custom size-appropriate, side-matched replica tibia model to simulate transtibial retrograde drilling of a 10-mm femoral tunnel in each specimen. The relationship of the tunnel relative to footprints of both bundles of the anterior cruciate ligament was recorded using a Microscribe MX digitizer. The angle of the femoral tunnel relative to the vertical 12-o'clock position was recorded for all 14 specimens; only 10 specimens were used for footprint measurements. On average, the 10-mm femoral tunnel overlapped 50% of the anteromedial bundle (range, 2%-83%) and 51% of the posterolateral bundle (range, 16%-97%). The footprint of the anteromedial bundle occupied 32% (range, 3%-49%) of the area of the tunnel; the footprint of the posterolateral bundle contributed 26% (range, 7%-41%). The remainder of the area of the 10-mm tunnel did not overlap with the anterior cruciate ligament footprint. The mean absolute angle of the femoral tunnel as measured directly on the specimen was 48 degrees (range, 42 degrees-53 degrees) from vertical, corresponding to approximately a 10:30 clock face position on a right knee. Anterior cruciate ligament reconstruction using a laterally oriented transtibial drilled femoral tunnel incorporates portions of the anteromedial and posterolateral bundle origins of the native anterior cruciate ligament. A laterally oriented transtibial drilled femoral tunnel placed at the 10:30 position (1:30 for left knees) reconstructs portions of the anteromedial and posterolateral bundles of the anterior cruciate ligament.

Bundling of elastic filaments induced by hydrodynamic interactions

NASA Astrophysics Data System (ADS)

Man, Yi; Page, William; Poole, Robert J.; Lauga, Eric

2017-12-01

Peritrichous bacteria swim in viscous fluids by rotating multiple helical flagellar filaments. As the bacterium swims forward, all its flagella rotate in synchrony behind the cell in a tight helical bundle. When the bacterium changes its direction, the flagellar filaments unbundle and randomly reorient the cell for a short period of time before returning to their bundled state and resuming swimming. This rapid bundling and unbundling is, at its heart, a mechanical process whereby hydrodynamic interactions balance with elasticity to determine the time-varying deformation of the filaments. Inspired by this biophysical problem, we present in this paper what is perhaps the simplest model of bundling whereby two or more straight elastic filaments immersed in a viscous fluid rotate about their centerline, inducing rotational flows which tend to bend the filaments around each other. We derive an integrodifferential equation governing the shape of the filaments resulting from mechanical balance in a viscous fluid at low Reynolds number. We show that such equation may be evaluated asymptotically analytically in the long-wavelength limit, leading to a local partial differential equation governed by a single dimensionless bundling number. A numerical study of the dynamics predicted by the model reveals the presence of two configuration instabilities with increasing bundling numbers: first to a crossing state where filaments touch at one point and then to a bundled state where filaments wrap along each other in a helical fashion. We also consider the case of multiple filaments and the unbundling dynamics. We next provide an intuitive physical model for the crossing instability and show that it may be used to predict analytically its threshold and adapted to address the transition to a bundling state. We then use a macroscale experimental implementation of the two-filament configuration in order to validate our theoretical predictions and obtain excellent agreement. This long-wavelength model of bundling will be applicable to other problems in biological physics and provides the groundwork for further, more realistic, models of flagellar bundling.

Bundling in Place: Translating the NGSS into Place-Based Earth-System Science Curricula

NASA Astrophysics Data System (ADS)

Semken, S. C.

2016-12-01

Bundling is the process of grouping Performance Expectations (PEs) from the Next Generation Science Standards (NGSS) into coherent units based on a defined topic, idea, question, or phenomenon. Bundling sorts the PEs for a given grade or grade band into a teachable narrative: a key stage in building curriculum, instruction, and assessment from the NGSS. To encourage and facilitate this, bundling guidelines have recently been released on the NGSS website (nextgenscience.org/glossary/bundlesbundling), and example bundles for different grade bands and disciplines are also being developed and posted there. According to these guidelines the iterative process of bundling begins with organization of PEs according to natural connections among them, and alignment of the three NGSS dimensions (Disciplinary Core Ideas, Cross-Cutting Concepts, and Science and Engineering Practices) that underpin each PE. Bundles are grouped by coherence and increasing complexity into courses, and courses into course sets that should encompass all PEs for a grade band. Bundling offers a natural way to translate the NGSS into highly contextualized curricula such as place-based (PB) teaching, which is situated in specific places or regions and focused on natural and cultural features, processes, phenomena, history, and challenges to sustainability therein. Attributes of place and our individual and collective connections to place (sense of place) directly inform PB curriculum, pedagogy, and assessment. PEs can be bundled by their relevance to these themes. Following the NGSS guidelines, I model the process for PB instruction by bundling PEs around the themes of Paleozoic geology and carbonate deposition and their relationships to mining and calcining of limestone in Anthropocene cement production for developing communities. The bundles integrate aspects of Earth history, the carbon cycle, mineral resources, climate change, and sustainability using specific local examples and narratives. They are designed for a hypothetical place-based high-school Earth-science course situated in the Greater American Southwest, but could be readily modified for another region with similar geology and resource use.

Effectiveness of a Model Bundle Payment Initiative for Femur Fracture Patients.

PubMed

Lott, Ariana; Belayneh, Rebekah; Haglin, Jack; Konda, Sanjit; Egol, Kenneth A

2018-05-28

Analyze the effectiveness of a BPCI (Bundle Payments for Care Improvement) initiative for patients who would be included in a future potential Surgical Hip and Femur Fracture Treatment (SHFFT) bundle. Retrospective cohort SETTING:: Single Academic Institution PATIENTS/PARTICIPANTS:: Patients discharged with operative fixation of a hip or femur fracture (DRG codes 480-482) between 1/2015-10/2016 were included. A BPCI initiative based upon an established program for BPCI Total Joint Arthroplasty (TJA) was initiated for patients with hip and femur fractures in January 2016. Patients were divided into non-bundle (care before initiative) and bundle (care with initiative) cohorts. Application of BPCI principles MAIN OUTCOME MEASURES:: Length of stay, location of discharge, readmissions RESULTS:: 116 patients participated in the "institutional bundle," and 126 received care prior to the initiative. There was a trend towards decreased mean length of stay, (7.3 ± 6.3 days vs. 6.8 ± 4.0 days, p=0.457) and decreased readmission within 90 days (22.2% vs. 18.1%, p=0.426). The number of patients discharged home doubled (30.2% vs. 14.3%, p=0.008). There was no difference in readmission rates in bundle vs. non-bundle patients based on discharged home status; however, bundle patients discharged to SNF trended towards less readmissions than non-bundle patients discharged to SNF (37.3% vs. 50.6%, p=0.402). Mean episode cost reduction due to initiative was estimated to be $6,450 using Medicare reimbursement data. This study demonstrates the potential success of a BPCI initiative at one institution in decreasing post-acute care facility utilization and cost of care when used for a hip and femur fracture population. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

* Hierarchically Structured Electrospun Scaffolds with Chemically Conjugated Growth Factor for Ligament Tissue Engineering.

PubMed

Pauly, Hannah M; Sathy, Binulal N; Olvera, Dinorath; McCarthy, Helen O; Kelly, Daniel J; Popat, Ketul C; Dunne, Nicholas J; Haut Donahue, Tammy Lynn

2017-08-01

The anterior cruciate ligament (ACL) of the knee is vital for proper joint function and is commonly ruptured during sports injuries or car accidents. Due to a lack of intrinsic healing capacity and drawbacks with allografts and autografts, there is a need for a tissue-engineered ACL replacement. Our group has previously used aligned sheets of electrospun polycaprolactone nanofibers to develop solid cylindrical bundles of longitudinally aligned nanofibers. We have shown that these nanofiber bundles support cell proliferation and elongation and the hierarchical structure and material properties are similar to the native human ACL. It is possible to combine multiple nanofiber bundles to create a scaffold that attempts to mimic the macroscale structure of the ACL. The goal of this work was to develop a hierarchical bioactive scaffold for ligament tissue engineering using connective tissue growth factor (CTGF)-conjugated nanofiber bundles and evaluate the behavior of mesenchymal stem cells (MSCs) on these scaffolds in vitro and in vivo. CTGF was immobilized onto the surface of individual nanofiber bundles or scaffolds consisting of multiple nanofiber bundles. The conjugation efficiency and the release of conjugated CTGF were assessed using X-ray photoelectron spectroscopy, assays, and immunofluorescence staining. Scaffolds were seeded with MSCs and maintained in vitro for 7 days (individual nanofiber bundles), in vitro for 21 days (scaled-up scaffolds of 20 nanofiber bundles), or in vivo for 6 weeks (small scaffolds of 4 nanofiber bundles), and ligament-specific tissue formation was assessed in comparison to non-CTGF-conjugated control scaffolds. Results showed that CTGF conjugation encouraged cell proliferation and ligament-specific tissue formation in vitro and in vivo. The results suggest that hierarchical electrospun nanofiber bundles conjugated with CTGF are a scalable and bioactive scaffold for ACL tissue engineering.

Method and apparatus for extracting tritium and preparing radioactive waste for disposal

DOEpatents

Heung, Leung K.

1994-01-01

Apparatus for heating an object such as a nuclear target bundle to release and recover hydrogen and contain the disposable residue for disposal. The apparatus comprises an inverted furnace, a sleeve/crucible assembly for holding and enclosing the bundle, conveying equipment for placing the sleeve onto the crucible and loading the bundle into the sleeve/crucible, a lift for raising the enclosed bundle into the furnace, and hydrogen recovery equipment including a trap and strippers, all housed in a containment having negative internal pressure. The crucible/sleeve assembly has an internal volume that is sufficient to enclose and hold the bundle before heating; the crucible's internal volume is sufficient by itself to hold and enclose the bundle's volume after heating. The crucible can then be covered and disposed of; the sleeve, on the other hand, can be reused.

Spinor Geometry and Signal Transmission in Three-Space

NASA Astrophysics Data System (ADS)

Binz, Ernst; Pods, Sonja; Schempp, Walter

2002-09-01

For a singularity free gradient field in an open set of an oriented Euclidean space of dimension three we define a natural principal bundle out of an immanent complex line bundle. The elements of both bundles are called internal variables. Several other natural bundles are associated with the principal bundle and, in turn, determine the vector field. Two examples are given and it is shown that for a constant vector field circular polarized waves travelling along a field line can be considered as waves of internal variables. Einstein's equation epsilon = m [middle dot] c2 is derived from the geometry of the principal bundle. On SU(2) a relation between spin representations and Schrodinger representations is established. The link between the spin 1/2-model and the Schrodinger representations yields a connection between a microscopic and a macroscopic viewpoint.

System and method for reducing combustion dynamics in a combustor

DOEpatents

Uhm, Jong Ho; Johnson, Thomas Edward; Zuo, Baifang; York, William David

2015-09-01

A system for reducing combustion dynamics in a combustor includes an end cap having an upstream surface axially separated from a downstream surface, and tube bundles extend from the upstream surface through the downstream surface. A divider inside a tube bundle defines a diluent passage that extends axially through the downstream surface, and a diluent supply in fluid communication with the divider provides diluent flow to the diluent passage. A method for reducing combustion dynamics in a combustor includes flowing a fuel through tube bundles, flowing a diluent through a diluent passage inside a tube bundle, wherein the diluent passage extends axially through at least a portion of the end cap into a combustion chamber, and forming a diluent barrier in the combustion chamber between the tube bundle and at least one other adjacent tube bundle.

Fuel transfer system

DOEpatents

Townsend, Harold E.; Barbanti, Giancarlo

1994-01-01

A nuclear fuel bundle fuel transfer system includes a transfer pool containing water at a level above a reactor core. A fuel transfer machine therein includes a carriage disposed in the transfer pool and under the water for transporting fuel bundles. The carriage is selectively movable through the water in the transfer pool and individual fuel bundles are carried vertically in the carriage. In a preferred embodiment, a first movable bridge is disposed over an upper pool containing the reactor core, and a second movable bridge is disposed over a fuel storage pool, with the transfer pool being disposed therebetween. A fuel bundle may be moved by the first bridge from the reactor core and loaded into the carriage which transports the fuel bundle to the second bridge which picks up the fuel bundle and carries it to the fuel storage pool.

Fuel transfer system

DOEpatents

Townsend, H.E.; Barbanti, G.

1994-03-01

A nuclear fuel bundle fuel transfer system includes a transfer pool containing water at a level above a reactor core. A fuel transfer machine therein includes a carriage disposed in the transfer pool and under the water for transporting fuel bundles. The carriage is selectively movable through the water in the transfer pool and individual fuel bundles are carried vertically in the carriage. In a preferred embodiment, a first movable bridge is disposed over an upper pool containing the reactor core, and a second movable bridge is disposed over a fuel storage pool, with the transfer pool being disposed therebetween. A fuel bundle may be moved by the first bridge from the reactor core and loaded into the carriage which transports the fuel bundle to the second bridge which picks up the fuel bundle and carries it to the fuel storage pool. 6 figures.

Darcy Permeability of Hollow Fiber Bundles Used in Blood Oxygenation Devices

PubMed Central

Pacella, Heather E.; Eash, Heidi J.; Federspiel, William J.

2011-01-01

Many industrial and biomedical devices (e.g. blood oxygenators and artificial lungs) use bundles of hollow fiber membranes for separation processes. Analyses of flow and mass transport within the shell-side of the fiber bundles most often model the bundle for simplicity as a packed bed or porous media, using a Darcy permeability coefficient estimated from the Blake-Kozeny equation to account for viscous drag from the fibers. In this study, we developed a simple method for measuring the Darcy permeability of hollow fiber membrane bundles and evaluated how well the Blake-Kozeny (BK) equation predicted the Darcy permeability for these bundles. Fiber bundles were fabricated from commercially available Celgard® ×30-240 fiber fabric (300 μm outer diameter fibers @ 35 and 54 fibers/inch) and from a fiber fabric with 193 μm fibers (61 fibers/inch). The fiber bundles were mounted to the bottom of an acrylic tube and Darcy permeability was determined by measuring the elapsed time for a column of glycerol solution to flow through a fiber bundle. The ratio of the measured Darcy permeability to that predicted from the BK equation varied from 1.09 to 0.56. A comprehensive literature review suggested a modified BK equation with the “constant” correlated to porosity. This modification improved the predictions of the BK equation, with the ratio of measured to predicted permeability varying from 1.13 to 0.84. PMID:22927706

Mutational Analyses of HAMP Helices Suggest a Dynamic Bundle Model of Input-Output Signaling in Chemoreceptors

PubMed Central

Zhou, Qin; Ames, Peter; Parkinson, John S.

2009-01-01

SUMMARY To test the gearbox model of HAMP signaling in the E. coli serine receptor, Tsr, we generated a series of amino acid replacements at each residue of the AS1 and AS2 helices. The residues most critical for Tsr function defined hydrophobic packing faces consistent with a 4-helix bundle. Suppression patterns of helix lesions conformed to the the predicted packing layers in the bundle. Although the properties and patterns of most AS1 and AS2 lesions were consistent with both proposed gearbox structures, some mutational features specifically indicate the functional importance of an x-da bundle over an alternative a-d bundle. These genetic data suggest that HAMP signaling could simply involve changes in the stability of its x-da bundle. We propose that Tsr HAMP controls output signals by modulating destabilizing phase clashes between the AS2 helices and the adjoining kinase control helices. Our model further proposes that chemoeffectors regulate HAMP bundle stability through a control cable connection between the transmembrane segments and AS1 helices. Attractant stimuli, which cause inward piston displacements in chemoreceptors, should reduce cable tension, thereby stabilizing the HAMP bundle. This study shows how transmembrane signaling and HAMP input-output control could occur without the helix rotations central to the gearbox model. PMID:19656294

Use of ventilator associated pneumonia bundle and statistical process control chart to decrease VAP rate in Syria.

PubMed

Alsadat, Reem; Al-Bardan, Hussam; Mazloum, Mona N; Shamah, Asem A; Eltayeb, Mohamed F E; Marie, Ali; Dakkak, Abdulrahman; Naes, Ola; Esber, Faten; Betelmal, Ibrahim; Kherallah, Mazen

2012-10-01

Implementation of ventilator associated pneumonia (VAP) bundle as a performance improvement project in the critical care units for all mechanically ventilated patients aiming to decrease the VAP rates. VAP bundle was implemented in 4 teaching hospitals after educational sessions and compliance rates along with VAP rates were monitored using statistical process control charts. VAP bundle compliance rates were steadily increasing from 33 to 80% in hospital 1, from 33 to 86% in hospital 2 and from 83 to 100% in hospital 3 during the study period. The VAP bundle was not applied in hospital 4 therefore no data was available. A target level of 95% was reached only in hospital 3. This correlated with a decrease in VAP rates from 30 to 6.4 per 1000 ventilator days in hospital 1, from 12 to 4.9 per 1000 ventilator days in hospital 3, whereas VAP rate failed to decrease in hospital 2 (despite better compliance) and it remained high around 33 per 1000 ventilator days in hospital 4 where VAP bundle was not implemented. VAP bundle has performed differently in different hospitals in our study. Prevention of VAP requires a multidimensional strategy that includes strict infection control interventions, VAP bundle implementation, process and outcome surveillance and education.

In-hospital outcome in patients with ST elevation myocardial infarction and right bundle branch block. A sub-study from RENASICA II, a national multicenter registry.

PubMed

Juárez-Herrera, Ursulo; Jerjes Sánchez, Carlos; González-Pacheco, Héctor; Martínez-Sánchez, Carlos

2010-01-01

Compare in-hospital outcome in patients with ST-elevation myocardial infarction with right versus left bundle branch block. RENASICA II, a national Mexican registry enrolled 8098 patients with final diagnosis of acute coronary syndrome secondary to ischemic heart disease. In 4555 STEMI patients, 545 had bundle branch block, 318 (58.3%) with right and 225 patients with left (41.6%). Both groups were compared in terms of in-hospital outcome through major cardiovascular adverse events; (cardiovascular death, recurrent ischemia and reinfarction). Multivariable analysis was performed to identify in-hospital mortality risk among right and left bundle branch block patients. There were not statistical differences in both groups regarding baseline characteristics, time of ischemia, myocardial infarction location, ventricular dysfunction and reperfusion strategies. In-hospital outcome in bundle branch block group was characterized by a high incidence of major cardiovascular adverse events with a trend to higher mortality in patients with right bundle branch block (OR 1.70, CI 1.19 - 2.42, p < 0.003), compared to left bundle branch block patients. In this sub-study right bundle branch block accompanying ST-elevation myocardial infarction of any location at emergency room presentation was an independent predictor of high in-hospital mortality.

Enhanced field emission properties of carbon nanotube bundles confined in SiO2 pits

NASA Astrophysics Data System (ADS)

Lim, Yu Dian; Grapov, Dmitry; Hu, Liangxing; Kong, Qinyu; Tay, Beng Kang; Labunov, Vladimir; Miao, Jianmin; Coquet, Philippe; Aditya, Sheel

2018-02-01

It has been widely reported that carbon nanotubes (CNTs) exhibit superior field emission (FE) properties due to their high aspect ratios and unique structural properties. Among the various types of CNTs, random growth CNTs exhibit promising FE properties due to their reduced inter-tube screening effect. However, growing random growth CNTs on individual catalyst islands often results in spread out CNT bundles, which reduces overall field enhancement. In this study, significant improvement in FE properties in CNT bundles is demonstrated by confining them in microfabricated SiO2 pits. Growing CNT bundles in narrow (0.5 μm diameter and 2 μm height) SiO2 pits achieves FE current density of 1-1.4 A cm-2, which is much higher than for freestanding CNT bundles (76.9 mA cm-2). From the Fowler Nordheim plots, confined CNT bundles show a higher field enhancement factor. This improvement can be attributed to the reduced bundle diameter by SiO2 pit confinement, which yields bundles with higher aspect ratios. Combining the obtained outcomes, it can be conclusively summarized that confining CNTs in SiO2 pits yields higher FE current density due to the higher field enhancement of confined CNTs.

Vacuum Powder Injector

NASA Technical Reports Server (NTRS)

Working, Dennis C.

1991-01-01

Method developed to provide uniform impregnation of bundles of carbon-fiber tow with low-solubility, high-melt-flow polymer powder materials to produce composite prepregs. Vacuum powder injector expands bundle of fiber tow, applies polymer to it, then compresses bundle to hold powder. System provides for control of amount of polymer on bundle. Crystallinity of polymer maintained by controlled melt on takeup system. All powder entrapped, and most collected for reuse. Process provides inexpensive and efficient method for making composite materials. Allows for coating of any bundle of fine fibers with powders. Shows high potential for making prepregs of improved materials and for preparation of high-temperature, high-modulus, reinforced thermoplastics.

Optical absorption and thermal transport of individual suspended carbon nanotube bundles.

PubMed

Hsu, I-Kai; Pettes, Michael T; Bushmaker, Adam; Aykol, Mehmet; Shi, Li; Cronin, Stephen B

2009-02-01

A focused laser beam is used to heat individual single-walled carbon nanotube bundles bridging two suspended microthermometers. By measurement of the temperature rise of the two thermometers, the optical absorption of 7.4-10.3 nm diameter bundles is found to be between 0.03 and 0.44% of the incident photons in the 0.4 microm diameter laser spot. The thermal conductance of the bundle is obtained with the additional measurement of the temperature rise of the nanotubes in the laser spot from shifts in the Raman G band frequency. According to the nanotube bundle diameter determined by transmission electron microscopy, the thermal conductivity is obtained.

Coulomb explosion: a novel approach to separate single-walled carbon nanotubes from their bundle.

PubMed

Liu, Guangtong; Zhao, Yuanchun; Zheng, Kaihong; Liu, Zheng; Ma, Wenjun; Ren, Yan; Xie, Sishen; Sun, Lianfeng

2009-01-01

A novel approach based on Coulomb explosion has been developed to separate single-walled carbon nanotubes (SWNTs) from their bundle. With this technique, we can readily separate a bundle of SWNTs into smaller bundles with uniform diameter as well as some individual SWNTs. The separated SWNTs have a typical length of several microns and form a nanotree at one end of the original bundle. More importantly, this separating procedure involves no surfactant and includes only one-step physical process. The separation method offers great conveniences for the subsequent individual SWNT or multiterminal SWNTs device fabrication and their physical properties studies.

Mammalian Auditory Hair Cell Bundle Stiffness Affects Frequency Tuning by Increasing Coupling along the Length of the Cochlea.

PubMed

Dewey, James B; Xia, Anping; Müller, Ulrich; Belyantseva, Inna A; Applegate, Brian E; Oghalai, John S

2018-06-05

The stereociliary bundles of cochlear hair cells convert mechanical vibrations into the electrical signals required for auditory sensation. While the stiffness of the bundles strongly influences mechanotransduction, its influence on the vibratory response of the cochlear partition is unclear. To assess this, we measured cochlear vibrations in mutant mice with reduced bundle stiffness or with a tectorial membrane (TM) that is detached from the sensory epithelium. We found that reducing bundle stiffness decreased the high-frequency extent and sharpened the tuning of vibratory responses obtained postmortem. Detaching the TM further reduced the high-frequency extent of the vibrations but also lowered the partition's resonant frequency. Together, these results demonstrate that the bundle's stiffness and attachment to the TM contribute to passive longitudinal coupling in the cochlea. We conclude that the stereociliary bundles and TM interact to facilitate passive-wave propagation to more apical locations, possibly enhancing active-wave amplification in vivo. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Experimental observation of spatially resolved photo-luminescence intensity distribution in dual mode upconverting nanorod bundles

PubMed Central

Kumar, Pawan; Singh, Satbir; Singh, V. N.; Singh, Nidhi; Gupta, R. K.; Gupta, Bipin Kumar

2017-01-01

A novel method for demonstration of photoluminescence intensity distribution in upconverting nanorod bundles using confocal microscopy is reported. Herein, a strategy for the synthesis of highly luminescent dual mode upconverting/downshift Y1.94O3:Ho3+0.02/Yb3+0.04 nanorod bundles by a facile hydrothermal route has been introduced. These luminescent nanorod bundles exhibit strong green emission at 549 nm upon excitations at 449 nm and 980 nm with quantum efficiencies of ~6.3% and ~1.1%, respectively. The TEM/HRTEM results confirm that these bundles are composed of several individual nanorods with diameter of ~100 nm and length in the range of 1–3 μm. Furthermore, two dimensional spatially resolved photoluminescence intensity distribution study has been carried out using confocal photoluminescence microscope throughout the nanorod bundles. This study provides a new direction for the potential use of such emerging dual mode nanorod bundles as photon sources for next generation flat panel optical display devices, bio-medical applications, luminescent security ink and enhanced energy harvesting in photovoltaic applications. PMID:28211891

New Feature Observed in the Raman Resonance Excitation Profiles of (6 , 5) -Enriched, Selectively Bundled SWCNTs

NASA Astrophysics Data System (ADS)

Hight Walker, A. R.; Simpson, J. R.; Roslyak, O.; Haroz, E.; Telg, H.; Duque, J. G.; Crochet, J. J.; Piryatinski, A.; Doorn, S. K.

Understanding the photophysics of exciton behavior in single wall carbon nanotube (SWCNT) bundles remains important for opto-electronic device applications. We report resonance Raman spectroscopy (RRS) measurements on (6 , 5) -enriched SWCNTs, dispersed in aqueous solutions and separated using density gradient ultracentrifugation into fractions of increasing bundling. Near-IR to UV absorption spectroscopy shows a redshift and broadening of the main excitonic transitions with increasing bundling. A continuously tunable dye laser coupled to a triple-grating spectrometer affords measurement of Raman resonance excitation profiles (REPs) over a range of wavelengths covering the (6 , 5) -E22 range (505 to 585) nm. REPs of both the radial breathing mode (RBM) and G-band reveal a redshifting and broadening of the (6 , 5) E22 transition energy with increasing bundling. Additionally, we observe an unexpected peak in the REP of bundled SWCNTs, which is shifted lower in energy than the main E22 and is anomalously narrow. We compare these observations to a theoretical model that examines the origin of this peak in relation to bundle polarization-enhanced exciton response.

Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle

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

Gao, Kai; Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101; University of Chinese Academy of Sciences, Beijing 100049

Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminalmore » and C-terminal helix. -- Highlights: •Unfolding of HIV-1 gp41 six-helix bundle is studied by molecular dynamics simulations. •Specific interactions responsible for the stability of HIV-1 envelope post-fusion conformation were identified. •The gp41 six-helix bundle transition inducing membrane fusion might be a cooperative process of the three subunits.« less

BiSet: Semantic Edge Bundling with Biclusters for Sensemaking.

PubMed

Sun, Maoyuan; Mi, Peng; North, Chris; Ramakrishnan, Naren

2016-01-01

Identifying coordinated relationships is an important task in data analytics. For example, an intelligence analyst might want to discover three suspicious people who all visited the same four cities. Existing techniques that display individual relationships, such as between lists of entities, require repetitious manual selection and significant mental aggregation in cluttered visualizations to find coordinated relationships. In this paper, we present BiSet, a visual analytics technique to support interactive exploration of coordinated relationships. In BiSet, we model coordinated relationships as biclusters and algorithmically mine them from a dataset. Then, we visualize the biclusters in context as bundled edges between sets of related entities. Thus, bundles enable analysts to infer task-oriented semantic insights about potentially coordinated activities. We make bundles as first class objects and add a new layer, "in-between", to contain these bundle objects. Based on this, bundles serve to organize entities represented in lists and visually reveal their membership. Users can interact with edge bundles to organize related entities, and vice versa, for sensemaking purposes. With a usage scenario, we demonstrate how BiSet supports the exploration of coordinated relationships in text analytics.

48 CFR 7.107 - Additional requirements for acquisitions involving bundling.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the agency must conduct market research to determine whether bundling is necessary and justified (15 U.S.C. 644(e)(2)). Market research may indicate that bundling is necessary and justified if an agency...

Bundle Security Protocol for ION

NASA Technical Reports Server (NTRS)

Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

2011-01-01

This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

Local load-sharing fiber bundle model in higher dimensions.

PubMed

Sinha, Santanu; Kjellstadli, Jonas T; Hansen, Alex

2015-08-01

We consider the local load-sharing fiber bundle model in one to five dimensions. Depending on the breaking threshold distribution of the fibers, there is a transition where the fracture process becomes localized. In the localized phase, the model behaves as the invasion percolation model. The difference between the local load-sharing fiber bundle model and the equal load-sharing fiber bundle model vanishes with increasing dimensionality with the characteristics of a power law.

Method and apparatus for extracting tritium and preparing radioactive waste for disposal

DOEpatents

Heung, L.K.

1994-03-29

Apparatus is described for heating an object such as a nuclear target bundle to release and recover hydrogen and contain the disposable residue for disposal. The apparatus comprises an inverted furnace, a sleeve/crucible assembly for holding and enclosing the bundle, conveying equipment for placing the sleeve onto the crucible and loading the bundle into the sleeve/crucible, a lift for raising the enclosed bundle into the furnace, and hydrogen recovery equipment including a trap and strippers, all housed in a containment having negative internal pressure. The crucible/sleeve assembly has an internal volume that is sufficient to enclose and hold the bundle before heating; the crucible's internal volume is sufficient by itself to hold and enclose the bundle's volume after heating. The crucible can then be covered and disposed of; the sleeve, on the other hand, can be reused. 4 figures.

Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles*

PubMed Central

Nagy, Stanislav; Rock, Ronald S.

2010-01-01

Without guidance cues, cytoskeletal motors would traffic components to the wrong destination with disastrous consequences for the cell. Recently, we identified a motor protein, myosin X, that identifies bundled actin filaments for transport. These bundles direct myosin X to a unique destination, the tips of cellular filopodia. Because the structural and kinetic features that drive bundle selection are unknown, we employed a domain-swapping approach with the nonselective myosin V to identify the selectivity module of myosin X. We found a surprising role of the myosin X tail region (post-IQ) in supporting long runs on bundles. Moreover, the myosin X head is adapted for initiating processive runs on bundles. We found that the tail is structured and biases the orientation of the two myosin X heads because a targeted insertion that introduces flexibility in the tail abolishes selectivity. Together, these results suggest how myosin motors may manage to read cellular addresses. PMID:20538587

Patterned growth of carbon nanotubes over vertically aligned silicon nanowire bundles for achieving uniform field emission.

PubMed

Hung, Yung-Jr; Huang, Yung-Jui; Chang, Hsuan-Chen; Lee, Kuei-Yi; Lee, San-Liang

2014-01-01

A fabrication strategy is proposed to enable precise coverage of as-grown carbon nanotube (CNT) mats atop vertically aligned silicon nanowire (VA-SiNW) bundles in order to realize a uniform bundle array of CNT-SiNW heterojunctions over a large sample area. No obvious electrical degradation of as-fabricated SiNWs is observed according to the measured current-voltage characteristic of a two-terminal single-nanowire device. Bundle arrangement of CNT-SiNW heterojunctions is optimized to relax the electrostatic screening effect and to maximize the field enhancement factor. As a result, superior field emission performance and relatively stable emission current over 12 h is obtained. A bright and uniform fluorescent radiation is observed from CNT-SiNW-based field emitters regardless of its bundle periodicity, verifying the existence of high-density and efficient field emitters on the proposed CNT-SiNW bundle arrays.

Sampling system and method

DOEpatents

Decker, David L.; Lyles, Brad F.; Purcell, Richard G.; Hershey, Ronald Lee

2017-03-07

In one embodiment, the present disclosure provides an apparatus and method for supporting a tubing bundle during installation or removal. The apparatus includes a clamp for securing the tubing bundle to an external wireline. In various examples, the clamp is external to the tubing bundle or integral with the tubing bundle. According to one method, a tubing bundle and wireline are deployed together and the tubing bundle periodically secured to the wireline using a clamp. In another embodiment, the present disclosure provides an apparatus and method for coupling conduit segments together. A first pump obtains a sample and transmits it through a first conduit to a reservoir accessible by a second pump. The second pump further conducts the sample from the reservoir through a second conduit. In a specific example, one or more clamps are used to connect the first and/or second conduits to an external wireline.

Topological distribution of four-alpha-helix bundles.

PubMed Central

Presnell, S R; Cohen, F E

1989-01-01

The four-alpha-helix bundle, a common structural motif in globular proteins, provides an excellent forum for the examination of predictive constraints for protein backbone topology. An exhaustive examination of the Brookhaven Crystallographic Protein Data Bank and other literature sources has lead to the discovery of 20 putative four-alpha-helix bundles. Application of an analytical method that examines the difference between solvent-accessible surface areas in packed and partially unpacked bundles reduced the number of structures to 16. Angular requirements further reduced the list of bundles to 13. In 12 of these bundles, all pairs of neighboring helices were oriented in an anti-parallel fashion. This distribution is in accordance with structure types expected if the helix macro dipole effect makes a substantial contribution to the stability of the native structure. The characterizations and classifications made in this study prompt a reevaluation of constraints used in structure prediction efforts. Images PMID:2771946

Fiber bundle phase conjugate mirror

DOEpatents

Ward, Benjamin G.

2012-05-01

An improved method and apparatus for passively conjugating the phases of a distorted wavefronts resulting from optical phase mismatch between elements of a fiber laser array are disclosed. A method for passively conjugating a distorted wavefront comprises the steps of: multiplexing a plurality of probe fibers and a bundle pump fiber in a fiber bundle array; passing the multiplexed output from the fiber bundle array through a collimating lens and into one portion of a non-linear medium; passing the output from a pump collection fiber through a focusing lens and into another portion of the non-linear medium so that the output from the pump collection fiber mixes with the multiplexed output from the fiber bundle; adjusting one or more degrees of freedom of one or more of the fiber bundle array, the collimating lens, the focusing lens, the non-linear medium, or the pump collection fiber to produce a standing wave in the non-linear medium.

Sperm bundle and reproductive organs of carabid beetles tribe Pterostichini (Coleoptera: Carabidae)

NASA Astrophysics Data System (ADS)

Sasakawa, Kôji

2007-05-01

The morphological characteristics of sperm and reproductive organs may offer clues as to how reproductive systems have evolved. In this paper, the morphologies of the sperm and male reproductive organs of carabid beetles in the tribe Pterostichini (Coleoptera: Carabidae) are described, and the morphological associations among characters are examined. All species form sperm bundles in which the head of the sperm was embedded in a rod-shaped structure, i.e., spermatodesm. The spermatodesm shape (left-handed spiral, right-handed spiral, or without conspicuous spiral structure) and the condition of the sperm on the spermatodesm surface (with the tail free-moving or forming a thin, sheetlike structure) vary among species. In all species, the spiral directions of the convoluted seminal vesicles and vasa deferentia are the same on both sides of the body; that is, they show an asymmetric structure. The species in which the sperm bundle and the seminal vesicles both have a spiral structure could be classified into two types, with significant differences in sperm-bundle length between the two types. The species with a sperm-bundle spiral and seminal-vesicle spiral of almost the same diameter have longer sperm bundles than the species with a sperm-bundle spiral and seminal-vesicle tube of almost the same diameter. In the former type, the spiral directions of the sperm bundles and seminal vesicles are inevitably the same, whereas they differ in some species with the later type. Therefore, increased sperm bundle length appears to have been facilitated by the concordance of the sperm bundle’s coiling direction with the coiling direction of the seminal vesicle.

Management bundles for candidaemia: the impact of compliance on clinical outcomes

PubMed Central

Takesue, Yoshio; Ueda, Takashi; Mikamo, Hiroshige; Oda, Shigeto; Takakura, Shunji; Kitagawa, Yuko; Kohno, Shigeru; Masuda, A.; Yoshida, C.; Yasunaga, C.; Yamashita, C.; Nakataki, E.; Ohyagi, H.; Yagi, H.; Johnai, H.; Murai, H.; Hanamoto, H.; Nakamura, I.; Sanada, I.; Tandai, I.; Kuroki, J.; Ogawa, J.; Kawahara, K.; Amino, K.; Nakajima, K.; Yoshimoto, K.; Takeda, K.; Nakamura, K.; Suzuki, K.; Yamada, K.; Aizawa, M.; Hashimoto, M.; Ogata, M.; Shirano, M.; Kawada, M.; Kaneda, M.; Yoshioka, M.; Okuda, N.; Sugita, N.; Kikuchi, N.; Fuke, S.; Tsuchihashi, S.; Sugitani, S.; Ikuta, S.; Honda, S.; Nei, T.; Iwamura, T.; Yagi, T.; Kaji, T.; Ichimiya, Y.; Kobayashi, Y.; Minamishima, Y.; Goto, Y.; Hatano, Y.; Nagao, Y.; Yamagishi, Y.; Sashihara, J.; Tsukamoto, A.; Kawaoka, T.; Kobayashi, M.

