Error Correction using Quantum Quasi-Cyclic Low-Density Parity-Check(LDPC) Codes

NASA Astrophysics Data System (ADS)

Jing, Lin; Brun, Todd; Quantum Research Team

Quasi-cyclic LDPC codes can approach the Shannon capacity and have efficient decoders. Manabu Hagiwara et al., 2007 presented a method to calculate parity check matrices with high girth. Two distinct, orthogonal matrices Hc and Hd are used. Using submatrices obtained from Hc and Hd by deleting rows, we can alter the code rate. The submatrix of Hc is used to correct Pauli X errors, and the submatrix of Hd to correct Pauli Z errors. We simulated this system for depolarizing noise on USC's High Performance Computing Cluster, and obtained the block error rate (BER) as a function of the error weight and code rate. From the rates of uncorrectable errors under different error weights we can extrapolate the BER to any small error probability. Our results show that this code family can perform reasonably well even at high code rates, thus considerably reducing the overhead compared to concatenated and surface codes. This makes these codes promising as storage blocks in fault-tolerant quantum computation. Error Correction using Quantum Quasi-Cyclic Low-Density Parity-Check(LDPC) Codes.

Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cells

NASA Technical Reports Server (NTRS)

Nguyen, K. T.; Frye, S. R.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

2001-01-01

Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.

Biomechanical characterization of double-bundle femoral press-fit fixation techniques.

PubMed

Ettinger, M; Haasper, C; Hankemeier, S; Hurschler, C; Breitmeier, D; Krettek, C; Jagodzinski, M

2011-03-01

Press-fit fixation of patellar tendon bone anterior cruciate ligament autografts is an interesting technique because no hardware is necessary. To date, no biomechanical data exist describing an implant-free double-bundle press-fit procedure. The purpose of this study was to characterize the biomechanical properties of three double-bundle press-fit fixations. In a controlled laboratory study, the patellar-, quadriceps- and hamstring tendons of 10 human cadavers (age: 49.2 ± 18.5 years) were used. An inside out press-fit fixation with a knot in the semitendinosus and gracilis tendons (SG) combined with an additional bone block, with two quadriceps tendon bone block grafts (QU) was compared with press-fit fixation of two bone patellar tendon bone block (PT) grafts in 30 porcine femora. Constructs were cyclically stretched and then loaded until failure. Maximum load to failure, stiffness and elongation during failure testing and cyclical loading were investigated. The maximum load to failure was 703 ± 136 N for SG fixation, 632 ± 130 N for QU and 656 ± 127 N for PT fixation. Stiffness of the constructs averaged 138 ± 26 N/mm for SG, 159 ± 74 N/mm for QU, and 154 ± 50 N/mm for PT fixation. Elongation during initial cyclical loading was 1.2 ± 1.4 mm for SG, 2.0 ± 1.4 mm for QU, and 1.0 ± 0.6 mm for PT (significantly larger for PT and QU between the first 5 cycles compared with cycles 15-20th, P < 0.01). All investigated double-bundle fixation techniques were equal in terms of maximum load to failure, stiffness, and elongation. Unlike with single-bundle press-fit fixation techniques that have been published, no difference was observed between pure tendon combined with an additional bone block and tendon bone grafts. All techniques exhibited larger elongation during initial cyclical loading. All three press-fit fixation techniques that were investigated exhibit comparable biomechanical properties. Preconditioning of the constructs is critical.

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels.

PubMed

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun; Jiang, Youxing

2015-09-01

Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block. © 2015 Lam et al.

Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair

PubMed Central

Knott, Eric P.; Assi, Mazen; Rao, Sudheendra N. R.; Ghosh, Mousumi; Pearse, Damien D.

2017-01-01

A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies. The only known negative regulators of cyclic nucleotides are a family of enzymes called phosphodiesterases (PDEs) that hydrolyze cyclic nucleotides into adenosine monophosphate (AMP) or guanylate monophosphate (GMP). Herein, we discuss the structure and physiological function as well as the roles PDEs play in pathological processes of the diseased or injured CNS. Further we review the approaches that have been employed therapeutically in experimental paradigms to block PDE expression or activity and in turn elevate cyclic nucleotide levels to mediate neuroprotection or neurorepair as well as discuss both the translational pathway and current limitations in moving new PDE-targeted therapies to the clinic. PMID:28338622

Mechanisms of Regulation of Olfactory Transduction and Adaptation in the Olfactory Cilium

PubMed Central

Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

2014-01-01

Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR cycling and tune the levels of second messengers in OSNs, and not only by CNG channel desensitization as previously thought. PMID:25144232

Strategic origins of early semantic facilitation in the blocked-cyclic naming paradigm.

PubMed

Belke, Eva; Shao, Zeshu; Meyer, Antje S

2017-10-01

In the blocked-cyclic naming paradigm, participants repeatedly name small sets of objects that do or do not belong to the same semantic category. A standard finding is that, after a first presentation cycle where one might find semantic facilitation, naming is slower in related (homogeneous) than in unrelated (heterogeneous) sets. According to competitive theories of lexical selection, this is because the lexical representations of the object names compete more vigorously in homogeneous than in heterogeneous sets. However, Navarrete, del Prato, Peressotti, and Mahon (2014) argued that this pattern of results was not due to increased lexical competition but to weaker repetition priming in homogeneous compared to heterogeneous sets. They demonstrated that when homogeneous sets were not repeated immediately but interleaved with unrelated sets, semantic relatedness induced facilitation rather than interference. We replicate this finding but also show that the facilitation effect has a strategic origin: It is substantial when sets are separated by pauses, making it easy for participants to notice the relatedness within some sets and use it to predict upcoming items. However, the effect is much reduced when these pauses are eliminated. In our view, the semantic facilitation effect does not constitute evidence against competitive theories of lexical selection. It can be accounted for within any framework that acknowledges strategic influences on the speed of object naming in the blocked-cyclic naming paradigm. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fabrication of Carbon Nanotube Networks on Three-Dimensional Building Blocks and Their Applications

DTIC Science & Technology

2012-10-27

increases the detection efficiency via sorting of analyte. There are some reports for sorting or separating blood cell, colloidal and bacteria by...the substrates for cyclic voltammetry (CV), pulsed bias of ECD was applied at -1.2 V during 90, 120 and 150 sec for 1, 3 and 5 μm pillar substrates...Deposition with Al2O3: The atomic layer deposition (ALD, Cyclic 4000, Genitech) was introduced to deposit the Al2O3 on the surfaces of network

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide–gated channels

PubMed Central

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun

2015-01-01

Calcium permeability and the concomitant calcium block of monovalent ion current (“Ca2+ block”) are properties of cyclic nucleotide–gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca2+ block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca2+ block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca2+ block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca2+ block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca2+ block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca2+ block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca2+ block. PMID:26283200

Amphiphilic and Hydrophilic Block Copolymers from Aliphatic N-Substituted 8-Membered Cyclic Carbonates: A Versatile Macromolecular Platform for Biomedical Applications.

PubMed

Venkataraman, Shrinivas; Tan, Jeremy P K; Ng, Victor W L; Tan, Eddy W P; Hedrick, James L; Yang, Yi Yan

2017-01-09

Introduction of hydrophilic components, particularly amines and zwitterions, onto a degradable polymer platform, while maintaining precise control over the polymer composition, has been a challenge. Recognizing the importance of these hydrophilic residues in multiple aspects of the nanobiomedicine field, herein, a straightforward synthetic route to access well-defined amphiphilic and hydrophilic degradable block copolymers from diethanolamine-derived functional eight-membered N-substituted aliphatic cyclic carbonates is reported. By this route, tertiary amine, secondary amine, and zwitterion residues can be incorporated across the polymer backbone. Demonstration of pH-responsiveness of these hydrophilic residues and their utility in the development of drug-delivery vehicles, catered for the specific requirements of respective model drugs (doxorubicin and diclofenac sodium salt) are shown. As hydrophilic components in degradable polymers play crucial roles in the biological interactions, these materials offers opportunities to expand the scope and applicability of aliphatic cyclic carbonates. Our approach to these functional polycarbonates will expand the range of biocompatible and biodegradable synthetic materials available for nanobiomedicine, including drug and gene delivery, antimicrobials, and hydrophilic polymers as poly(ethylene glycol) (PEG) alternatives.