2015-01-01

Objectives The Mycoses Forum in Japan has developed management bundles for candidaemia to incorporate into bedside practice. The aim of this study was to investigate nationwide compliance with the bundles and their impact on clinical outcomes. Methods Non-neutropenic patients treated with antifungals for candidaemia were surveyed. Bundles consist of nine items to complete. Data were sent to the central office between July 2011 and April 2012. Results Six hundred and eight patients were analysed. The compliance rate for achieving all elements was 6.9%, and it increased to 21.4% when compliance was analysed by the bundle except for oral switch. There was a significant difference in clinical success between patients with and without compliance [92.9% versus 75.8% (P = 0.011)]. Compliance with the bundles, however, failed to be an independent factor associated with favourable outcomes. When step-down oral therapy was excluded from the elements of compliance, compliance with the bundles was revealed to be an independent predictor of clinical success (OR 4.42, 95% CI 2.05–9.52) and mortality (OR 0.27, 95% CI 0.13–0.57). Independent individual elements contributing to clinical success were removal of central venous catheters within 24 h, assessment of clinical efficacy on the third to the fifth day and at least 2 weeks of therapy after clearance of candidaemia. Conclusions Compliance with the bundles for candidaemia had a beneficial effect on clinical outcomes. Promotion of the bundles approach may have the potential to narrow the gap between clinical evidence and bedside practice. PMID:25326087

Reduction of Surgical Site Infections after Implementation of a Bundle of Care

PubMed Central

Crolla, Rogier M. P. H.; van der Laan, Lijckle; Veen, Eelco J.; Hendriks, Yvonne; van Schendel, Caroline; Kluytmans, Jan

2012-01-01

Background Surgical Site Infections (SSI) are relatively frequent complications after colorectal surgery and are associated with substantial morbidity and mortality. Objective Implementing a bundle of care and measuring the effects on the SSI rate. Design Prospective quasi experimental cohort study. Methods A prospective surveillance for SSI after colorectal surgery was performed in the Amphia Hospital, Breda, from January 1, 2008 until January 1, 2012. As part of a National patient safety initiative, a bundle of care consisting of 4 elements covering the surgical process was introduced in 2009. The elements of the bundle were perioperative antibiotic prophylaxis, hair removal before surgery, perioperative normothermia and discipline in the operating room. Bundle compliance was measured every 3 months in a random sample of surgical procedures. Results Bundle compliance improved significantly from an average of 10% in 2009 to 60% in 2011. 1537 colorectal procedures were performed during the study period and 300 SSI (19.5%) occurred. SSI were associated with a prolonged length of stay (mean additional length of stay 18 days) and a significantly higher 6 months mortality (Adjusted OR: 2.71, 95% confidence interval 1.76–4.18). Logistic regression showed a significant decrease of the SSI rate that paralleled the introduction of the bundle. The adjusted Odds ratio of the SSI rate was 36% lower in 2011 compared to 2008. Conclusion The implementation of the bundle was associated with improved compliance over time and a 36% reduction of the SSI rate after adjustment for confounders. This makes the bundle an important tool to improve patient safety. PMID:22962619

Magnetic Bead Actuation of Saccular Hair Cells

NASA Astrophysics Data System (ADS)

Rowland, David; Ramunno-Johnson, Damien; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

2011-11-01

When decoupled from the overlying membrane, hair bundles of the amphibian sacculus exhibit spontaneous oscillation. To explore the dynamics of this innate motility without an imposed external load, we recorded their oscillations with a high-speed CMOS camera, and applied mechanical manipulation that minimally alters the geometry of an individual hair bundle. We present a technique that utilizes micron-sized magnetic particles to actuate the stereociliary bundle with a magnetized probe. Quasi-steady-state displacements were imposed on freely oscillating bundles. Our data indicate that deflection of the bundle affects both the frequency and the amplitude of the oscillations, with a crossing of the bifurcation that is dependent on the direction and speed of the applied offset.

Filamentary structures that self-organize due to adhesion

NASA Astrophysics Data System (ADS)

Sengab, A.; Picu, R. C.

2018-03-01

We study the self-organization of random collections of elastic filaments that interact adhesively. The evolution from an initial fully random quasi-two-dimensional state is controlled by filament elasticity, adhesion and interfilament friction, and excluded volume. Three outcomes are possible: the system may remain locked in the initial state, may organize into isolated fiber bundles, or may form a stable, connected network of bundles. The range of system parameters leading to each of these states is identified. The network of bundles is subisostatic and is stabilized by prestressed triangular features forming at bundle-to-bundle nodes, similar to the situation in foams. Interfiber friction promotes locking and expands the parametric range of nonevolving systems.

Topological T-duality for torus bundles with monodromy

NASA Astrophysics Data System (ADS)

Baraglia, David

2015-05-01

We give a simplified definition of topological T-duality that applies to arbitrary torus bundles. The new definition does not involve Chern classes or spectral sequences, only gerbes and morphisms between them. All the familiar topological conditions for T-duals are shown to follow. We determine necessary and sufficient conditions for existence of a T-dual in the case of affine torus bundles. This is general enough to include all principal torus bundles as well as torus bundles with arbitrary monodromy representations. We show that isomorphisms in twisted cohomology, twisted K-theory and of Courant algebroids persist in this general setting. We also give an example where twisted K-theory groups can be computed by iterating T-duality.

Polyelectrolyte bundles

NASA Astrophysics Data System (ADS)

Limbach, H. J.; Sayar, M.; Holm, C.

2004-06-01

Using extensive Molecular Dynamics simulations we study the behavior of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction, and the bundle size. We show that for the parameter range relevant for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting to the possibility that the size of DNA aggregates is under certain circumstances thermodynamically limited.

Development and pilot testing of a patient-participatory pressure ulcer prevention care bundle.

PubMed

Gillespie, Brigid M; Chaboyer, Wendy; Sykes, Mark; O'Brien, Jennifer; Brandis, Susan

2014-01-01

This study developed and piloted a patient-centered pressure ulcer prevention care bundle for adult hospitalized patients to promote patient participation in prevention. The care bundle had 3 core messages: (1) keep moving, (2) care for your skin, and (3) ensure a good diet. A brief video, combined brochure/checklist, and poster were developed as training resources. Patient evaluation identified benefits of the care bundle; however, the combined checklist/brochure was rarely used.

New system speeds bundling of split firewood

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

Not Available

1979-01-01

A firewood compacting and strapping machine is manufactured by Carolson Stapler and Shippers Supply, Omaha, and FMC Industrial Packaging Division, Philadelphia. A hydraulic compactor applies 20,000 lbs of compressive force to each bundle of split logs, reducing each package to a diameter of about 12 inches. A polypropylene band is applied and heat sealed around each bundle. Bundles are stacked on end, twenty-four to a pallet, and the entire load is banded with one horizontal strap.

Two-phase pressure drop reduction BWR assembly design

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

Dix, G.E.; Crowther, R.L.; Colby, M.J.

1992-05-12

This patent describes a boiling water reactor having discrete bundles of fuel rods confined within channel enclosed fuel assemblies, an improvement to a fuel bundle assembly for placement in the reactor. It comprises a fuel channel having vertically extending walls forming a continuous channel around a fuel assembly volume, the channel being open at the bottom end for engagement to a lower tie plate and open at the upper end for engagement to an upper tie plate; rods for placement within the chamber, each the rod containing fissile material for producing nuclear reaction when in the presence of sufficient moderatedmore » neutron flux; a lower tie plate for supporting the bundle of rods within the channel, the lower tie plate for supporting the bundle of rods within the channel, the lower tie plate joining the bottom of the channel to close the bottom end of the channel, the lower tie plate providing defined apertures for the inflow of water in the channel between the rods for the generating of steam during the nuclear reaction; the plurality of fuel rods extending from the lower tie plate wherein a single phase region of the water in the bundle is defined to an upward portion of the bundle wherein a two phase region of the water and steam in the bundle is defined during nuclear steam generating reaction in the fuel bundle.« less

The Actions of Calcium on Hair Bundle Mechanics in Mammalian Cochlear Hair Cells

PubMed Central

Beurg, Maryline; Nam, Jong-Hoon; Crawford, Andrew; Fettiplace, Robert

2008-01-01

Sound stimuli excite cochlear hair cells by vibration of each hair bundle, which opens mechanotransducer (MT) channels. We have measured hair-bundle mechanics in isolated rat cochleas by stimulation with flexible glass fibers and simultaneous recording of the MT current. Both inner and outer hair-cell bundles exhibited force-displacement relationships with a nonlinearity that reflects a time-dependent reduction in stiffness. The nonlinearity was abolished, and hair-bundle stiffness increased, by maneuvers that diminished calcium influx through the MT channels: lowering extracellular calcium, blocking the MT current with dihydrostreptomycin, or depolarizing to positive potentials. To simulate the effects of Ca2+, we constructed a finite-element model of the outer hair cell bundle that incorporates the gating-spring hypothesis for MT channel activation. Four calcium ions were assumed to bind to the MT channel, making it harder to open, and, in addition, Ca2+ was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca2+ effects on adaptation and bundle mechanics comparable to those measured experimentally. We suggest that fast adaptation and force generation by the hair bundle may stem from the action of Ca2+ on the channel complex and do not necessarily require the direct involvement of a myosin motor. The significance of these results for cochlear transduction and amplification are discussed. PMID:18178649

Food bundling as a health nudge: Investigating consumer fruit and vegetable selection using behavioral economics.

PubMed

Carroll, Kathryn A; Samek, Anya; Zepeda, Lydia

2018-02-01

Displaying bundles of healthy foods at the grocery store is a health nudge that simplifies shopping and may have the potential for increasing fruit and vegetable (F&V) purchasing. To evaluate the impact of food bundling, we conduct an artefactual field experiment with community participants in a laboratory set up as a grocery store. Dual-self theory suggests that food choices may differ depending on whether shoppers are under cognitive load - in our experiment, we exogenously vary whether bundles are displayed (with and without a price discount) and whether shoppers are under cognitive load. Our findings align with prior studies that suggest unhealthy options are more likely to be selected when cognitive resources are constrained. When bundles are displayed, we observe increased F&V purchasing. We also observe a significant interaction between cognitive load and price discounting. We find discounted bundles are more effective in the absence of cognitive load, but non-discounted bundles are more effective when shoppers are under cognitive load. Although more research is warranted, our findings suggest that when shopping under cognitive load, it is possible that discounts impose additional cognitive strain on the shopping experience. For retailers and policymakers, our results point to the potential power of bundling as a strategy for increasing healthy food purchasing. Copyright © 2017 Elsevier Ltd. All rights reserved.

The bundling of actin with polyethylene glycol 8000 in the presence and absence of gelsolin.

PubMed Central

Goverman, J; Schick, L A; Newman, J

1996-01-01

Actin filament and bundle formation occur in the cytosol under conditions of very high total macromolecular concentration. In this study we have utilized the inert molecule polyethylene glycol 8000 (PEG) as a means of simulating crowded conditions in vitro. Column-purified Ca-actin was polymerized in the absence and presence of gelsolin (to regulate mean filament lengths between 50 and 5000 mers) and PEG (2-8%) using various concentrations of KCl and/or 2 mM divalent cations. Bundling was characterized by the scattered light intensity and mean diffusion coefficients obtained from dynamic light scattering, as well as by fluorescence and phase-contrast microscopy. The minimum concentration of KCl required for bundling decreases both with increasing concentration of PEG at a fixed mean filament length, and with decreasing filament length at a fixed concentration of PEG. In the absence of divalent cation, bundling is reversible on dilution, as determined by intensity levels, diffusion coefficients, and microscopy. However, with either 2 mM Mg2+ or Ca2+ added, bundling is irreversible under conditions of higher PEG concentrations or longer filaments, indicating that osmotic pressure effects cannot fully explain actin bundling with PEG. Weaker divalent cation-binding sites on actin as well as disulfide bonds appear to be involved in the irreversible bundling. Images FIGURE 7 PMID:8874022

Spontaneous Oscillation by Hair Bundles of the Bullfrog's Sacculus

PubMed Central

Martin, Pascal; Bozovic, D.; Choe, Y.; Hudspeth, A. J.

2007-01-01

One prominent manifestation of mechanical activity in hair cells is spontaneous otoacoustic emission, the unprovoked emanation of sound by an internal ear. Because active hair-bundle motility probably constitutes the active process of non-mammalian hair cells, we investigated the ability of hair bundles in the bullfrog's sacculus to produce oscillations that might underlie spontaneous otoacoustic emissions. When maintained in the ear's normal ionic milieu, many bundles oscillated spontaneously through distances as great as 80 nm at frequencies of 5-50 Hz. Whole-cell recording disclosed that the positive phase of movement was associated with the opening of transduction channels. Gentamicin, which blocks transduction channels, reversibly arrested oscillation; drugs that affect the cAMP phosphorylation pathway and might influence myosin's activity altered the rate of oscillation. Increasing the Ca2+ concentration rendered oscillations faster and smaller until they were suppressed; lowering the Ca2+ concentration moderately with chelators had the opposite effect. When a bundle was offset with a stimulus fiber, oscillations were transiently suppressed but gradually resumed. Loading a bundle by partial displacement clamping, which simulated the presence of the accessory structures to which a bundle is ordinarily attached, increased the frequency and diminished the magnitude of oscillation. These observations accord with a model in which oscillations arise from the interplay of the hair bundle's negative stiffness with the activity of adaptation motors and with Ca2+-dependent relaxation of gating springs. PMID:12805294

Probing sequence dependence of folding pathway of α-helix bundle proteins through free energy landscape analysis.

PubMed

Shao, Qiang

2014-06-05

A comparative study on the folding of multiple three-α-helix bundle proteins including α3D, α3W, and the B domain of protein A (BdpA) is presented. The use of integrated-tempering-sampling molecular dynamics simulations achieves reversible folding and unfolding events in individual short trajectories, which thus provides an efficient approach to sufficiently sample the configuration space of protein and delineate the folding pathway of α-helix bundle. The detailed free energy landscape analyses indicate that the folding mechanism of α-helix bundle is not uniform but sequence dependent. A simple model is then proposed to predict folding mechanism of α-helix bundle on the basis of amino acid composition: α-helical proteins containing higher percentage of hydrophobic residues than charged ones fold via nucleation-condensation mechanism (e.g., α3D and BdpA) whereas proteins having opposite tendency in amino acid composition more likely fold via the framework mechanism (e.g., α3W). The model is tested on various α-helix bundle proteins, and the predicted mechanism is similar to the most approved one for each protein. In addition, the common features in the folding pathway of α-helix bundle protein are also deduced. In summary, the present study provides comprehensive, atomic-level picture of the folding of α-helix bundle proteins.

A novel approach to leveraging electronic health record data to enhance pediatric surgical quality improvement bundle process compliance.

PubMed

Fisher, Jason C; Godfried, David H; Lighter-Fisher, Jennifer; Pratko, Joseph; Sheldon, Mary Ellen; Diago, Thelma; Kuenzler, Keith A; Tomita, Sandra S; Ginsburg, Howard B

2016-06-01

Quality improvement (QI) bundles have been widely adopted to reduce surgical site infections (SSI). Improvement science suggests when organizations achieve high-reliability to QI processes, outcomes dramatically improve. However, measuring QI process compliance is poorly supported by electronic health record (EHR) systems. We developed a custom EHR tool to facilitate capture of process data for SSI prevention with the aim of increasing bundle compliance and reducing adverse events. Ten SSI prevention bundle processes were linked to EHR data elements that were then aggregated into a snapshot display superimposed on weekly case-log reports. The data aggregation and user interface facilitated efficient review of all SSI bundle elements, providing an exact bundle compliance rate without random sampling or chart review. Nine months after implementation of our custom EHR tool, we observed centerline shifts in median SSI bundle compliance (46% to 72%). Additionally, as predicted by high reliability principles, we began to see a trend toward improvement in SSI rates (1.68 to 0.87 per 100 operations), but a discrete centerline shift was not detected. Simple informatics solutions can facilitate extraction of QI process data from the EHR without relying on adjunctive systems. Analyses of these data may drive reductions in adverse events. Pediatric surgical departments should consider leveraging the EHR to enhance bundle compliance as they implement QI strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

[Evaluation of the clinical results in patients with symptomatic partial tears of the anterior cruciate ligament diagnosed arthroscopically].

PubMed

Zeman, P; Cibulková, J; Nepraš, P; Koudela, K; Matějka, J

2013-01-01

The study presents a retrospective evaluation of clinical data and arthroscopic findings in a group of our patients with symptomatic knee instability due to a partial tear of the anterior cruciate ligament (ACL). The group included 31 patients diagnosed with symptomatic partial ACL tears, i.e. an isolated tear of the posterolateral (PL) or the anteromedial (AM) bundle. The patients' average age was 26.5 years. A side-to-side difference in ventral knee laxity was assessed using the anterior drawer test and the Lachman test under general anaesthesia before arthroscopy was commenced; rotational knee laxity was evaluated by the pivot shift test. An objective evaluation of side-to-side ventral laxity differences in both knees was performed on the GNRB® arthrometer with an applied pressure of 134 N and 250 N in the conscious patient. During arthroscopic examination, findings on the two ACL bundles were recorded. All 31 patients were diagnosed with symptomatic partial ACL tears, of them 22 had a PL bundle lesion and nine had an AM bundle tear. All patients with PL bundle lesions only reported problems in association with pivot sports, and all patients with AM bundle tears had problems regardless of any sports activities. In all patients with isolated AM bundle tears, the lesion was located close to its femoral attachment. In the patients with PL bundle tears, femoral location was found in 68% and tibial location in 32% of the patients. In the patients with partial PL bundle lesions, + and ++ results in the pivot shift test were recorded in 32% and 68% of the treated patients, respectively. The Lachman test showed + and ++ results in 71% and 9% of the patients, respectively. The anterior drawer test had negative results in 87% and positive + results in 13% of the patients. The side-to-side difference on the GNRB arthrometer ranged from 0.4 to 2.3 mm at a pressure of 134 N and from 1.2 to 4.2 mm at 250 N in the patients with isolated PL bundle lesions. In the patients with AM bundle lesions, the results were as follows: pivot shift test, 89% negative. 11% positive +; Lachman test, 56% negative, 44% positive +; anterior drawer test, 89% +, 11% ++; GNRB test, 2.2 to 4.4 mm at 134 N, and 4.3 to 7.1 at 250 N. The diagnosis of partial ACL lesions, i.e., isolated tears of the AM or the PL bundle, requires accurate knowledge of knee anatomy and its biomechanics. In accordance with other authors our results showed that an arthroscopic examination of both bundles of the ligament as well as knee laxity evaluation under general anaesthesia are most essential for making the definite diagnosis in partial ACL tears. They also confirmed that, in isolated AM bundle lesions, ventral laxity is present more often particularly at a higher degree of knee flexion while, in PL bundle lesions, rotational laxity is more frequent and ranges from 0 to 30 degrees of knee flexion. To make the definite diagnosis of partial ACL tears, patient medical history, clinical knee examination including instability type and degree assessment under general anaesthesia and, most importantly, arthroscopic findings on both ACL bundles are necessary.

Application of a transient heat transfer model for bundled, multiphase pipelines

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

Brown, T.S.; Clapham, J.; Danielson, T.J.

1996-12-31

A computer model has been developed which accurately describes transient heat transfer in pipeline bundles. An arbitrary number of internal pipelines containing different fluids, flowing in either direction along with the input of heat to one or more of the fluids can be accommodated. The model is coupled to the transient, multiphase flow simulator OLGA. The lines containing the multiphase production fluids are modeled by OLGA, and the heat transfer between the internal lines, carrier pipe, and surroundings is handled by the bundle model. The model has been applied extensively to the design of a subsea, heated bundle system formore » the Britannia gas condensate field in the North Sea. The 15-km bundle system contains a 14{double_prime} production line, an 8{double_prime} test line, a 3{double_prime} methanol line, and a 12{double_prime} internal heating medium line within a 37.25{double_prime} carrier. The heating medium (water) flows in the internal heating medium line and in the annulus at 82,500 BPD. The primary purpose of the bundle system is to avoid the formation of hydrates. A secondary purpose is to avoid the deposition of paraffin. The bundle model was used to (1) compare the merits of two coaxial lines vs. a single bundle; (2) optimize the insulation levels on the carrier and internal lines; (3) determine the minimum time required to heat up the bundle; (4) determine heat input requirements to avoid hydrates throughout the field life, (5) determine temperature profiles along the lines for a range of production rates; (6) study ruptures of the production line into the bundle annulus; (7) determine minimum temperatures during depressurization; and (8) determine cool-down times. The results of these studies were used to size lines, select insulation levels, assess erosion potential, design for thermal expansion-induced stresses, and to select materials of construction.« less

Epitope topography controls bioactivity in supramolecular nanofibers

PubMed Central

Sur, Shantanu; Tantakitti, Faifan; Matson, John B.; Stupp, Samuel I.

2015-01-01

Incorporating bioactivity into artificial scaffolds using peptide epitopes present in the extracellular matrix (ECM) is a well-known approach. A common strategy has involved epitopes that provide cells with attachment points and external cues through interaction with integrin receptors. Although a variety of bioactive sequences have been identified so far, less is known about their optimal display in a scaffold. We report here on the use of self-assembled peptide amphiphile (PA) nanofiber matrices to investigate the impact of spatial presentation of the fibronectin derived epitope RGDS on cell response. Using one, three, or five glycine residues, RGDS epitopes were systematically spaced out from the surface of the rigid nanofibers. We found that cell morphology was strongly affected by the separation of the epitope from the nanofiber surface, with the longest distance yielding the most cell-spreading, bundling of actin filaments, and a round-to-polygonal transformation of cell shape. Cell response to this type of epitope display was also accompanied with activated integrin-mediated signaling and formation of stronger adhesions between cells and substrate. Interestingly, unlike length, changing the molecular flexibility of the linker had minimal influence on cell behavior on the substrate for reasons that remain poorly understood. The use in this study of high persistence length nanofibers rather than common flexible polymers allows us to conclude that epitope topography at the nanoscale structure of a scaffold influences its bioactive properties independent of epitope density and mechanical properties. PMID:25745558

Distribution of vasotocin- and vasoactive intestinal peptide-like immunoreactivity in the brain of blue tit (Cyanistes coeruleus)

PubMed Central

Montagnese, Catherine M.; Székely, Tamás; Csillag, András; Zachar, Gergely

2015-01-01

Blue tits (Cyanistes coeruleus) are songbirds, used as model animals in numerous studies covering a wide field of research. Nevertheless, the distribution of neuropeptides in the brain of this avian species remains largely unknown. Here we present some of the first results on distribution of Vasotocine (AVT) and Vasoactive intestinal peptide (VIP) in the brain of males and females of this songbird species, using immunohistochemistry mapping. The bulk of AVT-like cells are found in the hypothalamic supraoptic, paraventricular and suprachiasmatic nuclei, bed nucleus of the stria terminalis, and along the lateral forebrain bundle. Most AVT-like fibers course toward the median eminence, some reaching the arcopallium, and lateral septum. Further terminal fields occur in the dorsal thalamus, ventral tegmental area and pretectal area. Most VIP-like cells are in the lateral septal organ and arcuate nucleus. VIP-like fibers are distributed extensively in the hypothalamus, preoptic area, lateral septum, diagonal band of Broca. They are also found in the bed nucleus of the stria terminalis, amygdaloid nucleus of taenia, robust nucleus of the arcopallium, caudo-ventral hyperpallium, nucleus accumbens and the brainstem. Taken together, these results suggest that both AVT and VIP immunoreactive structures show similar distribution to other avian species, emphasizing evolutionary conservatism in the history of vertebrates. The current study may enable future investigation into the localization of AVT and VIP, in relation to behavioral and ecological traits in the brain of tit species. PMID:26236200

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

PubMed Central

Lelli, Andrea; Michel, Vincent; Boutet de Monvel, Jacques; Cortese, Matteo; Bosch-Grau, Montserrat; Aghaie, Asadollah; Perfettini, Isabelle; Dupont, Typhaine; Avan, Paul

2016-01-01

The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a−/−Myo3b−/− mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b−/− mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a−/−Myo3b−/− cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a−/−Myo3b−/− stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping. PMID:26754646

Application Transparent HTTP Over a Disruption Tolerant Smartnet

DTIC Science & Technology

2014-09-01

American Standard Code for Information Interchange BP Bundle Protocol BPA bundle protocol agent CLA convergence layer adapters CPU central processing...forwarding them through the plugin pipeline. The initial version of the DTNInput plugin uses the BBN Spindle bundle protocol agent ( BPA ) implementation

Analytic convergence of harmonic metrics for parabolic Higgs bundles

NASA Astrophysics Data System (ADS)

Kim, Semin; Wilkin, Graeme

2018-04-01

In this paper we investigate the moduli space of parabolic Higgs bundles over a punctured Riemann surface with varying weights at the punctures. We show that the harmonic metric depends analytically on the weights and the stable Higgs bundle. This gives a Higgs bundle generalisation of a theorem of McOwen on the existence of hyperbolic cone metrics on a punctured surface within a given conformal class, and a generalisation of a theorem of Judge on the analytic parametrisation of these metrics.

Analysis of multimode fiber bundles for endoscopic spectral-domain optical coherence tomography

PubMed Central

Risi, Matthew D.; Makhlouf, Houssine; Rouse, Andrew R.; Gmitro, Arthur F.

2016-01-01

A theoretical analysis of the use of a fiber bundle in spectral-domain optical coherence tomography (OCT) systems is presented. The fiber bundle enables a flexible endoscopic design and provides fast, parallelized acquisition of the OCT data. However, the multimode characteristic of the fibers in the fiber bundle affects the depth sensitivity of the imaging system. A description of light interference in a multimode fiber is presented along with numerical simulations and experimental studies to illustrate the theoretical analysis. PMID:25967012

Teaching of anterior cruciate ligament function in osteopathic medical education.

PubMed

Surek, Christopher Chase; Lorimer, Shannon D; Dougherty, John J; Stephens, Robert E

2011-04-01

The anterior cruciate ligament (ACL) of the knee and the function of its anteromedial (AM) and posterolateral (PL) bundles are a focus of orthopedic research. Because of the probability that third-year and fourth-year osteopathic medical students will encounter ACL injuries during clinical rotations, it is of paramount importance that students fully understand the functions of the AM and PL bundles as 2 distinct functional components of the ACL. The authors assess the degree to which the AM and PL bundles are discussed within basic science curricula at colleges of osteopathic medicine (COMs). In September 2008, a 6-question survey addressing various aspects of ACL education was mailed to instructors of lower-extremity anatomy at all 28 COMs that existed at that time. Nine of the 21 responding institutions (42.9%) indicated that both the AM and PL bundles of the ACL are discussed within their basic science curricula. Four of these 9 COMs indicated that their instruction mentions that the bundles are parallel in extension and crossed in flexion. Nine of the 21 responding COMs (42.9%) indicated that they instruct students that the AM bundle is a major anterior-posterior restrictor, and 12 (57.1%) indicated that they instruct students that the PL bundle is the major rotational stabilizer of the ACL. In 7 of the 21 responding COMs (33.3%), the AM and PL bundles are identified via direct visualization during anatomic dissection of the ACL. The authors conclude that their findings suggest the need for enhanced presentation of the AM and PL bundles within the basic science curricula at COMs to provide osteopathic medical students with a more comprehensive education in anatomy.

Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma.

PubMed

Chen, Monica F; Chui, Toco Y P; Alhadeff, Paula; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Hood, Donald C

2015-01-08

To better understand the nature of glaucomatous damage of the macula, especially the structural changes seen between relatively healthy and clearly abnormal (AB) retinal regions, using an adaptive optics scanning light ophthalmoscope (AO-SLO). Adaptive optics SLO images and optical coherence tomography (OCT) vertical line scans were obtained on one eye of seven glaucoma patients, with relatively deep local arcuate defects on the 10-2 visual field test in one (six eyes) or both hemifields (one eye). Based on the OCT images, the retinal nerve fiber (RNF) layer was divided into two regions: (1) within normal limits (WNL), relative RNF layer thickness within mean control values ±2 SD; and (2) AB, relative thickness less than -2 SD value. As seen on AO-SLO, the pattern of AB RNF bundles near the border of the WNL and AB regions differed across eyes. There were normal-appearing bundles in the WNL region of all eyes and AB-appearing bundles near the border with the AB region. This region with AB bundles ranged in extent from a few bundles to the entire AB region in the case of one eye. All other eyes had a large AB region without bundles. However, in two of these eyes, a few bundles were seen within this region of otherwise missing bundles. The AO-SLO images revealed details of glaucomatous damage that are difficult, if not impossible, to see with current OCT technology. Adaptive optics SLO may prove useful in following progression in clinical trials, or in disease management, if AO-SLO becomes widely available and easy to use. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Confocal Adaptive Optics Imaging of Peripapillary Nerve Fiber Bundles: Implications for Glaucomatous Damage Seen on Circumpapillary OCT Scans.

PubMed

Hood, Donald C; Chen, Monica F; Lee, Dongwon; Epstein, Benjamin; Alhadeff, Paula; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Chui, Toco Y P

2015-04-01

To improve our understanding of glaucomatous damage as seen on circumpapillary disc scans obtained with frequency-domain optical coherence tomography (fdOCT), fdOCT scans were compared to images of the peripapillary retinal nerve fiber (RNF) bundles obtained with an adaptive optics-scanning light ophthalmoscope (AO-SLO). The AO-SLO images and fdOCT scans were obtained on 6 eyes of 6 patients with deep arcuate defects (5 points ≤-15 db) on 10-2 visual fields. The AO-SLO images were montaged and aligned with the fdOCT images to compare the RNF bundles seen with AO-SLO to the RNF layer thickness measured with fdOCT. All 6 eyes had an abnormally thin (1% confidence limit) RNF layer (RNFL) on fdOCT and abnormal (hyporeflective) regions of RNF bundles on AO-SLO in corresponding regions. However, regions of abnormal, but equal, RNFL thickness on fdOCT scans varied in appearance on AO-SLO images. These regions could be largely devoid of RNF bundles (5 eyes), have abnormal-appearing bundles of lower contrast (6 eyes), or have isolated areas with a few relatively normal-appearing bundles (2 eyes). There also were local variations in reflectivity of the fdOCT RNFL that corresponded to the variations in AO-SLO RNF bundle appearance. Relatively similar 10-2 defects with similar fdOCT RNFL thickness profiles can have very different degrees of RNF bundle damage as seen on fdOCT and AO-SLO. While the results point to limitations of fdOCT RNFL thickness as typically analyzed, they also illustrate the potential for improving fdOCT by attending to variations in local intensity.

Identifying the challenges and facilitators of implementing a COPD care bundle.

PubMed

Lennox, Laura; Green, Stuart; Howe, Cathy; Musgrave, Hannah; Bell, Derek; Elkin, Sarah

2014-01-01

Care bundles have been shown to improve outcomes, reduce hospital readmissions and reduce length of hospital stay; therefore increasing the speed of uptake and delivery of care bundles should be a priority in order to deliver more timely improvements and consistent high-quality care. Previous studies have detailed the difficulties of obtaining full compliance to bundle elements but few have described the underlying reasons for this. In order to improve future implementation this paper investigates the challenges encountered by clinical teams implementing a chronic obstructive pulmonary disease (COPD) care bundle and describes actions taken to overcome these challenges. An initial retrospective documentary analysis of data from seven clinical implementation teams was undertaken to review the challenges faced by the clinical teams. Three focus groups with healthcare professionals and managers explored solutions to these challenges developed during the project. Documentary analysis identified 28 challenges which directly impacted implementation of the COPD care bundle within five themes; staffing, infrastructure, process, use of improvement methodology and patient and public involvement. Focus groups revealed that the five most significant challenges for all groups were: staff too busy, staff shortages, lack of staff engagement, added workload of the bundle and patient coding issues. The participants shared facilitating factors used to overcome issues including: shifting perceptions to improve engagement, further education sessions to increase staff participation and gaining buy-in from managers through payment frameworks. Maximising the impact of a care bundle relies on its successful and timely implementation. Teams implementing the COPD care bundle encountered challenges that were common to all teams and sites. Understanding and learning from the challenges faced by previous endeavours and identifying the facilitators to overcoming these barriers provides an opportunity to mitigate issues that waste time and resources, and ensures that training can be tailored to the anticipated challenges.

Anatomical versus non-anatomical single bundle anterior cruciate ligament reconstruction: a cadaveric study of comparison of knee stability.

PubMed

Lim, Hong-Chul; Yoon, Yong-Cheol; Wang, Joon-Ho; Bae, Ji-Hoon

2012-12-01

The purpose of this study was to compare the initial stability of anatomical and non-anatomical single bundle anterior cruciate ligament (ACL) reconstruction and to determine which would better restore intact knee kinematics. Our hypothesis was that the initial stability of anatomical single bundle ACL reconstruction would be superior to that of non-anatomical single bundle ACL reconstruction. Anterior tibial translation (ATT) and internal rotation of the tibia were measured with a computer navigation system in seven pairs of fresh-frozen cadaveric knees under two testing conditions (manual maximum anterior force, and a manual maximum anterior force combined with an internal rotational force). Tests were performed at 0, 30, 60, and 90 degrees of flexion with the ACL intact, the ACL transected, and after reconstruction of one side of a pair with either anatomical or non-anatomical single bundle ACL reconstruction. Under manual maximal anterior force, both reconstruction techniques showed no significant difference of ATT when compared to ACL intact knee state at 30° of knee flexion (p > 0.05). Under the combined anterior and internal rotatory force, non-anatomical single-bundle ACL reconstruction showed significant difference of ATT compared to those in ACL intact group (p < 0.05). In contrast, central anatomical single bundle ACL reconstruction showed no significant difference of ATT compared to those in ACL intact group (p > 0.05). Internal rotation of the tibia showed no significant difference in the ACL intact, the ACL transected, non-anatomical reconstructed and anatomical reconstructed knees. Anatomical single bundle ACL reconstruction restored the initial stability closer to the native ACL under combined anterior and internal rotational forces when compared to non-anatomical ACL single bundle reconstruction.

An Exploration of Human Well-Being Bundles as Identifiers of Ecosystem Service Use Patterns

PubMed Central

Biggs, Reinette; Reyers, Belinda

2016-01-01

We take a social-ecological systems perspective to investigate the linkages between ecosystem services and human well-being in South Africa. A recent paper identified different types of social-ecological systems in the country, based on distinct bundles of ecosystem service use. These system types were found to represent increasingly weak direct feedbacks between nature and people, from rural “green-loop” communities to urban “red-loop” societies. Here we construct human well-being bundles and explore whether the well-being bundles can be used to identify the same social-ecological system types that were identified using bundles of ecosystem service use. Based on national census data, we found three distinct well-being bundle types that are mainly characterized by differences in income, unemployment and property ownership. The distribution of these well-being bundles approximates the distribution of ecosystem service use bundles to a substantial degree: High levels of income and education generally coincided with areas characterised by low levels of direct ecosystem service use (or red-loop systems), while the majority of low well-being areas coincided with medium and high levels of direct ecosystem service use (or transition and green-loop systems). However, our results indicate that transformations from green-loop to red-loop systems do not always entail an immediate improvement in well-being, which we suggest may be due to a time lag between changes in the different system components. Using human well-being bundles as an indicator of social-ecological dynamics may be useful in other contexts since it is based on socio-economic data commonly collected by governments, and provides important insights into the connections between ecosystem services and human well-being at policy-relevant sub-national scales. PMID:27695120

An Exploration of Human Well-Being Bundles as Identifiers of Ecosystem Service Use Patterns.

PubMed

Hamann, Maike; Biggs, Reinette; Reyers, Belinda

2016-01-01

We take a social-ecological systems perspective to investigate the linkages between ecosystem services and human well-being in South Africa. A recent paper identified different types of social-ecological systems in the country, based on distinct bundles of ecosystem service use. These system types were found to represent increasingly weak direct feedbacks between nature and people, from rural "green-loop" communities to urban "red-loop" societies. Here we construct human well-being bundles and explore whether the well-being bundles can be used to identify the same social-ecological system types that were identified using bundles of ecosystem service use. Based on national census data, we found three distinct well-being bundle types that are mainly characterized by differences in income, unemployment and property ownership. The distribution of these well-being bundles approximates the distribution of ecosystem service use bundles to a substantial degree: High levels of income and education generally coincided with areas characterised by low levels of direct ecosystem service use (or red-loop systems), while the majority of low well-being areas coincided with medium and high levels of direct ecosystem service use (or transition and green-loop systems). However, our results indicate that transformations from green-loop to red-loop systems do not always entail an immediate improvement in well-being, which we suggest may be due to a time lag between changes in the different system components. Using human well-being bundles as an indicator of social-ecological dynamics may be useful in other contexts since it is based on socio-economic data commonly collected by governments, and provides important insights into the connections between ecosystem services and human well-being at policy-relevant sub-national scales.

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

Qi, Zhi; Pan, Chungen; Lu, Hong

Research highlights: {yields} One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. {yields} N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. {yields} These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) andmore » vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.« less

Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells

PubMed Central

Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

2017-01-01

Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment. PMID:28187434

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats.

PubMed

Gordon, Rita; Podolski, Igor; Makarova, Ekaterina; Deev, Alexander; Mugantseva, Ekaterina; Khutsyan, Sergey; Sengpiel, Frank; Murashev, Arkady; Vorobyov, Vasily

2017-01-01

Primary memory impairments associated with increased level of amyloid-β (Aβ) in the brain have been shown to be linked, partially, with early pathological changes in the entorhinal cortex (EC) which spread on the whole limbic system. While the hippocampus is known to play a key role in learning and memory mechanisms, it is as yet unclear how its structures are involved in the EC pathology. In this study, changes in memory and neuronal morphology in male Wistar rats intrahippocampally injected with Aβ25-35 were correlated on days 14 and 45 after the injection to reveal specific cognitive-structural associations. The main focus was on the dentate gyrus (DG) and hippocampal areas of CA1 and CA3 because of their involvement in afferent flows from EC to the hippocampus through tri-synaptic (EC → DG → CA3 → CA1) and/or mono-synaptic (EC → CA1) pathways. Evident memory impairments were observed at both time points after Aβ25-35 injection. However, on day 14, populations of morphological intact neurons were decreased in CA3 and, drastically, in CA1, and the DG supramedial bundle was significantly damaged. On day 45, this bundle largely and CA1 neurons partially recovered, whereas CA3 neurons remained damaged. We suggest that Aβ25-35 primarily affects the tri-synaptic pathway, destroying the granular cells in the DG supramedial area and neurons in CA3 and, through the Schaffer collaterals, in CA1. Intrahippocampal pretreatment with hydrated fullerene C60 allows the neurons and their connections to survive the amyloidosis, thus supporting the memory mechanisms.

Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells.

PubMed

Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

2017-03-07

Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.

Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4

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

Allen, Samantha J.; Parthasarathy, Gopal; Darke, Paul L.

G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the process of GPCR desensitization and internalization. GRK4 is implicated in the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associated with hypertension. Here, we describe the 2.6 Å structure of human GRK4α A486V crystallized in the presence of 5'-adenylyl β,γ-imidodiphosphate. The structure of GRK4α is similar to other GRKs, although slight differences exist within the RGS homology (RH) bundle subdomain, substrate-binding site, and kinase C-tail. The RH bundle subdomain and kinase C-terminal lobe form a strikingly acidic surface, whereas the kinase N-terminal lobemore » and RH terminal subdomain surfaces are much more basic. In this respect, GRK4α is more similar to GRK2 than GRK6. A fully ordered kinase C-tail reveals interactions linking the C-tail with important determinants of kinase activity, including the αB helix, αD helix, and the P-loop. Autophosphorylation of wild-type GRK4α is required for full kinase activity, as indicated by a lag in phosphorylation of a peptide from the dopamine D1 receptor without ATP preincubation. In contrast, this lag is not observed in GRK4α A486V. Phosphopeptide mapping by mass spectrometry indicates an increased rate of autophosphorylation of a number of residues in GRK4α A486V relative to wild-type GRK4α, including Ser-485 in the kinase C-tail.« less

Right bundle branch block and anterior wall ST elevation myocardial infarction.

PubMed

Trofin, Monica; Israel, Carsten W; Barold, S Serge

2017-09-01

We report the case of an acute anterior wall ST elevation myocardial infarction with new left anterior fascicular block and pre-existing right bundle branch block. Due to a wide right bundle branch block, no ST segment elevation was visible in lead V1. The left anterior fascicular block was caused by proximal occlusion of the left artery descending and disappeared after acute revascularization. However, also the R' of the right bundle branch block became significantly shorter after revascularization, dismanteling a minor ST segment elevation. The ST elevation in lead V1 in anterior wall infarction and right bundle branch block may merge with the R' and cause a further QRS widening as an "equivalent" to the ST elevation.

Pulsating flow past a tube bundle

NASA Astrophysics Data System (ADS)

Molochnikov, V. M.; Mikheev, N. I.; Vazeev, T. A.; Paereliy, A. A.

2017-11-01

Visualization of the pulsating cross-flow past the in-line and staggered tube bundles has been performed. The frequency and amplitude of forced flow pulsations and the tube pitch in the bundle varied in the experiments. The main attention was focused on the flow pattern in the near wake of the third-row tube. The most indicative regimes of flow past a tube in a bundle have been revealed depending on forced flow unsteadiness parameters. The obtained data have been generalized in the flow maps in the space of dimensionless frequency (Strouhal number, St) and relative pulsation amplitude, β, individually for the in-line and staggered tube arrangement. Three most indicative regimes of pulsating flow past the tubes in a bundle have been singled out in each flow map.

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

Lu Yanning; Beijing Center for Diseases Prevention and Control, 16 Hepingli Middle Street, Dongcheng District, Beijing 100013; Neo, T.L.

SARS-CoV entry is mediated by spike glycoprotein. During the viral and host cellular membrane fusion, HR1 and HR2 form 6-helix bundle, positioning the fusion peptide closely to the C-terminal region of ectodomain to drive apposition and subsequent membrane fusion. Connecting to the HR2 region is a Trp-rich region which is absolutely conserved in members of coronaviruses. To investigate the importance of Trp-rich region in SARS-CoV entry, we produced different mutated S proteins using Alanine scan strategy. SARS-CoV pseudotyped with mutated S protein was used to measure viral infectivity. To restore the aromaticity of Ala-mutants, we performed rescue experiments using phenylalaninemore » substitutions. Our results show that individually substituted Ala-mutants substantially decrease infectivity by >90%, global Ala-mutants totally abrogated infectivity. In contrast, Phe-substituted mutants are able to restore 10-25% infectivity comparing to the wild-type. The results suggest that the Trp-rich region of S protein is essential for SARS-CoV infectivity.« less

Consensus Bundle on Prevention of Surgical Site Infections After Major Gynecologic Surgery.

PubMed

Pellegrini, Joseph E; Toledo, Paloma; Soper, David E; Bradford, William C; Cruz, Deborah A; Levy, Barbara S; Lemieux, Lauren A

2017-01-01

Surgical site infections are the most common complication of surgery in the United States. Of surgeries in women of reproductive age, hysterectomy is one of the most frequently performed, second only to cesarean birth. Therefore, prevention of surgical site infections in women undergoing gynecologic surgery is an ideal topic for a patient safety bundle. The primary purpose of this safety bundle is to provide recommendations that can be implemented into any surgical environment in an effort to reduce the incidence of surgical site infection. This bundle was developed by a multidisciplinary team convened by the Council on Patient Safety in Women's Health Care. The bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. In addition to recommendations for practice, each of the domains stresses communication and teamwork between all members of the surgical team. Although the bundle components are designed to be adaptable to work in a variety of clinical settings, standardization within institutions is encouraged.

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

PubMed Central

Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Mugnaini, Enrico; Bartles, James R.

2008-01-01

The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca2+. In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. PMID:16909209

Improvements to Wire Bundle Thermal Modeling for Ampacity Determination

NASA Technical Reports Server (NTRS)

Rickman, Steve L.; Iannello, Christopher J.; Shariff, Khadijah

2017-01-01

Determining current carrying capacity (ampacity) of wire bundles in aerospace vehicles is critical not only to safety but also to efficient design. Published standards provide guidance on determining wire bundle ampacity but offer little flexibility for configurations where wire bundles of mixed gauges and currents are employed with varying external insulation jacket surface properties. Thermal modeling has been employed in an attempt to develop techniques to assist in ampacity determination for these complex configurations. Previous developments allowed analysis of wire bundle configurations but was constrained to configurations comprised of less than 50 elements. Additionally, for vacuum analyses, configurations with very low emittance external jackets suffered from numerical instability in the solution. A new thermal modeler is presented allowing for larger configurations and is not constrained for low bundle infrared emissivity calculations. Formulation of key internal radiation and interface conductance parameters is discussed including the effects of temperature and air pressure on wire to wire thermal conductance. Test cases comparing model-predicted ampacity and that calculated from standards documents are presented.

Increased reliability of nuclear magnetic resonance protein structures by consensus structure bundles.

PubMed

Buchner, Lena; Güntert, Peter

2015-02-03

Nuclear magnetic resonance (NMR) structures are represented by bundles of conformers calculated from different randomized initial structures using identical experimental input data. The spread among these conformers indicates the precision of the atomic coordinates. However, there is as yet no reliable measure of structural accuracy, i.e., how close NMR conformers are to the "true" structure. Instead, the precision of structure bundles is widely (mis)interpreted as a measure of structural quality. Attempts to increase precision often overestimate accuracy by tight bundles of high precision but much lower accuracy. To overcome this problem, we introduce a protocol for NMR structure determination with the software package CYANA, which produces, like the traditional method, bundles of conformers in agreement with a common set of conformational restraints but with a realistic precision that is, throughout a variety of proteins and NMR data sets, a much better estimate of structural accuracy than the precision of conventional structure bundles. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new role for the architecture of microvillar actin bundles in apical retention of membrane proteins.

PubMed

Revenu, Céline; Ubelmann, Florent; Hurbain, Ilse; El-Marjou, Fatima; Dingli, Florent; Loew, Damarys; Delacour, Delphine; Gilet, Jules; Brot-Laroche, Edith; Rivero, Francisco; Louvard, Daniel; Robine, Sylvie

2012-01-01

Actin-bundling proteins are identified as key players in the morphogenesis of thin membrane protrusions. Until now, functional redundancy among the actin-bundling proteins villin, espin, and plastin-1 has prevented definitive conclusions regarding their role in intestinal microvilli. We report that triple knockout mice lacking these microvillar actin-bundling proteins suffer from growth delay but surprisingly still develop microvilli. However, the microvillar actin filaments are sparse and lack the characteristic organization of bundles. This correlates with a highly inefficient apical retention of enzymes and transporters that accumulate in subapical endocytic compartments. Myosin-1a, a motor involved in the anchorage of membrane proteins in microvilli, is also mislocalized. These findings illustrate, in vivo, a precise role for local actin filament architecture in the stabilization of apical cargoes into microvilli. Hence, the function of actin-bundling proteins is not to enable microvillar protrusion, as has been assumed, but to confer the appropriate actin organization for the apical retention of proteins essential for normal intestinal physiology.

Association of a Bundled-Payment Program With Cost and Outcomes in Full-Cycle Breast Cancer Care.

PubMed

Wang, C Jason; Cheng, Skye H; Wu, Jen-You; Lin, Yi-Ping; Kao, Wen-Hsin; Lin, Chia-Li; Chen, Yin-Jou; Tsai, Shu-Ling; Kao, Feng-Yu; Huang, Andrew T

2017-03-01

Value-driven payment system reform is a potential tool for aligning economic incentives with the improvement of quality and efficiency of health care and containment of cost. Such a payment system has not been researched satisfactorily in full-cycle cancer care. To examine the association of outcomes and medical expenditures with a bundled-payment pay-for-performance program for breast cancer in Taiwan compared with a fee-for-service (FFS) program. Data were obtained from the Taiwan Cancer Database, National Health Insurance Claims Data, the National Death Registry, and the bundled-payment enrollment file. Women with newly diagnosed breast cancer and a documented first cancer treatment from January 1, 2004, to December 31, 2008, were selected from the Taiwan Cancer Database and followed up for 5 years, with the last follow-up data available on December 31, 2013. Patients in the bundled-payment program were matched at a ratio of 1:3 with control individuals in an FFS program using a propensity score method. The final sample of 17 940 patients included 4485 (25%) in the bundled-payment group and 13 455 (75%) in the FFS group. Rates of adherence to quality indicators, survival rates, and medical payments (excluding bonuses paid in the bundled-payment group). The Kaplan-Meier method was used to calculate 5-year overall and event-free survival rates by cancer stage, and the Cox proportional hazards regression model was used to examine the effect of the bundled-payment program on overall and event-free survival. Sensitivity analysis for bonus payments in the bundled-payment group was also performed. The study population included 17 940 women (mean [SD] age, 52.2 [10.3] years). In the bundled-payment group, 1473 of 4215 patients (34.9%) with applicable quality indicators had full (100%) adherence to quality indicators compared with 3438 of 12 506 patients (27.5%) with applicable quality indicators in the FFS group (P < .001). The 5-year event-free survival rates for patients with stages 0 to III breast cancer were 84.48% for the bundled-payment group and 80.88% for the FFS group (P < .01). Although the 5-year medical payments of the bundled-payment group remained stable, the cumulative medical payments for the FFS group steadily increased from $16 000 to $19 230 and exceeded pay-for-performance bundled payments starting in 2008. In Taiwan, compared with the regular FFS program, bundled payment may lead to better adherence to quality indicators, better outcomes, and more effective cost-control over time.

Reducing Clostridium difficile in the inpatient setting: A systematic review of the adherence to and effectiveness of C. difficile prevention bundles

PubMed Central

Barker, Anna; Ngam, Caitlyn; Musuuza, Jackson; Vaughn, Valerie M.; Safdar, Nasia

2017-01-01

Background Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea and its prevention is an urgent public health priority. However, reduction of CDI is challenging, because of its complex pathogenesis, large reservoirs of colonized patients, and persistence of infectious spores. The literature lacks high quality evidence for evaluating interventions, and many hospitals have implemented bundled interventions to reduce CDI with variable results. Thus, we conducted a systematic review to examine the components of CDI bundles, their implementation processes, and their impact on CDI rates. Methods We conducted a comprehensive literature search of multiple computerized databases from their date of inception through April 30, 2016. The protocol was registered in PROSPERO. Bundle effectiveness, adherence, and study quality was assessed for each study meeting criteria for inclusion. Results In the 26 studies that met inclusion criteria for this review, we found that implementation and adherence factors to interventions were variably and incompletely reported, making study reproducibility and replicability challenging. Despite contextual differences and the variety of bundle components utilized, all 26 studies reported an improvement in CDI rates. However, given the lack of randomized controlled trials in the literature, assessing a causal relationship between bundled interventions and CDI rates is currently impossible. Conclusions Cluster randomized trials that include a rigorous assessment of the implementation of bundled interventions are urgently needed to causally test the effect of intervention bundles on CDI rates. PMID:28343455

Distal Extension of the Direct Anterior Approach to the Hip: A Cadaveric Feasibility Study.

PubMed

Ghijselings, Stijn G M; Driesen, Ronald; Simon, Jean-Pierre; Corten, Kristoff

2017-01-01

The direct anterior approach (DAA) is becoming more popular as the standard surgical approach for primary total hip arthroplasty. However, femoral complications of up to 2.8% have been reported. Therefore, it is important for surgeons to understand the periarticular neurovascular anatomy in order to safely deal with intraoperative complications. Anatomic dissections were performed on 20 cadaveric hips. The neurovascular structures anterior to the femur and distal to the intertrochanteric line were dissected and its position was described in relation to anatomic landmarks easily identified through the DAA: anterior superior iliac spine (ASIS), the insertion of the gluteus minimus (GM), and the lesser trochanter (LT). Two clearly distinguishable neurovascular bundles running to the vastus lateralis were seen in 17 of 20 specimens. The average distances to the landmarks were as follows: ASIS-1st bundle = 12.3 cm (range, 9.7-14.5); GM-1st bundle = 3.2 cm (range, 2.2-4); LT-1st bundle = 1.6 cm (range, 0.7-2.8); 1st bundle-2nd bundle = 3.3 cm (range, 1.8-6.1). A consistent pattern of 2 clearly distinguishable neurovascular bundles was seen in 85% of the specimens. Knowledge of the position of these neurovascular bundles in relation to the anatomic landmarks makes distal femoral extension of the DAA feasible. Further clinical studies are needed to confirm the safety of the extensile anterior approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical design of endoscopic shape-tracker using quantum dots embedded in fiber bundles

NASA Astrophysics Data System (ADS)

Eisenstein, Jessica; Gavalis, Robb; Wong, Peter Y.; Cao, Caroline G. L.

2009-08-01

Colonoscopy is the current gold standard for colon cancer screening and diagnosis. However, the near-blind navigation process employed during colonoscopy results in endoscopist disorientation and scope looping, leading to missed detection of tumors, incorrect localization, and pain for the patient. A fiber optic bend sensor, which would fit into the working channel of a colonoscope, is developed to aid navigation through the colon during colonoscopy. The bend sensor is comprised of a bundle of seven fibers doped with quantum dots (QDs). Each fiber within the bundle contains a unique region made up of three zones with differently-colored QDs, spaced 120° apart circumferentially on the fiber. During bending at the QD region, light lost from the fiber's core is coupled into one of the QD zones, inducing fluorescence of the corresponding color whose intensity is proportional to the degree of bending. A complementary metal oxide semiconductor camera is used to obtain an image of the fluorescing end faces of the fiber bundle. The location of the fiber within the bundle, the color of fluorescence, and the fluorescence intensity are used to determine the bundle's bending location, direction, and degree of curvature, respectively. Preliminary results obtained using a single fiber with three QD zones and a seven-fiber bundle containing one active fiber with two QDs (180° apart) demonstrate the feasibility of the concept. Further developments on fiber orientation during bundling and the design of a graphical user interface to communicate bending information are also discussed.

Differences in work environment for staff as an explanation for variation in central line bundle compliance in intensive care units.

PubMed

Lee, Yuna S H; Stone, Patricia W; Pogorzelska-Maziarz, Monika; Nembhard, Ingrid M

Central line-associated bloodstream infections (CLABSIs) are a common and costly quality problem, and their prevention is a national priority. A decade ago, researchers identified an evidence-based bundle of practices that reduce CLABSIs. Compliance with this bundle remains low in many hospitals. The aim of this study was to assess whether differences in core aspects of work environments-workload, quality of relationships, and prioritization of quality-are associated with variation in maximal CLABSI bundle compliance, that is, compliance 95%-100% of the time in intensive care units (ICUs). A cross-sectional study of hospital medical-surgical ICUs in the United States was done. Data on work environment and bundle compliance were obtained from the Prevention of Nosocomial Infections and Cost-Effectiveness Refined Survey completed in 2011 by infection prevention directors, and data on ICU and hospital characteristics were obtained from the National Healthcare Safety Network. Factor and multilevel regression analyses were conducted. Reasonable workload and prioritization of quality were positively associated with maximal CLABSI bundle compliance. High-quality relationships, although a significant predictor when evaluated apart from workload and prioritization of quality, had no significant effect after accounting for these two factors. Aspects of the staff work environment are associated with maximal CLABSI bundle compliance in ICUs. Our results suggest that hospitals can foster improvement in ensuring maximal CLABSI bundle compliance-a crucial precursor to reducing CLABSI infection rates-by establishing reasonable workloads and prioritizing quality.

Transduction channels' gating can control friction on vibrating hair-cell bundles in the ear.

PubMed

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-05-20

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell's characteristic frequency of responsiveness.

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

PubMed Central

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-01-01

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force–displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness. PMID:24799674

Telemetry in bundles: delay-tolerant networking for delay-challenged applications

NASA Technical Reports Server (NTRS)

Burleigh, S.

2003-01-01

This paper presents an overview of DTN concepts, including bundles and the Bundling overlay protocol. One possible scenario for the application of DTN to a telemetry return problem is described, and there is a brief discussion of the current state of DTN technology development.

"Bundling" in Learning.

ERIC Educational Resources Information Center

Spiegel, U.; Templeman, J.

1996-01-01

Applies the literature of bundling, tie-in sales, and vertical integration to higher education. Students are often required to purchase a package of courses, some of which are unrelated to their major. This kind of bundling policy can be utilized as a profit-maximizing strategy for universities exercising a degree of monopolistic power. (12…

The MIMIC Model as a Tool for Differential Bundle Functioning Detection

ERIC Educational Resources Information Center

Finch, W. Holmes

2012-01-01

Increasingly, researchers interested in identifying potentially biased test items are encouraged to use a confirmatory, rather than exploratory, approach. One such method for confirmatory testing is rooted in differential bundle functioning (DBF), where hypotheses regarding potential differential item functioning (DIF) for sets of items (bundles)…

Stability of the parabolic Poincaré bundle

NASA Astrophysics Data System (ADS)

Basu, Suratno; Biswas, Indranil; Dan, Krishanu

Given a compact Riemann surface X and a moduli space Mα(Λ) of parabolic stable bundles on it of fixed determinant of complete parabolic flags, we prove that the Poincaré parabolic bundle on X × Mα(Λ) is parabolic stable with respect to a natural polarization on X × Mα(Λ).

Passive millimeter wave differential interference contrast polarimetry

DOEpatents

Bernacki, Bruce E; Kelly, James F; Sheen, David M; Tedeschi, Jonathan R; Hall, Thomas E; Hatchell, Brian K; Valdez, Patrick; McMakin, Douglas L

2014-04-29

Differential polarization imaging systems include an axicon configured to provide a displacement of ray bundles associated with different image patches. The displaced ray bundles are directed to antenna horns and orthomode transducers so as to provide outputs correspond to orthogonal linear states of polarization (SOPs). The outputs are directed to a differential radiometer so that Stokes parameter differences between image patches can be obtained. The ray bundle displacements can be selected to correspond to a mechanical spacing of antenna horns. In some examples, ray bundle displacement corresponds to a displacement less than the diffraction limit.

Characterization of a space orbited incoherent fiber optic bundle

NASA Technical Reports Server (NTRS)

Dewalt, Stephen A.; Taylor, Edward W.

1993-01-01

The results of a study performed to determine the effects of adverse space environments on a bundle of over 1800 optical fibers orbited for 69 months are reported. Experimental results are presented on an incoherent fiber optic bundle oriented in low Earth orbit aboard the Long Duration Exposure Facility (LDEF) satellite as part of the Space Environment Effects Experiment (M0006). Measurements were performed to determine if space induced radiation effects changed the fiber bundle characteristics. Data demonstrating the success of light transmitting fibers to withstand the adverse space environment are presented.

A Heisenberg Algebra Bundle of a Vector Field in Three-Space and its Weyl Quantization

NASA Astrophysics Data System (ADS)

Binz, Ernst; Pods, Sonja

2006-01-01

In these notes we associate a natural Heisenberg group bundle Ha with a singularity free smooth vector field X = (id,a) on a submanifold M in a Euclidean three-space. This bundle yields naturally an infinite dimensional Heisenberg group HX∞. A representation of the C*-group algebra of HX∞ is a quantization. It causes a natural Weyl-deformation quantization of X. The influence of the topological structure of M on this quantization is encoded in the Chern class of a canonical complex line bundle inside Ha.

Ab initio density functional theory investigation of crystalline bundles of polygonized single-walled silicon carbide nanotubes

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2008-11-01

By using ab initio density functional theory, the structural characterizations and electronic properties of two large-diameter (13, 13) and (14, 14) armchair silicon carbide nanotube (SiCNT) bundles are investigated. Full structural optimizations show that the cross sections of these large-diameter SiCNTs in the bundles have a nearly hexagonal shape. The effects of inter-tube coupling on the electronic dispersions of large-diameter SiCNT bundles are demonstrated. By comparing the band structures of the triangular lattices of (14, 14) SiCNTs with nearly hexagonal and circular cross sections we found that the polygonization of the tubes in the bundle leads to a further dispersion of the occupied bands and an increase in the bandgap by 0.18 eV.

Ab initio density functional theory investigation of crystalline bundles of polygonized single-walled silicon carbide nanotubes.

PubMed

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2008-11-19

By using ab initio density functional theory, the structural characterizations and electronic properties of two large-diameter (13, 13) and (14, 14) armchair silicon carbide nanotube (SiCNT) bundles are investigated. Full structural optimizations show that the cross sections of these large-diameter SiCNTs in the bundles have a nearly hexagonal shape. The effects of inter-tube coupling on the electronic dispersions of large-diameter SiCNT bundles are demonstrated. By comparing the band structures of the triangular lattices of (14, 14) SiCNTs with nearly hexagonal and circular cross sections we found that the polygonization of the tubes in the bundle leads to a further dispersion of the occupied bands and an increase in the bandgap by 0.18 eV.

Effects of inter-tube coupling on the electro-optical properties of silicon carbide nanotube bundles studied by density functional theory

NASA Astrophysics Data System (ADS)

Behzad, Somayeh

2015-09-01

The electronic and optical properties of bundled armchair and zigzag silicon carbide nanotubes (SiCNTs) are investigated by using density functional theory. The effects of inter-tube coupling on the electronic dispersions of SiCNT bundles are demonstrated. It was found that the band structure of (6, 0) SiCNT bundle shows metallic feature. The calculated dielectric functions of the armchair and zigzag bundles are similar to that of the isolated tubes, except for the appearance of broadened peaks, small shifts of peak positions about 0.1 eV and increasing of peak intensities. For (6, 0) SiCNT with smaller radius, by considering interband and interaband transitions, the band structure coupling causes an extra peak at low energies.

Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study

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

Rakovec, P.; Kranjec, I.; Fettich, J.J.

1985-01-01

Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combinedmore » electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates.« less

Absence of bundle structure in the neocortex of the reeler mouse at the embryonic stage. Studies by scanning electron microscopic fractography.

PubMed

Mikoshiba, K; Nishimura, Y; Tsukada, Y

The reeler mutant mouse is characterized by a derangement of the cerebral cortical structure due to abnormalities during the migration step at the embryonic stage. We have analyzed both the control and reeler cerebral cortex by means of scanning electron microscopic fractography. In the control cerebral cortex, the bundle formation was composed of fine fibers on which the migrating neuroblasts were attached perpendicular to the pial surface, whereas no bundle formation was observed in the reeler; instead, there was a fine meshwork of fibers surrounding the neuroblasts. The possible role of bundle formation in the normal cerebral cortex and the correlation between the inability of cells to migrate and the absence of bundle formation in the reeler is discussed.

The impact of Lean bundles on hospital performance: does size matter?

PubMed

Al-Hyari, Khalil; Abu Hammour, Sewar; Abu Zaid, Mohammad Khair Saleem; Haffar, Mohamed

2016-10-10

Purpose The purpose of this paper is to study the effect of the implementation of Lean bundles on hospital performance in private hospitals in Jordan and evaluate how much the size of organization can affect the relationship between Lean bundles implementation and hospital performance. Design/methodology/approach The research is considered as quantitative method (descriptive and hypothesis testing). Three statistical techniques were adopted to analyse the data. Structural equation modeling techniques and multi-group analysis were used to examine the research's hypothesis, and to perform the required statistical analysis of the data from the survey. Reliability analysis and confirmatory factor analysis were used to test the construct validity, reliability and measurement loadings that were performed. Findings Lean bundles have been identified as an effective approach that can dramatically improve the organizational performance of private hospitals in Jordan. Main Lean bundles - just in time, human resource management, and total quality management are applicable to large, small and medium hospitals without significant differences in advantages that depend on size. Originality/value According to the researchers' best knowledge, this is the first research that studies the impact of Lean bundles implementation in healthcare sector in Jordan. This research also makes a significant contribution for decision makers in healthcare to increase their awareness of Lean bundles.

Implementing the ABCDE Bundle into Everyday Care: Opportunities, Challenges and Lessons Learned for Implementing the ICU Pain, Agitation and Delirium (PAD) Guidelines

PubMed Central

Balas, Michele C.; Burke, William J.; Gannon, David; Cohen, Marlene Z.; Colburn, Lois; Bevil, Catherine; Franz, Doug; Olsen, Keith M.; Ely, E. Wesley; Vasilevskis, Eduard E.

2014-01-01

Objective The Awakening and Breathing Coordination, Delirium monitoring/management and Early exercise/mobility (ABCDE) bundle is an evidence-based, interprofessional, multicomponent strategy for minimizing sedative exposure, reducing duration of mechanical ventilation and managing intensive care unit (ICU) acquired delirium and weakness. The purpose of this study was to identify facilitators and barriers to ABCDE bundle adoption and to evaluate the extent to which bundle implementation was effective, sustainable, and conducive to dissemination. Design Prospective, before-after, mixed-methods study. Setting Five adult ICUs, 1 step-down unit, and a special care unit located in a 624 bed, academic medical center Subjects Interprofessional ICU team members at participating institution. Interventions and Measurements In collaboration with the participating institution, we developed, implemented, and refined an ABCDE bundle policy. Over the course of an 18 month period, all ICU team members were offered the opportunity to participate in numerous, multimodal educational efforts. Three focus group sessions, 3 online surveys, and 1 educational evaluation were administered in an attempt to identify facilitators and barriers to bundle adoption. Main Results Factors believed to facilitate bundle implementation included: 1) the performance of daily, interdisciplinary, rounds, 2) engagement of key implementation leaders, 3) sustained and diverse educational efforts, and 4) the bundle's quality and strength. Barriers identified included: 1) intervention related issues (e.g. timing of trials, fear of adverse events), 2) communication and care coordination challenges, 3) knowledge deficits, 4) workload concerns, and 5) documentation burden. Despite these challenges, participants believed implementation ultimately benefited patients, improved interdisciplinary communication, and empowered nurses and other ICU team members. Conclusions In this study of the implementation of the ABCDE bundle in a tertiary care setting, clear factors were identified that both advanced and impeded adoption of this complex intervention that requires interprofessional education, coordination, and cooperation. Focusing on these factors preemptively should enable a more effective and lasting implementation of the bundle and better care for critically ill patients. Lessons learned from this study will also help healthcare providers optimize implementation of the recent ICU Pain, Agitation and Delirium (PAD) Guidelines, which has many similarities but also some important differences as compared to the ABCDE bundle PMID:23989089

Are perioperative bundles associated with reduced postoperative morbidity in women undergoing benign hysterectomy? Retrospective cohort analysis of 16,286 cases in Michigan.

PubMed

Harris, John A; Sammarco, Anne G; Swenson, Carolyn W; Uppal, Shitanshu; Kamdar, Neil; Campbell, Darrel; Evilsizer, Sarah; DeLancey, John O; Morgan, Daniel M

2017-05-01

Healthcare teams that frequently follow a bundle of evidence-based processes provide care with lower rates of morbidity. Few process bundles to improve surgical outcomes in hysterectomy have been identified. The purpose of this study was to investigate whether a bundle of 4 perioperative care processes is associated with fewer postoperative complications and readmissions for hysterectomies in the Michigan Surgical Quality Collaborative. A bundle of perioperative care process goals was developed retrospectively with 30-day peri- and postoperative outcome data from the Hysterectomy Initiative in Michigan Surgical Quality Collaborative. All benign hysterectomies that had been performed between January 2013 and January 2015 were included. Based on evidence of lower complication rates after benign hysterectomy, the following processes were considered to be the "bundle": use of guideline-appropriate preoperative antibiotics, a minimally invasive surgical approach, operative duration <120 minutes, and avoidance of intraoperative hemostatic agent use. Each process was considered present or absent, and the number of processes was summed for a bundle score that ranged from 0-4. Cases with a score of zero were excluded. Outcomes measured were rates of complications (any and major) and hospital readmissions, all within 30 days of surgery. Postoperative events that were considered a "major complication" included acute renal failure, cardiac arrest that required cardiopulmonary resuscitation, central line infection, cerebral vascular accident, death, deep vein thrombosis, intestinal obstruction, myocardial infarction, pelvic abscess, pulmonary embolism, rectovaginal fistula, sepsis, surgical site infection (deep and organ-space), unplanned intubation, ureteral obstruction, and ureterovaginal and vesicovaginal fistula. The outcome "any complication" included all those events already described in addition to blood transfusion within 72 hours of surgery, urinary tract infection, and superficial surgical site infection. Outcomes were adjusted for patient demographics, surgical factors, and hospital-level clustering effects. There were 16,286 benign hysterectomies available for analysis. Among all hysterectomies that were reviewed, 33.6% met criteria for all bundle processes; however, there was wide variation in the rate among the 56 hospitals in the study sample with 9.1% of cases at the lowest quartile and 60.4% at the highest quartile of hospitals that met criteria for all bundle processes. Overall, the rate of any complication was 6.8% and of any major complication was 2.3%. The rate of hospital readmissions was 3.6%. After adjustment for confounders, in cases in which all bundle criterion were met compared with cases in which all bundle criterion were not met, the rate of any complications increased from 4.3-7.8% (P<.001); major complications increased from 1.7-2.6% (P<.001), and readmissions increased from 2.6-4.1% (P<.001). After adjustment for confounders, hospitals with greater rates of meeting all 4 criteria were associated significantly with lower hospital-level rates of postoperative complications (P<.001) and readmissions (P<.001). This multiinstitutional evaluation reveals that reduced morbidity and readmission are associated with rates of bundle compliance. The proposed bundle is a surgical goal, which is not possible in every case, and there is significant variation in the proportion of cases meeting all 4 bundle processes in Michigan hospitals. Implementation of evidence-based process bundles at a healthcare system level are worthy of prospective study to determine whether improvements in patient outcomes are possible. Copyright © 2017 Elsevier Inc. All rights reserved.

CO 2 Capture by Cold Membrane Operation with Actual Power Plant Flue Gas

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

Chaubey, Trapti; Kulkarni, Sudhir; Hasse, David

The main objective of the project was to develop a post-combustion CO 2 capture process based on the hybrid cold temperature membrane operation. The CO 2 in the flue gas from coal fired power plant is pre-concentrated to >60% CO 2 in the first stage membrane operation followed by further liquefaction of permeate stream to achieve >99% CO 2 purity. The aim of the project was based on DOE program goal of 90% CO 2 capture with >95% CO 2 purity from Pulverized Coal (PC) fired power plants with $40/tonne of carbon capture cost by 2025. The project moves themore » technology from TRL 4 to TRL 5. The project involved optimization of Air Liquide commercial 12” PI-1 bundle to improve the bundle productivity by >30% compared to the previous baseline (DE-FE0004278) using computational fluid dynamics (CFD) modeling and bundle testing with synthetic flue gas at 0.1 MWe bench scale skid located at Delaware Research and Technology Center (DRTC). In parallel, the next generation polyimide based novel PI-2 membrane was developed with 10 times CO 2 permeance compared to the commercial PI-1 membrane. The novel PI-2 membrane was scaled from mini-permeator to 1” permeator and 1” bundle for testing. Bundle development was conducted with a Development Spin Unit (DSU) installed at MEDAL. Air Liquide’s cold membrane technology was demonstrated with real coal fired flue gas at the National Carbon Capture Center (NCCC) with a 0.3 MWe field-test unit (FTU). The FTU was designed to incorporate testing of two PI-1 commercial membrane bundles (12” or 6” diameter) in parallel or series. A slip stream was sent to the next generation PI-2 membrane for testing with real flue gas. The system exceeded performance targets with stable PI-1 membrane operation for over 500 hours of single bundle, steady state testing. The 12” PI-1 bundle exceeded the productivity target by achieving ~600 Nm3/hr, where the target was set at ~455 Nm3/hr at 90% capture rate. The cost of 90% CO 2 capture from a 550 MWe net coal power plant was estimated between 40 and $45/tonne. A 6” PI-1 bundle exhibited superior bundle performance compared to the 12” PI-1 bundle. However, the carbon capture cost was not lower with the 6” PI-1 bundle due to the higher bundle installed cost. A 1” PI-1 bundle was tested to compare bundles with different length / diameter ratios. This bundle exhibited the lowest performance due to the different fiber winding pattern and increased bundle non-ideality. Several long-term and parametric tests were conducted with 3,200 hours of total run-time at NCCC. Finally, the new PI-2 membrane fiber was tested at a small scale (1” modules) in real flue gas and exhibited up to 10 times the CO 2 permeance and slightly lower CO 2/N 2 selectivity as the commercial PI-1 fiber. This corresponded to a projected 4 - 5 times increase in the productivity per bundle and a potential cost reduction of $3/tonne for CO2 capture, as compared with PI-1. An analytical campaign was conducted to trace different impurities such as NOx, mercury, Arsenic, Selenium in gas and liquid samples through the carbon capture system. An Environmental, Health and Safety (EH&S) analysis was completed to estimate emissions from a 550 MWe net power plant with carbon capture using cold membrane. A preliminary design and cost analysis was completed for 550 tpd (~25 MWe) plant to assess the capital investment and carbon capture cost for PI-1 and PI-2 membrane solutions from coal fired flue gas. A comparison was made with an amine based solution with significant cost advantage for the membrane at this scale. Additional preliminary design and cost analysis was completed between coal, natural gas and SMR flue gas for carbon capture at 550 tpd (~25 MWe) plant.« less

Project IMPACT Pilot Report: Feasibility of Implementing a Hospital-to-Home Transition Bundle.