Intrinsic Folding Proclivities in Cyclic β-Peptide Building Blocks: Configuration and Heteroatom Effects Analyzed by Conformer-Selective Spectroscopy and Quantum Chemistry.

PubMed

Alauddin, Mohammad; Gloaguen, Eric; Brenner, Valérie; Tardivel, Benjamin; Mons, Michel; Zehnacker-Rentien, Anne; Declerck, Valérie; Aitken, David J

2015-11-09

This work describes the use of conformer-selective laser spectroscopy following supersonic expansion to probe the local folding proclivities of four-membered ring cyclic β-amino acid building blocks. Emphasis is placed on stereochemical effects as well as on the structural changes induced by the replacement of a carbon atom of the cycle by a nitrogen atom. The amide A IR spectra are obtained and interpreted with the help of quantum chemistry structure calculations. Results provide evidence that the building block with a trans-substituted cyclobutane ring has a predilection to form strong C8 hydrogen bonds. Nitrogen-atom substitution in the ring induces the formation of the hydrazino turn, with a related but distinct hydrogen-bonding network: the structure is best viewed as a bifurcated C8/C5 bond with the N heteroatom lone electron pair playing a significant acceptor role, which supports recent observations on the hydrazino turn structure in solution. Surprisingly, this study shows that the cis-substituted cyclobutane ring derivative also gives rise predominantly to a C8 hydrogen bond, although weaker than in the two former cases, a feature that is not often encountered for this building block. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cyclic Deformation of Ultra-Fine Grained Commercial Purity Aluminum Processed by Accumulative Roll-Bonding.

PubMed

Kwan, Charles C F; Wang, Zhirui

2013-08-13

Accumulative Roll-Bonding (ARB) is one of the more recently developed techniques capable of producing bulk ultra-fine grained (ufg) metals. There are still many aspects of the behavior of ufg metals that lacks an in-depth understanding, such as a generalized view of the factors that govern the cyclic deformation mechanism(s). This study aims to advance the understanding of the cyclic deformation behavior of ufg metals through the systematic investigation of ARB processed aluminum upon cyclic loading. It was found that the cyclic softening response often reported for ufg metals is largely influenced by the microstructure stability as the cyclic softening response is facilitated by grain coarsening which becomes inhibited with highly stable microstructure. On one hand, shear bands resembling braids of dislocations trespassing multiple grains have been observed to operate for the accommodation of the imposed cyclic strain in cases where grain coarsening is largely restricted. On the other hand, it was found that the microstructure stability can be overcome at higher applied cyclic plastic strain levels, leading to grain coarsening and thus a cyclic softening response. The findings in this study have further confirmed that the cyclic softening behavior found in many ufg metals, which may be detrimental in practical applications, can be inhibited by improvements in the microstructure stability.

Cyclic Deformation of Ultra-Fine Grained Commercial Purity Aluminum Processed by Accumulative Roll-Bonding

PubMed Central

Kwan, Charles C.F.; Wang, Zhirui

2013-01-01

Accumulative Roll-Bonding (ARB) is one of the more recently developed techniques capable of producing bulk ultra-fine grained (ufg) metals. There are still many aspects of the behavior of ufg metals that lacks an in-depth understanding, such as a generalized view of the factors that govern the cyclic deformation mechanism(s). This study aims to advance the understanding of the cyclic deformation behavior of ufg metals through the systematic investigation of ARB processed aluminum upon cyclic loading. It was found that the cyclic softening response often reported for ufg metals is largely influenced by the microstructure stability as the cyclic softening response is facilitated by grain coarsening which becomes inhibited with highly stable microstructure. On one hand, shear bands resembling braids of dislocations trespassing multiple grains have been observed to operate for the accommodation of the imposed cyclic strain in cases where grain coarsening is largely restricted. On the other hand, it was found that the microstructure stability can be overcome at higher applied cyclic plastic strain levels, leading to grain coarsening and thus a cyclic softening response. The findings in this study have further confirmed that the cyclic softening behavior found in many ufg metals, which may be detrimental in practical applications, can be inhibited by improvements in the microstructure stability. PMID:28811446

cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

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

Jones, S.B.; Toews, M.L.; Turner, J.T.

1987-03-01

Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-timemore » for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.« less

Soluble lymphocytic mediators

PubMed Central

Pick, E.

1974-01-01

The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

Pullout strength of bone-patellar tendon-bone allograft bone plugs: a comparison of cadaver tibia and rigid polyurethane foam.

PubMed

Barber, F Alan

2013-09-01

To compare the load-to-failure pullout strength of bone-patellar tendon-bone (BPTB) allografts in human cadaver tibias and rigid polyurethane foam blocks. Twenty BPTB allografts were trimmed creating 25 mm × 10 mm × 10 mm tibial plugs. Ten-millimeter tunnels were drilled in 10 human cadaver tibias and 10 rigid polyurethane foam blocks. The BPTB anterior cruciate ligament allografts were inserted into these tunnels and secured with metal interference screws, with placement of 10 of each type in each material. After preloading (10 N), cyclic loading (500 cycles, 10 to 150 N at 200 mm/min) and load-to-failure testing (200 mm/min) were performed. The endpoints were ultimate failure load, cyclic loading elongation, and failure mode. No difference in ultimate failure load existed between grafts inserted into rigid polyurethane foam blocks (705 N) and those in cadaver tibias (669 N) (P = .69). The mean rigid polyurethane foam block elongation (0.211 mm) was less than that in tibial bone (0.470 mm) (P = .038), with a smaller standard deviation (0.07 mm for foam) than tibial bone (0.34 mm). All BPTB grafts successfully completed 500 cycles. The rigid polyurethane foam block showed less variation in test results than human cadaver tibias. Rigid polyurethane foam blocks provide an acceptable substitute for human cadaver bone tibia for biomechanical testing of BPTB allografts and offer near-equivalent results. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl− channels

PubMed Central

Fan, Hai-Tian; Morishima, Shigeru; Kida, Hajime; Okada, Yasunobu

2001-01-01

Some phenol derivatives are known to block volume-sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume-sensitive Cl− channels in comparison with cyclic AMP-activated CFTR Cl− channels and Ca2+-activated Cl− channels using the whole-cell patch-clamp technique.Extracellular application of phloretin (over 10 μM) voltage-independently, and in a concentration-dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.In contrast, at 30 μM phloretin failed to inhibit cyclic AMP-activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage-dependent manner.At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+-dependent Cl− currents induced by ionomycin in T84 cells.It is concluded that phloretin preferentially blocks volume-sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP-activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+-activated Cl− channels in epithelial cells. PMID:11487521

Accuracy Analysis on Large Blocks of High Resolution Images

NASA Technical Reports Server (NTRS)

Passini, Richardo M.

2007-01-01

Although high altitude frequencies effects are removed at the time of basic image generation, low altitude (Yaw) effects are still present in form of affinity/angular affinity. They are effectively removed by additional parameters. Bundle block adjustment based on properly weighted ephemeris/altitude quaternions (BBABEQ) are not enough to remove the systematic effect. Moreover, due to the narrow FOV of the HRSI, position and altitude are highly correlated making it almost impossible to separate and remove their systematic effects without extending the geometric model (Self-Calib.) The systematic effects gets evident on the increase of accuracy (in terms of RMSE at GCPs) for looser and relaxed ground control at the expense of large and strong block deformation with large residuals at check points. Systematic errors are most freely distributed and their effects propagated all over the block.

Extending HPF for advanced data parallel applications

NASA Technical Reports Server (NTRS)

Chapman, Barbara; Mehrotra, Piyush; Zima, Hans

1994-01-01

The stated goal of High Performance Fortran (HPF) was to 'address the problems of writing data parallel programs where the distribution of data affects performance'. After examining the current version of the language we are led to the conclusion that HPF has not fully achieved this goal. While the basic distribution functions offered by the language - regular block, cyclic, and block cyclic distributions - can support regular numerical algorithms, advanced applications such as particle-in-cell codes or unstructured mesh solvers cannot be expressed adequately. We believe that this is a major weakness of HPF, significantly reducing its chances of becoming accepted in the numeric community. The paper discusses the data distribution and alignment issues in detail, points out some flaws in the basic language, and outlines possible future paths of development. Furthermore, we briefly deal with the issue of task parallelism and its integration with the data parallel paradigm of HPF.