PubMed

Mallory, Leah A; Osorio, Snezana Nena; Prato, B Stephen; DiPace, Jennifer; Schmutter, Lisa; Soung, Paula; Rogers, Amanda; Woodall, William J; Burley, Kayla; Gage, Sandra; Cooperberg, David

2017-03-01

To improve hospital to home transitions, a 4-element pediatric patient-centered transition bundle was developed, including: a transition readiness checklist; predischarge teach-back education; timely and complete written handoff to the primary care provider; and a postdischarge phone call. The objective of this study was to demonstrate the feasibility of bundle implementation and report initial outcomes at 4 pilot sites. Outcome measures included postdischarge caregiver ability to teach-back key home management information and 30-day reuse rates. A multisite, observational time series using multiple planned sequential interventions to implement bundle components with non-technology-supported and technology-supported patients. Data were collected via electronic health record reviews and during postdischarge phone calls. Statistical process control charts were used to assess outcomes. Four pilot sites implemented the bundle between January 2014 and May 2015 for 2601 patients, of whom 1394 had postdischarge telephone encounters. Improvement was noted in the implementation of all bundle elements with the transitions readiness checklist posing the greatest feasibility challenge. Phone contact connection rates were 69%. Caregiver ability to teach-back essential home management information postdischarge improved from 18% to 82%. No improvement was noted in reuse rates, which differed dramatically between technology-supported and non-technology-supported patients. A pediatric care transition bundle was successfully tested and implemented, as demonstrated by improvement in all process measures, as well as caregiver home management skills. Important considerations for successful implementation and evaluation of the discharge bundle include the role of local context, electronic health record integration, and subgroup analysis for technology-supported patients. Copyright © 2017 by the American Academy of Pediatrics.

Decreased Surgical Site Infection Rate in Hysterectomy: Effect of a Gynecology-Specific Bundle.

PubMed

Andiman, Sarah E; Xu, Xiao; Boyce, John M; Ludwig, Elizabeth M; Rillstone, Heidi R W; Desai, Vrunda B; Fan, Linda L

2018-06-01

We implemented a hysterectomy-specific surgical site infection prevention bundle after a higher-than-expected surgical site infection rate was identified at our institution. We evaluate how this bundle affected the surgical site infection rate, length of hospital stay, and 30-day postoperative readmission rate. This is a quality improvement study featuring retrospective analysis of a prospectively implemented, multidisciplinary team-designed surgical site infection prevention bundle that consisted of chlorhexidine-impregnated preoperative wipes, standardized aseptic surgical preparation, standardized antibiotic dosing, perioperative normothermia, surgical dressing maintenance, and direct feedback to clinicians when the protocol was breached. There were 2,099 hysterectomies completed during the 33-month study period. There were 61 surgical site infections (4.51%) in the pre-full bundle implementation period and 14 (1.87%) in the post-full bundle implementation period; we found a sustained reduction in the proportion of patients experiencing surgical site infection during the last 8 months of the study period. After adjusting for clinical characteristics, patients who underwent surgery after full implementation were less likely to develop a surgical site infection (adjusted odds ratio [OR] 0.46, P=.01) than those undergoing surgery before full implementation. Multivariable regression analysis showed no statistically significant difference in postoperative days of hospital stay (adjusted mean ratio 0.95, P=.09) or rate of readmission for surgical site infection-specific indication (adjusted OR 2.65, P=.08) between the before and after full-bundle implementation periods. The multidisciplinary implementation of a gynecologic perioperative surgical site infection prevention bundle was associated with a significant reduction in surgical site infection rate in patients undergoing hysterectomy.

Bundling of Reimbursement for Inferior Vena Cava Filter Placement Resulted in Significantly Decreased Utilization between 2012 and 2014.

PubMed

Glocker, Roan J; TerBush, Matthew J; Hill, Elaine L; Guido, Joseph J; Doyle, Adam; Ellis, Jennifer L; Raman, Kathleen; Morrow, Gary R; Stoner, Michael C

2017-01-01

On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled. Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location. In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P < 0.0001) with 2012, 2013, and 2014 having lower rates of ICVF utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P < 0.0001). Following the bundling of reimbursement for IVCF placement, procedural utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist. Copyright © 2016 Elsevier Inc. All rights reserved.

The 5 Clinical Pillars of Value for Total Joint Arthroplasty in a Bundled Payment Paradigm.

PubMed

Kim, Kelvin; Iorio, Richard

2017-06-01

Our large, urban, tertiary, university-based institution reflects on its 4-year experience with Bundled Payments for Care Improvement. We will describe the importance of 5 clinical pillars that have contributed to the early success of our bundled payment initiative. We are convinced that value-based care delivered through bundled payment initiatives is the best method to optimize patient outcomes while rewarding surgeons and hospitals for adapting to the evolving healthcare reforms. We summarize a number of experiences and lessons learned since the implementation of Bundled Payments for Care Improvement at our institution. Our experience has led to the development of more refined clinical pathways and coordination of care through evidence-based approaches. We have established that the success of the bundled payment program rests on the following 5 main clinical pillars: (1) optimizing patient selection and comorbidities; (2) optimizing care coordination, patient education, shared decision making, and patient expectations; (3) using a multimodal pain management protocol and minimizing narcotic use to facilitate rapid rehabilitation; (4) optimizing blood management, and standardizing venous thromboembolic disease prophylaxis treatment by risk standardizing patients and minimizing the use of aggressive anticoagulation; and (5) minimizing post-acute facility and resource utilization, and maximizing home resources for patient recovery. From our extensive experience with bundled payment models, we have established 5 clinical pillars of value for bundled payments. Our hope is that these principles will help ease the transition to value-based care for less-experienced healthcare systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Using the HELIOS facility for assessment of bundle-jacket thermal coupling in a CICC

NASA Astrophysics Data System (ADS)

Lacroix, B.; Rousset, B.; Cloez, H.; Decool, P.; Duchateau, J. L.; Hoa, C.; Luchier, N.; Nicollet, S.; Topin, F.

2016-12-01

In a Cable In Conduit Conductor (CICC) cooled by forced circulation of supercritical helium, the heat exchange in the bundle region can play a significant role for conductor safe operation, while remaining a quite uncertain parameter. Heat exchange between bundle and jacket depends on the relative contributions of convective heat transfer due to the helium flow inside the bundle and of thermal resistance due to the wrappings between the cable and the conduit. In order to qualify this thermal coupling at realistic operating conditions, a dedicated experiment on a 1.2 m sample of ITER Toroidal Field (TF) dummy conductor was designed and performed in the HELIOS test facility at CEA Grenoble. Several methods were envisaged, and the choice was made to assess bundle-jacket heat transfer coefficient by measuring the temperature of a solid copper cylinder inserted over the conductor jacket and submitted to heat deposition on its outer surface. The mock-up was manufactured and tested in spring 2015. Bundle-jacket heat transfer coefficient was found in the range 300-500 W m-2 K-1. Results analysis suggests that the order of magnitude of convective heat transfer coefficient inside bundle is closer to Colburn-Reynolds analogy than to Dittus-Boelter correlation, and that bundle-jacket thermal coupling is mainly limited by thermal resistance due to wrappings. A model based on an equivalent layer of stagnant helium between wraps and jacket was proposed and showed a good consistency with the experiment, with relevant values for the helium layer thickness.

Positional relationships between the masticatory muscles and their innervating nerves with special reference to the lateral pterygoid and the midmedial and discotemporal muscle bundles of temporalis

PubMed Central

AKITA, KEIICHI; SHIMOKAWA, TAKASHI; SATO, TATSUO

2000-01-01

For an accurate assessment of jaw movement, it is crucial to understand the comprehensive formation of the masticatory muscles with special reference to the relationship to the disc of the temporomandibular joint. Detailed dissection was performed on 26 head halves of 14 Japanese cadavers in order to obtain precise anatomical information of the positional relationships between the masticatory muscles and the branches of the mandibular nerve. After complete removal of the bony elements, the midmedial muscle bundle in all specimens and the discotemporal muscle bundle in 6 specimens, derivatives of the temporalis, which insert into the disc were observed. On the anterior area of the articular capsule and the disc of the temporomandibular joint, the upper head of the lateral pterygoid, the midmedial muscle bundle of temporalis and the discotemporal bundle of temporalis were attached mediolaterally, and in 3 specimens the posterosuperior margin of the zygomaticomandibularis was attached to the anterolateral area of the disc. It is suggested that these muscles and muscle bundles contribute to various mandibular movements. Although various patterns of the positional relationships between the muscles and muscle bundles and the their innervating nerves are observed in the present study, relative positional relationships of the muscles and muscle bundles and of nerves of the mandibular nerve are consistent. A possible scheme of the developmental formation of the masticatory muscles based on the findings of the positional relationships between the muscles and the nerves is presented. PMID:11005720

Sequence Bundles: a novel method for visualising, discovering and exploring sequence motifs

PubMed Central

2014-01-01

Background We introduce Sequence Bundles--a novel data visualisation method for representing multiple sequence alignments (MSAs). We identify and address key limitations of the existing bioinformatics data visualisation methods (i.e. the Sequence Logo) by enabling Sequence Bundles to give salient visual expression to sequence motifs and other data features, which would otherwise remain hidden. Methods For the development of Sequence Bundles we employed research-led information design methodologies. Sequences are encoded as uninterrupted, semi-opaque lines plotted on a 2-dimensional reconfigurable grid. Each line represents a single sequence. The thickness and opacity of the stack at each residue in each position indicates the level of conservation and the lines' curved paths expose patterns in correlation and functionality. Several MSAs can be visualised in a composite image. The Sequence Bundles method is designed to favour a tangible, continuous and intuitive display of information. Results We have developed a software demonstration application for generating a Sequence Bundles visualisation of MSAs provided for the BioVis 2013 redesign contest. A subsequent exploration of the visualised line patterns allowed for the discovery of a number of interesting features in the dataset. Reported features include the extreme conservation of sequences displaying a specific residue and bifurcations of the consensus sequence. Conclusions Sequence Bundles is a novel method for visualisation of MSAs and the discovery of sequence motifs. It can aid in generating new insight and hypothesis making. Sequence Bundles is well disposed for future implementation as an interactive visual analytics software, which can complement existing visualisation tools. PMID:25237395

A Framework for Personalized Dynamic Cross-Selling in E-Commerce Retailing

ERIC Educational Resources Information Center

Timalsina, Arun Kumar

2012-01-01

Cross-selling and product bundling are prevalent strategies in the retail sector. Instead of static bundling offers, i.e. giving the same offer to everyone, personalized dynamic cross-selling generates targeted bundle offers and can help maximize revenues and profits. In resolving the two basic problems of dynamic cross-selling, which involves…

Textbook-Bundled Metacognitive Tools: A Study of LearnSmart's Efficacy in General Chemistry

ERIC Educational Resources Information Center

Thadani, Vandana; Bouvier-Brown, Nicole C.

2016-01-01

College textbook publishers increasingly bundle sophisticated technology-based study tools with their texts. These tools appear promising, but empirical work on their efficacy is needed. We examined whether LearnSmart, a study tool bundled with McGraw-Hill's textbook "Chemistry" (Chang & Goldsby, 2013), improved learning in an…

Plant-based torsional actuator with memory

Treesearch

Nayomi Plaza; Samuel L. Zelinka; Don S. Stone; Joseph E. Jakes

2013-01-01

A bundle of a few loblolly pine (Pinus taeda) cells are moisture-activated torsional actuators that twist multiple revolutions per cm length in direct proportion to moisture content. The bundles generate 10 N m kg􀀀1 specific torque during both twisting and untwisting, which is higher than an electric motor. Additionally, the bundles exhibit a moisture-...

Hemlock woolly adelgid (Homoptera: Adelgidae): stylet bundle insertion and feeding sites

Treesearch

Rebecca F. Young; Kathleen S. Shields; Graeme P. Berlyn

1995-01-01

Stylet bundle insertion site, path traveled, and feeding site were examined for the hemlock woolly adelgid, Adelges tsugae Annand, on needles from current and previous years of eastern hemlock, Tsuga canadensis Carriere. The stylet bundle is composed of 4 individual stylets--2 outer mandibular stylets and 2 inner maxillary stylets...

Unwrapping the Bundle: An Examination of Research Libraries and the "Big Deal"

ERIC Educational Resources Information Center

Strieb, Karla L.; Blixrud, Julia C.

2014-01-01

This study presents and analyzes the findings of a 2012 survey of member libraries belonging to the Association of Research Libraries (ARL) about publishers' large journal bundles and compares the results to earlier surveys. The data illuminate five research questions: market penetration, journal bundle construction, collection format shifts,…

47 CFR 76.1514 - Bundling of video and local exchange services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Bundling of video and local exchange services... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1514 Bundling of video and local exchange services. An open video system operator may offer video and local exchange...

47 CFR 76.1514 - Bundling of video and local exchange services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Bundling of video and local exchange services... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1514 Bundling of video and local exchange services. An open video system operator may offer video and local exchange...

47 CFR 76.1514 - Bundling of video and local exchange services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Bundling of video and local exchange services... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1514 Bundling of video and local exchange services. An open video system operator may offer video and local exchange...

47 CFR 76.1514 - Bundling of video and local exchange services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Bundling of video and local exchange services... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1514 Bundling of video and local exchange services. An open video system operator may offer video and local exchange...

47 CFR 76.1514 - Bundling of video and local exchange services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Bundling of video and local exchange services... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1514 Bundling of video and local exchange services. An open video system operator may offer video and local exchange...

Presenting Lexical Bundles for Explicit Noticing with Schematic Linguistic Representation

ERIC Educational Resources Information Center

Thomson, Haidee Elizabeth

2016-01-01

Lexical bundles are essential for fluency, but their incompleteness is a stumbling block for learners. In this study, two presentation methods to increase awareness of lexical bundles through explicit noticing are explored and compared with incidental exposure. The three conditions in this study were as follows: noticing with schematic linguistic…

Lexical Bundles: Facilitating University "Talk" in Group Discussions

ERIC Educational Resources Information Center

Heng, Chan Swee; Kashiha, Hadi; Tan, Helen

2014-01-01

Group discussion forms an integral language experience for most language learners, providing them with an opportunity to express themselves in a naturalistic setting. Multi-word expressions are commonly used and one of them is lexical bundles. Lexical bundles are types of extended collocations that occur more commonly than we expect; they are…

Ecosystem service bundles for analyzing tradeoffs in diverse landscapes

PubMed Central

Raudsepp-Hearne, C.; Peterson, G. D.; Bennett, E. M.

2010-01-01

A key challenge of ecosystem management is determining how to manage multiple ecosystem services across landscapes. Enhancing important provisioning ecosystem services, such as food and timber, often leads to tradeoffs between regulating and cultural ecosystem services, such as nutrient cycling, flood protection, and tourism. We developed a framework for analyzing the provision of multiple ecosystem services across landscapes and present an empirical demonstration of ecosystem service bundles, sets of services that appear together repeatedly. Ecosystem service bundles were identified by analyzing the spatial patterns of 12 ecosystem services in a mixed-use landscape consisting of 137 municipalities in Quebec, Canada. We identified six types of ecosystem service bundles and were able to link these bundles to areas on the landscape characterized by distinct social–ecological dynamics. Our results show landscape-scale tradeoffs between provisioning and almost all regulating and cultural ecosystem services, and they show that a greater diversity of ecosystem services is positively correlated with the provision of regulating ecosystem services. Ecosystem service-bundle analysis can identify areas on a landscape where ecosystem management has produced exceptionally desirable or undesirable sets of ecosystem services. PMID:20194739

The fabrication of vertically aligned and periodically distributed carbon nanotube bundles and periodically porous carbon nanotube films through a combination of laser interference ablation and metal-catalyzed chemical vapor deposition.

PubMed

Yuan, Dajun; Lin, Wei; Guo, Rui; Wong, C P; Das, Suman

2012-06-01

Scalable fabrication of carbon nanotube (CNT) bundles is essential to future advances in several applications. Here, we report on the development of a simple, two-step method for fabricating vertically aligned and periodically distributed CNT bundles and periodically porous CNT films at the sub-micron scale. The method involves laser interference ablation (LIA) of an iron film followed by CNT growth via iron-catalyzed chemical vapor deposition. CNT bundles with square widths ranging from 0.5 to 1.5 µm in width, and 50-200 µm in length, are grown atop the patterned catalyst over areas spanning 8 cm(2). The CNT bundles exhibit a high degree of control over square width, orientation, uniformity, and periodicity. This simple scalable method of producing well-placed and oriented CNT bundles demonstrates a high application potential for wafer-scale integration of CNT structures into various device applications, including IC interconnects, field emitters, sensors, batteries, and optoelectronics, etc.

Calculation of Non-Bonded Forces Due to Sliding of Bundled Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Frankland, S. J. V.; Bandorawalla, T.; Gates, T. S.

2003-01-01

An important consideration for load transfer in bundles of single-walled carbon nanotubes is the nonbonded (van der Waals) forces between the nanotubes and their effect on axial sliding of the nanotubes relative to each other. In this research, the non-bonded forces in a bundle of seven hexagonally packed (10,10) single-walled carbon nanotubes are represented as an axial force applied to the central nanotube. A simple model, based on momentum balance, is developed to describe the velocity response of the central nanotube to the applied force. The model is verified by comparing its velocity predictions with molecular dynamics simulations that were performed on the bundle with different force histories applied to the central nanotube. The model was found to quantitatively predict the nanotube velocities obtained from the molecular dynamics simulations. Both the model and the simulations predict a threshold force at which the nanotube releases from the bundle. This force converts to a shear yield strength of 10.5-11.0 MPa for (10,10) nanotubes in a bundle.

Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

PubMed

Kendig, Susan; Keats, John P; Hoffman, M Camille; Kay, Lisa B; Miller, Emily S; Moore Simas, Tiffany A; Frieder, Ariela; Hackley, Barbara; Indman, Pec; Raines, Christena; Semenuk, Kisha; Wisner, Katherine L; Lemieux, Lauren A

2017-03-01

Perinatal mood and anxiety disorders are among the most common mental health conditions encountered by women of reproductive age. When left untreated, perinatal mood and anxiety disorders can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide, and infanticide. Perinatal mood and anxiety disorders are associated with increased risks of maternal and infant mortality and morbidity and are recognized as a significant patient safety issue. In 2015, the Council on Patient Safety in Women's Health Care convened an interdisciplinary workgroup to develop an evidence-based patient safety bundle to address maternal mental health. The focus of this bundle is perinatal mood and anxiety disorders. The bundle is modeled after other bundles released by the Council on Patient Safety in Women's Health Care and provides broad direction for incorporating perinatal mood and anxiety disorder screening, intervention, referral, and follow-up into maternity care practice across health care settings. This commentary provides information to assist with bundle implementation.

Consensus Bundle on Prevention of Surgical Site Infections After Major Gynecologic Surgery.

PubMed

Pellegrini, Joseph E; Toledo, Paloma; Soper, David E; Bradford, William C; Cruz, Deborah A; Levy, Barbara S; Lemieux, Lauren A

Surgical site infections are the most common complications of surgery in the United States. Of surgeries in women of reproductive age, hysterectomy is one of the most frequently performed, second only to cesarean birth. Therefore, prevention of surgical site infections in women undergoing gynecologic surgery is an ideal topic for a patient safety bundle. The primary purpose of this safety bundle is to provide recommendations that can be implemented into any surgical environment in an effort to reduce the incidence of surgical site infection. This bundle was developed by a multidisciplinary team convened by the Council on Patient Safety in Women's Health Care. The bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. In addition to recommendations for practice, each of the domains stresses communication and teamwork between all members of the surgical team. Although the bundle components are designed to be adaptable to work in a variety of clinical settings, standardization within institutions is encouraged. Copyright © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Consensus Bundle on Prevention of Surgical Site Infections After Major Gynecologic Surgery.

PubMed

Pellegrini, Joseph E; Toledo, Paloma; Soper, David E; Bradford, William C; Cruz, Deborah A; Levy, Barbara S; Lemieux, Lauren A

2017-02-06

Surgical site infections are the most common complication of surgery in the United states. Of surgeries in women of reproductive age, hysterectomy is one of the most frequently performed, second only to cesarean birth. Therefore, prevention of surgical site infections in women undergoing gynecologic surgery is an ideal topic for a patient safety bundle. The primary purpose of this safety bundle is to provide recommendations that can be implemented into any surgical environment in an effot to reduce the incidence of surgical site infection. This bundle was developed by a multidisciplinary team convened by the Council on Patient Safety in Women's Health Care. The bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. In addition to recommendations for practice, each of the domains stresses communication and teamwork between all members of the surgical team. Although the bundle components are designed to be adaptable to work in a variety of clinical settings, standardization within institutions is encouraged. Copyright ©2016 American College of Obstetricians and Gynecologists.

Self-Sensing Composites: In-Situ Detection of Fibre Fracture

PubMed Central

Malik, Shoaib A.; Wang, Liwei; Curtis, Paul T.; Fernando, Gerard F.

2016-01-01

The primary load-bearing component in a composite material is the reinforcing fibres. This paper reports on a technique to study the fracture of individual reinforcing fibres or filaments in real-time. Custom-made small-diameter optical fibres with a diameter of 12 (±2) micrometres were used to detect the fracture of individual filaments during tensile loading of unreinforced bundles and composites. The unimpregnated bundles were end-tabbed and tensile tested to failure. A simple technique based on resin-infusion was developed to manufacture composites with a negligible void content. In both cases, optical fibre connectors were attached to the ends of the small-diameter optical fibre bundles to enable light to be coupled into the bundle via one end whilst the opposite end was photographed using a high-speed camera. The feasibility of detecting the fracture of each of the filaments in the bundle and composite was demonstrated. The in-situ damage detection technique was also applied to E-glass bundles and composites; this will be reported in a subsequent publication. PMID:27136555

Evidence of Intertube Excitons Observed in the Raman Resonance Excitation Profiles of (6 , 5) -Enriched SWCNT Bundles

NASA Astrophysics Data System (ADS)

Simpson, J. R.; Hight Walker, A. R.; Roslyak, O.; Haroz, E.; Telg, H.; Duque, J. G.; Crochet, J. J.; Piryatinkski, A.; Doorn, S. K.

Understanding the photophysics of exciton behavior in single wall carbon nanotube (SWCNT) bundles remains important for opto-electronic device applications. We report resonance Raman spectroscopy (RRS) measurements on (6 , 5) -enriched SWCNTs, dispersed in aqueous solutions and separated using density gradient ultracentrifugation into fractions of increasing bundle size. Near-IR to UV absorption spectroscopy demonstrates a redshift and broadening of the main excitonic transitions with bundling. A continuously tunable dye laser coupled to a triple-grating spectrometer affords measurement of Raman resonance excitation profiles (REPs) over a range of wavelengths, (505 to 585) nm, covering the (6 , 5) -E22S excitation. REPs of both the radial breathing mode (RBM) and GLO+reveal a redshifting and broadening of the (6 , 5) E22S transition energy with increasing bundle size. Most interestingly, we observe an additional peak in both the RBM and GLO+REPs of bundled SWCNTs, which is shifted lower in energy than the main E22S and is anomalously narrow. We attribute this additional peak to a transverse, intertube exciton.

Fabrication of Gate-Electrode Integrated Carbon-Nanotube Bundle Field Emitters

NASA Technical Reports Server (NTRS)

Toda, Risaku; Bronikowski, Michael; Luong, Edward; Manohara, Harish

2008-01-01

A continuing effort to develop carbon-nanotube-based field emitters (cold cathodes) as high-current-density electron sources has yielded an optimized device design and a fabrication scheme to implement the design. One major element of the device design is to use a planar array of bundles of carbon nanotubes as the field-emission tips and to optimize the critical dimensions of the array (principally, heights of bundles and distances between them) to obtain high area-averaged current density and high reliability over a long operational lifetime a concept that was discussed in more detail in Arrays of Bundles of Carbon Nanotubes as Field Emitters (NPO-40817), NASA Tech Briefs, Vol. 31, No. 2 (February 2007), page 58. Another major element of the design is to configure the gate electrodes (anodes used to extract, accelerate, and/or focus electrons) as a ring that overhangs a recess wherein the bundles of nanotubes are located, such that by virtue of the proximity between the ring and the bundles, a relatively low applied potential suffices to generate the large electric field needed for emission of electrons.

Broadband and flexible acoustic focusing by metafiber bundles

NASA Astrophysics Data System (ADS)

Sun, Hong-Xiang; Chen, Jia-He; Ge, Yong; Yuan, Shou-Qi; Liu, Xiao-Jun

2018-06-01

We report a broadband and flexible acoustic focusing through metafiber bundles in air, in which each metafiber consists of eight circular and narrow rectangular cavities. The fractional bandwidth of the acoustic focusing could reach about 0.2, which arises from the eigenmodes of the metafiber structure. Besides, owing to the flexible characteristic of the metafibers, the focus position can be manipulated by bending the metafiber bundles, and the metafiber bundles could bypass rigid scatterers inside the lens structure. More interestingly, the acoustic propagation and focusing directions can be changed by using a designed right-angled direction converter fabricated by the metafibers, and a waveform converter and a focusing lens of the cylindrical acoustic source are realized based on the metafiber bundles. The proposed focusing lens has the advantages of broad bandwidth, flexible structure, and high focusing performance, showing great potentials in versatile applications.

Square-core bundles for astronomical imaging

NASA Astrophysics Data System (ADS)

Bryant, Julia J.; Bland-Hawthorn, Joss

2012-09-01

Optical fibre imaging bundles (hexabundles) are proving to be the next logical step for large galaxy surveys as they offer spatially-resolved spectroscopy of galaxies and can be used with conventional fibre positioners. Hexabundles have been effectively demonstrated in the Sydney-AAO Multi-object IFS (SAMI) instrument at the Anglo- Australian Telescope[5]. Based on the success of hexabundles that have circular cores, we have characterised a bundle made instead from square-core fibres. Square cores naturally pack more evenly, which reduces the interstitial holes and can increase the covering, or filling fraction. Furthermore the regular packing simplifies the process of combining and dithering the final images. We discuss the relative issues of filling fraction, focal ratio degradation (FRD), and cross-talk, and find that square-core bundles perform well enough to warrant further development as a format for imaging fibre bundles.

Sepsis and Shock Response Team: Impact of a Multidisciplinary Approach to Implementing Surviving Sepsis Campaign Guidelines and Surviving the Process.

PubMed

Grek, Ami; Booth, Sandra; Festic, Emir; Maniaci, Michael; Shirazi, Ehsan; Thompson, Kristine; Starbuck, Angela; Mcree, Chad; Naessens, James M; Moreno Franco, Pablo

The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.

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

Wen, Zhigang, E-mail: xh168688@126.com; State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083; Department of Chemistry and Chemical Engineering, Qiannan Normal College for Nationalities, Duyun 558000

SnO{sub 2} nanorod bundles were synthesized by hydrothermal method. Field-emission scanning electron microscopy and transmission electron microscopy images showed that the as-prepared flowerlike SnO{sub 2} nanorod bundles consist of tetragonal nanorods with size readily tunable. Their electrochemical properties and application as anode for lithium-ion battery were evaluated by galvanostatic discharge–charge testing and cycle voltammetry. SnO{sub 2} nanorod flowers possess improved discharge capacity of 694 mA h g{sup −1} up to 40th cycle at 0.1 C. - Highlights: ► The flowerlike SnO{sub 2} nanorod bundles were synthesized by hydrothermal method. ► SnO{sub 2} nanorod bundles with tunable size by controlling concentrationmore » of SnCl{sub 4}. ► A probable formation mechanism of SnO{sub 2} nanorod bundles has been proposed.« less

A macroscopic scale model of bacterial flagellar bundling

NASA Astrophysics Data System (ADS)

Kim, Munju; Bird, James C.; van Parys, Annemarie J.; Breuer, Kenneth S.; Powers, Thomas R.

2003-12-01

Escherichia coli and other bacteria use rotating helical filaments to swim. Each cell typically has about four filaments, which bundle or disperse depending on the sense of motor rotation. To study the bundling process, we built a macroscopic scale model consisting of stepper motor-driven polymer helices in a tank filled with a high-viscosity silicone oil. The Reynolds number, the ratio of viscous to elastic stresses, and the helix geometry of our experimental model approximately match the corresponding quantities of the full-scale E. coli cells. We analyze digital video images of the rotating helices to show that the initial rate of bundling is proportional to the motor frequency and is independent of the characteristic relaxation time of the filament. We also determine which combinations of helix handedness and sense of motor rotation lead to bundling.

Comparative transduction mechanisms of hair cells in the bullfrog uticulus. 2: Sensitivity and response dynamics to hair bundle displacement

NASA Technical Reports Server (NTRS)

Baird, Richard A.

1994-01-01

The present study was motivated by an interest in seeing whether hair cell types in the bullfrog utriculus might differ in their voltage responses to hair bundle displacement. Particular interest was in assessing the contributions of two factors to the responses of utricular hair cells. First, interest in examining the effect of hair bundle morphology on the sensitivity of hair cells to natural stimulation was motivated by the observation that vestibular hair cells, unlike many auditory hair cells, are not free-standing but rather linked to an accessory cupular or otolithic membrane via the tip of their kinocilium. Interest also laid in examining the contribution, if any, of adaptation to the response properties of utricular hair cells. Hair cells in auditory and vibratory inner ear endorgans adapt to maintained displacements of their hair bundles, sharply limiting their low frequency sensitivity. This adaptation is mediated by a shift in the displacement-response curve (DRC) of the hair cell along the displacement axis. Observations suggest that the adaptation process occurs within the hair bundle and precedes mechanoelectric transduction. Recent observations of time-dependent changes in hair bundle stiffness are consistent with this conclusion. Adaptation would be expected to be most useful in inner ear endorgans in which hair cells are subject to large static displacements that could potentially saturate their instantaneous response and compromise their sensitivity to high frequency stimulation. The adaptation process also permits hair cells to maintain their sensory hair bundle in the most sensitive portion of their DRC. In vestibular otolith organs in which static sensitivity is desirable, any adaptation process in the hair cells may be undesirable. The rate and extent of the decline of the voltage responses was measured of utricular hair cells to step and sinusoidal hair bundle displacements. Then for similar resting potentials and response amplitudes, the voltage responses of individual hair cells were compared to both hair bundle displacement and intracellular current.

Experience with Delay-Tolerant Networking from Orbit

NASA Technical Reports Server (NTRS)

Ivancic, W.; Eddy, W. M.; Stewart, D.; Wood, L.; Northam, J.; Jackson, C.

2010-01-01

We describe the first use from space of the Bundle Protocol for Delay-Tolerant Networking (DTN) and lessons learned from experiments made and experience gained with this protocol. The Disaster Monitoring Constellation (DMC), constructed by Surrey Satellite Technology Ltd (SSTL), is a multiple-satellite Earth-imaging low-Earth-orbit sensor network in which recorded image swaths are stored onboard each satellite and later downloaded from the satellite payloads to a ground station. Store-and-forward of images with capture and later download gives each satellite the characteristics of a node in a disruption-tolerant network. Originally developed for the Interplanetary Internet, DTNs are now under investigation in an Internet Research Task Force (IRTF) DTN research group (RG), which has developed a bundle architecture and protocol. The DMC is technically advanced in its adoption of the Internet Protocol (IP) for its imaging payloads and for satellite command and control, based around reuse of commercial networking and link protocols. These satellites use of IP has enabled earlier experiments with the Cisco router in Low Earth Orbit (CLEO) onboard the constellation s UK-DMC satellite. Earth images are downloaded from the satellites using a custom IP-based high-speed transfer protocol developed by SSTL, Saratoga, which tolerates unusual link environments. Saratoga has been documented in the Internet Engineering Task Force (IETF) for wider adoption. We experiment with the use of DTNRG bundle concepts onboard the UK-DMC satellite, by examining how Saratoga can be used as a DTN convergence layer to carry the DTNRG Bundle Protocol, so that sensor images can be delivered to ground stations and beyond as bundles. Our practical experience with the first successful use of the DTNRG Bundle Protocol in a space environment gives us insights into the design of the Bundle Protocol and enables us to identify issues that must be addressed before wider deployment of the Bundle Protocol. Published in 2010 by John Wiley & Sons, Ltd. KEY WORDS: Internet; UK-DMC; satellite; Delay-Tolerant Networking (DTN); Bundle Protocol

Cryopreservation of sperm bundles (spermatozeugmata) from endangered livebearing goodeids.

PubMed

Liu, Yue; Torres, Leticia; Tiersch, Terrence R

2018-04-14

More than half of fishes in the family Goodeidae are considered to be endangered, threatened, or vulnerable. Sperm cryopreservation is an effective tool for conserving genetic resources of imperiled populations, but development of protocols with livebearing fishes faces numerous challenges including the natural packaging of sperm into bundles. In this study the cryopreservation of sperm bundles (spermatozeugmata) of three goodeids species was evaluated. Sperm quality was evaluated by activation with NaCl-NaOH solution (at 300 mOsmol/kg and pH 11.8), and analysis of dissociable bundles and dissociation duration. Using Redtail Splitfin (Xenotoca eiseni) as a model, the effects of cryoprotectants (dimethyl sulfoxide, methanol, and glycerol) with different concentrations (5-15% v/v %), equilibration exposure times (1-60 min), cooling rates (5-40 °C/min), concentrations (4 × 10 4 -4 × 10 6 bundles/ml), buffers (HBSS, PBS and NaCl), and buffer osmolalities (200-400 mOsmol/kg) were investigated. After cooling and thawing, sperm bundles maintained their packed form. A specific protocol was developed (10% dimethyl sulfoxide, 20-min equilibration, 10 °C/min cooling rate, 4 × 10 6 bundles/ml, and 300 mOsmol/kg HBSS). This protocol yielded 89 ± 5% of post-thaw dissociable bundles with 209 ± 10 s of dissociation duration for X. eiseni, 96 ± 9% with 814 ± 14 s for Blackfin Goodea (Goodea atripinni), and 66 ± 2% with 726 ± 25 s for Striped Goodeid (Ataeniobius toweri). This is the first study of cryopreservation of sperm within bundles for livebearing fishes and provides a basis for establishment of germplasm repositories for goodeids and other livebearers. Copyright © 2018 Elsevier Inc. All rights reserved.

Causes and Effects of Changes in Xylem Functionality in Apple Fruit

PubMed Central

DRAŽETA, LAZAR; LANG, ALEXANDER; HALL, ALISTAIR J.; VOLZ, RICHARD K.; JAMESON, PAULA E.

2004-01-01

• Background and Aims The xylem in fruit of a number of species becomes dysfunctional as the fruit develops, resulting in a reduction of xylem inflow to the fruit. Such a reduction may have consequential effects on the mineral balance of the fruit. The aim of this study was to elucidate the dynamics and nature of xylem failure in developing apples (Malus domestica) showing differing susceptibilities to bitter pit, a calcium‐related disorder. • Methods Developmental changes in xylem functionality of the fruit were investigated in ‘Braeburn’ and ‘Granny Smith’ apples by using a dye infusion technique, to stain the vasculature along the path of dye movement. The vascular bundles were clearly visible in transverse section when fruit were sectioned equatorially. The intensity of staining of the vascular bundles in the fruit was recorded at regular intervals throughout the season. Tissue containing dysfunctional bundles was fixed and embedded in wax for subsequent sectioning and examination. • Key Results As the season progressed, an increasing proportion of vascular bundles failed to show any staining, with the most marked change occurring in the primary bundles, and in nearly all bundles with increasing distance from the stalk end of the fruit. Decreased conductance in the primary bundles of ‘Braeburn’ occurred earlier than in ‘Granny Smith’. Microscopy revealed that the xylem in vascular bundles of the fruit suffered substantial damage, indicating that the mode of dysfunction was via the physical disruption of the xylem caused by expansion of the flesh. • Conclusions Results support the view that the relative calcium deficiency of apple fruit is due to a progressive breakdown of xylem conductance caused by growth‐induced damage to the xylem strand in the bundle. The earlier onset of xylem dysfunction in the cultivar more susceptible to bitter pit suggests that the relative growth dynamics of the fruit may control the occurrence of calcium‐related disorders. PMID:14988096

Implementing a pressure ulcer prevention bundle in an adult intensive care.