Movement kinematics and cyclic fatigue of NiTi rotary instruments: a systematic review.

PubMed

Ferreira, F; Adeodato, C; Barbosa, I; Aboud, L; Scelza, P; Zaccaro Scelza, M

2017-02-01

The aim of this review was to provide a detailed analysis of the literature concerning the correlation between different movement kinematics and the cyclic fatigue resistance of NiTi rotary endodontic instruments. From June 2014 to August 2015, four independent reviewers comprehensively and systematically searched the Medline (PubMed), EMBASE, Web of Science, Scopus and Google Scholar databases for works published since January 2005, using the following search terms: endodontics; nickel-titanium rotary files; continuous rotation; reciprocating motion; cyclic fatigue. In addition to the electronic searches, manual searches were performed to include articles listed in the reference sections of high-impact published articles that were not indexed in the databases. Laboratory studies in English language were considered for this review. The electronic and manual searches resulted in identification of 75 articles. Based on the inclusion criteria, 32 articles were selected for analysis of full-text copies. Specific analysis was then made of 20 articles that described the effects of reciprocating and continuous movements on cyclic fatigue of the instruments. A wide range of testing conditions and methodologies have been used to compare the cyclic fatigue resistance of rotary endodontic instruments. Most studies report that reciprocating motion improves the fatigue resistance of endodontic instruments, compared to continuous rotation, independent of other variables such as the speed of rotation, the angle or radius of curvature of simulated canals, geometry and taper, or the surface characteristics of the NiTi instruments. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Extensive reprogramming of the genetic code for genetically encoded synthesis of highly N-alkylated polycyclic peptidomimetics.

PubMed

Kawakami, Takashi; Ishizawa, Takahiro; Murakami, Hiroshi

2013-08-21

Cyclic structures can increase the proteolytic stability and conformational rigidity of peptides, and N-alkylation of the peptide backbone can make peptides more cell-permeable and resistant to proteolysis. Therefore, cyclic N-alkyl amino acids are expected to be useful building blocks to increase simultaneously these pharmacological properties of peptides. In this study, we screened various cyclic N-alkyl amino acids for their ribosomal incorporation into peptides and identified cyclic N-alkyl amino acids that can be efficiently and successively incorporated. We also demonstrated genetic code reprogramming for reassigning 16 NNU codons to 16 different cyclic N-alkyl amino acids with high fidelity to synthesize highly N-alkylated polycyclic peptidomimetics and an mRNA-displayed library of completely N-alkylated polycyclic peptidomimetics by using our recently developed TRAP (transcription/translation coupled with association of puromycin linker) display. In vitro selection from a highly diverse library of such completely N-alkylated polycyclic peptidomimetics could become a powerful means to discover small-molecule ligands such as drug candidates that can be targeted to biomolecules inside living cells.

Nonlinear, nonbinary cyclic group codes

NASA Technical Reports Server (NTRS)

Solomon, G.

1992-01-01

New cyclic group codes of length 2(exp m) - 1 over (m - j)-bit symbols are introduced. These codes can be systematically encoded and decoded algebraically. The code rates are very close to Reed-Solomon (RS) codes and are much better than Bose-Chaudhuri-Hocquenghem (BCH) codes (a former alternative). The binary (m - j)-tuples are identified with a subgroup of the binary m-tuples which represents the field GF(2 exp m). Encoding is systematic and involves a two-stage procedure consisting of the usual linear feedback register (using the division or check polynomial) and a small table lookup. For low rates, a second shift-register encoding operation may be invoked. Decoding uses the RS error-correcting procedures for the m-tuple codes for m = 4, 5, and 6.

[Tibial press-fit fixation of flexor tendons for reconstruction of the anterior cruciate ligament].

PubMed

Ettinger, M; Liodakis, E; Haasper, C; Hurschler, C; Breitmeier, D; Krettek, C; Jagodzinski, M

2012-09-01

Press-fit fixation of hamstring tendon autografts for anterior cruciate ligament reconstruction is an interesting technique because no hardware is necessary. This study compares the biomechanical properties of press-fit fixations to an interference screw fixation. Twenty-eight human cadaveric knees were used for hamstring tendon explantation. An additional bone block was harvested from the tibia. We used 28 porcine femora for graft fixation. Constructs were cyclically stretched and then loaded until failure. Maximum load to failure, stiffness and elongation during failure testing and cyclic loading were investigated. The maximum load to failure was 970±83 N for the press-fit tape fixation (T), 572±151 N for the bone bridge fixation (TS), 544±109 N for the interference screw fixation (I), 402±77 N for the press-fit suture fixation (S) and 290±74 N for the bone block fixation technique (F). The T fixation had a significantly better maximum load to failure compared to all other techniques (p<0.001). This study demonstrates that a tibial press-fit technique which uses an additional bone block has better maximum load to failure results compared to a simple interference screw fixation.

Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress.

PubMed

Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K; Nagaraja, Archana S; Dorniak, Piotr L; Pallikuth, Sandeep; Waters, Christopher M; Sood, Anil; Rao, RadhaKrishna

2017-02-20

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca 2+ by 1,2-bis-( o -aminophenoxy)ethane- N , N , N ', N '-tetraacetic acid. Knockdown of Ca V 1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N -Acetyl l-cysteine (NAC) and l- N G -Nitroarginine methyl ester (l-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and l-NAME also blocked stress-induced activation of c-Jun N -terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca 2+ , activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Calcium-Mediated Oxidative Stress: a Common Mechanism in Tight Junction Disruption by Different Types of Cellular Stress

PubMed Central

Gangwar, Ruchika; Meena, Avtar S.; Shukla, Pradeep K.; Nagaraja, Archana S.; Dorniak, Piotr L.; Pallikuth, Sandeep; Waters, Christopher M.; Sood, Anil; Rao, RadhaKrishna

2017-01-01

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction disruption was investigated in Caco-2 cell monolayers in vitro, and restraint stress-induced barrier dysfunction in mouse colon in vivo. Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca2+ by BAPTA. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated tight junction disruption and barrier dysfunction. N-acetyl L-cysteine (NAC) and L-nitroarginine methyl ester (L-NAME) blocked stress-induced tight junction disruption and barrier dysfunction. NAC and L-NAME also blocked stress-induced activation of JNK and c-Src. ROS was co-localized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, tight junction disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and tight junction disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca2+, activation of JNK and c-Src, and disruption of tight junction in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, tight junction disruption and protein thiol oxidation in colonic mucosa. This study demonstrates that oxidative stress is a common signal in the mechanism of tight junction disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo. PMID:28057718

Effect of proof testing on the flaw growth characteristics of 304 stainless steel. [crack propagation in welded joints

NASA Technical Reports Server (NTRS)

Finger, R. W.

1974-01-01

The effects of proof overload frequency and magnitude on the cyclic crack growth rates of 304 stainless steel weldments were investigated. The welding procedure employed was typical of those used on over-the-road cryogenic vessels. Tests were conducted at room temperature with an overload ratio of 1.50 to determine the effect of overload frequency. Effect of overload magnitude was determined from tests where a room temperature overload was applied between blocks of 1000 cycles applied at 78 K (-320 F). The cyclic stress level used in all tests was typical of the nominal membrane stress generally encountered in full scale vessels. Test results indicate that judicious selection of proof overload frequency and magnitude can reduce crack growth rates for cyclic stress levels.

The diastolic function to cyclic variation of myocardial ultrasonic backscatter relation: the influence of parameterized diastolic filling (PDF) formalism determined chamber properties.

PubMed

Lloyd, Christopher W; Shmuylovich, Leonid; Holland, Mark R; Miller, James G; Kovács, Sándor J

2011-08-01

Myocardial tissue characterization represents an extension of currently available echocardiographic imaging. The systematic variation of backscattered energy during the cardiac cycle (the "cyclic variation" of backscatter) has been employed to characterize cardiac function in a wide range of investigations. However, the mechanisms responsible for observed cyclic variation remain incompletely understood. As a step toward determining the features of cardiac structure and function that are responsible for the observed cyclic variation, the present study makes use of a kinematic approach of diastolic function quantitation to identify diastolic function determinants that influence the magnitude and timing of cyclic variation. Echocardiographic measurements of 32 subjects provided data for determination of the cyclic variation of backscatter to diastolic function relation characterized in terms of E-wave determined, kinematic model-based parameters of chamber stiffness, viscosity/relaxation and load. The normalized time delay of cyclic variation appears to be related to the relative viscoelasticity of the chamber and predictive of the kinematic filling dynamics as determined using the parameterized diastolic filling formalism (with r-values ranging from .44 to .59). The magnitude of cyclic variation does not appear to be strongly related to the kinematic parameters. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1

PubMed Central

Liu, Xiao-ming; Peyton, Kelly J.

2013-01-01

Endothelial cells (ECs) are constantly subjected to cyclic strain that arises from periodic change in vessel wall diameter as a result of pulsatile blood flow. Application of physiological levels of cyclic strain inhibits EC apoptosis; however, the underlying mechanism is not known. Since heme oxygenase-1 (HO-1) is a potent inhibitor of apoptosis, the present study investigated whether HO-1 contributes to the antiapoptotic action of cyclic strain. Administration of physiological cyclic strain (6% at 1 Hz) to human aortic ECs stimulated an increase in HO-1 activity, protein, and mRNA expression. The induction of HO-1 was preceded by a rise in reactive oxygen species (ROS) and Nrf2 protein expression. Cyclic strain also stimulated an increase in HO-1 promoter activity that was prevented by mutating the antioxidant responsive element in the promoter or by overexpressing dominant-negative Nrf2. In addition, the strain-mediated induction of HO-1 and activation of Nrf2 was abolished by the antioxidant N-acetyl-l-cysteine. Finally, application of cyclic strain blocked inflammatory cytokine-mediated EC death and apoptosis. However, the protective action of cyclic strain was reversed by the HO inhibitor tin protoporphyrin-IX and was absent in ECs isolated from HO-1-deficient mice. In conclusion, the present study demonstrates that a hemodynamically relevant level of cyclic strain stimulates HO-1 gene expression in ECs via the ROS-Nrf2 signaling pathway to inhibit EC death. The ability of cyclic strain to induce HO-1 expression may provide an important mechanism by which hemodynamic forces promote EC survival and vascular homeostasis. PMID:23604711

Examining the Role of Perioperative Nerve Blocks in Hip Arthroscopy: A Systematic Review.

PubMed

Kay, Jeffrey; de Sa, Darren; Memon, Muzammil; Simunovic, Nicole; Paul, James; Ayeni, Olufemi R

2016-04-01

This systematic review examined the efficacy of perioperative nerve blocks for pain control after hip arthroscopy. The databases Embase, PubMed, and Medline were searched on June 2, 2015, for English-language studies that reported on the use of perioperative nerve blocks for hip arthroscopy. The studies were systematically screened and data abstracted in duplicate. Nine eligible studies were included in this review (2 case reports, 2 case series, 3 non-randomized comparative studies, and 2 randomized controlled trials). In total, 534 patients (534 hips), with a mean age of 37.2 years, who underwent hip arthroscopy procedures were administered nerve blocks for pain management. Specifically, femoral (2 studies), fascia iliaca (2 studies), lumbar plexus (3 studies), and L1 and L2 paravertebral (2 studies) nerve blocks were used. All studies reported acceptable pain scores after the use of nerve blocks, and 4 studies showed significantly lower postoperative pain scores acutely with the use of nerve blocks over general anesthesia alone. The use of nerve blocks also resulted in a decrease in opioid consumption in 4 studies and provided a higher level of patient satisfaction in 2 studies. No serious acute complications were reported in any study, and long-term complications from lumbar plexus blocks, such as local anesthetic system toxicity (0.9%) and long-term neuropathy (2.8%), were low in incidence. The use of perioperative nerve blocks provides effective pain management after hip arthroscopy and may be more effective in decreasing acute postoperative pain and supplemental opioid consumption than other analgesic techniques. Level IV, systematic review of Level I to Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Computational Design of Self-Assembling Cyclic Protein Homo-oligomers

PubMed Central

Fallas, Jorge A.; Ueda, George; Sheffler, William; Nguyen, Vanessa; McNamara, Dan E.; Sankaran, Banumathi; Pereira, Jose Henrique; Parmeggiani, Fabio; Brunette, TJ; Cascio, Duilio; Yeates, Todd R.; Zwart, Peter; Baker, David

2016-01-01

Self-assembling cyclic protein homo-oligomers play important roles in biology and the ability to generate custom homo-oligomeric structures could enable new approaches to probe biological function. Here we report a general approach to design cyclic homo-oligomers that employs a new residue pair transform method for assessing the design ability of a protein-protein interface. This method is sufficiently rapid to enable systematic enumeration of cyclically docked arrangements of a monomer followed by sequence design of the newly formed interfaces. We use this method to design interfaces onto idealized repeat proteins that direct their assembly into complexes that possess cyclic symmetry. Of 96 designs that were experimentally characterized, 21 were found to form stable monodisperse homo-oligomers in solution, and 15 (4 homodimers, 6 homotrimers, 6 homotetramers and 1 homopentamer) had solution small angle X-ray scattering data consistent with the design models. X-ray crystal structures were obtained for five of the designs and each of these were shown to be very close to their design model. PMID:28338692

High-efficiency Gaussian key reconciliation in continuous variable quantum key distribution

NASA Astrophysics Data System (ADS)

Bai, ZengLiang; Wang, XuYang; Yang, ShenShen; Li, YongMin

2016-01-01

Efficient reconciliation is a crucial step in continuous variable quantum key distribution. The progressive-edge-growth (PEG) algorithm is an efficient method to construct relatively short block length low-density parity-check (LDPC) codes. The qua-sicyclic construction method can extend short block length codes and further eliminate the shortest cycle. In this paper, by combining the PEG algorithm and qua-si-cyclic construction method, we design long block length irregular LDPC codes with high error-correcting capacity. Based on these LDPC codes, we achieve high-efficiency Gaussian key reconciliation with slice recon-ciliation based on multilevel coding/multistage decoding with an efficiency of 93.7%.

Shear damage mechanisms in a woven, Nicalon-reinforced ceramic-matrix composite

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

Keith, W.P.; Kedward, K.T.

The shear response of a Nicalon-reinforced ceramic-matrix composite was investigated using Iosipescu tests. Damage was characterized by X-ray, optical, and SEM techniques. The large inelastic strains which were observed were attributed to rigid body sliding of longitudinal blocks of material. These blocks are created by the development and extension of intralaminar cracks and ply delaminations. This research reveals that the debonding and sliding characteristics of the fiber-matrix interface control the shear strength, strain softening, and cyclic degradation of the material.

Synthesis of new Cα-tetrasubstituted α-amino acids

PubMed Central

Grauer, Andreas A

2009-01-01

Summary Cα-Tetrasubstituted α-amino acids are important building blocks for the synthesis of peptidemimetics with stabilized secondary structure, because of their ability to rigidify the peptide backbone. Recently our group reported a new class of cyclic Cα-tetrasubstituted tetrahydrofuran α-amino acids prepared from methionine and aromatic aldehydes. We now report the extension of this methodology to aliphatic aldehydes. Although such aldehydes are prone to give aldol products under the reaction conditions used, we were able to obtain the target cyclic amino acids in low to moderate yields and in some cases with good diastereoselectivity. PMID:19259341

Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone

PubMed Central

Ono, Y.; Woodmass, J. M.; Nelson, A. A.; Boorman, R. S.; Thornton, G. M.