PubMed

Tayyib, Nahla; Coyer, Fiona; Lewis, Peter A

2016-12-01

The incidence of pressure ulcers (PUs) in intensive care units (ICUs) is high and numerous strategies have been implemented to address this issue. One approach is the use of a PU prevention bundle. However, to ensure success care bundle implementation requires monitoring to evaluate the care bundle compliance rate, and to evaluate the effectiveness of implementation strategies in facilitating practice change. The aims of this study were to appraise the implementation of a series of high impact intervention care bundle components directed at preventing the development of PUs, within ICU, and to evaluate the effectiveness of strategies used to enhance the implementation compliance. An observational prospective study design was used. Implementation strategies included regular education, training, audit and feed-back and the presence of a champion in the ICU. Implementation compliance was measured along four time points using a compliance checklist. Of the 60 registered nurses (RNs) working in the critical care setting, 11 participated in this study. Study participants demonstrated a high level of compliance towards the PU prevention bundle implementation (78.1%), with 100% participant acceptance. No significant differences were found between participants' demographic characteristics and the compliance score. There was a significant effect for time in the implementation compliance (Wilks Lambda=0.29, F (3, 8)=6.35, p<0.016), indicating that RNs needed time to become familiar with the bundle and routinely implement it into their practice. PU incidence was not influenced by the compliance level of participants. The implementation strategies used showed a positive impact on compliance. Assessing and evaluating implementation compliance is critical to achieve a desired outcome (reduction in PU incidence). This study's findings also highlighted that while RNs needed time to familiarise themselves with the care bundle elements, their clinical practice was congruent with the bundle elements. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying the challenges and facilitators of implementing a COPD care bundle

PubMed Central

Lennox, Laura; Green, Stuart; Howe, Cathy; Musgrave, Hannah; Bell, Derek; Elkin, Sarah

2014-01-01

Background Care bundles have been shown to improve outcomes, reduce hospital readmissions and reduce length of hospital stay; therefore increasing the speed of uptake and delivery of care bundles should be a priority in order to deliver more timely improvements and consistent high-quality care. Previous studies have detailed the difficulties of obtaining full compliance to bundle elements but few have described the underlying reasons for this. In order to improve future implementation this paper investigates the challenges encountered by clinical teams implementing a chronic obstructive pulmonary disease (COPD) care bundle and describes actions taken to overcome these challenges. Methods An initial retrospective documentary analysis of data from seven clinical implementation teams was undertaken to review the challenges faced by the clinical teams. Three focus groups with healthcare professionals and managers explored solutions to these challenges developed during the project. Results Documentary analysis identified 28 challenges which directly impacted implementation of the COPD care bundle within five themes; staffing, infrastructure, process, use of improvement methodology and patient and public involvement. Focus groups revealed that the five most significant challenges for all groups were: staff too busy, staff shortages, lack of staff engagement, added workload of the bundle and patient coding issues. The participants shared facilitating factors used to overcome issues including: shifting perceptions to improve engagement, further education sessions to increase staff participation and gaining buy-in from managers through payment frameworks. Conclusions Maximising the impact of a care bundle relies on its successful and timely implementation. Teams implementing the COPD care bundle encountered challenges that were common to all teams and sites. Understanding and learning from the challenges faced by previous endeavours and identifying the facilitators to overcoming these barriers provides an opportunity to mitigate issues that waste time and resources, and ensures that training can be tailored to the anticipated challenges. PMID:25478183

Fiber optic spectroscopic digital imaging sensor and method for flame properties monitoring

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

Zelepouga, Serguei A; Rue, David M; Saveliev, Alexei V

2011-03-15

A system for real-time monitoring of flame properties in combustors and gasifiers which includes an imaging fiber optic bundle having a light receiving end and a light output end and a spectroscopic imaging system operably connected with the light output end of the imaging fiber optic bundle. Focusing of the light received by the light receiving end of the imaging fiber optic bundle by a wall disposed between the light receiving end of the fiber optic bundle and a light source, which wall forms a pinhole opening aligned with the light receiving end.

Avoiding revenue loss due to 'lesser of' contract clauses.

PubMed

Stodolak, Frederick; Gutierrez, Henry

2014-08-01

Finance managers seeking to avoid lost revenue attributable to lesser-of-charge-or-fixed-fee (lesser-of) clauses in their contracts should: Identify payer contracts that contain lesser-of clauses. Prepare lesser-of lost-revenue reports for non-bundled and bundled rates. For claims with covered charges below the bundled rate, identify service codes associated with the greatest proportion of total gross revenue and determine new, higher charge levels for those codes. Establish an approach for setting charges for non-bundled fee schedules to address lost-revenue-related issues. Incorporate changes into overall strategic or hospital zero-based pricing modeling and parameters.

RX: a nonimaging concentrator.

PubMed

Miñano, J C; Benítez, P; González, J C

1995-05-01

A detailed description of the design procedure for a new concentrator, RX, and some examples of it's use are given. The method of design is basically the same as that used in the design of two other concentrators: the RR and the XR [Appl. Opt. 31, 3051 (1992)]. The RX is ideal in two-dimensional geometry. The performance of the rotational RX is good when the average angular spread of the input bundle is small: up to 95% of the power of the input bundle can be transferred to the output bundle (with the assumption of a constant radiance for the rays of the input bundle).

Fabrication of bundle-structured tube-leaky optical fibers for infrared thermal imaging

NASA Astrophysics Data System (ADS)

Kobayashi, T.; Katagiri, T.; Matsuura, Y.

2017-02-01

Bundled glass tubular fibers were fabricated by glass drawing technique for endoscopic infrared-thermal imaging. The bundle fibers were made of borosilicate glass and have a structure like a photonic crystal fiber having multiple hollow cores. Fabricated fibers have a length of 90 cm and each pixel sizes are less than 80 μm. By setting the thickness of glass wall to a quarter-wavelength optical thickness, light is confined in the air core as a leaky mode with a low loss owing to the interference effect of the thin glass wall and this type of hollow-core fibers is known as tube leaky fibers. The transmission losses of bundled fibers were firstly measured and it was found that bundled tube-leaky fibers have reasonably low transmission losses in spite of the small pixel size. Then thermal images were delivered by the bundled fibers combining with an InSb infrared camera. Considering applications with rigid endoscopes, an imaging system composed of a 30-cm long fiber bundle and a half-ball lens with a diameter of 2 mm was fabricated. By using this imaging system, a metal wire with a thickness of 200 μm was successfully observed and another test showed that the minimum detected temperature was 32.0 °C and the temperature resolution of the system was around 0.7 °C.

Enameloid microstructure of the serrated cutting edges in certain fossil carcharhiniform and lamniform sharks.

PubMed

Andreev, Plamen S

2010-07-01

The triple-layered enameloid organization of neoselachian teeth has proven to be a reliable systematic character of the group. This study uses scanning electron microscopy to investigate the orientation of the parallel enameloid bundles in the area of the serrated cutting edges in certain fossil elasmobranchs. The examined teeth come from two Upper Cretaceous Squalicorax species and the Upper Miocene carcharhiniforms Galeocerdo sp., Carcharhinus sp., and Hemipristis serra. The parallel bundles are revealed by surface etching, which removes the superficial shiny-layered enameloid. In the teeth of Squalicorax, the bundles around the cutting edge bend once, before they reach the serrations. The studied carcharhiniform species show a more complicated pattern with a change of parallel bundle course inside the serrations. H. serra teeth do not display the first bending of the bundles, whereas it was present in the other two carcharhiniforms. The course of the crystalline bundles in both Squalicorax species is not affected by the presence of the serrations, regardless of the twofold difference in tooth size between them. In the carcharhiniform species, the bended bundles occur within the primary and secondary serrations and are always associated with them. This feature might have functional significance by strengthening the cutting edge or could simply develop as a consequence of the enameloid mineralization around the individual serrae. (c) 2009 Wiley-Liss, Inc.

Isolation of Mesophyll Cells and Bundle Sheath Cells from Digitaria sanguinalis (L.) Scop. Leaves and a Scanning Microscopy Study of the Internal Leaf Cell Morphology 1

PubMed Central

Edwards, Gerald E.; Black, Clanton C.

1971-01-01

A technique is described for the separation of mesophyll and bundle sheath cells from Digitaria sanguinalis leaves and evidence for separation is given with light and scanning electron micrographs. Gentle grinding of fully differentiated leaves in a mortar releases mesophyll cells which are isolated on nylon nets by filtration. More extensive grinding of the remaining tissue yields bundle sheath strands which are isolated by filtration with stainless steel sieves and nylon nets. Further grinding of bundle sheath strands in a tissue homogenizer releases bundle sheath cells which are collected on nylon nets. Percentage of purity derived from cell counts and yield data on a chlorophyll basis are given. The internal leaf cell morphology is presented in scanning electron micrographs and compared with light micrographs of fully-differentiated D. sanguinalis leaves. In leaves of plants which possess the C4-dicarboxylic acid cycle of photosynthesis, the relationship of leaf morphology to photosynthesis in mesophyll and bundle sheath cells is considered, and the hypothesis is presented that as atmospheric CO2 enters a leaf about 85% is fixed by the C4-dicarboxylic acid cycle in the mesophyll cells and 10 to 15% is fixed by the reductive pentose phosphate cycle in the bundle sheath cells. A technique also is given for the isolation of mesophyll cells from spinach leaves. Images PMID:16657571

A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach.

PubMed

Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-03-01

Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices. Published by Elsevier Inc.

Enhanced central venous catheter bundle for pediatric parenteral-dependent intestinal failure.

PubMed

Ormsby, Jennifer A; Bukoye, Bola; Lajoie, Debra; Shermont, Herminia; Martin, Lisa; Leger, Kierrah; Mahoney, Judy; Potter-Bynoe, Gail; Carpenter, Jane; Ozonoff, Al; Lee, Grace M

2018-05-16

Central line-associated bloodstream infections (CLABSIs) cause substantial morbidity and increase antimicrobial use and length of stay among hospitalized children in the United States. CLABSI occurs more frequently among high-risk pediatric patients, such as those with intestinal failure (IF) who are parenteral nutrition (PN) dependent. Following an increase in CLABSI rates, a quality improvement (QI) initiative was implemented. Using QI methodology, an enhanced central venous catheter (CVC) maintenance bundle was developed and implemented on 2 units for pediatric PN-dependent patients with IF. CLABSI rates were prospectively monitored pre- and postimplementation, and bundle element adherence was monitored. Enhanced bundle elements included chlorhexidine-impregnated patch, daily bathing, ethanol locks, 2 nurses for CVC care in a distraction-free zone, peripheral laboratory draws, bundling routine laboratory tests, and PN administration set changes every 24 hours. Adherence to enhanced bundle elements increased to >90% over 3 months. CLABSI rates averaged 1.41 per 1,000 central line days preimplementation compared with 0.40 per 1,000 device days postimplementation (P = .003), an 85% absolute reduction in CLABSI rates over 12 months. Patients with IF are at an increased risk for CLABSI. Enhanced CVC maintenance bundles that specifically target prevention practices in this population may be beneficial. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The Readmission Reduction Program of Kaiser Permanente Southern California—Knowledge Transfer and Performance Improvement

PubMed Central

Tuso, Philip; Huynh, Dan Ngoc; Garofalo, Lynn; Lindsay, Gail; Watson, Heather L; Lenaburg, Douglas L; Lau, Helen; Florence, Brandy; Jones, Jason; Harvey, Patti; Kanter, Michael H

2013-01-01

In 2011, Kaiser Permanente Northwest Region (KPNW) won the Lawrence Patient Safety Award for its innovative work in reducing hospital readmission rates. In 2012, Kaiser Permanente Southern California (KPSC) won the Transfer Projects Lawrence Safety Award for the successful implementation of the KPNW Region’s “transitional care” bundle to a Region that was almost 8 times the size of KPNW. The KPSC Transition in Care Program consists of 6 KPNW bundle elements and 2 additional bundle elements added by the KPSC team. The 6 KPNW bundle elements were risk stratification, standardized discharge summary, medication reconciliation, a postdischarge phone call, timely follow-up with a primary care physician, and a special transition phone number on discharge instructions. The 2 additional bundle elements added by KPSC were palliative care consult if indicated and a complex-case conference. KPSC has implemented most of the KPNW and KPSC bundle elements during the first quarter of 2012 for our Medicare risk population at all of our 13 medical centers. Each year, KPSC discharges approximately 40,000 Medicare risk patients. After implementation of bundle elements, KPSC Medicare risk all-cause 30-day Healthcare Effectiveness Data and Information Set readmissions observed-over-expected ratio and readmission rates from December 2010 to November 2012 decreased from approximately 1.0 to 0.80 and 12.8% to 11%, respectively. PMID:24355891

In-Depth Analysis of the Structure and Properties of Two Varieties of Natural Luffa Sponge Fibers

PubMed Central

Chen, Yuxia; Su, Na; Zhang, Kaiting; Zhu, Shiliu; Zhao, Lei; Fang, Fei; Ren, Linyan; Guo, Yong

2017-01-01

The advancement in science and technology has led to luffa sponge (LS) being widely used as a natural material in industrial application because of its polyporous structure and light texture. To enhance the utility of LS fibers as the reinforcement of lightweight composite materials, the current study investigates their water absorption, mechanical properties, anatomical characteristics and thermal performance. Hence, moisture regain and tensile properties of LS fiber bundles were measured in accordance with American Society for Testing and Materials (ASTM) standards while their structural characteristics were investigated via microscopic observation. Scanning electron microscopy (SEM) was used to observe the surface morphology and fractured surface of fiber bundles. The test results show that the special structure where the phloem tissues degenerate to cavities had a significant influence on the mechanical properties of LS fiber bundles. Additionally, the transverse sectional area occupied by fibers in a fiber bundle (SF), wall thickness, ratio of wall to lumen of fiber cell, and crystallinity of cellulose had substantial impact on the mechanical properties of LS fiber bundles. Furthermore, the density of fiber bundles of LS ranged within 385.46–468.70 kg/m3, significantly less than that of jute (1360.40 kg/m3) and Arenga engleri (950.20 kg/m3). However, LS fiber bundles demonstrated superior specific modulus than Arenga engleri. PMID:28772838

Methicillin-resistant Staphylococcus aureus prevention practices in hospitals throughout a rural state.

PubMed

McDanel, Jennifer S; Ward, Melissa A; Leder, Laurie; Schweizer, Marin L; Dawson, Jeffrey D; Diekema, Daniel J; Smith, Tara C; Chrischilles, Elizabeth A; Perencevich, Eli N; Herwaldt, Loreen A

2014-08-01

The Institute for Healthcare Improvement (IHI) created an evidence-based bundle to help reduce methicillin-resistant Staphylococcus aureus (MRSA) health care-associated infections. The study aim was to identify which components of the IHI's MRSA bundle that rural hospitals have implemented and to identify barriers that hindered implementation of bundle components. Four surveys about the IHI's MRSA bundle were administered at the Iowa Statewide Infection Prevention Seminar between 2007 and 2011. Surveys were mailed to infection preventionists (IPs) who did not attend the meetings. The percentage of IPs reporting that their hospital implemented a hand hygiene program (range by year, 87%-94%) and used contact precautions for patients infected (range by year, 97%-100%) or colonized (range by year, 77%-92%) with MRSA did not change significantly. The number of hospitals that monitored the effectiveness of environmental cleaning significantly increased from 23%-71% (P < .01). Few hospitals assessed daily if central lines were necessary (range by year, 22%-26%). IPs perceived lack of support to be a major barrier to implementing bundle components. Most IPs reported that their hospitals had implemented most components of the MRSA bundle. Support within the health care system is essential for implementing each component of an evidence-based bundle. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

An evaluation of the impact of the ventilator care bundle.

PubMed

Crunden, Eddie; Boyce, Carolyn; Woodman, Helen; Bray, Barbara

2005-01-01

A number of interventions have been shown to improve the outcomes of patients who are invasively ventilated in intensive care units (ICUs). However, significant problems still exist in implementing research findings into clinical practice. The aim of this study was to assess whether the systematic and methodical implementation of evidence-based interventions encapsulated in a care bundle influenced length of ventilation and ICU length of stay (LOS). A ventilator care bundle was introduced within a general ICU and evaluated 1 year later. The care bundle was composed of four protocols that consisted of prophylaxis against peptic ulceration, prophylaxis against deep vein thrombosis, daily cessation of sedation and elevation of the patient's head and chest to at least 30 degrees to the horizontal. Compliance with the bundle was assessed, as was ICU LOS, ICU mortality and ICU/high-dependency unit patient throughput. Mean ICU LOS was reduced from 13-75 [standard deviation (SD) 19.11] days to 8.36 (SD 10.21) days (p<0.05). Mean ventilator days were reduced from 10.8 (SD 15.58) days to 6.1 (SD 8.88) days. Unit patient throughput increased by 30.1% and the number of invasively ventilated patients increased by 39.5%. Care bundles encourage the consistent and systematic application of evidence-based protocols used in particular treatment regimes. Since the introduction of the ventilator care bundle, length of ventilation and ICU LOS have reduced significantly.

Randomized controlled trial of care bundles with chlorhexidine dressing and advanced dressings to prevent catheter-related bloodstream infections in pediatric hematology-oncology patients.

PubMed

Gerçeker, Gülçin Özalp; Yardımcı, Figen; Aydınok, Yeşim

2017-06-01

To compare the effects of the care bundles including chlorhexidine dressing and advanced dressings on the catheter-related bloodstream infection (CRBSI) rates in pediatric hematology-oncology patients with central venous catheters (CVCs). Twenty-seven PHO patients were recruited to participate in a prospective, randomized study in Turkey. The researcher used care bundles with chlorhexidine dressing in the experimental group (n = 14), and care bundles with advanced dressings in the control group (n = 13). According to the study results, 28.6% of the patients in the experimental group had CRBSI, while this rate was 38.5% in the control group patients. The CRBSI rate in the experimental group was 3.9, and the control group had 4.4 per 1000 inpatient catheter days. There was no exit-site infection in the experimental group. However, the control group had 1.7 per 1000 inpatient catheter days. Even though there was no difference between the two groups in which the researcher implemented care bundles with chlorhexidine dressing and advanced dressings in terms of CRBSI development, there was reduction in the CRBSI rates thanks to the care bundle approach. It is possible to control the CRBSI rates using care bundles in pediatric hematology-oncology patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrocardiogram: his bundle potentials can be recorded noninvasively beat by beat on surface electrocardiogram.

PubMed

Wang, Gaopin; Liu, Renguang; Chang, Qinghua; Xu, Zhaolong; Zhang, Yingjie; Pan, Dianzhu

2017-03-15

The micro waveform of His bundle potential can't be recorded beat-to-beat on surface electrocardiogram yet. We have found that the micro-wavelets before QRS complex may be related to atrioventricular conduction system potentials. This study is to explore the possibility of His bundle potential can be noninvasively recorded on surface electrocardiogram. We randomized 65 patients undergoing radiofrequency catheter ablation of paroxysmal superventricular tachycardia (exclude overt Wolff-Parkinson-White syndrome) to receive "conventional electrocardiogram" and "new electrocardiogram" before the procedure. His bundle electrogram was collected during the procedure. Comparative analysis of PA s (PA interval recorded on surface electrocardiogram), AH s (AH interval recorded on surface electrocardiogram) and HV s (HV interval recorded on surface electrocardiogram) interval recorded on surface "new electrocardiogram" and PA, AH, HV interval recorded on His bundle electrogram was investigated. There was no difference (P > 0.05) between groups in HV s interval (49.63 ± 6.19 ms) and HV interval (49.35 ± 6.49 ms). Results of correlational analysis found that HV S interval was significantly positively associated with HV interval (r = 0.929; P < 0.01). His bundle potentials can be noninvasively recorded on surface electrocardiogram. Noninvasive His bundle potential tracing might represent a new method for locating the site of atrioventricular block and identifying the origin of a wide QRS complex.

Isolation of Mesophyll Cells and Bundle Sheath Cells from Digitaria sanguinalis (L.) Scop. Leaves and a Scanning Microscopy Study of the Internal Leaf Cell Morphology.

PubMed

Edwards, G E; Black, C C

1971-01-01

A technique is described for the separation of mesophyll and bundle sheath cells from Digitaria sanguinalis leaves and evidence for separation is given with light and scanning electron micrographs. Gentle grinding of fully differentiated leaves in a mortar releases mesophyll cells which are isolated on nylon nets by filtration. More extensive grinding of the remaining tissue yields bundle sheath strands which are isolated by filtration with stainless steel sieves and nylon nets. Further grinding of bundle sheath strands in a tissue homogenizer releases bundle sheath cells which are collected on nylon nets. Percentage of purity derived from cell counts and yield data on a chlorophyll basis are given.The internal leaf cell morphology is presented in scanning electron micrographs and compared with light micrographs of fully-differentiated D. sanguinalis leaves. In leaves of plants which possess the C(4)-dicarboxylic acid cycle of photosynthesis, the relationship of leaf morphology to photosynthesis in mesophyll and bundle sheath cells is considered, and the hypothesis is presented that as atmospheric CO(2) enters a leaf about 85% is fixed by the C(4)-dicarboxylic acid cycle in the mesophyll cells and 10 to 15% is fixed by the reductive pentose phosphate cycle in the bundle sheath cells.A technique also is given for the isolation of mesophyll cells from spinach leaves.

Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders.

PubMed

George, Sudeep P; Wang, Yaohong; Mathew, Sijo; Srinivasan, Kamalakkannan; Khurana, Seema

2007-09-07

Villin is a major actin-bundling protein in the brush border of epithelial cells. In this study we demonstrate for the first time that villin can bundle actin filaments using a single F-actin binding site, because it has the ability to self-associate. Using fluorescence resonance energy transfer, we demonstrate villin self-association in living cells in microvilli and in growth factor-stimulated cells in membrane ruffles and lamellipodia. Using sucrose density gradient, size-exclusion chromatography, and matrix-assisted laser desorption ionization time-of-flight, the majority of villin was identified as a monomer or dimer. Villin dimers were also identified in Caco-2 cells, which endogenously express villin and Madin-Darby canine kidney cells that ectopically express villin. Using truncation mutants of villin, site-directed mutagenesis, and fluorescence resonance energy transfer, an amino-terminal dimerization site was identified that regulated villin self-association in parallel conformation as well as actin bundling by villin. This detailed analysis describes for the first time microvillus assembly by villin, redefines the actin-bundling function of villin, and provides a molecular mechanism for actin bundling by villin, which could have wider implications for other actin cross-linking proteins that share a villin-like headpiece domain. Our study also provides a molecular basis to separate the morphologically distinct actin-severing and actin-bundling properties of villin.

Bundles to prevent ventilator-associated pneumonia: how valuable are they?

PubMed

Wip, Charity; Napolitano, Lena

2009-04-01

To review the value of care bundles to prevent ventilator-associated pneumonia (VAP). The Ventilator Bundle contains four components, elevation of the head of the bed to 30-45 degrees, daily 'sedation vacation' and daily assessment of readiness to extubate, peptic ulcer disease prophylaxis, and deep venous thrombosis prophylaxis, aimed to improve outcome in mechanically ventilated patients, but not all are associated with VAP prevention. Daily spontaneous awakening and breathing trials are associated with early liberation from mechanical ventilation and VAP reduction. Although a small prospective, randomized clinical study documented that the semirecumbent position was associated with a significant reduction in VAP, more recent studies have documented that the semirecumbent position is difficult to maintain in mechanically ventilated patients and may not impact VAP reduction. Prophylaxis for peptic ulcer disease and deep venous thrombosis do not directly impact VAP reduction. Other methods to reduce VAP, such as oral care and hygiene, chlorhexidine in the posterior pharynx, and specialized endotracheal tubes (continuous aspiration of subglottic secretions, silver-coated), should be considered for inclusion in a revised Ventilator Bundle more specifically aimed at VAP prevention. The Ventilator Bundle is an effective method to reduce VAP rates in ICUs. The ventilator bundle should be modified and expanded to include specific processes of care that have been definitively demonstrated to be effective in VAP reduction or a specific VAP bundle created to focus on VAP prevention.

Management and Economic Implications of Bundling and Block Booking of Television and Cable Programming.

ERIC Educational Resources Information Center

Picard, Robert G.

Bundling, a practice which has increased dramatically in the television and cable industries in recent years, occurs when program distributors package groups of movies and episodes of series, and then sell licenses to use these packages to TV stations and cable channels. Typically, such bundled packages include both highly desirable and less…

Lexical Bundles in the Academic Writing of Advanced Chinese EFL Learners

ERIC Educational Resources Information Center

Wei, Yaoyu; Lei, Lei

2011-01-01

The present study investigated the use of lexical bundles in the academic writing of advanced Chinese EFL learners. A corpus of doctoral dissertations by the learners and a corpus of published journal articles by professional writers were collected for the study. Four-word lexical bundles in the two corpora were identified and analysed. Results…

Assessing the Effect of Language Demand in Bundles of Math Word Problems

ERIC Educational Resources Information Center

Banks, Kathleen; Jeddeeni, Ahmad; Walker, Cindy M.

2016-01-01

Differential bundle functioning (DBF) analyses were conducted to determine whether seventh and eighth grade second language learners (SLLs) had lower probabilities of answering bundles of math word problems correctly that had heavy language demands, when compared to non-SLLs of equal math proficiency. Math word problems on each of four test forms…

Constructed microhabitat bundles for sampling fishes and crayfishes in coastal plain streams

Treesearch

Melvin L. Warren; A.L. Sheldon; W.R. Haag

2009-01-01

We investigated fish and crayfish use of standardized, constructed microhabitats (bundles) in three northern Mississippi streams. Cypress Creek and the Little Tallahatchie Canal were channelized and incised and had little woody cover; Puskus Creek was unchannelized and unincised and had abundant woody cover. We constructed three types of bundles (cane, leaf, and string...

Lexical Bundle Analysis in Mathematics Classroom Discourse: The Significance of Stance

ERIC Educational Resources Information Center

Herbel-Eisenmann, Beth; Wagner, David; Cortes, Viviana

2010-01-01

In this article, we introduce the lexical bundle, defined by corpus linguists as a group of three or more words that frequently recur together, in a single group, in a particular register (Biber, Johansson, Leech, Conrad, & Finegan, 2006; Cortes, "English for Specific Purposes" 23:397-423, 2004). Attention to lexical bundles helps to explore…

An analytical fiber bundle model for pullout mechanics of root bundles

NASA Astrophysics Data System (ADS)

Cohen, D.; Schwarz, M.; Or, D.

2011-09-01

Roots in soil contribute to the mechanical stability of slopes. Estimation of root reinforcement is challenging because roots form complex biological networks whose geometrical and mechanical characteristics are difficult to characterize. Here we describe an analytical model that builds on simple root descriptors to estimate root reinforcement. Root bundles are modeled as bundles of heterogeneous fibers pulled along their long axes neglecting root-soil friction. Analytical expressions for the pullout force as a function of displacement are derived. The maximum pullout force and corresponding critical displacement are either derived analytically or computed numerically. Key model inputs are a root diameter distribution (uniform, Weibull, or lognormal) and three empirical power law relations describing tensile strength, elastic modulus, and length of roots as functions of root diameter. When a root bundle with root tips anchored in the soil matrix is pulled by a rigid plate, a unique parameter, ?, that depends only on the exponents of the power law relations, dictates the order in which roots of different diameters break. If ? < 1, small roots break first; if ? > 1, large roots break first. When ? = 1, all fibers break simultaneously, and the maximum tensile force is simply the roots' mean force times the number of roots in the bundle. Based on measurements of root geometry and mechanical properties, the value of ? is less than 1, usually ranging between 0 and 0.7. Thus, small roots always fail first. The model shows how geometrical and mechanical characteristics of roots and root diameter distribution affect the pullout force, its maximum and corresponding displacement. Comparing bundles of roots that have similar mean diameters, a bundle with a narrow variance in root diameter will result in a larger maximum force and a smaller displacement at maximum force than a bundle with a wide diameter distribution. Increasing the mean root diameter of a bundle without changing the distribution's shape increases both the maximum force and corresponding displacement. Estimates of the maximum pullout forces for bundles of 100 roots with identical diameter distribution for different species range from less than 1 kN for barley (Hordeum vulgare) to almost 16 kN for pistachio (Pistacia lentiscus). The model explains why a commonly used assumption that all roots break simultaneously overpredicts the maximum pullout force by a factor of about 1.6-2. This ratio may exceed 3 for diameter distributions that have a large number of small roots like the exponential distribution.

Comparison of in situ forces and knee kinematics in anteromedial and high anteromedial bundle augmentation for partially ruptured anterior cruciate ligament.

PubMed

Xu, Yan; Liu, Jianyu; Kramer, Scott; Martins, Cesar; Kato, Yuki; Linde-Rosen, Monica; Smolinski, Patrick; Fu, Freddie H

2011-02-01

High tunnel placement is common in single- and double-bundle anterior cruciate ligament (ACL) reconstructions. Similar nonanatomic tunnel placement may also occur in ACL augmentation surgery. In this study, in situ forces and knee kinematics were compared between nonanatomic high anteromedial (AM) and anatomic AM augmentation in a knee with isolated AM bundle injury. Controlled laboratory study. Seven fresh-frozen cadaver knees were used (age, 48 ± 12.5 years). First, intact knee kinematics was tested with a robotic-universal force sensor testing system under 2 loading conditions. An 89-N anterior load was applied, and an anterior tibial translation was measured at knee flexion angles of 0°, 30°, 60°, and 90°. Then, combined rotatory loads of 7-N·m valgus and 5-N·m internal tibial rotation were applied at 15° and 30° of knee flexion angles, which mimic the pivot shift. Afterward, only the AM bundle of the ACL was cut arthroscopically, keeping the posterolateral bundle intact. The knee was again tested using the intact knee kinematics to measure the in situ force of the AM bundle. Then, arthroscopic anatomic AM bundle reconstruction was performed with an allograft, and the knee was tested to give the in situ force of the reconstructed AM bundle. Knee kinematics under the 3 conditions (intact, anatomic AM augmentation, and nonanatomic high AM augmentation) and the in situ force were compared and analyzed. The high AM graft had significantly lower in situ force than the intact and anatomic reconstructed AM bundle at 0° of knee flexion (P < .05) and the intact AM bundle at 30° of knee flexion under anterior tibial loading. There were no differences between anatomic graft and intact AM bundle. The high AM graft also had a significantly lower in situ force than the intact and anatomic reconstructed AM with simulated pivot-shift loading at 15° and 30° of flexion (P < .05). Under anterior tibial and rotatory loading, there was a difference in tibial displacement between anatomic and high AM reconstructions and between the high AM graft and intact ACL under rotational loading with the knee at 15° of flexion. Anatomic AM augmentation can lead to biomechanical advantages at time zero when compared with the nonanatomic (high AM) augmentation. Anatomic AM augmentation better restores the knee kinematics to the intact ACL state.

Implementing the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle into everyday care: opportunities, challenges, and lessons learned for implementing the ICU Pain, Agitation, and Delirium Guidelines.

PubMed

Balas, Michele C; Burke, William J; Gannon, David; Cohen, Marlene Z; Colburn, Lois; Bevil, Catherine; Franz, Doug; Olsen, Keith M; Ely, E Wesley; Vasilevskis, Eduard E

2013-09-01

The awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle is an evidence-based interprofessional multicomponent strategy for minimizing sedative exposure, reducing duration of mechanical ventilation, and managing ICU-acquired delirium and weakness. The purpose of this study was to identify facilitators and barriers to awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle adoption and to evaluate the extent to which bundle implementation was effective, sustainable, and conducive to dissemination. Prospective, before-after, mixed-methods study. Five adult ICUs, one step-down unit, and a special care unit located in a 624-bed academic medical center : Interprofessional ICU team members at participating institution. In collaboration with the participating institution, we developed, implemented, and refined an awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle policy. Over the course of an 18-month period, all ICU team members were offered the opportunity to participate in numerous multimodal educational efforts. Three focus group sessions, three online surveys, and one educational evaluation were administered in an attempt to identify facilitators and barriers to bundle adoption. Factors believed to facilitate bundle implementation included: 1) the performance of daily, interdisciplinary, rounds; 2) engagement of key implementation leaders; 3) sustained and diverse educational efforts; and 4) the bundle's quality and strength. Barriers identified included: 1) intervention-related issues (e.g., timing of trials, fear of adverse events), 2) communication and care coordination challenges, 3) knowledge deficits, 4) workload concerns, and 5) documentation burden. Despite these challenges, participants believed implementation ultimately benefited patients, improved interdisciplinary communication, and empowered nurses and other ICU team members. In this study of the implementation of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle in a tertiary care setting, clear factors were identified that both advanced and impeded adoption of this complex intervention that requires interprofessional education, coordination, and cooperation. Focusing on these factors preemptively should enable a more effective and lasting implementation of the bundle and better care for critically ill patients. Lessons learned from this study will also help healthcare providers optimize implementation of the recent ICU pain, agitation, and delirium guidelines, which has many similarities but also some important differences as compared with the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle.

Risk Adjustment for Medicare Total Knee Arthroplasty Bundled Payments.

PubMed

Clement, R Carter; Derman, Peter B; Kheir, Michael M; Soo, Adrianne E; Flynn, David N; Levin, L Scott; Fleisher, Lee

2016-09-01

The use of bundled payments is growing because of their potential to align providers and hospitals on the goal of cost reduction. However, such gain sharing could incentivize providers to "cherry-pick" more profitable patients. Risk adjustment can prevent this unintended consequence, yet most bundling programs include minimal adjustment techniques. This study was conducted to determine how bundled payments for total knee arthroplasty (TKA) should be adjusted for risk. The authors collected financial data for all Medicare patients (age≥65 years) undergoing primary unilateral TKA at an academic center over a period of 2 years (n=941). Multivariate regression was performed to assess the effect of patient factors on the costs of acute inpatient care, including unplanned 30-day readmissions. This analysis mirrors a bundling model used in the Medicare Bundled Payments for Care Improvement initiative. Increased age, American Society of Anesthesiologists (ASA) class, and the presence of a Medicare Major Complications/Comorbid Conditions (MCC) modifier (typically representing major complications) were associated with increased costs (regression coefficients, $57 per year; $729 per ASA class beyond I; and $3122 for patients meeting MCC criteria; P=.003, P=.001, and P<.001, respectively). Differences in costs were not associated with body mass index, sex, or race. If the results are generalizable, Medicare bundled payments for TKA encompassing acute inpatient care should be adjusted upward by the stated amounts for older patients, those with elevated ASA class, and patients meeting MCC criteria. This is likely an underestimate for many bundling models, including the Comprehensive Care for Joint Replacement program, incorporating varying degrees of postacute care. Failure to adjust for factors that affect costs may create adverse incentives, creating barriers to care for certain patient populations. [Orthopedics. 2016; 39(5):e911-e916.]. Copyright 2016, SLACK Incorporated.

Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation.

PubMed

Carey, Irene; Shouls, Susanna; Bristowe, Katherine; Morris, Michelle; Briant, Linda; Robinson, Carole; Caulkin, Ruth; Griffiths, Mathew; Clark, Kieron; Koffman, Jonathan; Hopper, Adrian

2015-03-01

Despite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1-2 months. This paper suggests an approach to improve this care. A care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up. This paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development. It has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation.

PubMed

Carey, Irene; Shouls, Susanna; Bristowe, Katherine; Morris, Michelle; Briant, Linda; Robinson, Carole; Caulkin, Ruth; Griffiths, Mathew; Clark, Kieron; Koffman, Jonathan; Hopper, Adrian

2015-12-01

Despite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1-2 months. This paper suggests an approach to improve this care. A care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up. This paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development. It has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Actin filament bundling by fimbrin is important for endocytosis, cytokinesis, and polarization in fission yeast.