2016-01-01

Objectives This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). Methods Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of ‘suture cutting through bone’. Results In cadaveric bone and foam blocks, MultiFIX P anchors had significantly greater initial displacement, and lower number of cycles and lower load at 3 mm displacement than SpeedScrew anchors. Video analysis revealed ‘suture cutting through bone’ as the predominant source of suture displacement in cadaveric bone (qualitative) and greater ‘suture cutting through bone’ comparing MultiFIX P with SpeedScrew anchors in foam blocks (quantitative). The greater suture displacement in MultiFIX P anchors was predominantly from suture cutting through bone, which was enhanced in an osteopenic bone model. Conclusions Anchors with sutures external to the anchor body are at risk for suture cutting through bone since the suture eyelet is at the distal tip of the implant and the suture directly abrades against the bone edge during cyclic loading. Suture cutting through bone may be a significant source of fixation failure, particularly in osteopenic bone. Cite this article: Y. Ono, J. M. Woodmass, A. A. Nelson, R. S. Boorman, G. M. Thornton, I. K. Y. Lo. Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. Bone Joint Res 2016;5:269–275. DOI: 10.1302/2046-3758.56.2000535. PMID:27357383

Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone.

PubMed

Ono, Y; Woodmass, J M; Nelson, A A; Boorman, R S; Thornton, G M; Lo, I K Y

2016-06-01

This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of 'suture cutting through bone'. In cadaveric bone and foam blocks, MultiFIX P anchors had significantly greater initial displacement, and lower number of cycles and lower load at 3 mm displacement than SpeedScrew anchors. Video analysis revealed 'suture cutting through bone' as the predominant source of suture displacement in cadaveric bone (qualitative) and greater 'suture cutting through bone' comparing MultiFIX P with SpeedScrew anchors in foam blocks (quantitative). The greater suture displacement in MultiFIX P anchors was predominantly from suture cutting through bone, which was enhanced in an osteopenic bone model. Anchors with sutures external to the anchor body are at risk for suture cutting through bone since the suture eyelet is at the distal tip of the implant and the suture directly abrades against the bone edge during cyclic loading. Suture cutting through bone may be a significant source of fixation failure, particularly in osteopenic bone.Cite this article: Y. Ono, J. M. Woodmass, A. A. Nelson, R. S. Boorman, G. M. Thornton, I. K. Y. Lo. Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. Bone Joint Res 2016;5:269-275. DOI: 10.1302/2046-3758.56.2000535. © 2016 Lo et al.

A Triblock Copolymer Design Leads to Robust Hybrid Hydrogels for High-Performance Flexible Supercapacitors.

PubMed

Zhang, Guangzhao; Chen, Yunhua; Deng, Yonghong; Wang, Chaoyang

2017-10-18

We report here an intriguing hybrid conductive hydrogel as electrode for high-performance flexible supercapacitor. The key is using a rationally designed water-soluble ABA triblock copolymer (termed as IAOAI) containing a central poly(ethylene oxide) block (A) and terminal poly(acrylamide) (PAAm) block with aniline moieties randomly incorporated (B), which was synthesized by reversible additional fragment transfer polymerization. The subsequent copolymerization of aniline monomers with the terminated aniline moieties on the IAOAI polymer generates a three-dimensional cross-linking hybrid network. The hybrid hydrogel electrode demonstrates robust mechanical flexibility, remarkable electrochemical capacitance (919 F/g), and cyclic stability (90% capacitance retention after 1000 cycles). Moreover, the flexible supercapacitor based on this hybrid hydrogel electrode presents a large specific capacitance (187 F/g), superior to most reported conductive hydrogel-based supercapacitors. With the demonstrated additional favorable cyclic stability and excellent capacitive and rate performance, this hybrid hydrogel-based supercapacitor holds great promise for flexible energy-storage device.

The styryl dye FM1-43 suppresses odorant responses in a subset of olfactory neurons by blocking cyclic nucleotide-gated (CNG) channels.

PubMed

Breunig, Esther; Kludt, Eugen; Czesnik, Dirk; Schild, Detlev

2011-08-12

Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.

Cyclic Square Wave Voltammetry of Surface-Confined Quasireversible Electron Transfer Reactions.

PubMed

Mann, Megan A; Bottomley, Lawrence A

2015-09-01

The theory for cyclic square wave voltammetry of surface-confined quasireversible electrode reactions is presented and experimentally verified. Theoretical voltammograms were calculated following systematic variation of empirical parameters to assess their impact on the shape of the voltammogram. From the trends obtained, diagnostic criteria for this mechanism were deduced. These criteria were experimentally confirmed using two well-established surface-confined analytes. When properly applied, these criteria will enable non-experts in voltammetry to assign the electrode reaction mechanism and accurately measure electrode reaction kinetics.

Block of Brain Sodium Channels by Peptide Mimetics of the Isoleucine, Phenylalanine, and Methionine (IFM) Motif from the Inactivation Gate

PubMed Central

Eaholtz, Galen; Colvin, Anita; Leonard, Daniele; Taylor, Charles; Catterall, William A.

1999-01-01

Inactivation of sodium channels is thought to be mediated by an inactivation gate formed by the intracellular loop connecting domains III and IV. A hydrophobic motif containing the amino acid sequence isoleucine, phenylalanine, and methionine (IFM) is required for the inactivation process. Peptides containing the IFM motif, when applied to the cytoplasmic side of these channels, produce two types of block: fast block, which resembles the inactivation process, and slow, use-dependent block stimulated by strong depolarizing pulses. Fast block by the peptide ac-KIFMK-NH2, measured on sodium channels whose inactivation was slowed by the α-scorpion toxin from Leiurus quinquestriatus (LqTx), was reversed with a time constant of 0.9 ms upon repolarization. In contrast, control and LqTx-modified sodium channels were slower to recover from use-dependent block. For fast block, linear peptides of three to six amino acid residues containing the IFM motif and two positive charges were more effective than peptides with one positive charge, whereas uncharged IFM peptides were ineffective. Substitution of the IFM residues in the peptide ac-KIFMK-NH2 with smaller, less hydrophobic residues prevented fast block. The positively charged tripeptide IFM-NH2 did not cause appreciable fast block, but the divalent cation IFM-NH(CH2)2NH2 was as effective as the pentapeptide ac-KIFMK-NH2. The constrained peptide cyclic KIFMK containing two positive charges did not cause fast block. These results indicate that the position of the positive charges is unimportant, but flexibility or conformation of the IFM-containing peptide is important to allow fast block. Slow, use-dependent block was observed with IFM-containing peptides of three to six residues having one or two positive charges, but not with dipeptides or phenylalanine-amide. In contrast to its lack of fast block, cyclic KIFMK was an effective use-dependent blocker. Substitutions of amino acid residues in the tripeptide IFM-NH2 showed that large hydrophobic residues are preferred in all three positions for slow, use-dependent block. However, substitution of the large hydrophobic residue diphenylalanine or the constrained residues phenylglycine or tetrahydroisoquinoline for phe decreased potency, suggesting that this phe residue must be able to enter a restricted hydrophobic pocket during the binding of IFM peptides. Together, the results on fast block and slow, use-dependent block indicate that IFM peptides form two distinct complexes of different stability and structural specificity with receptor site(s) on the sodium channel. It is proposed that fast block represents binding of these peptides to the inactivation gate receptor, while slow, use-dependent block represents deeper binding of the IFM peptides in the pore. PMID:9925825

Cyclic fatigue of endodontic nickel titanium rotary instruments: static and dynamic tests.

PubMed

Li, Uei-Ming; Lee, Bor-Shiunn; Shih, Chin-Tsai; Lan, Wan-Hong; Lin, Chun-Pin

2002-06-01

Endodontic instruments upon rotation are subjected to both tensile and compressive stress in curved canals. This stress is localized at the point of curvature. The purpose of this study was to evaluate the cyclic fatigue of 0.04 ProFile nickel titanium rotary instruments operating at different rotational speeds and varied distances of pecking motion in metal blocks that simulated curved canals. A total of 150 ProFile instruments were made to rotate freely in sloped metal blocks at speeds of 200, 300, or 400 rpm by a contra-angle handpiece mounted on an Instron machine. The electric motor and Instron machine were activated until the instruments were broken in two different modes, static and dynamic pecking-motion. The fractured surfaces of separated instruments were examined under a scanning electron microscope. All data obtained were analyzed by a stepwise multiple regression method using a 95% confidence interval. The results demonstrated that the time to failure significantly decreased as the angles of curvature or the rotational speeds increased. However, as pecking distances increased, the time to failure increased. This is because a longer pecking distance gives the instrument a longer time interval before it once again passes through the highest stress area. Microscopic evaluation indicated that ductile fracture was the major cyclic failure mode. To prevent breakage of a NiTi rotary instrument, appropriate rotational speeds and continuous pecking motion in the root canals are recommended.

Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence?

PubMed Central

2008-01-01

There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia. PMID:18830450

Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence?

PubMed

Carmichael, A R

2008-09-01

There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.

Cyclic density functional theory: A route to the first principles simulation of bending in nanostructures

NASA Astrophysics Data System (ADS)

Banerjee, Amartya S.; Suryanarayana, Phanish

2016-11-01

We formulate and implement Cyclic Density Functional Theory (Cyclic DFT) - a self-consistent first principles simulation method for nanostructures with cyclic symmetries. Using arguments based on Group Representation Theory, we rigorously demonstrate that the Kohn-Sham eigenvalue problem for such systems can be reduced to a fundamental domain (or cyclic unit cell) augmented with cyclic-Bloch boundary conditions. Analogously, the equations of electrostatics appearing in Kohn-Sham theory can be reduced to the fundamental domain augmented with cyclic boundary conditions. By making use of this symmetry cell reduction, we show that the electronic ground-state energy and the Hellmann-Feynman forces on the atoms can be calculated using quantities defined over the fundamental domain. We develop a symmetry-adapted finite-difference discretization scheme to obtain a fully functional numerical realization of the proposed approach. We verify that our formulation and implementation of Cyclic DFT is both accurate and efficient through selected examples. The connection of cyclic symmetries with uniform bending deformations provides an elegant route to the ab-initio study of bending in nanostructures using Cyclic DFT. As a demonstration of this capability, we simulate the uniform bending of a silicene nanoribbon and obtain its energy-curvature relationship from first principles. A self-consistent ab-initio simulation of this nature is unprecedented and well outside the scope of any other systematic first principles method in existence. Our simulations reveal that the bending stiffness of the silicene nanoribbon is intermediate between that of graphene and molybdenum disulphide - a trend which can be ascribed to the variation in effective thickness of these materials. We describe several future avenues and applications of Cyclic DFT, including its extension to the study of non-uniform bending deformations and its possible use in the study of the nanoscale flexoelectric effect.

Content-based multiple bitstream image transmission over noisy channels.

PubMed

Cao, Lei; Chen, Chang Wen

2002-01-01

In this paper, we propose a novel combined source and channel coding scheme for image transmission over noisy channels. The main feature of the proposed scheme is a systematic decomposition of image sources so that unequal error protection can be applied according to not only bit error sensitivity but also visual content importance. The wavelet transform is adopted to hierarchically decompose the image. The association between the wavelet coefficients and what they represent spatially in the original image is fully exploited so that wavelet blocks are classified based on their corresponding image content. The classification produces wavelet blocks in each class with similar content and statistics, therefore enables high performance source compression using the set partitioning in hierarchical trees (SPIHT) algorithm. To combat the channel noise, an unequal error protection strategy with rate-compatible punctured convolutional/cyclic redundancy check (RCPC/CRC) codes is implemented based on the bit contribution to both peak signal-to-noise ratio (PSNR) and visual quality. At the receiving end, a postprocessing method making use of the SPIHT decoding structure and the classification map is developed to restore the degradation due to the residual error after channel decoding. Experimental results show that the proposed scheme is indeed able to provide protection both for the bits that are more sensitive to errors and for the more important visual content under a noisy transmission environment. In particular, the reconstructed images illustrate consistently better visual quality than using the single-bitstream-based schemes.

Segregation process and phase transition in cyclic predator-prey models with an even number of species.

PubMed

Szabó, György; Szolnoki, Attila; Sznaider, Gustavo Ariel

2007-11-01

We study a spatial cyclic predator-prey model with an even number of species (for n=4, 6, and 8) that allows the formation of two defensive alliances consisting of the even and odd label species. The species are distributed on the sites of a square lattice. The evolution of spatial distribution is governed by iteration of two elementary processes on neighboring sites chosen randomly: if the sites are occupied by a predator-prey pair then the predator invades the prey's site; otherwise the species exchange their sites with a probability X . For low X values, a self-organizing pattern is maintained by cyclic invasions. If X exceeds a threshold value, then two types of domain grow up that are formed by the odd and even label species, respectively. Monte Carlo simulations indicate the blocking of this segregation process within a range of X for n=8.

Physiological desensitization of carbohydrate permeases and adenylate cyclase to regulation by the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli and Salmonella typhimurium. Involvement of adenosine cyclic 3',5'-phosphate and inducer.

PubMed

Saier, M H; Keeler, D K; Feucht, B U

1982-03-10

Adenylate cyclase and a number of carbohydrate transport systems are subject to regulation by the phosphoenolpyruvate:sugar phosphotransferase system. These sensitive carbohydrate transport systems are desensitized to regulation by the phosphotransferase system, and adenylate cyclase is deactivated when cells are grown in medium containing cyclic AMP. These effects are specific for cyclic AMP and are potentiated by the genetic loss of cyclic AMP phosphodiesterase. Inclusion in the growth medium of an inducer of a sensitive transport system also promotes desensitization of that particular transport system. Inducer-promoted desensitization is specific for the particular target transport system, while cyclic AMP-promoted desensitization is general and affects several systems. Desensitization of the permeases to regulation, and inactivation of adenylate cyclase, are slow processes which are blocked by chloramphenicol and are therefore presumably dependent on protein synthesis. Several sugar substrates of the phosphotransferase system are capable of regulating the sensitive carbohydrate transport systems. The evidence suggests that desensitization to this regulation does not result from a direct effect on the functioning of Enzyme I, a small heat-stable protein of the phosphotransferase system, HPr, or an Enzyme II of the phosphotransferase system, but specifically uncouples the permease systems from regulation.

Damage evolution analysis of coal samples under cyclic loading based on single-link cluster method

NASA Astrophysics Data System (ADS)

Zhang, Zhibo; Wang, Enyuan; Li, Nan; Li, Xuelong; Wang, Xiaoran; Li, Zhonghui

2018-05-01

In this paper, the acoustic emission (AE) response of coal samples under cyclic loading is measured. The results show that there is good positive relation between AE parameters and stress. The AE signal of coal samples under cyclic loading exhibits an obvious Kaiser Effect. The single-link cluster (SLC) method is applied to analyze the spatial evolution characteristics of AE events and the damage evolution process of coal samples. It is found that a subset scale of the SLC structure becomes smaller and smaller when the number of cyclic loading increases, and there is a negative linear relationship between the subset scale and the degree of damage. The spatial correlation length ξ of an SLC structure is calculated. The results show that ξ fluctuates around a certain value from the second cyclic loading process to the fifth cyclic loading process, but spatial correlation length ξ clearly increases in the sixth loading process. Based on the criterion of microcrack density, the coal sample failure process is the transformation from small-scale damage to large-scale damage, which is the reason for changes in the spatial correlation length. Through a systematic analysis, the SLC method is an effective method to research the damage evolution process of coal samples under cyclic loading, and will provide important reference values for studying coal bursts.

Revisiting Parallel Cyclic Reduction and Parallel Prefix-Based Algorithms for Block Tridiagonal System of Equations

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

Seal, Sudip K; Perumalla, Kalyan S; Hirshman, Steven Paul

2013-01-01

Simulations that require solutions of block tridiagonal systems of equations rely on fast parallel solvers for runtime efficiency. Leading parallel solvers that are highly effective for general systems of equations, dense or sparse, are limited in scalability when applied to block tridiagonal systems. This paper presents scalability results as well as detailed analyses of two parallel solvers that exploit the special structure of block tridiagonal matrices to deliver superior performance, often by orders of magnitude. A rigorous analysis of their relative parallel runtimes is shown to reveal the existence of a critical block size that separates the parameter space spannedmore » by the number of block rows, the block size and the processor count, into distinct regions that favor one or the other of the two solvers. Dependence of this critical block size on the above parameters as well as on machine-specific constants is established. These formal insights are supported by empirical results on up to 2,048 cores of a Cray XT4 system. To the best of our knowledge, this is the highest reported scalability for parallel block tridiagonal solvers to date.« less

The Influence of Uncompensated Solution Resistance on the Determination and Standard Electrochemical Rate Constants Using Cyclic Voltammetry, and Some Comparisons with AC Voltammetry.

DTIC Science & Technology

1987-09-25

rate constants, k2r using cyclic voltametry . The res tss are expressed in terms of systematic deviations oP sapparent measured" rate constants, k~b(app...concentration was taken to be lum unless otherwise noted. The voltammetric sweep rate was set at 20 V sŕ unless specified otherwise. The general procedure...peaks for the negative- and positive-going potential sweeps have opposite signs, the measured cathodic-anodic peak separation, AEp, will clearly be

Diagnostic Criteria for the Characterization of Electrode Reactions with Chemically Coupled Reactions Preceding the Electron Transfer by Cyclic Square Wave Voltammetry.

PubMed

Helfrick, John C; Mann, Megan A; Bottomley, Lawrence A

2016-08-18

Theory for cyclic square wave voltammetry of electrode reactions with chemical reactions preceding the electron transfer is presented. Theoretical voltammograms were calculated following systematic variation of empirical parameters to assess their impact on the shape of the voltammogram. From the trends obtained, diagnostic criteria for this mechanism were deduced. When properly applied, these criteria will enable non-experts in voltammetry to assign the electrode reaction mechanism and accurately measure reaction kinetics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wrong-site nerve blocks: A systematic literature review to guide principles for prevention.

PubMed

Deutsch, Ellen S; Yonash, Robert A; Martin, Donald E; Atkins, Joshua H; Arnold, Theresa V; Hunt, Christina M

2018-05-01

Wrong-site nerve blocks (WSBs) are a significant, though rare, source of perioperative morbidity. WSBs constitute the most common type of perioperative wrong-site procedure reported to the Pennsylvania Patient Safety Authority. This systematic literature review aggregates information about the incidence, patient consequences, and conditions that contribute to WSBs, as well as evidence-based methods to prevent them. A systematic search of English-language publications was performed, using the PRISMA process. Seventy English-language publications were identified. Analysis of four publications reporting on at least 10,000 blocks provides a rate of 0.52 to 5.07 WSB per 10,000 blocks, unilateral blocks, or "at risk" procedures. The most commonly mentioned potential consequence was local anesthetic toxicity. The most commonly mentioned contributory factors were time pressure, personnel factors, and lack of site-mark visibility (including no site mark placed). Components of the block process that were addressed include preoperative nerve-block verification, nerve-block site marking, time-outs, and the healthcare facility's structure and culture of safety. A lack of uniform reporting criteria and divergence in the data and theories presented may reflect the variety of circumstances affecting when and how nerve blocks are performed, as well as the infrequency of a WSB. However, multiple authors suggest three procedural steps that may help to prevent WSBs: (1) verify the nerve-block procedure using multiple sources of information, including the patient; (2) identify the nerve-block site with a visible mark; and (3) perform time-outs immediately prior to injection or instillation of the anesthetic. Hospitals, ambulatory surgical centers, and anesthesiology practices should consider creating site-verification processes with clinician input and support to develop sustainable WSB-prevention practices. Copyright © 2017 Elsevier Inc. All rights reserved.

Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation.

PubMed

Louage, Benoit; Zhang, Qilu; Vanparijs, Nane; Voorhaar, Lenny; Vande Casteele, Sofie; Shi, Yang; Hennink, Wim E; Van Bocxlaer, Jan; Hoogenboom, Richard; De Geest, Bruno G

2015-01-12

Low solubility of potent (anticancer) drugs is a major driving force for the development of noncytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of block copolymers based on 2-hydroxyethyl acrylate (HEA) and the acid-sensitive ketal-containing monomer (2,2-dimethyl-1,3-dioxolane-4-yl)methyl acrylate (DMDMA) to form responsive drug nanocarriers. Block copolymers were successfully synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization, in which we combined a hydrophilic poly(HEA)x block with a (responsive) hydrophobic poly(HEAm-co-DMDMAn)y copolymer block. The DMDMA content of the hydrophobic block was systematically varied to investigate the influence of polymer design on physicochemical properties and in vitro biological performance. We found that a DMDMA content higher than 11 mol % is required for self-assembly behavior in aqueous medium. All particles showed colloidal stability in PBS at 37 °C for at least 4 days, with sizes ranging from 23 to 338 nm, proportional to the block copolymer DMDMA content. Under acidic conditions, the nanoparticles decomposed into soluble unimers, of which the decomposition rate was inversely proportional to the block copolymer DMDMA content. Flow cytometry and confocal microscopy showed dose-dependent, active in vitro cellular uptake of the particles loaded with hydrophobic octadecyl rhodamine B chloride (R18). The block copolymers showed no intrinsic in vitro cytotoxicity, while loaded with paclitaxel (PTX), a significant decrease in cell viability was observed comparable or better than the two commercial PTX nanoformulations Abraxane and Genexol-PM at equal PTX dose. This systematic approach evaluated and showed the potential of these block copolymers as nanocarriers for hydrophobic drugs.

Effect of Hierarchical Microstructures of Lath Martensite on the Transitional Behavior of Fatigue Crack Growth Rate

NASA Astrophysics Data System (ADS)

Yang, Ming; Zhong, Yi; Liang, Yi-long

2018-04-01

In this study, the fatigue-crack growth (FCG) behavior of 20CrMTiH steel with different substructure sizes was investigated. The results showed that coarsen microstructures exhibit excellent growth resistance. Moreover, two transitional behaviors were observed in the FCG curves of all specimens. The first transition point occurs in the near-threshold regime, whereas the second transition point occurs in the Paris regime. A comparison of substructure size to cyclic plastic size showed that the block size is almost equal to cyclic plastic size at ΔKT1, indicating that block size is an effective grain size to control the first transitional behavior of fatigue-crack propagation, whereas the second transitional behavior is related to the packet width or grain size. According to the fracture morphology, the fracture mechanism above and below the transition point responsible for the above phenomenon were distinguished. In addition, two prediction models based on microstructure size were established for lath martensite to evaluate the threshold and stress intensity factor range at the transition point.

Noncommutative Wilson lines in higher-spin theory and correlation functions of conserved currents for free conformal fields

NASA Astrophysics Data System (ADS)

Bonezzi, Roberto; Boulanger, Nicolas; De Filippi, David; Sundell, Per

2017-11-01

We first prove that, in Vasiliev’s theory, the zero-form charges studied in Sezgin E and Sundell P 2011 (arXiv:1103.2360 [hep-th]) and Colombo N and Sundell P 20 (arXiv:1208.3880 [hep-th]) are twisted open Wilson lines in the noncommutative Z space. This is shown by mapping Vasiliev’s higher-spin model on noncommutative Yang-Mills theory. We then prove that, prior to Bose-symmetrising, the cyclically-symmetric higher-spin invariants given by the leading order of these n-point zero-form charges are equal to corresponding cyclically-invariant building blocks of n-point correlation functions of bilinear operators in free conformal field theories (CFT) in three dimensions. On the higher spin gravity side, our computation reproduces the results of Didenko V and Skvortsov E 2013 J. High Energy Phys. JHEP04(2013)158 using an alternative method amenable to the computation of subleading corrections obtained by perturbation theory in normal order. On the free CFT side, our proof involves the explicit computation of the separate cyclic building blocks of the correlation functions of n conserved currents in arbitrary dimension d>2 using polarization vectors, which is an original result. It is shown to agree, for d=3 , with the results obtained in Gelfond O A and Vasiliev M A 2013 Nucl. Phys. B 876 871-917 in various dimensions and where polarization spinors were used.

Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine.

PubMed Central

Souness, J. E.; Brazdil, R.; Diocee, B. K.; Jordan, R.