PubMed

Skau, Colleen T; Courson, David S; Bestul, Andrew J; Winkelman, Jonathan D; Rock, Ronald S; Sirotkin, Vladimir; Kovar, David R

2011-07-29

Through the coordinated action of diverse actin-binding proteins, cells simultaneously assemble actin filaments with distinct architectures and dynamics to drive different processes. Actin filament cross-linking proteins organize filaments into higher order networks, although the requirement of cross-linking activity in cells has largely been assumed rather than directly tested. Fission yeast Schizosaccharomyces pombe assembles actin into three discrete structures: endocytic actin patches, polarizing actin cables, and the cytokinetic contractile ring. The fission yeast filament cross-linker fimbrin Fim1 primarily localizes to Arp2/3 complex-nucleated branched filaments of the actin patch and by a lesser amount to bundles of linear antiparallel filaments in the contractile ring. It is unclear whether Fim1 associates with bundles of parallel filaments in actin cables. We previously discovered that a principal role of Fim1 is to control localization of tropomyosin Cdc8, thereby facilitating cofilin-mediated filament turnover. Therefore, we hypothesized that the bundling ability of Fim1 is dispensable for actin patches but is important for the contractile ring and possibly actin cables. By directly visualizing actin filament assembly using total internal reflection fluorescence microscopy, we determined that Fim1 bundles filaments in both parallel and antiparallel orientations and efficiently bundles Arp2/3 complex-branched filaments in the absence but not the presence of actin capping protein. Examination of cells exclusively expressing a truncated version of Fim1 that can bind but not bundle actin filaments revealed that bundling activity of Fim1 is in fact important for all three actin structures. Therefore, fimbrin Fim1 has diverse roles as both a filament "gatekeeper" and as a filament cross-linker.

Morphometry of the distribution of hydrostatic pulmonary oedema in dogs.

PubMed Central

Michel, R. P.; Meterissian, S.; Poulsen, R. S.

1986-01-01

Light microscopic morphometry was utilized to examine the distribution of fluid in the interstitium around arteries, veins and within bronchovascular bundles in hydrostatic oedema, comparing it with previous control and permeability oedema experiments. Pulmonary artery wedge pressure was raised with fluid overload and an aortic balloon in five anaesthetized dogs to produce oedema (wet weight to dry weight ratios of 11.66 +/- 0.84). Lung lobes were fixed by freeze-substitution at 20 mmHg airway pressure. Photomicrographs of arteries, veins and bronchovascular bundles were taken, and areas were digitized to obtain the following: for arteries and veins, an oedema ratio=perivascular oedema cuff area/vessel area; for bronchovascular bundles, T=total bundle area, A1=interstitial area around airways, B=airway (respiratory bronchiole, bronchiole, or bronchus) area, A2=periarterial interstitium, V=artery area. From these, oedema ratios were calculated as A1/B and A2/V. We found that the oedema ratios were greater (P less than 0.01) for arteries (1.18, n=675) than veins (0.56, n=263), and were greater for the larger vessels; A1 rose significantly (P less than 0.01) only in bronchovascular bundles with bronchioles and bronchi, not in those with respiratory bronchioles; A2 increased from three- to 25-fold (P less than 0.01) in all bundles; A1/B only increased in bundles with bronchi while A2/V increased two- to six-fold in all bundles with oedema compared with controls. We conclude that these preferential patterns of distribution resemble those reported in permeability oedema, and may shed light on mechanisms of accumulation, and on the physiological effects of oedema on airways and vessels of the lung. Images Fig. 1 Fig. 2 PMID:3801300

Stationary organization of the actin cytoskeleton in Vallisneria: the role of stable microfilaments at the end walls.

PubMed

Ryu, J H; Takagi, S; Nagai, R

1995-04-01

In mesophyll cells of the aquatic angiosperm Vallisneria gigantea, bundles of microfilaments (MFs) serve as tracks for the rotational streaming of the cytoplasm, which occurs along the two longer side walls and the two shorter end walls. The stationary organization of these bundles has been shown to depend on the association of the bundles with the plasma membrane at the end walls. To identify the sites of such association, the effects of cytochalasin B (CB) on the configuration of the bundles of MFs were examined. In the case of the side walls, MFs were completely disrupted after treatment with CB at 100 micrograms/ml for 24 hours. By contrast, in the case of the end walls, a number of partially disrupted MFs remained even after 48 hours of treatment. After removal of CB, a completely normal arrangement of bundles of MFs was once again evident within 24 hours after a rather complicated process of reassembly. When reassembly had been completed, the direction of cytoplasmic streaming was reversed only in a small fraction of the treated cells, suggesting that bundles of MFs are anchored and stabilized at the end walls of each cell and that the polarity of reorganized bundles and, therefore, the direction of the cytoplasmic streaming is determined in a manner that depends on the original polarity of MFs that remained in spite of the disruptive action of CB. By contrast, the direction of reinitiated cytoplasmic streaming was reversed in 50% of cells in which the bundles of MFs had been completely disrupted by exogenously applied trypsin prior treatment with CB.(ABSTRACT TRUNCATED AT 250 WORDS)

National Partnership for Maternal Safety: Consensus Bundle on Venous Thromboembolism.

PubMed

D'Alton, Mary E; Friedman, Alexander M; Smiley, Richard M; Montgomery, Douglas M; Paidas, Michael J; D'Oria, Robyn; Frost, Jennifer L; Hameed, Afshan B; Karsnitz, Deborah; Levy, Barbara S; Clark, Steven L

2016-10-01

Obstetric venous thromboembolism is a leading cause of severe maternal morbidity and mortality. Maternal death from thromboembolism is amenable to prevention, and thromboprophylaxis is the most readily implementable means of systematically reducing the maternal death rate. Observational data support the benefit of risk-factor-based prophylaxis in reducing obstetric thromboembolism. This bundle, developed by a multidisciplinary working group and published by the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care, supports routine thromboembolism risk assessment for obstetric patients, with appropriate use of pharmacologic and mechanical thromboprophylaxis. Safety bundles outline critical clinical practices that should be implemented in every maternity unit. The safety bundle is organized into four domains: Readiness, Recognition, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged.

Ab initio density functional theory investigation of Li-intercalated silicon carbide nanotube bundles

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2009-06-01

We present the results of ab initio density functional theory calculations on the energetic, and geometric and electronic structure of Li-intercalated ( 6,6) silicon carbide nanotube (SiCNT) bundles. Our results show that intercalation of lithium leads to the significant changes in the geometrical structure. The most prominent effect of Li intercalation on the electronic band structure is a shift of the Fermi energy which occurs as a result of charge transfer from lithium to the SiCNTs. All the Li-intercalated ( 6,6) SiCNT bundles are predicted to be metallic representing a substantial change in electronic properties relative to the undoped bundle, which is a wide band gap semiconductor. Both inside of the nanotube and the interstitial space are susceptible for intercalation. The present calculations suggest that the SiCNT bundle is a promising candidate for the anode material in battery applications.

Bundle-sheath thylakoids from NADP-malic enzyme-type C4 plants require an exogenous electron donor for enzyme light activation.

PubMed

Lavergne, D; Droux, M; Jacquot, J P; Miginiac-Maslow, M; Champigny, M L; Gadal, P

1985-10-01

Light activation of either NADP-malate dehydrogenase (EC 1.1.1.82) or fructose-1,6-bisphosphate phosphatase (EC 3.1.3.11) was assayed in a reconstituted chloroplastic, system comprising the isolated proteins of the ferredoxin-thioredoxin light-activation system and thylakoids from either mesophyll or bundle-sheath tissues of different C4 plants. While C4-plant thylakoids functionned almost equally well with C3-or C4-plant proteins, the photosyntem-II-deficient bundle-sheath thylakoids from the NADP-malic enzyme type, were unable to perform enzyme photoactivation unless supplemented with an electron donor to photosystem I. Bundle-sheath thylakoids isolated from plants showing no photosystem-II deficiency did not require such an addition. The results are discussed with respect to a possible requirement for a physiological reductant of ferredoxin for enzyme light activation in bundle-sheath, tissues.

Effects of Bundle Type and Substitution with Spent Laying Hen Surimi on Quality Characteristics of Imitation Crabsticks.

PubMed

Jin, Sang-Keun; Choi, Jung-Seok; Kim, Gap-Don

2017-01-01

The purpose of this study was to evaluate the effects of bundle type (BT) and substitution with spent laying hen (SH) surimi on quality characteristics of imitation crabsticks made from Alaska Pollack (AP) during 6 wk of cold storage. Diagonally bundled samples had poorer gel characteristics and more lipid oxidation when compared with straight bundled ones ( p <0.05). The color of diagonally bundled imitation crabsticks deteriorated with storage time ( p <0.01). However, BT did not affect sensory characteristics ( p >0.05). SH substitution had an effect on most quality characteristics of imitation crabsticks; darker and poorer gel characteristics were observed and its effect on sensory evaluation was seen at the initial storage. Thus, BT and SH substitution can be considered to have a slight effect on eating quality of imitation crabsticks, despite their negative effects on color, gel characteristics, and lipid oxidation.

Quantum Bundle Description of Quantum Projective Spaces

NASA Astrophysics Data System (ADS)

Ó Buachalla, Réamonn

2012-12-01

We realise Heckenberger and Kolb's canonical calculus on quantum projective ( N - 1)-space C q [ C p N-1] as the restriction of a distinguished quotient of the standard bicovariant calculus for the quantum special unitary group C q [ SU N ]. We introduce a calculus on the quantum sphere C q [ S 2 N-1] in the same way. With respect to these choices of calculi, we present C q [ C p N-1] as the base space of two different quantum principal bundles, one with total space C q [ SU N ], and the other with total space C q [ S 2 N-1]. We go on to give C q [ C p N-1] the structure of a quantum framed manifold. More specifically, we describe the module of one-forms of Heckenberger and Kolb's calculus as an associated vector bundle to the principal bundle with total space C q [ SU N ]. Finally, we construct strong connections for both bundles.

System and method for reducing combustion dynamics in a combustor

DOEpatents

Uhm, Jong Ho; Johnson, Thomas Edward; Zuo, Baifang; York, William David

2013-08-20

A system for reducing combustion dynamics in a combustor includes an end cap having an upstream surface axially separated from a downstream surface, and tube bundles extend through the end cap. A diluent supply in fluid communication with the end cap provides diluent flow to the end cap. Diluent distributors circumferentially arranged inside at least one tube bundle extend downstream from the downstream surface and provide fluid communication for the diluent flow through the end cap. A method for reducing combustion dynamics in a combustor includes flowing fuel through tube bundles that extend axially through an end cap, flowing a diluent through diluent distributors into a combustion chamber, wherein the diluent distributors are circumferentially arranged inside at least one tube bundle and each diluent distributor extends downstream from the end cap, and forming a diluent barrier in the combustion chamber between at least one pair of adjacent tube bundles.

Bundled Payments in Total Joint Replacement: Keeping Our Care Affordable and High in Quality.

PubMed

McLawhorn, Alexander S; Buller, Leonard T

2017-09-01

The purpose of this review was to evaluate the literature regarding bundle payment reimbursement models for total joint arthroplasty (TJA). From an economic standpoint, TJA are cost-effective, but they represent a substantial expense to the Centers for Medicare & Medicaid Services (CMS). Historically, fee-for-service payment models resulted in highly variable cost and quality. CMS introduced Bundled Payments for Care Improvement (BPCI) in 2012 and subsequently the Comprehensive Care for Joint Replacement (CJR) reimbursement model in 2016 to improve the value of TJA from the perspectives of both CMS and patients, by improving quality via cost control. Early results of bundled payments are promising, but preserving access to care for patients with high comorbidity burdens and those requiring more complex care is a lingering concern. Hospitals, regardless of current participation in bundled payments, should develop care pathways for TJA to maximize efficiency and patient safety.

Improved Conjugate Gradient Bundle Adjustment of Dunhuang Wall Painting Images

NASA Astrophysics Data System (ADS)

Hu, K.; Huang, X.; You, H.

2017-09-01

Bundle adjustment with additional parameters is identified as a critical step for precise orthoimage generation and 3D reconstruction of Dunhuang wall paintings. Due to the introduction of self-calibration parameters and quasi-planar constraints, the structure of coefficient matrix of the reduced normal equation is banded-bordered, making the solving process of bundle adjustment complex. In this paper, Conjugate Gradient Bundle Adjustment (CGBA) method is deduced by calculus of variations. A preconditioning method based on improved incomplete Cholesky factorization is adopt to reduce the condition number of coefficient matrix, as well as to accelerate the iteration rate of CGBA. Both theoretical analysis and experimental results comparison with conventional method indicate that, the proposed method can effectively conquer the ill-conditioned problem of normal equation and improve the calculation efficiency of bundle adjustment with additional parameters considerably, while maintaining the actual accuracy.

A simple numerical model for membrane oxygenation of an artificial lung machine

NASA Astrophysics Data System (ADS)

Subraveti, Sai Nikhil; Sai, P. S. T.; Viswanathan Pillai, Vinod Kumar; Patnaik, B. S. V.

2015-11-01

Optimal design of membrane oxygenators will have far reaching ramification in the development of artificial heart-lung systems. In the present CFD study, we simulate the gas exchange between the venous blood and air that passes through the hollow fiber membranes on a benchmark device. The gas exchange between the tube side fluid and the shell side venous liquid is modeled by solving mass, momentum conservation equations. The fiber bundle was modelled as a porous block with a bundle porosity of 0.6. The resistance offered by the fiber bundle was estimated by the standard Ergun correlation. The present numerical simulations are validated against available benchmark data. The effect of bundle porosity, bundle size, Reynolds number, non-Newtonian constitutive relation, upstream velocity distribution etc. on the pressure drop, oxygen saturation levels etc. are investigated. To emulate the features of gas transfer past the alveoli, the effect of pulsatility on the membrane oxygenation is also investigated.

The Shape of a Ponytail and the Statistical Physics of Hair Fiber Bundles

NASA Astrophysics Data System (ADS)

Goldstein, Raymond E.; Warren, Patrick B.; Ball, Robin C.

2012-02-01

From Leonardo to the Brothers Grimm our fascination with hair has endured in art and science. Yet, a quantitative understanding of the shapes of a hair bundles has been lacking. Here we combine experiment and theory to propose an answer to the most basic question: What is the shape of a ponytail? A model for the shape of hair bundles is developed from the perspective of statistical physics, treating individual fibers as elastic filaments with random intrinsic curvatures. The combined effects of bending elasticity, gravity, and bundle compressibility are recast as a differential equation for the envelope of a bundle, in which the compressibility enters through an ``equation of state.'' From this, we identify the balance of forces in various regions of the ponytail, extract the equation of state from analysis of ponytail shapes, and relate the observed pressure to the measured random curvatures of individual hairs.

Bundles of Norms About Teen Sex and Pregnancy.

PubMed

Mollborn, Stefanie; Sennott, Christie

2015-09-01

Teen pregnancy is a cultural battleground in struggles over morality, education, and family. At its heart are norms about teen sex, contraception, pregnancy, and abortion. Analyzing 57 interviews with college students, we found that "bundles" of related norms shaped the messages teens hear. Teens did not think their communities encouraged teen sex or pregnancy, but normative messages differed greatly, with either moral or practical rationalizations. Teens readily identified multiple norms intended to regulate teen sex, contraception, abortion, childbearing, and the sanctioning of teen parents. Beyond influencing teens' behavior, norms shaped teenagers' public portrayals and post hoc justifications of their behavior. Although norm bundles are complex to measure, participants could summarize them succinctly. These bundles and their conflicting behavioral prescriptions create space for human agency in negotiating normative pressures. The norm bundles concept has implications for teen pregnancy prevention policies and can help revitalize social norms for understanding health behaviors. © The Author(s) 2014.

On the diffraction pattern of bundled rare-earth silicide nanowires on Si(0 0 1).

PubMed

Timmer, F; Bahlmann, J; Wollschläger, J

2017-11-01

Motivated by the complex diffraction pattern observed for bundled rare-earth silicide nanowires on the Si(0 0 1) surface, we investigate the influence of the width and the spacing distribution of the nanowires on the diffraction pattern. The diffraction pattern of the bundled rare-earth silicide nanowires is analyzed by the binary surface technique applying a kinematic approach to diffraction. Assuming a categorical distribution for the (individual) nanowire size and a Poisson distribution for the size of the spacing between adjacent nanowire-bundles, we are able to determine the parameters of these distributions and derive an expression for the distribution of the nanowire-bundle size. Additionally, the comparison of our simulations to the experimental diffraction pattern reveal that a (1  ×  1)-periodicity on top of the nanowires has to be assumed for a good match.

Infrared imaging spectrometry by the use of bundled chalcogenide glass fibers and a PtSi CCD camera

NASA Astrophysics Data System (ADS)

Saito, Mitsunori; Kikuchi, Katsuhiro; Tanaka, Chinari; Sone, Hiroshi; Morimoto, Shozo; Yamashita, Toshiharu T.; Nishii, Junji

1999-10-01

A coherent fiber bundle for infrared image transmission was prepared by arranging 8400 chalcogenide (AsS) glass fibers. The fiber bundle, 1 m in length, is transmissive in the infrared spectral region of 1 - 6 micrometer. A remote spectroscopic imaging system was constructed with the fiber bundle and an infrared PtSi CCD camera. The system was used for the real-time observation (frame time: 1/60 s) of gas distribution. Infrared light from a SiC heater was delivered to a gas cell through a chalcogenide fiber, and transmitted light was observed through the fiber bundle. A band-pass filter was used for the selection of gas species. A He-Ne laser of 3.4 micrometer wavelength was also used for the observation of hydrocarbon gases. Gases bursting from a nozzle were observed successfully by a remote imaging system.

Heterotic line bundle models on elliptically fibered Calabi-Yau three-folds

NASA Astrophysics Data System (ADS)

Braun, Andreas P.; Brodie, Callum R.; Lukas, Andre

2018-04-01

We analyze heterotic line bundle models on elliptically fibered Calabi-Yau three-folds over weak Fano bases. In order to facilitate Wilson line breaking to the standard model group, we focus on elliptically fibered three-folds with a second section and a freely-acting involution. Specifically, we consider toric weak Fano surfaces as base manifolds and identify six such manifolds with the required properties. The requisite mathematical tools for the construction of line bundle models on these spaces, including the calculation of line bundle cohomology, are developed. A computer scan leads to more than 400 line bundle models with the right number of families and an SU(5) GUT group which could descend to standard-like models after taking the ℤ2 quotient. A common and surprising feature of these models is the presence of a large number of vector-like states.

Delay Tolerant Networking - Bundle Protocol Simulation

NASA Technical Reports Server (NTRS)

SeGui, John; Jenning, Esther

2006-01-01

In this paper, we report on the addition of MACHETE models needed to support DTN, namely: the Bundle Protocol (BP) model. To illustrate the useof MACHETE with the additional DTN model, we provide an example simulation to benchmark its performance. We demonstrate the use of the DTN protocol and discuss statistics gathered concerning the total time needed to simulate numerous bundle transmissions.

Lagrangians and Euler morphisms from connections on the frame bundle

NASA Astrophysics Data System (ADS)

Kurek, J.; Mikulski, W. M.

2011-07-01

We classify all natural operators transforming torsion free classical linear connections ∇ on m-dimensional manifolds M into r-th order Lagrangians λ(∇) and Euler morphisms E(∇) on the linear frame bundle P1M. We also briefly write how this classification result can be generalized on higher order frame bundles PkM instead of P1M.

"The Purpose of This Study Is to": Connecting Lexical Bundles and Moves in Research Article Introductions

ERIC Educational Resources Information Center

Cortes, Viviana

2013-01-01

This article presents a group of lexical bundles identified in a corpus of research article introductions as the first step in the analysis of these expressions in the different sections of the research article. A one-million word corpus of research article introductions from various disciplines was compiled and the lexical bundles identified in…

76 FR 61561 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new... clearance and any wire bundle damage between wire bundle W443 and the left forward rudder quadrant, followed by adjusting the minimum clearance between the wire bundle and the left forward rudder quadrant, and...

76 FR 2840 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

...: We propose to adopt a new airworthiness directive (AD) for certain Model 737-600, -700, -700C, -800... and any wire bundle damage between wire bundle W443 and the left forward rudder quadrant, followed by adjusting the minimum clearance between the wire bundle and the left forward rudder quadrant, and repairing...

Development of deployable fibre integral-field-units for the E-ELT

NASA Astrophysics Data System (ADS)

Kelz, Andreas; Jahn, Thomas; Neumann, Justus; Roth, Martin M.; Rutowska, Monika; Sandin, Christer; Nicklas, Harald; Anwand, Heiko; Schmidt, C.

2014-07-01

The use of deployable fibre-bundles plays an increasing role in the design of future Multi-Object-Spectrographs (MOS). Within a research and development project for "Enabling Technologies for the E-ELT", various miniaturized, fibrebundles were designed, built and tested for their suitability for a proposed ELT-MOS instrument. The paper describes the opto-mechanical designs of the bundles and the different manufacture approaches, using glued, stacked and fused optical fibre bundles. The fibre bundles are characterized for performance, using dedicated testbenches in the laboratory and at a telescope simulator. Their performance is measured with respect to geometric accuracy, throughput, FRD behavior and cross-talk between channels.

Engineering biomimetic hair bundle sensors for underwater sensing applications

NASA Astrophysics Data System (ADS)

Kottapalli, Ajay Giri Prakash; Asadnia, Mohsen; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2018-05-01

We present the fabrication of an artificial MEMS hair bundle sensor designed to approximate the structural and functional principles of the flow-sensing bundles found in fish neuromast hair cells. The sensor consists of micro-pillars of graded height connected with piezoelectric nanofiber "tip-links" and encapsulated by a hydrogel cupula-like structure. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. These biomimetic sensors achieve an ultrahigh sensitivity of 0.286 mV/(mm/s) and an extremely low threshold detection limit of 8.24 µm/s. A complete version of this paper has been published [1].

Evaluating big deal journal bundles

PubMed Central

Bergstrom, Theodore C.; Courant, Paul N.; McAfee, R. Preston; Williams, Michael A.

2014-01-01

Large commercial publishers sell bundled online subscriptions to their entire list of academic journals at prices significantly lower than the sum of their á la carte prices. Bundle prices differ drastically between institutions, but they are not publicly posted. The data that we have collected enable us to compare the bundle prices charged by commercial publishers with those of nonprofit societies and to examine the types of price discrimination practiced by commercial and nonprofit journal publishers. This information is of interest to economists who study monopolist pricing, librarians interested in making efficient use of library budgets, and scholars who are interested in the availability of the work that they publish. PMID:24979785

Evaluating big deal journal bundles.

PubMed

Bergstrom, Theodore C; Courant, Paul N; McAfee, R Preston; Williams, Michael A

2014-07-01

Large commercial publishers sell bundled online subscriptions to their entire list of academic journals at prices significantly lower than the sum of their á la carte prices. Bundle prices differ drastically between institutions, but they are not publicly posted. The data that we have collected enable us to compare the bundle prices charged by commercial publishers with those of nonprofit societies and to examine the types of price discrimination practiced by commercial and nonprofit journal publishers. This information is of interest to economists who study monopolist pricing, librarians interested in making efficient use of library budgets, and scholars who are interested in the availability of the work that they publish.

Revascularization of diaphyseal bone segments by vascular bundle implantation.

PubMed

Nagi, O N

2005-11-01

Vascularized bone transfer is an effective, established treatment for avascular necrosis and atrophic or infected nonunions. However, limited donor sites and technical difficulty limit its application. Vascular bundle transplantation may provide an alternative. However, even if vascular ingrowth is presumed to occur in such situations, its extent in aiding revascularization for ultimate graft incorporation is not well understood. A rabbit tibia model was used to study and compare vascularized, segmental, diaphyseal, nonvascularized conventional, and vascular bundle-implanted grafts with a combination of angiographic, radiographic, histopathologic, and bone scanning techniques. Complete graft incorporation in conventional grafts was observed at 6 months, whereas it was 8 to 12 weeks with either of the vascularized grafts. The pattern of radionuclide uptake and the duration of graft incorporation between vascular segmental bone grafts (with intact endosteal blood supply) and vascular bundle-implanted segmental grafts were similar. A vascular bundle implanted in the recipient bone was found to anastomose extensively with the intraosseous circulation at 6 weeks. Effective revascularization of bone could be seen when a simple vascular bundle was introduced into a segment of bone deprived of its normal blood supply. This simple technique offers promise for improvement of bone graft survival in clinical circumstances.

Inner hair cell stereocilia movements captured in-situ by a high-speed camera with subpixel image processing

NASA Astrophysics Data System (ADS)

Wang, Yanli; Puria, Sunil; Steele, Charles R.; Ricci, Anthony J.

2018-05-01

Mechanical stimulation of the stereocilia hair bundles of the inner and outer hair cells (IHCs and OHCs, respectively) drives IHC synaptic release and OHC electromotility. The modes of hair-bundle motion can have a dramatic influence on the electrophysiological responses of the hair cells. The in vivo modes of motion are, however, unknown for both IHC and OHC bundles. In this work, we are developing technology to investigate the in situ hair-bundle motion in excised mouse cochleae, for which the hair bundles of the OHCs are embedded in the tectorial membrane but those of the IHCs are not. Motion is generated by pushing onto the stapes at 1 kHz with a glass probe coupled to a piezo stack, and recorded using a high-speed camera at 10,000 frames per second. The motions of individual IHC stereocilia and the cell boundary are analyzed using 2D and 1D Gaussian fitting algorithms, respectively. Preliminary results show that the IHC bundle moves mainly in the radial direction and exhibits a small degree of splay, and that the stereocilia in the second row move less than those in the first row, even in the same focal plane.

Hair bundles of cochlear outer hair cells are shaped to minimize their fluid-dynamic resistance.

PubMed

Ciganović, Nikola; Wolde-Kidan, Amanuel; Reichenbach, Tobias

2017-06-15

The mammalian sense of hearing relies on two types of sensory cells: inner hair cells transmit the auditory stimulus to the brain, while outer hair cells mechanically modulate the stimulus through active feedback. Stimulation of a hair cell is mediated by displacements of its mechanosensitive hair bundle which protrudes from the apical surface of the cell into a narrow fluid-filled space between reticular lamina and tectorial membrane. While hair bundles of inner hair cells are of linear shape, those of outer hair cells exhibit a distinctive V-shape. The biophysical rationale behind this morphology, however, remains unknown. Here we use analytical and computational methods to study the fluid flow across rows of differently shaped hair bundles. We find that rows of V-shaped hair bundles have a considerably reduced resistance to crossflow, and that the biologically observed shapes of hair bundles of outer hair cells are near-optimal in this regard. This observation accords with the function of outer hair cells and lends support to the recent hypothesis that inner hair cells are stimulated by a net flow, in addition to the well-established shear flow that arises from shearing between the reticular lamina and the tectorial membrane.

Dependence of flux-flow critical frequencies and generalized bundle sizes on distance of fluxoid traversal and fluxoid length in foil samples

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

Thompson, J.D.; Joiner, W.C.H.

1979-10-01

Flux-flow noise power spectra taken on Pb/sub 80/In/sub 20/ foils as a function of the orientation of the magnetic field with respect to the sample surfaces are used to study changes in frequencies and bundle sizes as distances of fluxoid traversal and fluxoid lengths change. The results obtained for the frequency dependence of the noise spectra are entirely consistent with our model for flux motion interrupted by pinning centers, provided one makes the reasonable assumption that the distance between pinning centers which a fluxoid may encounter scales inversely with the fluxoid length. The importance of pinning centers in determining themore » noise characteristics is also demonstrated by the way in which subpulse distributions and generalized bundle sizes are altered by changes in the metallurgical structure of the sample. In unannealed samples the dependence of bundle size on magnetic field orientation is controlled by a structural anisotropy, and we find a correlation between large bundle size and the absence of short subpulse times. Annealing removes this anisotropy, and we find a stronger angular variation of bundle size than would be expected using present simplified models.« less

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

NASA Astrophysics Data System (ADS)

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-09-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance.

PubMed

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P; Triantafyllou, Michael

2016-09-13

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

Surgical Management of Neurovascular Bundle in Uterine Fibroid Pseudocapsule

PubMed Central

Malvasi, Antonio; Hurst, Brad S.; Tsin, Daniel A.; Davila, Fausto; Dominguez, Guillermo; Dell'edera, Domenico; Cavallotti, Carlo; Negro, Roberto; Gustapane, Sarah; Teigland, Chris M.; Mettler, Liselotte

2012-01-01

The uterine fibroid pseudocapsule is a fibro-neurovascular structure surrounding a leiomyoma, separating it from normal peripheral myometrium. The fibroid pseudocapsule is composed of a neurovascular network rich in neurofibers similar to the neurovascular bundle surrounding a prostate. The nerve-sparing radical prostatectomy has several intriguing parallels to myomectomy. It may serve either as a useful model in modern fibroid surgical removal, or it may accelerate our understanding of the role of the fibrovascular bundle and neurotransmitters in the healing and restoration of reproductive potential after intracapsular myomectomy. Surgical innovations, such as laparoscopic or robotic myomectomy applied to the intracapsular technique with magnification of the fibroid pseudocapsule surrounding a leiomyoma, originated from the radical prostatectomy method that highlighted a careful dissection of the neurovascular bundle to preserve sexual functioning after prostatectomy. Gentle uterine leiomyoma detachment from the pseudocapsule neurovascular bundle has allowed a reduction in uterine bleeding and uterine musculature trauma with sparing of the pseudocapsule neuropeptide fibers. This technique has had a favorable impact on functionality in reproduction and has improved fertility outcomes. Further research should determine the role of the myoma pseudocapsule neurovascular bundle in the formation, growth, and pathophysiological consequences of fibroids, including pain, infertility, and reproductive outcomes. PMID:22906340

Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

PubMed

Kendig, Susan; Keats, John P; Hoffman, M Camille; Kay, Lisa B; Miller, Emily S; Simas, Tiffany A Moore; Frieder, Ariela; Hackley, Barbara; Indman, Pec; Raines, Christena; Semenuk, Kisha; Wisner, Katherine L; Lemieux, Lauren A

2017-03-01

Perinatal mood and anxiety disorders are among the most common mental health conditions encountered by women of reproductive age. When left untreated, perinatal mood and anxiety disorders can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide, and infanticide. Perinatal mood and anxiety disorders are associated with increased risks of maternal and infant mortality and morbidity and are recognized as a significant patient safety issue. In 2015, the Council on Patient Safety in Women's Health Care convened an interdisciplinary work group to develop an evidence-based patient safety bundle to address maternal mental health. The focus of this bundle is perinatal mood and anxiety disorders. The bundle is modeled after other bundles released by the Council on Patient Safety in Women's Health Care and provides broad direction for incorporating perinatal mood and anxiety disorder screening, intervention, referral, and follow-up into maternity care practice across health care settings. This commentary provides information to assist with bundle implementation. © 2017 by the American College of Nurse-Midwives.

Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

PubMed

Kendig, Susan; Keats, John P; Hoffman, M Camille; Kay, Lisa B; Miller, Emily S; Moore Simas, Tiffany A; Frieder, Ariela; Hackley, Barbara; Indman, Pec; Raines, Christena; Semenuk, Kisha; Wisner, Katherine L; Lemieux, Lauren A

Perinatal mood and anxiety disorders are among the most common mental health conditions encountered by women of reproductive age. When left untreated, perinatal mood and anxiety disorders can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide, and infanticide. Perinatal mood and anxiety disorders are associated with increased risks of maternal and infant mortality and morbidity and are recognized as a significant patient safety issue. In 2015, the Council on Patient Safety in Women's Health Care convened an interdisciplinary workgroup to develop an evidence-based patient safety bundle to address maternal mental health. The focus of this bundle is perinatal mood and anxiety disorders. The bundle is modeled after other bundles released by the Council on Patient Safety in Women's Health Care and provides broad direction for incorporating perinatal mood and anxiety disorder screening, intervention, referral, and follow-up into maternity care practice across health care settings. This commentary provides information to assist with bundle implementation. Copyright © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Differential geometric invariants for time-reversal symmetric Bloch-bundles: The “Real” case

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

De Nittis, Giuseppe, E-mail: gidenittis@mat.puc.cl; Gomi, Kiyonori, E-mail: kgomi@math.shinshu-u.ac.jp

2016-05-15

Topological quantum systems subjected to an even (resp. odd) time-reversal symmetry can be classified by looking at the related “Real” (resp. “Quaternionic”) Bloch-bundles. If from one side the topological classification of these time-reversal vector bundle theories has been completely described in De Nittis and Gomi [J. Geom. Phys. 86, 303–338 (2014)] for the “Real” case and in De Nittis and Gomi [Commun. Math. Phys. 339, 1–55 (2015)] for the “Quaternionic” case, from the other side it seems that a classification in terms of differential geometric invariants is still missing in the literature. With this article and its companion [G. Demore » Nittis and K. Gomi (unpublished)] we want to cover this gap. More precisely, we extend in an equivariant way the theory of connections on principal bundles and vector bundles endowed with a time-reversal symmetry. In the “Real” case we generalize the Chern-Weil theory and we show that the assignment of a “Real” connection, along with the related differential Chern class and its holonomy, suffices for the classification of “Real” vector bundles in low dimensions.« less

A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

PubMed

Raschke, Robert A; Groves, Robert H; Khurana, Hargobind S; Nikhanj, Nidhi; Utter, Ethel; Hartling, Didi; Stoffer, Brenda; Nunn, Kristina; Tryon, Shona; Bruner, Michelle; Calleja, Maria; Curry, Steven C

2017-01-01

Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

Thick Filament Length and Isoform Composition Determine Self-Organized Contractile Units in Actomyosin Bundles

PubMed Central

Thoresen, Todd; Lenz, Martin; Gardel, Margaret L.

2013-01-01

Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. PMID:23442916

Time-dependent fiber bundles with local load sharing.

PubMed

Newman, W I; Phoenix, S L

2001-02-01

Fiber bundle models, where fibers have random lifetimes depending on their load histories, are useful tools in explaining time-dependent failure in heterogeneous materials. Such models shed light on diverse phenomena such as fatigue in structural materials and earthquakes in geophysical settings. Various asymptotic and approximate theories have been developed for bundles with various geometries and fiber load-sharing mechanisms, but numerical verification has been hampered by severe computational demands in larger bundles. To gain insight at large size scales, interest has returned to idealized fiber bundle models in 1D. Such simplified models typically assume either equal load sharing (ELS) among survivors, or local load sharing (LLS) where a failed fiber redistributes its load onto its two nearest flanking survivors. Such models can often be solved exactly or asymptotically in increasing bundle size, N, yet still capture the essence of failure in real materials. The present work focuses on 1D bundles under LLS. As in previous works, a fiber has failure rate following a power law in its load level with breakdown exponent rho. Surviving fibers under fixed loads have remaining lifetimes that are independent and exponentially distributed. We develop both new asymptotic theories and new computational algorithms that greatly increase the bundle sizes that can be treated in large replications (e.g., one million fibers in thousands of realizations). In particular we develop an algorithm that adapts several concepts and methods that are well-known among computer scientists, but relatively unknown among physicists, to dramatically increase the computational speed with no attendant loss of accuracy. We consider various regimes of rho that yield drastically different behavior as N increases. For 1/2< or =rho< or =1, ELS and LLS have remarkably similar behavior (they have identical lifetime distributions at rho=1) with approximate Gaussian bundle lifetime statistics and a finite limiting mean. For rho>1 this Gaussian behavior also applies to ELS, whereas LLS behavior diverges sharply showing brittle, weakest volume behavior in terms of characteristic elements derived from critical cluster formation. For 0

Osteoblastic/Cementoblastic and Neural Differentiation of Dental Stem Cells and Their Applications to Tissue Engineering and Regenerative Medicine

PubMed Central

Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong

2012-01-01

Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine. PMID:22224548

Osteoblastic/cementoblastic and neural differentiation of dental stem cells and their applications to tissue engineering and regenerative medicine.

PubMed

Kim, Byung-Chul; Bae, Hojae; Kwon, Il-Keun; Lee, Eun-Jun; Park, Jae-Hong; Khademhosseini, Ali; Hwang, Yu-Shik

2012-06-01

Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine.

Solution Structure of Acidocin B, a Circular Bacteriocin Produced by Lactobacillus acidophilus M46

PubMed Central

Acedo, Jeella Z.; van Belkum, Marco J.; Lohans, Christopher T.; McKay, Ryan T.; Miskolzie, Mark

2015-01-01

Acidocin B, a bacteriocin produced by Lactobacillus acidophilus M46, was originally reported to be a linear peptide composed of 59 amino acid residues. However, its high sequence similarity to gassericin A, a circular bacteriocin from Lactobacillus gasseri LA39, suggested that acidocin B might be circular as well. Acidocin B was purified from culture supernatant by a series of hydrophobic interaction chromatographic steps. Its circular nature was ascertained by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry and tandem mass spectrometry (MS/MS) sequencing. The peptide sequence was found to consist of 58 amino acids with a molecular mass of 5,621.5 Da. The sequence of the acidocin B biosynthetic gene cluster was also determined and showed high nucleotide sequence similarity to that of gassericin A. The nuclear magnetic resonance (NMR) solution structure of acidocin B in sodium dodecyl sulfate micelles was elucidated, revealing that it is composed of four α-helices of similar length that are folded to form a compact, globular bundle with a central pore. This is a three-dimensional structure for a member of subgroup II circular bacteriocins, which are classified based on their isoelectric points of ∼7 or lower. Comparison of acidocin B with carnocyclin A, a subgroup I circular bacteriocin with four α-helices and a pI of 10, revealed differences in the overall folding. The observed variations could be attributed to inherent diversity in their physical properties, which also required the use of different solvent systems for three-dimensional structural elucidation. PMID:25681186

A strategy for improved computational efficiency of the method of anchored distributions

NASA Astrophysics Data System (ADS)

Over, Matthew William; Yang, Yarong; Chen, Xingyuan; Rubin, Yoram

2013-06-01

This paper proposes a strategy for improving the computational efficiency of model inversion using the method of anchored distributions (MAD) by "bundling" similar model parametrizations in the likelihood function. Inferring the likelihood function typically requires a large number of forward model (FM) simulations for each possible model parametrization; as a result, the process is quite expensive. To ease this prohibitive cost, we present an approximation for the likelihood function called bundling that relaxes the requirement for high quantities of FM simulations. This approximation redefines the conditional statement of the likelihood function as the probability of a set of similar model parametrizations "bundle" replicating field measurements, which we show is neither a model reduction nor a sampling approach to improving the computational efficiency of model inversion. To evaluate the effectiveness of these modifications, we compare the quality of predictions and computational cost of bundling relative to a baseline MAD inversion of 3-D flow and transport model parameters. Additionally, to aid understanding of the implementation we provide a tutorial for bundling in the form of a sample data set and script for the R statistical computing language. For our synthetic experiment, bundling achieved a 35% reduction in overall computational cost and had a limited negative impact on predicted probability distributions of the model parameters. Strategies for minimizing error in the bundling approximation, for enforcing similarity among the sets of model parametrizations, and for identifying convergence of the likelihood function are also presented.

Impact of a value-based insurance design for physical therapy to treat back pain on care utilization and cost.

PubMed

Maeng, Daniel D; Graboski, Anthony; Allison, Peiling L; Fisher, Dorothy Y; Bulger, John B

2017-01-01

To assess the impact of a value-based insurance design providing enhanced access to physical therapy (PT) for treatment of back pain on treatment patterns and cost of care. A retrospective analysis of claims data obtained from Geisinger Health Plan (GHP). In April 2013, GHP began offering "PT bundle" - i.e., a bundle of up to five PT visits for a single one-time copay that can be renewed for another bundle of five PT visits - for its employer-based plan members with back pain. A cohort of GHP members who were preauthorized for the PT bundle were compared against a contemporaneous cohort of GHP members who were preauthorized for PT under the standard per-visit copay arrangement between January 2013 and October 2014. Among the PT bundle cohort, the PT visit rate during the first 9 months since the PT preauthorization date had dramatically increased and then gradually decreased in subsequent months. The PT bundle was also associated with 29%-35% short-term reductions in emergency department visits and with 12%-20% reductions in primary care visits after 6 months. No significant impact on hospitalization or cost was observed. Implementation of the PT bundle appears to have led to a change in the treatment pattern of back pain that is more consistent with the recommended guidelines to use more conservative management such as PT as the first-line treatment for back pain.

Role of bundle helices in a regulatory crosstalk in the trimeric betaine transporter BetP.

PubMed

Gärtner, Rebecca M; Perez, Camilo; Koshy, Caroline; Ziegler, Christine

2011-12-02

The Na(+)-coupled betaine symporter BetP regulates transport activity in response to hyperosmotic stress only in its trimeric state, suggesting a regulatory crosstalk between individual protomers. BetP shares the overall fold of two inverted structurally related five-transmembrane (TM) helix repeats with the sequence-unrelated Na(+)-coupled symporters LeuT, vSGLT, and Mhp1, which are neither trimeric nor regulated in transport activity. Conformational changes characteristic for this transporter fold involve the two first helices of each repeat, which form a four-TM-helix bundle. Here, we identify two ionic networks in BetP located on both sides of the membrane that might be responsible for BetP's unique regulatory behavior by restricting the conformational flexibility of the four-TM-helix bundle. The cytoplasmic ionic interaction network links both first helices of each repeat in one protomer to the osmosensing C-terminal domain of the adjacent protomer. Moreover, the periplasmic ionic interaction network conformationally locks the four-TM-helix bundle between the same neighbor protomers. By a combination of site-directed mutagenesis, cross-linking, and betaine uptake measurements, we demonstrate how conformational changes in individual bundle helices are transduced to the entire bundle by specific inter-helical interactions. We suggest that one purpose of bundle networking is to assist crosstalk between protomers during transport regulation by specifically modulating the transition from outward-facing to inward-facing state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Mechanical Loading on the Dynamics of Hair-Cell Stereociliary Bundles

NASA Astrophysics Data System (ADS)

Fredrickson, Lea

Hearing is remarkably sensitive and still not entirely understood. Hair cells of the inner ear are the mechano-electrical transducers of sound and understanding how they function is essential to the understanding of hearing in general. Spontaneous oscillations exhibited by stereociliary bundles of the bullfrog sacculus provide a useful probe for the study of the hair cells' internal dynamic state. In this work we study the effects of mechanical loading on these hair-cell bundles in order to study their dynamics. When applying stiffness loads, we find that the spontaneous oscillation profile changes from multimode to single mode with light loading, and decreases in amplitude and increases in frequency with stiffer loads. We also find that tuning decreases with increasing load such that at loads comparable to in vivo conditions the tuning is flat. We further explore loading via deflections to hair cell bundles, both in the form of steady-state offsets and slow ramps. We find that steady state offsets lead to significant modulation of the characteristic frequency of response, decreasing the frequency in the channels closed direction (negative) and increasing it in the channels open direction (positive). Attachment to the overlying membrane was found, in vitro, to affect bundle offset position in hair cells of the bullfrog sacculus. Application of similar offsets on free-standing, spontaneously oscillating hair bundles shows modulation of their dynamic state, i.e. oscillation profile, characteristic frequency, and response to stimulus. Large offsets are found to arrest spontaneous oscillations, which recover upon reversal of the stimulus. The dynamical state of the hair bundle is dependent on both the history and direction of the offset stimulus. Oscillation suppression occurs much more readily in the negative direction and the bundle behavior approaching quiescence is distinct from that in the positive direction. With the change in spontaneous oscillation frequency and profile comes a change in the phase-locked response amplitude, dependent on bundle offset, winch extends the range of detection frequencies of the hair cell. We explore the broadband phase-locked response of spontaneously oscillating saccular hair cell bundles subject to time-dependent mechanical deflections. The experimental phase-locked amplitude shows an Arnold Tongue, consistent with theoretically predicted dynamical behavior. An offset that steadily increases in time, imposed on the position of the bundle to explore its dynamics at the zero frequency limit, is observed to progressively suppress spontaneous oscillations in a transition that displays strong frequency modulation, with the frequency vanishing at the critical point. When deflected at a faster rate and when allowed to recover to the oscillatory regime, the bundles also displayed a modulation in the amplitude of oscillation. We propose the dynamics of this transition to be dominated by a multi-critical region such that slight variations of a control parameter can produce either an infinite-period, supercritical Hopf, or Bogdanov-Takens bifurcation.

77 FR 39305 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change Amending...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... connects in multiples of six (e.g., six or 12 cross connects). The Exchange is proposing fees for bundled...\\ All multiple cross connects within the bundle would be installed at once and only in multiples of six... economical to purchase a bundle of six (with two unused) for a $500 initial charge plus a $1,500 monthly...

A Corpus-Based Study on the Use of Three-Word Lexical Bundles in the Academic Writing by Native English and Turkish Non-Native Writers

ERIC Educational Resources Information Center

Ucar, Serpil

2017-01-01

The utilization of English recurrent word combinations--lexical bundles--play a fundamental role in academic prose (Karabacak & Qin, 2013). There has been highly limited research about comparing Turkish non-native and native English writers' use of lexical bundles in academic prose in terms of frequency, structure and functions of lexical…

Sur le spectre du laplacien des fibrés en tores qui s'effondrent

NASA Astrophysics Data System (ADS)

Jammes, Pierre

2005-06-01

We study the small eigenvalues of the Hodge Laplacian on collaping torus bundles with bounded curvature. In the first part of this dissertation, we consider examples of bundles on S^1 and T^2 with homogeneous structure. In the second part, we give a lower bound of the first non-zero eigenvalue of the 1-form Laplacian on principal torus bundles.

The difference in centre position in the ACL femoral footprint inclusive and exclusive of the fan-like extension fibres.

PubMed

Iriuchishima, Takanori; Ryu, Keinosuke; Aizawa, Shin; Fu, Freddie H

2016-01-01

The purpose of this study was to compare the centre position of each anterior cruciate ligament bundle in its femoral footprint in measurements including and excluding the fan-like extension fibres. Fourteen non-paired human cadaver knees were used. All soft tissues around the knee were resected except the ligaments. The ACL was divided into antero-medial (AM) and postero-lateral (PL) bundles according to the difference in tension patterns. The ACL was carefully dissected, and two outlines were made of the periphery of each bundle insertion site: those which included and those which excluded the fan-like extension fibres. An accurate lateral view of the femoral condyle was photographed with a digital camera, and the images were downloaded to a personal computer. The centre position of each bundle, including and excluding the fan-like extension fibres, was measured with ImageJ software (National Institution of Health). Evaluation of the centre position was performed using the modified quadrant method. The centre of the femoral AM bundle including the fan-like extension was located at 28.8% in a shallow-deep direction and 37.2% in a high-low direction. When the AM bundle was evaluated without the fan-like extension, the centre was significantly different at 34.6% in a shallow-deep direction (p = 0.000) and 36% in a high-low direction. The centre of the PL bundle including the fan-like extension was found at 37.1% in a shallow-deep direction and 73.4% in a high-low direction. When the PL bundle was evaluated without the fan-like extension, the centre was significantly different at 42.7% in a shallow-deep direction (p = 0.000) and 69.3% in a high-low direction (p = 0.000). The centre position of the AM and PL bundles in the femoral ACL footprint was significantly different depending on the inclusion or exclusion of the fan-like extension fibres. For the clinical relevance, to reproduce the direct femoral insertion in the anatomical ACL reconstruction, tunnels should be placed relatively shallow and high in the femoral ACL footprint.

Effectiveness and Safety of the Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Exercise/Mobility (ABCDE) Bundle

PubMed Central

Balas, Michele C.; Vasilevskis, Eduard E.; Olsen, Keith M.; Schmid, Kendra K.; Shostrom, Valerie; Cohen, Marlene Z.; Peitz, Gregory; Gannon, David E.; Sisson, Joseph; Sullivan, James; Stothert, Joseph C.; Lazure, Julie; Nuss, Suzanne L.; Jawa, Randeep S.; Freihaut, Frank; Ely, E. Wesley; Burke, William J.

2014-01-01

Objective The debilitating and persistent effects of intensive care unit (ICU)-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of implementing the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle into everyday practice. Design Eighteen-month, prospective, cohort, before-after study conducted between November 2010 and May 2012. Setting Five adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center. Patients Two hundred ninety-six patients (146 pre- and 150 post-bundle implementation), age ≥ 19 years, managed by the institutions’ medical or surgical critical care service. Interventions ABCDE bundle. Measurements For mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify the relationship between ABCDE bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Main Results Patients in the post-implementation period spent three more days breathing without mechanical assistance than did those in the pre-implementation period (median [IQR], 24 [7 to 26] vs. 21 [0 to 25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the ABCDE bundle experienced a near halving of the odds of delirium (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.33–0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (OR, 2.11; 95% CI, 1.29–3.45; p = 0.003). No significant differences were noted in self-extubation or reintubation rates. Conclusions Critically ill patients managed with the ABCDE bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care. PMID:24394627

Contact Graph Routing

NASA Technical Reports Server (NTRS)

Burleigh, Scott C.

2011-01-01

Contact Graph Routing (CGR) is a dynamic routing system that computes routes through a time-varying topology of scheduled communication contacts in a network based on the DTN (Delay-Tolerant Networking) architecture. It is designed to enable dynamic selection of data transmission routes in a space network based on DTN. This dynamic responsiveness in route computation should be significantly more effective and less expensive than static routing, increasing total data return while at the same time reducing mission operations cost and risk. The basic strategy of CGR is to take advantage of the fact that, since flight mission communication operations are planned in detail, the communication routes between any pair of bundle agents in a population of nodes that have all been informed of one another's plans can be inferred from those plans rather than discovered via dialogue (which is impractical over long one-way-light-time space links). Messages that convey this planning information are used to construct contact graphs (time-varying models of network connectivity) from which CGR automatically computes efficient routes for bundles. Automatic route selection increases the flexibility and resilience of the space network, simplifying cross-support and reducing mission management costs. Note that there are no routing tables in Contact Graph Routing. The best route for a bundle destined for a given node may routinely be different from the best route for a different bundle destined for the same node, depending on bundle priority, bundle expiration time, and changes in the current lengths of transmission queues for neighboring nodes; routes must be computed individually for each bundle, from the Bundle Protocol agent's current network connectivity model for the bundle s destination node (the contact graph). Clearly this places a premium on optimizing the implementation of the route computation algorithm. The scalability of CGR to very large networks remains a research topic. The information carried by CGR contact plan messages is useful not only for dynamic route computation, but also for the implementation of rate control, congestion forecasting, transmission episode initiation and termination, timeout interval computation, and retransmission timer suspension and resumption.

Design and impact of bundled payment for detox and follow-up care.

PubMed

Quinn, Amity E; Hodgkin, Dominic; Perloff, Jennifer N; Stewart, Maureen T; Brolin, Mary; Lane, Nancy; Horgan, Constance M

2017-11-01

Recent payment reforms promote movement from fee-for-service to alternative payment models that shift financial risk from payers to providers, incentivizing providers to manage patients' utilization. Bundled payment, an episode-based fixed payment that includes the prices of a group of services that would typically treat an episode of care, is expanding in the United States. Bundled payment has been recommended as a way to pay for comprehensive SUD treatment and has the potential to improve treatment engagement after detox, which could reduce detox readmissions, improve health outcomes, and reduce medical care costs. However, if moving to bundled payment creates large losses for some providers, it may not be sustainable. The objective of this study was to design the first bundled payment for detox and follow-up care and to estimate its impact on provider revenues. Massachusetts Medicaid beneficiaries' behavioral health, medical, and pharmacy claims from July 2010-April 2013 were used to build and test a detox bundled payment for continuously enrolled adults (N=5521). A risk adjustment model was developed using general linear modeling to predict beneficiaries' episode costs. The projected payments to each provider from the risk adjustment analysis were compared to the observed baseline costs to determine the potential impact of a detox bundled payment reform on organizational revenues. This was modeled in two ways: first assuming no change in behavior and then assuming a supply-side cost sharing behavioral response of a 10% reduction in detox readmissions and an increase of one individual counseling and one group counseling session. The mean total 90-day detox episode cost was $3743. Nearly 70% of the total mean cost consists of the index detox, psychiatric inpatient care, and short-term residential care. Risk mitigation, including risk adjustment, substantially reduced the variation of the mean episode cost. There are opportunities for organizations to gain revenue under this bundled payment design, but many providers will lose money under a bundled payment designed using historic payment and costs. Designing a bundled payment for detox and follow-up care is feasible, but low case volume and the adequacy of the payment are concerns. Thus, a detox episode-based payment will likely be more challenging for smaller, independent SUD treatment providers. These providers are experiencing many changes as financing shifts away from block grant funding toward Medicaid funding. A detox bundled payment in practice would need to consider different risk mitigation strategies, provider pooling, and costs based on episodes of care meeting quality standards, but could incentivize care coordination, which is important to reducing detox readmissions and engaging patients in care. Copyright © 2017 Elsevier Inc. All rights reserved.

Electronic structure and optical properties of boron nitride nanotube bundles from first principles

NASA Astrophysics Data System (ADS)

Behzad, Somayeh

2015-06-01

The electronic and optical properties of bundled armchair and zigzag boron nitride nanotubes (BNNTs) are investigated by using density functional theory. Owing to the inter-tube coupling, the dispersions along the tube axis and in the plane perpendicular to the tube axis of BNNT bundles are significantly varied, which are characterized by the decrease of band gap, the splitting of the doubly degenerated states, the expansions of valence and conduction bands. The calculated dielectric functions of the armchair and zigzag bundles are similar to that of the isolated tubes, except for the appearance of broadened peaks, small shifts of peak positions about 0.1 eV and increasing of peak intensities.

Gross, Arthroscopic, and Radiographic Anatomies of the Anterior Cruciate Ligament: Foundations for Anterior Cruciate Ligament Surgery.

PubMed

Irarrázaval, Sebastián; Albers, Marcio; Chao, Tom; Fu, Freddie H

2017-01-01

The anterior cruciate ligament (ACL) is one of the more studied structures in the knee joint. It is not a tubular structure, but is much narrower in its midsubstance and broader at its ends, producing an hourglass shape. The ACL is composed of 2 functional bundles, the anteromedial and posterolateral bundles, that are named for their location of insertion on the anterior surface of the tibial plateau. Although the relative contribution in terms of total cross-sectional area of the ACL has been noted to be equal in regards to each bundle, dynamically these bundles demonstrate different properties for knee function. Copyright © 2016 Elsevier Inc. All rights reserved.

Bicarbonate refractory QRS prolongation and left bundle-branch block following escitalopram and lamotrigine overdose: A case report and literature review of toxic left bundle-branch block.

PubMed

Farkas, A N; Marcott, M; Yanta, J H; Pizon, A F

2018-05-02

Toxic prolongation of the QRS interval most often results from blockade of cardiac voltage-gated sodium channels and manifests on electrocardiogram with a right bundle-branch block-like morphology. Rarely, a left bundle-branch block (LBBB) morphology has been reported. We report a case of transient LBBB resultant from ingestion of lamotrigine and citalopram which was refractory to sodium bicarbonate therapy and eventually resolved spontaneously. Cases of toxic LBBB are less likely to respond to bicarbonate therapy, suggesting that this finding is due to a mechanism other than sodium channel blockade. © 2018 John Wiley & Sons Ltd.

Magnetic actuation of hair cells

NASA Astrophysics Data System (ADS)

Rowland, David; Roongthumskul, Yuttana; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

2011-11-01

The bullfrog sacculus contains mechanically sensitive hair cells whose stereociliary bundles oscillate spontaneously when decoupled from the overlying membrane. Steady-state offsets on the resting position of a hair bundle can suppress or modulate this native motility. To probe the dynamics of spontaneous oscillation in the proximity of the critical point, we describe here a method for mechanical actuation that avoids loading the bundles or contributing to the viscous drag. Magnetite beads were attached to the tips of the stereocilia, and a magnetic probe was used to impose deflections. This technique allowed us to observe the transition from multi-mode to single-mode state in freely oscillating bundles, as well as the crossover from the oscillatory to the quiescent state.

Effect of Varying Posterior Cruciate Ligament (PCL) Recessions on Kinematics and Ligament Strains with Cruciate Retaining Total Knee Prostheses.

PubMed

Schwarzkopf, Ran; Laster, Scott K; Cross, Michael B; Lenz, Nathaniel M

2016-04-01

Proper ligament tension in flexion with posterior cruciate retaining (CR) total knee arthroplasty (TKA) has long been associated with clinical success. The purpose of this study was to determine the effect of varying levels of posterior cruciate ligament (PCL) release on the tibiofemoral kinematics and PCL strain. A computational analysis was performed and varying levels of PCL release were simulated. Tibiofemoral kinematics was evaluated. The maximum PCL strain was determined for each bundle to evaluate the risk of rupture based on the failure strain. The femoral AP position shifted anteriorly as the PCL stiffness was reduced. PCL strain in both bundles increased as stiffness was reduced. The model predicts that the AL bundle should not rupture for a 75% release. Risk of PM bundle rupture is greater than AL bundle. Our findings suggest that a partial PCL release impacts tibiofemoral kinematics and ligament tension and strain. The relationship is dynamic and care should be taken when seeking optimal balance intra-operatively.

Second Harmonic Generation Imaging Analysis of Collagen Arrangement in Human Cornea.

PubMed

Park, Choul Yong; Lee, Jimmy K; Chuck, Roy S

2015-08-01

To describe the horizontal arrangement of human corneal collagen bundles by using second harmonic generation (SHG) imaging. Human corneas were imaged with an inverted two photon excitation fluorescence microscope. The excitation laser (Ti:Sapphire) was tuned to 850 nm. Backscatter signals of SHG were collected through a 425/30-nm bandpass emission filter. Multiple, consecutive, and overlapping image stacks (z-stacks) were acquired to generate three dimensional data sets. ImageJ software was used to analyze the arrangement pattern (irregularity) of collagen bundles at each image plane. Collagen bundles in the corneal lamellae demonstrated a complex layout merging and splitting within a single lamellar plane. The patterns were significantly different in the superficial and limbal cornea when compared with deep and central regions. Collagen bundles were smaller in the superficial layer and larger in deep lamellae. By using SHG imaging, the horizontal arrangement of corneal collagen bundles was elucidated at different depths and focal regions of the human cornea.

Actualizing Flexible National Security Space Systems

DTIC Science & Technology

2011-01-01

single launch vehicle is a decision unique to small satellites that adds an extra dimension to the launch risk calculation. While bundling...following a launch failure. The ability to bundle multiple payloads on a single launch vehicle is a decision unique to small satellites that adds an extra ... dimension to the launch risk calculation. While bundling multiple small satellites on a single launch vehicle spreads the initial launch cost across

A retracting wire knife for cutting fiber bundles and making sheet lesions of brain tissue.

PubMed

Shibata, M; Russell, I S

1979-07-01

A retracting knife which has two cutting wires for the transection of fiber bundles is described. The knife holds the fiber bundles of the stria terminalis between the two cutting wires and transects them by a shearing movement as the wires close. In addition, the feasability of such a knife producing a sheet lesion around the n. caudatus is also described.

Groupoid Actions on Fractafolds

NASA Astrophysics Data System (ADS)

Ionescu, Marius; Kumjian, Alex

2014-06-01

We define a bundle over a totally disconnected set such that each fiber is homeomorphic to a fractal blowup. We prove that there is a natural action of a Renault-Deaconu groupoid on our fractafold bundle and that the resulting action groupoid is a Renault-Deaconu groupoid itself. We also show that when the bundle is locally compact the associated C^*-algebra is primitive and has a densely defined lower-semicontinuous trace.

Assembly and turnover of neurofilaments in growing axonal neurites.

PubMed

Boumil, Edward F; Vohnoutka, Rishel; Lee, Sangmook; Pant, Harish; Shea, Thomas B

2018-01-26

Neurofilaments (NFs) are thought to provide stability to the axon. We examined NF dynamics within axonal neurites of NB2a/d1 neuroblastoma by transient transfection with green fluorescent protein-tagged NF-heavy (GFP-H) under the control of a tetracycline-inducible promoter. Immunofluorescent and biochemical analyses demonstrated that GFP-H expressed early during neurite outgrowth associated with a population of centrally-situated, highly-phosphorylated crosslinked NFs along the length of axonal neurites ('bundled NFs'). By contrast, GFP-H expressed after considerable neurite outgrowth displayed markedly reduced association with bundled NFs and was instead more evenly distributed throughout the axon. This differential localization was maintained for up to 2 weeks in culture. Once considerable neurite outgrowth had progressed, GFP that had previously associated with the NF bundle during early expression was irreversibly depleted by photobleaching. Cessation of expression allowed monitoring of NF turnover. GFP-H associated bundled NFs underwent slower decay than GFP-H associated with surrounding, less-phosphorylated NFs. Notably, GFP associated with bundled NFs underwent similar decay rates within the core and edges of this bundle. These results are consistent with previous demonstration of a resident NF population within axonal neurites, but suggest that this population is more dynamic than previously considered. © 2018. Published by The Company of Biologists Ltd.

Assembly and turnover of neurofilaments in growing axonal neurites

PubMed Central

Boumil, Edward F.; Vohnoutka, Rishel; Lee, Sangmook; Pant, Harish

2018-01-01

ABSTRACT Neurofilaments (NFs) are thought to provide stability to the axon. We examined NF dynamics within axonal neurites of NB2a/d1 neuroblastoma by transient transfection with green fluorescent protein-tagged NF-heavy (GFP-H) under the control of a tetracycline-inducible promoter. Immunofluorescent and biochemical analyses demonstrated that GFP-H expressed early during neurite outgrowth associated with a population of centrally-situated, highly-phosphorylated crosslinked NFs along the length of axonal neurites (‘bundled NFs’). By contrast, GFP-H expressed after considerable neurite outgrowth displayed markedly reduced association with bundled NFs and was instead more evenly distributed throughout the axon. This differential localization was maintained for up to 2 weeks in culture. Once considerable neurite outgrowth had progressed, GFP that had previously associated with the NF bundle during early expression was irreversibly depleted by photobleaching. Cessation of expression allowed monitoring of NF turnover. GFP-H associated bundled NFs underwent slower decay than GFP-H associated with surrounding, less-phosphorylated NFs. Notably, GFP associated with bundled NFs underwent similar decay rates within the core and edges of this bundle. These results are consistent with previous demonstration of a resident NF population within axonal neurites, but suggest that this population is more dynamic than previously considered. PMID:29158321

Observed mechanism for the breakup of small bundles of cellulose Iα and Iβ in ionic liquids from molecular dynamics simulations.

PubMed

Rabideau, Brooks D; Agarwal, Animesh; Ismail, Ahmed E

2013-04-04

Explicit, all-atom molecular dynamics simulations are used to study the breakup of small bundles of cellulose Iα and Iβ in the ionic liquids [BMIM]Cl, [EMIM]Ac, and [DMIM]DMP. In all cases, significant breakup of the bundles is observed with the initial breakup following a common underlying mechanism. Anions bind strongly to the hydroxyl groups of the exterior strands of the bundle, forming negatively charged complexes. Binding also weakens the intrastrand hydrogen bonds present in the cellulose strands, providing greater strand flexibility. Cations then intercalate between the individual strands, likely due to charge imbalances, providing the bulk to push the individual moieties apart and initiating the separation. The peeling of an individual strand from the main bundle is observed in [EMIM]Ac with an analysis of its hydrogen bonds with other strands showing that the chain detaches glucan by glucan from the main bundle in discrete, rapid events. Further analysis shows that the intrastrand hydrogen bonds of each glucan tend to break for a sustained period of time before the interstrand hydrogen bonds break and strand detachment occurs. Examination of similar nonpeeling strands shows that, without this intrastrand hydrogen bond breakage, the structural rigidity of the individual unit can hinder its peeling despite interstrand hydrogen bond breakage.

EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles

DOE PAGES

Fan, Yao; Tan, Kemin; Chhor, Gekleng; ...

2015-07-03

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (~10 kDa), comprised of a helix-loop-helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for twomore » alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero-oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.« less

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

PubMed Central

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-01-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices. PMID:27622466

Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles.

PubMed

Thoresen, Todd; Lenz, Martin; Gardel, Margaret L

2013-02-05

Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Capturing the Central Line Bundle Infection Prevention Interventions: Comparison of Reflective and Composite Modeling Methods.

PubMed

Gilmartin, Heather M; Sousa, Karen H; Battaglia, Catherine

2016-01-01

The central line (CL) bundle interventions are important for preventing central line-associated bloodstream infections (CLABSIs), but a modeling method for testing the CL bundle interventions within a health systems framework is lacking. Guided by the Quality Health Outcomes Model (QHOM), this study tested the CL bundle interventions in reflective and composite, latent, variable measurement models to assess the impact of the modeling approaches on an investigation of the relationships between adherence to the CL bundle interventions, organizational context, and CLABSIs. A secondary data analysis study was conducted using data from 614 U.S. hospitals that participated in the Prevention of Nosocomial Infection and Cost-Effectiveness Refined study. The sample was randomly split into exploration and validation subsets. The two CL bundle modeling approaches resulted in adequate fitting structural models (RMSEA = .04; CFI = .94) and supported similar relationships within the QHOM. Adherence to the CL bundle had a direct effect on organizational context (reflective = .23; composite = .20; p = .01) and CLABSIs (reflective = -.28; composite = -.25; p = .01). The relationship between context and CLABSIs was not significant. Both modeling methods resulted in partial support of the QHOM. There were little statistical, but large, conceptual differences between the reflective and composite modeling approaches. The empirical impact of the modeling approaches was inconclusive, for both models resulted in a good fit to the data. Lessons learned are presented. The comparison of modeling approaches is recommended when initially modeling variables that have never been modeled or with directional ambiguity to increase transparency and bring confidence to study findings.

Adsorption site analysis of impurity embedded single-walled carbon nanotube bundles

USGS Publications Warehouse

Agnihotri, S.; Mota, J.P.B.; Rostam-Abadi, M.; Rood, M.J.

2006-01-01

Bundle morphology and adsorptive contributions from nanotubes and impurities are studied both experimentally and by simulation using a computer-aided methodology, which employs a small physisorbed probe molecule to explore the porosity of nanotube samples. Grand canonical Monte Carlo simulation of nitrogen adsorption on localized sites of a bundle is carried out to predict adsorption in its accessible internal pore volume and on its external surface as a function of tube diameter. External adsorption is split into the contributions from the clean surface of the outermost nanotubes of the bundle and from the surface of the impurities. The site-specific isotherms are then combined into a global isotherm for a given sample using knowledge of its tube-diameter distribution obtained by Raman spectroscopy. The structural parameters of the sample, such as the fraction of open-ended nanotubes and the contributions from impurities and nanotube bundles to total external surface area, are determined by fitting the experimental nitrogen adsorption data to the simulated isotherm. The degree of closure between experimental and calculated adsorption isotherms for samples manufactured by two different methods, to provide different nanotube morphology and contamination level, further strengthens the validity and resulting interpretations based on the proposed approach. The average number of nanotubes per bundle and average bundle size, within a sample, are also quantified. The proposed method allows for extrapolation of adsorption properties to conditions where the purification process is 100% effective at removing all impurities and opening access to all intrabundle adsorption sites. ?? 2006 Elsevier Ltd. All rights reserved.

Capturing the Central Line Bundle Infection Prevention Interventions: Comparison of Reflective and Composite Modeling Methods

PubMed Central

Gilmartin, Heather M.; Sousa, Karen H.; Battaglia, Catherine

2016-01-01

Background The central line (CL) bundle interventions are important for preventing central line-associated bloodstream infections (CLABSIs), but a modeling method for testing the CL bundle interventions within a health systems framework is lacking. Objectives Guided by the Quality Health Outcomes Model (QHOM), this study tested the CL bundle interventions in reflective and composite, latent, variable measurement models to assess the impact of the modeling approaches on an investigation of the relationships between adherence to the CL bundle interventions, organizational context, and CLABSIs. Methods A secondary data analysis study was conducted using data from 614 U.S. hospitals that participated in the Prevention of Nosocomial Infection and Cost-Effectiveness-Refined study. The sample was randomly split into exploration and validation subsets. Results The two CL bundle modeling approaches resulted in adequate fitting structural models (RMSEA = .04; CFI = .94) and supported similar relationships within the QHOM. Adherence to the CL bundle had a direct effect on organizational context (reflective = .23; composite = .20; p = .01), and CLABSIs (reflective = −.28; composite = −.25; p =.01). The relationship between context and CLABSIs was not significant. Both modeling methods resulted in partial support of the QHOM. Discussion There were little statistical, but large, conceptual differences between the reflective and composite modeling approaches. The empirical impact of the modeling approaches was inconclusive, for both models resulted in a good fit to the data. Lessons learned are presented. The comparison of modeling approaches is recommended when initially modeling variables that have never been modeled, or with directional ambiguity, to increase transparency and bring confidence to study findings. PMID:27579507

Promoters and Barriers to Implementation of Tracheal Intubation Airway Safety Bundle: A Mixed-Method Analysis.

PubMed

Finn Davis, Katherine; Napolitano, Natalie; Li, Simon; Buffman, Hayley; Rehder, Kyle; Pinto, Matthew; Nett, Sholeen; Jarvis, J Dean; Kamat, Pradip; Sanders, Ronald C; Turner, David A; Sullivan, Janice E; Bysani, Kris; Lee, Anthony; Parker, Margaret; Adu-Darko, Michelle; Giuliano, John; Biagas, Katherine; Nadkarni, Vinay; Nishisaki, Akira

2017-10-01

To describe promoters and barriers to implementation of an airway safety quality improvement bundle from the perspective of interdisciplinary frontline clinicians and ICU quality improvement leaders. Mixed methods. Thirteen PICUs of the National Emergency Airway Registry for Children network. Remote or on-site focus groups with interdisciplinary ICU staff. Two semistructured interviews with ICU quality improvement leaders with quantitative and qualitative data-based feedbacks. Bundle implementation success (compliance) was defined as greater than or equal to 80% use for tracheal intubations for 3 consecutive months. ICUs were classified as early or late adopters. Focus group discussions concentrated on safety concerns and promoters and barriers to bundle implementation. Initial semistructured quality improvement leader interviews assessed implementation tactics and provided recommendations. Follow-up interviews assessed degree of acceptance and changes made after initial interview. Transcripts were thematically analyzed and contrasted by early versus late adopters. Median duration to achieve success was 502 days (interquartile range, 182-781). Five sites were early (median, 153 d; interquartile range, 146-267) and eight sites were late adopters (median, 783 d; interquartile range, 773-845). Focus groups identified common "promoter" themes-interdisciplinary approach, influential champions, and quality improvement bundle customization-and "barrier" themes-time constraints, competing paperwork and quality improvement activities, and poor engagement. Semistructured interviews with quality improvement leaders identified effective and ineffective tactics implemented by early and late adopters. Effective tactics included interdisciplinary quality improvement team involvement (early adopter: 5/5, 100% vs late adopter: 3/8, 38%; p = 0.08); ineffective tactics included physician-only rollouts, lack of interdisciplinary education, lack of data feedback to frontline clinicians, and misconception of bundle as research instead of quality improvement intervention. Implementation of an airway safety quality improvement bundle with high compliance takes a long time across diverse ICUs. Both early and late adopters identified similar promoter and barrier themes. Early adopter sites customized the quality improvement bundle and had an interdisciplinary quality improvement team approach.

What Financial Incentives Will Be Created by Medicare Bundled Payments for Total Hip Arthroplasty?

PubMed

Clement, R Carter; Kheir, Michael M; Soo, Adrianne E; Derman, Peter B; Levin, L Scott; Fleisher, Lee A

2016-09-01

Bundled payments are gaining popularity in arthroplasty as a tactic for encouraging providers and hospitals to work together to reduce costs. However, this payment model could potentially motivate providers to avoid unprofitable patients, limiting their access to care. Rigorous risk adjustment can prevent this adverse effect, but most current bundling models use limited, if any, risk-adjustment techniques. This study aims to identify and quantify the financial incentives that are likely to develop with total hip arthroplasty (THA) bundled payments that are not accompanied by comprehensive risk stratification. Financial data were collected for all Medicare-eligible patients (age 65+) undergoing primary unilateral THA at an academic center over a 2-year period (n = 553). Bundles were considered to include operative hospitalizations and unplanned readmissions. Multivariate regression was performed to assess the impact of clinical and demographic factors on the variable cost of THA episodes, including unplanned readmissions. (Variable costs reflect the financial incentives that will emerge under bundled payments). Increased costs were associated with advanced age (P < .001), elevated body mass index (BMI; P = .005), surgery performed for hip fracture (P < .001), higher American Society of Anaesthesiologists (ASA) Physical Classification System grades (P < .001), and MCCs (Medicare modifier for major complications; P < .001). Regression coefficients were $155/y, $107/BMI point, $2775 for fracture cases, $2137/ASA grade, and $4892 for major complications. No association was found between costs and gender or race. If generalizable, our results suggest that Centers for Medicare and Medicaid Services bundled payments encompassing acute inpatient care should be adjusted upward by the aforementioned amounts (regression coefficients above) for advanced age, increasing BMI, cases performed for fractures, elevated ASA grade, and major complications (as defined by Medicare MCC modifiers). Furthermore, these figures likely underestimate costs in many bundling models which incorporate larger proportions of postdischarge care. Failure to adjust for factors affecting costs may create barriers to care for specific patient populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

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

Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

2016-11-01

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

Evidence-based care bundles for preventing surgical site infections in spinal instrumentation surgery.

PubMed

Yamada, Koji; Abe, Hiroaki; Higashikawa, Akiro; Tonosu, Juichi; Kuniya, Takashi; Nakajima, Koji; Fujii, Haruko; Niwa, Kazuki; Shinozaki, Tomohiro; Watanabe, Kenichi; Sakae, Tanaka; Okazaki, Hiroshi

2018-05-22

Retrospective study, using prospectively collected data. To evaluate the impact of evidence-based care bundles for preventing surgical site infections (SSI) in spinal instrumentation surgery. About half of all SSIs are preventable via evidence-based methods. For successful SSI prevention, the bacterial load must be minimized, and methicillin-resistant Staphylococcus aureus (MRSA) protection must be maximized. However, it is difficult to cover all of these requirements by single preventative method. We screened consecutive patients scheduled for spinal instrumentation surgeries at a single tertiary referral hospital for high surgical, SSI, and MRSA colonization risks. Evidence-based care bundles were implemented for high risk patients and included: 1) additional vancomycin prophylaxis, 2) diluted povidone-iodine irrigation, and 3) nasal and body decontamination. Patient demographics, comorbidities, operative features, and SSIs reported to the Japanese Nosocomial Infections Surveillance system were prospectively obtained in the same method by the same assessor and were used for the analyses. The results were compared before and after the application of the bundle. There were 1,042 spinal instrumentation surgeries (741 before and 301 after care bundles) performed from November 2010 to December 2015. Of 301 surgeries, 57 cases (18.9%) received care bundles. There were no significant differences in patient backgrounds before and after the intervention. The SSI rate decreased significantly from 3.8% to 0.7% (P < 0.01) after the intervention, with an overall 82% relative risk reduction. A significant protective effect was observed in the multivariate analysis (adjusted odds ratio 0.18, 95% confidence interval: 0.04-0.77, P = 0.02). There were no MRSA-related SSIs among those that received care bundles, even though MRSA was the predominant pathogen in the study population. Evidence-based care bundles, applied in selected high-risk spinal instrumentation cases, minimized bacterial load, maximized MRSA protection, and significantly reduced SSI rates without topical vancomycin powder. 4.

A nano-microstructured artificial-hair-cell-type sensor based on topologically graded 3D carbon nanotube bundles

NASA Astrophysics Data System (ADS)

Yilmazoglu, O.; Yadav, S.; Cicek, D.; Schneider, J. J.

2016-09-01

A design for a unique artificial-hair-cell-type sensor (AHCTS) based entirely on 3D-structured, vertically aligned carbon nanotube (CNT) bundles is introduced. Standard microfabrication techniques were used for the straightforward micro-nano integration of vertically aligned carbon nanotube arrays composed of low-layer multi-walled CNTs (two to six layers). The mechanical properties of the carbon nanotube bundles were intensively characterized with regard to various substrates and CNT morphology, e.g. bundle height. The CNT bundles display excellent flexibility and mechanical stability for lateral bending, showing high tear resistance. The integrated 3D CNT sensor can detect three-dimensional forces using the deflection or compression of a central CNT bundle which changes the contact resistance to the shorter neighboring bundles. The complete sensor system can be fabricated using a single chemical vapor deposition (CVD) process step. Moreover, sophisticated external contacts to the surroundings are not necessary for signal detection. No additional sensors or external bias for signal detection are required. This simplifies the miniaturization and the integration of these nanostructures for future microsystem set-ups. The new nanostructured sensor system exhibits an average sensitivity of 2100 ppm in the linear regime with the relative resistance change per micron (ppm μm-1) of the individual CNT bundle tip deflection. Furthermore, experiments have shown highly sensitive piezoresistive behavior with an electrical resistance decrease of up to ˜11% at 50 μm mechanical deflection. The detection sensitivity is as low as 1 μm of deflection, and thus highly comparable with the tactile hair sensors of insects, having typical thresholds on the order of 30-50 μm. The AHCTS can easily be adapted and applied as a flow, tactile or acceleration sensor as well as a vibration sensor. Potential applications of the latter might come up in artificial cochlear systems. In particular, the stable mechanical bending of the sensor up to 90° opens up unique application opportunities.

Effect of the application of a bundle of three measures (intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples) on the surgical site infection after elective laparoscopic colorectal cancer surgery.

PubMed

Ruiz-Tovar, Jaime; Llavero, Carolina; Morales, Vicente; Gamallo, Carlos

2018-01-18

Surgical site infection (SSI) prevention bundles include the simultaneous use of different measures, which individually have demonstrated an effect on prevention of SSI. The implementation of bundles can yield superior results to the implementation of individual measures. The aim of this study was to address the effect of the application of a bundle including intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, on the surgical site infection after elective laparoscopic colorectal cancer surgery. A prospective, randomized study was performed, including patients with diagnosis of colorectal neoplasms and plans to undergo an elective laparoscopic surgery. The patients were randomized into two groups: those patients following standard bundles (Group 1) and those ones following the experimental bundle with three additional measures, added to the standard bundle. Incisional and organ space SSI were investigated. The study was assessor-blinded. A total of 198 patients were included in the study, 99 in each group. The incisional SSI rate was 16% in Group 1 and 2% in Group 2 [p = 0.007; RR = 5.6; CI 95% (1.4-17.8)]. The organ-space SSI rate was 4% in Group 1 and 0% in Group 2 [p = 0.039; RR = 1.7; CI 95% (1.1-11.6)]. Median hospital stay was 5.5 days in Group 1 and 4 days in Group 2 (p = 0.028). The addition of intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, to a standard bundle of SSI prevention, reduces the incisional and organ-space SSI and consequently the hospital stay, after elective laparoscopic colorectal cancer surgery (ClinicalTrials.gov Identifier: NCT03081962).

Recombinant human erythropoietin (rHuEPO): cross-linking with disuccinimidyl esters and identification of the interfacing domains in EPO.

PubMed Central

Haniu, M.; Narhi, L. O.; Arakawa, T.; Elliott, S.; Rohde, M. F.

1993-01-01

Several amino groups of recombinant human erythropoietin are selectively cross-linked by specific cross-linkers including disuccinimidyl suberate or dithiobis(succinimidyl propionate). Intramolecular cross-linkings are obtained without significant change of the protein conformation using appropriate concentrations (0.2 mM) of the cross-linkers, which possess an 11-12-A length of a spacer between two reacting groups. Intramolecularly cross-linked peptides obtained suggest that several amino groups in erythropoietin (EPO) are positioned at a distance of near 12 A in the solution state. These interfacing amino groups include Lys 20-Lys 154, Lys 45-Lys 140, Lys 52-Lys 154, Lys 52-Lys 140, and Ala 1-Lys 116. A comparison of the cross-linking results between nonglycosylated EPO and glycosylated EPO suggests that both proteins retain high similarity regarding protein conformation. These results fit a structural model similar to that of human growth hormone, in which four alpha-helical bundles and a long stretch of beta-sheet structure are involved in the active protein. PMID:8401229

Membrane Fusion Proteins as Nanomachines

NASA Astrophysics Data System (ADS)

Tamm, Lukas

2009-03-01

Membrane fusion is key to fertilization, virus infection, and neurotransmission. Specific proteins work like nanomachines to stitch together fluid, yet highly ordered lipid bilayers. The energy gained from large exothermic conformational changes of these proteins is utilized to fuse lipid bilayers that do not fuse spontaneously. Structural studies using x-ray crystallography and NMR spectroscopy have yielded detailed information about architecture and inner workings of these molecular machines. The question now is: how is mechanical energy gained from such protein transformations harnessed to transform membrane topology? To answer this question, we have determined that a boomerang-shaped structure of the influenza fusion peptide is critical to generate a high-energy binding intermediate in the target membrane and to return the ``boomerang'' to its place of release near the viral membrane for completion of the fusion cycle. In presynaptic exocytosis, receptor and acceptor SNAREs are zippered to form a helical bundle that is arrested shortly before the membrane. Ca binding to interlocked synaptotagmin releases the fusion block. Structural NMR and single molecule fluorescence data are combined to arrive at and further refine this picture.

Helium Adsorption on Carbon Nanotube Bundles with Different Diameters:. Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Majidi, R.; Karami, A. R.

2013-05-01

We have used molecular dynamics simulation to study helium adsorption capacity of carbon nanotube bundles with different diameters. Homogeneous carbon nanotube bundles of (8,8), (9,9), (10,10), (11,11), and (12,12) single walled carbon nanotubes have been considered. The results indicate that the exohedral adsorption coverage does not depend on the diameter of carbon nanotubes, while the endohedral adsorption coverage is increased by increasing the diameter.

Muon Bundles as a Sign of Strangelets from the Universe

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

Kankiewicz, P.; Rybczyński, M.; Włodarczyk, Z.

Recently, the CERN ALICE experiment observed muon bundles of very high multiplicities in its dedicated cosmic ray (CR) run, thereby confirming similar findings from the LEP era at CERN (in the CosmoLEP project). Originally, it was argued that they apparently stem from the primary CRs with a heavy masses. We propose an alternative possibility arguing that muonic bundles of highest multiplicity are produced by strangelets, hypothetical stable lumps of strange quark matter infiltrating our universe. We also address the possibility of additionally deducing their directionality which could be of astrophysical interest. Significant evidence for anisotropy of arrival directions of themore » observed high-multiplicity muonic bundles is found. Estimated directionality suggests their possible extragalactic provenance.« less

Multiple pass gas absorption cell utilizing a spherical mirror opposite one or more pair of obliquely disposed flat mirrors

NASA Technical Reports Server (NTRS)

Pearson, Richard (Inventor); Lynch, Dana H. (Inventor); Gunter, William D. (Inventor)

1995-01-01

A method and apparatus for passing light bundles through a multiple pass sampling cell is disclosed. The multiple pass sampling cell includes a sampling chamber having first and second ends positioned along a longitudinal axis of the sampling cell. The sampling cell further includes an entrance opening, located adjacent the first end of the sampling cell at a first azimuthal angular position. The entrance opening permits a light bundle to pass into the sampling cell. The sampling cell also includes an exit opening at a second azimuthal angular position. The light exit permits a light bundle to pass out of the sampling cell after the light bundle has followed a predetermined path.

Cohomology of line bundles: Applications

NASA Astrophysics Data System (ADS)

Blumenhagen, Ralph; Jurke, Benjamin; Rahn, Thorsten; Roschy, Helmut

2012-01-01

Massless modes of both heterotic and Type II string compactifications on compact manifolds are determined by vector bundle valued cohomology classes. Various applications of our recent algorithm for the computation of line bundle valued cohomology classes over toric varieties are presented. For the heterotic string, the prime examples are so-called monad constructions on Calabi-Yau manifolds. In the context of Type II orientifolds, one often needs to compute cohomology for line bundles on finite group action coset spaces, necessitating us to generalize our algorithm to this case. Moreover, we exemplify that the different terms in Batyrev's formula and its generalizations can be given a one-to-one cohomological interpretation. Furthermore, we derive a combinatorial closed form expression for two Hodge numbers of a codimension two Calabi-Yau fourfold.

Process of Making Boron-Fiber Reinforced Composite Tape

NASA Technical Reports Server (NTRS)

Belvin, Harry L. (Inventor); Cano, Roberto J. (Inventor); Johnston, Norman J. (Inventor); Marchello, Joseph M. (Inventor)

2002-01-01

The invention is an apparatus and method for producing a hybrid boron reinforced polymer matrix composition from powder pre-impregnated fiber tow bundles and a linear array of boron fibers. The boron fibers are applied onto the powder pre-impregnated fiber tow bundles and then are processed within a processing component having an impregnation bar assembly. After passing through variable-dimension forming nip-rollers, the powder pre-impregnated fiber tow bundles with the boron fibers become a hybrid boron reinforced polymer matrix composite tape. A driving mechanism pulls the powder pre-impregnated fiber tow bundles with boron fibers through the processing line of the apparatus and a take-up spool collects the formed hybrid boron-fiber reinforced polymer matrix composite tape.

Cardiac resynchronization therapy with His bundle pacing as a method of treatment of chronic heart failure in patients with permanent atrial fibrillation and left bundle branch block.

PubMed

Boczar, Krzysztof; Sławuta, Agnieszka; Ząbek, Andrzej; Dębski, Maciej; Gajek, Jacek; Lelakowski, Jacek; Małecka, Barbara

CRT is a therapeutic option for patients with heart failure, sinus rhythm, prolonged QRS complex duration and reduced ejection fraction. We present a case of 71-year-old woman with dilated cardiomyopathy, NYHA functional class III and AF. We implanted CRT combined with direct His-bundle pacing. The indication for such a therapy was a left bundle branch block with a QRS complex of 178ms and a left ventricular EF of 15%, left ventricular end-diastolic diameter (LVEDD) of 75mm. After 8months of follow-up the LVEDD was 60mm with EF 35-40%. Copyright © 2017. Published by Elsevier Inc.

Morphological size evaluation of the mid-substance insertion areas and the fan-like extension fibers in the femoral ACL footprint.

PubMed

Suruga, Makoto; Horaguchi, Takashi; Iriuchishima, Takanori; Yahagi, Yoshiyuki; Iwama, Genki; Tokuhashi, Yasuaki; Aizawa, Shin

2017-08-01

The purpose of this study was to evaluate the detailed anatomy of the femoral anterior cruciate ligament (ACL) insertion site, with special attention given to the morphology of the mid-substance insertion areas and the fan-like extension fibers. Twenty-three non-paired human cadaver knees were used (7 Males, 16 Females, median age 83, range 69-96). All soft tissues around the knee were resected except the ligaments. The ACL was divided into antero-medial (AM) and postero-lateral (PL) bundles according to the difference in macroscopic tension patterns. The ACL was carefully dissected and two outlines were made of the periphery of each bundle insertion site: those which included and those which excluded the fan-like extension fibers. An accurate lateral view of the femoral condyle was photographed with a digital camera, and the images were downloaded to a personal computer. The area of each bundle, including and excluding the fan-like extension fibers, was measured with Image J software (National Institution of Health). The width and length of the mid-substance insertion sites were also evaluated using same image. The femoral ACL footprint was divided into four regions (mid-substance insertion sites of the AM and PL bundles, and fan-like extensions of the AM and PL bundles). The measured areas of the mid-substance insertion sites of the AM and PL bundles were 35.5 ± 12.5, and 32.4 ± 13.8 mm 2 , respectively. Whole width and length of the mid-substance insertion sites were 5.3 ± 1.4, and 15.5 ± 2.9 mm, respectively. The measured areas of the fan-like extensions of the AM and PL bundles were 27 ± 11.5, and 29.5 ± 12.4 mm 2 , respectively. The femoral ACL footprint was divided into quarters of approximately equal size (mid-substance insertion sites of the AM and PL bundles, and fan-like extensions of the AM and PL bundles). For clinical relevance, to perform highly reproducible anatomical ACL reconstruction, the presence of the fan-like extension fibers should be taken into consideration.

The cost-effectiveness of a patient centred pressure ulcer prevention care bundle: Findings from the INTACT cluster randomised trial.

PubMed

Whitty, Jennifer A; McInnes, Elizabeth; Bucknall, Tracey; Webster, Joan; Gillespie, Brigid M; Banks, Merrilyn; Thalib, Lukman; Wallis, Marianne; Cumsille, Jose; Roberts, Shelley; Chaboyer, Wendy

2017-10-01

Pressure ulcers are serious, avoidable, costly and common adverse outcomes of healthcare. To evaluate the cost-effectiveness of a patient-centred pressure ulcer prevention care bundle compared to standard care. Cost-effectiveness and cost-benefit analyses of pressure ulcer prevention performed from the health system perspective using data collected alongside a cluster-randomised trial. Eight tertiary hospitals in Australia. Adult patients receiving either a patient-centred pressure ulcer prevention care bundle (n=799) or standard care (n=799). Direct costs related to the intervention and preventative strategies were collected from trial data and supplemented by micro-costing data on patient turning and skin care from a 4-week substudy (n=317). The time horizon for the economic evaluation matched the trial duration, with the endpoint being diagnosis of a new pressure ulcer, hospital discharge/transfer or 28days; whichever occurred first. For the cost-effectiveness analysis, the primary outcome was the incremental costs of prevention per additional hospital acquired pressure ulcer case avoided, estimated using a two-stage cluster-adjusted non-parametric bootstrap method. The cost-benefit analysis estimated net monetary benefit, which considered both the costs of prevention and any difference in length of stay. All costs are reported in AU$(2015). The care bundle cost AU$144.91 (95%CI: $74.96 to $246.08) more per patient than standard care. The largest contributors to cost were clinical nurse time for repositioning and skin inspection. In the cost-effectiveness analysis, the care bundle was estimated to cost an additional $3296 (95%CI: dominant to $144,525) per pressure ulcer avoided. This estimate is highly uncertain. Length of stay was unexpectedly higher in the care bundle group. In a cost-benefit analysis which considered length of stay, the net monetary benefit for the care bundle was estimated to be -$2320 (95%CI -$3900, -$1175) per patient, suggesting the care bundle was not a cost-effective use of resources. A pressure ulcer prevention care bundle consisting of multicomponent nurse training and patient education may promote best practice nursing care but may not be cost-effective in preventing hospital acquired pressure ulcer. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The relationship of lateral anatomic structures to exiting guide pins during femoral tunnel preparation utilizing an accessory medial portal.

PubMed

Farrow, Lutul D; Parker, Richard D

2010-06-01

Anatomic reconstruction of the anterior cruciate ligament through an accessory medial portal has become increasingly popular. The purpose of this study is to describe the relationship of guide pin exit points to the lateral anatomic structures when preparing the anterior cruciate ligament femoral tunnel through an accessory medial portal. We utilized seven fresh frozen cadaveric knees. Utilizing an anteromedial approach, a guide wire was placed into the center of each bundle's footprint. Each guide wire was advanced through the lateral femoral cortex. The guide pins were passed at 90, 110, and 130 degrees of knee flexion. The distances from each guide pin to the closest relevant structures on the lateral side of the knee were measured. At 90 degrees the posterolateral bundle guide pin was closest to the lateral condyle articular cartilage (mean 5.4 +/- 2.2 mm) and gastrocnemius tendon (mean 5.7 +/- 2.1 mm). At 110 degrees the posterolateral bundle pin was closest to the gastrocnemius tendon (mean 4.5 +/- 3.4 mm). At 130 degrees the posterolateral bundle pin was closest to the gastrocnemius tendon (mean 7.2 +/- 5.5 mm) and lateral collateral ligament (mean 6.8 +/- 2.1 mm). At 90 degrees the anteromedial bundle guide pin was closest to the articular cartilage (mean 2.0 +/- 2.0 mm). At 110 degrees the anteromedial bundle pin was closest to the articular cartilage (mean 7.4 +/- 3.5 mm) and gastrocnemius tendon (mean 12.3 +/- 3.1 mm). At 130 degrees the AM bundle pin was closest to the gastrocnemius tendon (mean 8.2 +/- 3.2 mm) and LCL (mean 15.1 +/- 2.9 mm). Neither guide pin (anteromedial or posterolateral bundle) put the peroneal nerve at risk at any knee flexion angle. At low knee flexion angles the anteromedial and posterolateral bundle guide pins closely approximated multiple lateral structures when using an accessory medial arthroscopic portal. Utilizing higher flexion angles increases the margin of error when preparing both femoral tunnels. During preparation of the anterior cruciate ligament femoral tunnel through an accessory anteromedial portal the tunnels should be drilled in at least 110 degrees of knee flexion in order to move guide pin exit points away from important lateral knee structures.

Plant 115-kDa actin-filament bundling protein, P-115-ABP, is a homologue of plant villin and is widely distributed in cells.

PubMed

Yokota, Etsuo; Vidali, Luis; Tominaga, Motoki; Tahara, Hiroshi; Orii, Hidefumi; Morizane, Yosuke; Hepler, Peter K; Shimmen, Teruo

2003-10-01

In many cases, actin filaments are arranged into bundles and serve as tracks for cytoplasmic streaming in plant cells. We have isolated an actin-filament bundling protein, which is composed of 115-kDa polypeptide (P-115-ABP), from the germinating pollen of lily, Lilium longiflorum [Nakayasu et al. (1998) BIOCHEM: Biophys. Res. Commun. 249: 61]. P-115-ABP shared similar antigenicity with a plant 135-kDa actin-filament bundling protein (P-135-ABP), a plant homologue of villin. A full-length cDNA clone (ABP115; accession no. AB097407) was isolated from an expression cDNA library of lily pollen by immuno-screening using antisera against P-115-ABP and P-135-ABP. The amino acid sequence of P-115-ABP deduced from this clone showed high homology with those of P-135-ABP and four villin isoforms of Arabidopsis thaliana (AtVLN1, AtVLN2, AtVLN3 and AtVLN4), especially AtVLN4, indicating that P-115-ABP can also be classified as a plant villin. The P-115-ABP isolated biochemically from the germinating lily pollen was able to arrange F-actin filaments with uniform polarity into bundles and this bundling activity was suppressed by Ca2+-calmodulin (CaM), similar to the actin-filament bundling properties of P-135-ABP. The P-115-ABP type of plant villin was widely distributed in plant cells, from algae to land plants. In root hair cells of Hydrocharis dubia, this type of plant villin was co-localized with actin-filament bundles in the transvacuolar strands and the sub-cortical regions. Microinjection of the antiserum against P-115-ABP into living root hair cells caused the disappearance of transvaculor strands and alteration of the route of cytoplasmic streaming. In internodal cells of Chara corallina in which the P-135-ABP type of plant villin is lacking, the P-115-ABP type showed co-localization with actin-filament cables anchored on the intracellular surface of chloroplasts. These results indicated that plant villins are widely distributed and involved in the organization of actin filaments into bundles throughout the plant kingdom.

Active Donor Management During the Hospital Phase of Care Is Associated with More Organs Transplanted per Donor.

PubMed

Patel, Madhukar S; De La Cruz, Salvador; Sally, Mitchell B; Groat, Tahnee; Malinoski, Darren J

2017-10-01

Meeting donor management goals when caring for potential organ donors has been associated with more organs transplanted per donor (OTPD). Concern persists, however, as to whether this indicates that younger/healthier donors are more likely to meet donor management goals or whether active management affects outcomes. A prospective observational study of all standard criteria donors was conducted by 10 organ procurement organizations across United Network for Organ Sharing Regions 4, 5, and 6. Donor management goals representing normal critical care end points were measured at 2 time points: when a catastrophic brain injury was recognized and a referral was made to the organ procurement organization by the DH; and after brain death was declared and authorization for organ donation was obtained. Donor management goals Bundle "met" was defined as achieving any 7 of 9 end points. A positive Bundle status change was defined as not meeting the Bundle at referral and subsequently achieving it at authorization. The primary outcomes measure was having ≥4 OTPD. Data were collected for 1,398 standard criteria donors. Of the 1,166 (83%) who did not meet the Bundle at referral, only 254 (22%) had a positive Bundle status change. On adjusted analysis, positive Bundle status change increased the odds of achieving ≥4 OTPD significantly (odds ratio 2.04; 95% CI 1.49 to 2.81; p < 0.001). A positive donor management goal Bundle status change during donor hospital management is associated with a 2-fold increase in achieving ≥4 OTPD. Active critical care management of the potential organ donor, as evidenced by improvement in routinely measured critical care end points can be a means by which to substantially increase the number of organs available for transplantation. Published by Elsevier Inc.

Tibial rotation under combined in vivo loading after single- and double-bundle anterior cruciate ligament reconstruction.

PubMed

Tsarouhas, Alexander; Iosifidis, Michael; Spyropoulos, Giannis; Kotzamitelos, Dimitrios; Tsatalas, Themistoklis; Giakas, Giannis

2011-12-01

To evaluate in vivo the differences in tibial rotation between single- and double-bundle anterior cruciate ligament (ACL)-reconstructed knees under combined loading conditions. An 8-camera optoelectronic system and a force plate were used to collect kinematic and kinetic data from 14 patients with double-bundle ACL reconstruction, 14 patients with single-bundle reconstruction, 12 ACL-deficient subjects, and 12 healthy control individuals while performing 2 tasks. The first included walking, 60° pivoting, and stair ascending, and the second included stair descending, 60° pivoting, and walking. The 2 variables evaluated were the maximum range of internal-external tibial rotation and the maximum knee rotational moment. Tibial rotation angles were not significantly different across the 4 groups (P = .331 and P = .851, respectively) or when side-to-side differences were compared within groups (P = .216 and P = .371, respectively) for the ascending and descending maneuvers, nor were rotational moments among the 4 groups (P = .418 and P = .290, respectively). Similarly, for the descending maneuver, the rotational moments were not significantly different between sides (P = .192). However, for the ascending maneuver, rotational moments of the affected sides were significantly lower by 20.5% and 18.7% compared with their intact counterparts in the single-bundle (P = .015) and double-bundle (P = .05) groups, respectively. High-intensity activities combining stair ascending or descending with pivoting produce similar tibial rotation in single- and double-bundle ACL-reconstructed patients. During such maneuvers, the reconstructed knee may be subjected to significantly lower rotational loads compared with the intact knee. Level III, retrospective comparative study. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Experience with Designing and Implementing a Bundled Payment Program for Total Hip Replacement

PubMed Central

Whitcomb, Winthrop F.; Lagu, Tara; Krushell, Robert J.; Lehman, Andrew P.; Greenbaum, Jordan; McGirr, Joan; Pekow, Penelope S.; Calcasola, Stephanie; Benjamin, Evan; Mayforth, Janice; Lindenauer, Peter K.

2015-01-01

Background Bundled payments, also known as episode-based payments, are intended to contain health care costs and promote quality. In 2011 a bundled payment pilot program for total hip replacement was implemented by an integrated health care delivery system in conjunction with a commercial health plan subsidiary. In July 2015 the Centers for Medicare & Medicaid Services (CMS) proposed the Comprehensive Care for Joint Replacement Model to test bundled payment for hip and knee replacement. Methods Stakeholders were identified and a structure for program development and implementation was created. An Oversight Committee provided governance over a Clinical Model Subgroup and a Financial Model Subgroup. Results The pilot program included (1) a clinical model of care encompassing the period from the preoperative evaluation through the third postoperative visit, (2) a pricing model, (3) a program to share savings, and (4) a patient engagement and expectation strategy. Compared to 32 historical controls— patients treated before bundle implementation—45 post-bundle-implementation patients with total hip replacement had a similar length of hospital stay (3.0 versus 3.4 days, p = .24), higher rates of discharge to home or home with services than to a rehabilitation facility (87% versus 63%), similar adjusted median total payments ($22,272 versus $22,567, p = .43), and lower median posthospital payments ($704 versus $1,121, p = .002), and were more likely to receive guideline-consistent care (99% versus 95%, p = .05). Discussion The bundled payment pilot program was associated with similar total costs, decreased posthospital costs, fewer discharges to rehabilitation facilities, and improved quality. Successful implementation of the program hinged on buy-in from stakeholders and close collaboration between stakeholders and the clinical and financial teams. PMID:26289235

Use of the Delay-Tolerant Networking Bundle Protocol from Space

NASA Technical Reports Server (NTRS)

Wood, Lloyd; Ivancic, William D.; Eddy, Wesley M.; Stewart, Dave; Northam, James; Jackson, Chris; daSilvaCuriel, Alex

2009-01-01

The Disaster Monitoring Constellation (DMC), constructed by Survey Satellite Technology Ltd (SSTL), is a multisatellite Earth-imaging low-Earth-orbit sensor network where captured image swaths are stored onboard each satellite and later downloaded from the satellite payloads to a ground station. Store-and-forward of images with capture and later download gives each satellite the characteristics of a node in a Delay/Disruption Tolerant Network (DTN). Originally developed for the Interplanetary Internet, DTNs are now under investigation in an Internet Research Task Force (IRTF) DTN research group (RG), which has developed a bundle architecture and protocol. The DMC is currently unique in its adoption of the Internet Protocol (IP) for its imaging payloads and for satellite command and control, based around reuse of commercial networking and link protocols. These satellites use of IP has enabled earlier experiments with the Cisco router in Low Earth Orbit (CLEO) onboard the constellation's UK-DMC satellite. Earth images are downloaded from the satellites using a custom IPbased high-speed transfer protocol developed by SSTL, Saratoga, which tolerates unusual link environments. Saratoga has been documented in the Internet Engineering Task Force (IETF) for wider adoption. We experiment with use of DTNRG bundle concepts onboard the UKDMC satellite, by examining how Saratoga can be used as a DTN convergence layer to carry the DTNRG Bundle Protocol, so that sensor images can be delivered to ground stations and beyond as bundles. This is the first successful use of the DTNRG Bundle Protocol in a space environment. We use our practical experience to examine the strengths and weaknesses of the Bundle Protocol for DTN use, paying attention to fragmentation, custody transfer, and reliability issues.

Effects of accelerated artificial daylight aging on bending strength and bonding of glass fibers in fiber-embedded maxillofacial silicone prostheses.

PubMed

Hatamleh, Muhanad M; Watts, David C

2010-07-01

The purpose of this study was to test the effect of different periods of accelerated artificial daylight aging on bond strength of glass fiber bundles embedded into maxillofacial silicone elastomer and on bending strength of the glass fiber bundles. Forty specimens were fabricated by embedding resin-impregnated fiber bundles (1.5-mm diameter, 20-mm long) into maxillofacial silicone elastomer. Specimens were randomly allocated into four groups, and each group was subjected to different periods of accelerated daylight aging as follows (in hours); 0, 200, 400, and 600. The aging cycle included continuous exposure to quartz-filtered visible daylight (irradiance 760 W/m(2)) under an alternating weathering cycle (wet for 18 minutes, dry for 102 minutes). Pull-out tests were performed to evaluate bond strength between fiber bundles and silicone using a universal testing machine at 1 mm/min crosshead speed. Also a three-point bending test was performed to evaluate bending strength of the fiber bundles. One-way ANOVA and Bonferroni post hoc tests were carried out to detect statistical significance (p < 0.05). Mean (SD) values of maximum pull-out forces (in N) for groups 1 to 4 were: 13.63 (7.45), 19.67 (1.37), 13.58 (2.61), and 10.37 (2.52). Group 2 exhibited the highest pull-out force that was statistically significant when compared to the other groups. Maximum bending strengths of fiber bundles were in the range of 917.72 MPa to 1124.06 MPa. Bending strength significantly increased after 200 and 400 hours of aging only. After 200 hours of exposure to artificial daylight and moisture conditions, bond strength between glass fibers and heat-cured silicones is optimal, and the bending strength of the glass fiber bundles is enhanced.

Experience with Designing and Implementing a Bundled Payment Program for Total Hip Replacement.

PubMed

Whitcomb, Winthrop F; Lagu, Tara; Krushell, Robert J; Lehman, Andrew P; Greenbaum, Jordan; McGirr, Joan; Pekow, Penelope S; Calcasola, Stephanie; Benjamin, Evan; Mayforth, Janice; Lindenauer, Peter K

2015-09-01

Bundled payments, also known as episode-based payments, are intended to contain health care costs and promote quality. In 2011 a bundled payment pilot program for total hip replacement was implemented by an integrated health care delivery system in conjunction with a commercial health plan subsidiary. In July 2015 the Centers for Medicare & Medicaid Services (CMS) proposed the Comprehensive Care for Joint Replacement Model to test bundled payment for hip and knee replacement. Stakeholders were identified and a structure for program development and implementation was created. An Oversight Committee provided governance over a Clinical Model Subgroup and a Financial Model Subgroup. The pilot program included (1) a clinical model of care encompassing the period from the preoperative evaluation through the third postoperative visit, (2) a pricing model, (3) a program to share savings, and (4) a patient engagement and expectation strategy. Compared to 32 historical controls-patients treated before bundle implementation-45 post-bundle-implementation patients with total hip replacement had a similar length of hospital stay (3.0 versus 3.4 days, p=.24), higher rates of discharge to home or home with services than to a rehabilitation facility (87% versus 63%), similar adjusted median total payments ($22,272 versus $22,567, p=.43), and lower median posthospital payments ($704 versus $1,121, p=.002), and were more likely to receive guideline-consistent care (99% versus 95%, p=.05). The bundled payment pilot program was associated with similar total costs, decreased posthospital costs, fewer discharges to rehabilitation facilities, and improved quality. Successful implementation of the program hinged on buy-in from stakeholders and close collaboration between stakeholders and the clinical and financial teams.

Brill-Noether theory for vector bundles on projective curves

NASA Astrophysics Data System (ADS)

Ballico, E.

1998-11-01

In this paper we will study the Brill-Noether theory of vector bundles on a smooth projective curve X. As usual in papers on this topic we are mainly interested in stable or at least semistable bundles. Let Wkr, d(X) be the scheme of all stable vector bundles E on X with rank (E)=r, deg (E)=d and h0(X, E)[gt-or-equal, slanted]k+1. For a survey of the main known results, see the introduction of [6]. The referee has pointed out that the results in [6] were improved by V. Mercat in [14]; he proved that Wkr, d(X) is non-empty for d<2r if and only if k+1[less-than-or-eq, slant]r+(d[minus sign]r)/g. If X has general moduli the more interesting existence theorem was proved in [19]. However, in this paper we are mainly interested in very special curves X, e.g. the hyperelliptic or the bielliptic curves. We work over an algebraically closed base field K. In Section 5 we will assume char (K)=0. In Section 1 we will give some theorems of Clifford's type. In Section 2 we will construct several stable bundles with certain properties. Here the main tool is an operation (the +elementary transformation) which sends a vector bundle E on X to another vector bundle E[prime prime or minute] with rank (E[prime prime or minute])=rank (E) and deg (E[prime prime or minute])=deg (E)+1 (see Section 2 for its definition and its elementary properties). Using the +elementary transformations in Section 3 we will prove the following existence theorem which covers the case of a ‘small’ number of sections.

Bundling Post-Acute Care Services into MS-DRG Payments

PubMed Central

Vertrees, James C.; Averill, Richard F.; Eisenhandler, Jon; Quain, Anthony; Switalski, James

2013-01-01

Objective A bundled hospital payment system that encompasses both acute and post-acute care has been proposed as a means of creating financial incentives in the Medicare fee-for-service system to foster care coordination and to improve the current disorganized system of post care. The objective of this study was to evaluate the statistical stability of alternative designs of a hospital payment system that includes post-acute care services to determine the feasibility of using a combined hospital and post-acute care bundle as a unit of payment. Methods The Medicare Severity-Diagnosis Related Groups (MS-DRGs) were subdivided into clinical subclasses that measured a patient's chronic illness burden to test whether a patient's chronic illness burden had a substantial impact on post-acute care expenditures. Using Medicare data the statistical performance of the MS-DRGs with and without the chronic illness subclasses was evaluated across a wide range of post-acute care windows and combinations of post-acute care service bundles using both submitted charges and Medicare payments. Results The statistical performance of the MS-DRGs as measured by R2 was consistently better when the chronic illness subclasses are included indicating that MS-DRGs by themselves are an inadequate unit of payment for post-acute care payment bundles. In general, R2 values increased as the post-acute care window length increased and decreased as more services were added to the post-acute care bundle. Discussion The study results suggest that it is feasible to develop a payment system that incorporates significant post-acute care services into the MS-DRG inpatient payment bundle. This expansion of the basic DRG payment approach can provide a strong financial incentive for providers to better coordinate care potentially leading to improved efficiency and outcome quality. PMID:24753970