1989-01-01

1. The mechanism by which M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine (MIMAX), which have been described as selective cyclic GMP phosphodiesterase (PDE) inhibitors, relax rat aorta was investigated. 2. Three cyclic nucleotide PDEs were identified in the soluble fraction of rat aorta; a Ca2+-insensitive form exhibiting substrate selectivity for cyclic GMP (cGMP PDE), a Ca2+/calmodulin-stimulated form which also preferentially hydrolyzed cyclic GMP (Ca2+ PDE), and a form demonstrating substrate selectivity for cyclic AMP (cAMP PDE). 3. M&B 22,948 and MIMAX inhibited cGMP PDE (Ki = 0.16 microM and 0.43 microM, respectively) and Ca2+ PDE (Ki = 9.9 microM and 0.55 microM, respectively), but exhibited weak activity against cAMP PDE (Ki = 249 microM and 42 microM, respectively). MY-5445 selectivity inhibited cGMP PDE (Ki = 1.3 microM) and vinpocetine selectively inhibited Ca2+ PDE (Ki = 14 microM). 4. M&B 22,948 and MIMAX induced dose-dependent increases in the accumulation of cyclic GMP, but not cyclic AMP, in rat aorta pieces. These effects were greatly reduced by endothelial denudation and by methylene blue (5 microM) which blocks the actions of endothelium-derived relaxant factor. MY-5445 and vinpocetine had no effect on rat aorta cyclic GMP or cyclic AMP accumulation. 5. All four compounds caused dose-related relaxation of 5-hydroxytryptamine (10 microM) contracted, endothelium-intact rat aorta, the effects of M&B 22,948 and MIMAX being greatly reduced by methylene blue (5 microM). Methylene blue also caused 10 fold and 100 fold rightward shifts in the dose-response curves of MY-5445 and vinpocetine, respectively. 6. The results are consistent with the smooth muscle relaxant actions of M&B 22,948 and MIMAX, but not vinpocetine and MY-5445, being mediated through a mechanism involving inhibition of cyclic GMP hydrolysis. PMID:2480168

Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

PubMed Central

Peng, Qian-Yi; Zou, Yu; Zhang, Li-Na; Ai, Mei-Lin; Liu, Wei; Ai, Yu-Hang

2016-01-01

Background: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. Methods: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. Results: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. Conclusions: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI. PMID:27411462

Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation

PubMed Central

Maul, Timothy M.; Chew, Douglas W.; Nieponice, Alejandro

2011-01-01

Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle (SMCs) and endothelial cells (ECs). This was tested using a unique experimental platform to differentially apply various mechanical stimuli in parallel. Three forces, cyclic stretch, cyclic pressure, and laminar shear stress, were applied independently to mimic several vascular physiologic conditions. Experiments were conducted using subconfluent MSCs for 5 days and demonstrated significant effects on morphology and proliferation depending upon the type, magnitude, frequency, and duration of applied stimulation. We have defined thresholds of cyclic stretch that potentiate SMC protein expression, but did not find EC protein expression under any condition tested. However, a second set of experiments performed at confluence and aimed to elicit the temporal gene expression response of a select magnitude of each stimulus revealed that EC gene expression can be increased with cyclic pressure and shear stress in a cell-contact-dependent manner. Further, these MSCs also appear to express genes from multiple lineages simultaneously which may warrant further investigation into post-transcriptional mechanisms for controlling protein expression. To our knowledge, this is the first systematic examination of the effects of mechanical stimulation on MSCs and has implications for the understanding of stem cell biology, as well as potential bioreactor designs for tissue engineering and cell therapy applications. PMID:21253809

Helical tomotherapy setup variations in canine nasal tumor patients immobilized with a bite block.

PubMed

Kubicek, Lyndsay N; Seo, Songwon; Chappell, Richard J; Jeraj, Robert; Forrest, Lisa J

2012-01-01

The purpose of our study was to compare setup variation in four degrees of freedom (vertical, longitudinal, lateral, and roll) between canine nasal tumor patients immobilized with a mattress and bite block, versus a mattress alone. Our secondary aim was to define a clinical target volume (CTV) to planning target volume (PTV) expansion margin based on our mean systematic error values associated with nasal tumor patients immobilized by a mattress and bite block. We evaluated six parameters for setup corrections: systematic error, random error, patient-patient variation in systematic errors, the magnitude of patient-specific random errors (root mean square [RMS]), distance error, and the variation of setup corrections from zero shift. The variations in all parameters were statistically smaller in the group immobilized by a mattress and bite block. The mean setup corrections in the mattress and bite block group ranged from 0.91 mm to 1.59 mm for the translational errors and 0.5°. Although most veterinary radiation facilities do not have access to Image-guided radiotherapy (IGRT), we identified a need for more rigid fixation, established the value of adding IGRT to veterinary radiation therapy, and define the CTV-PTV setup error margin for canine nasal tumor patients immobilized in a mattress and bite block. © 2012 Veterinary Radiology & Ultrasound.

Effects of applying nerve blocks to prevent postherpetic neuralgia in patients with acute herpes zoster: a systematic review and meta-analysis

PubMed Central

Kim, Hyun Jung; Ahn, Hyeong Sik; Lee, Jae Young; Choi, Seong Soo; Cheong, Yu Seon; Kwon, Koo; Yoon, Syn Hae

2017-01-01

Background Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed. PMID:28119767

Fatigue characteristics of carbon nanotube blocks under compression

NASA Astrophysics Data System (ADS)

Suhr, J.; Ci, L.; Victor, P.; Ajayan, P. M.

2008-03-01

In this paper we investigate the mechanical response from repeated high compressive strains on freestanding, long, vertically aligned multiwalled carbon nanotube membranes and show that the arrays of nanotubes under compression behave very similar to soft tissue and exhibit viscoelastic behavior. Under compressive cyclic loading, the mechanical response of nanotube blocks shows initial preconditioning and hysteresis characteristic of viscoeleastic materials. Furthermore, no fatigue failure is observed even at high strain amplitudes up to half million cycles. The outstanding fatigue life and extraordinary soft tissue-like mechanical behavior suggest that properly engineered carbon nanotube structures could mimic artificial muscles.

Quantization Distortion in Block Transform-Compressed Data

NASA Technical Reports Server (NTRS)

Boden, A. F.

1995-01-01

The popular JPEG image compression standard is an example of a block transform-based compression scheme; the image is systematically subdivided into block that are individually transformed, quantized, and encoded. The compression is achieved by quantizing the transformed data, reducing the data entropy and thus facilitating efficient encoding. A generic block transform model is introduced.

A comparison of two reciprocating instruments using bending stress and cyclic fatigue tests.

PubMed

Scelza, Pantaleo; Harry, Davidowicz; Silva, Licinio Esmeraldo da; Barbosa, Igor Bastos; Scelza, Miriam Zaccaro

2015-01-01

The aim of this study was to comparatively evaluate the bending resistance at 45º, the static and dynamic cyclic fatigue life, and the fracture type of the WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) 25-08 and Reciproc (VDW, Munich, Germany) 25-08 instruments. A total of 60 nickel-titanium (NiTi) instruments (30 Reciproc and 30 WaveOne) from three different lots, each of which was 25 mm in length, were tested. The bending resistance was evaluated through the results of a cantilever-bending test conducted using a universal testing machine. Static and dynamic cyclic fatigue testing was conducted using a custom-made device. For the static and dynamic tests, a cast Ni-Cr-Mo-Ti alloy metal block with an artificial canal measuring 1.77 mm in diameter and 20.00 mm in total length was used. A scanning electron microscope was used to determine the type of fracture. Statistical analyses were performed on the results. The WaveOne instrument was less flexible than the Reciproc (p < 0.05). The Reciproc instrument showed better resistance in the static and dynamic cyclic fatigue tests (p < 0.05). The transverse cross-section and geometry of the instruments were important factors in their resistance to bending and cyclic fracture. Both of the instruments showed ductile-type fracture characteristics. It can be concluded that the Reciproc 25-08 instrument was more resistant to static and dynamic cyclic fatigue than the WaveOne 25-08 instrument, while the WaveOne 25-08 instrument was less flexible. Bending and resistance to cyclic fracture were influenced by the instruments' geometries and transverse cross-sections. Both of the instruments showed ductile-type fracture characteristics.

Long-Term Interference at the Semantic Level: Evidence from Blocked-Cyclic Picture Matching

ERIC Educational Resources Information Center

Wei, Tao; Schnur, Tatiana T.

2016-01-01

Processing semantically related stimuli creates interference across various domains of cognition, including language and memory. In this study, we identify the locus and mechanism of interference when retrieving meanings associated with words and pictures. Subjects matched a probe stimulus (e.g., cat) to its associated target picture (e.g., yarn)…

A No-Go Theorem for the Continuum Limit of a Periodic Quantum Spin Chain

NASA Astrophysics Data System (ADS)

Jones, Vaughan F. R.

2018-01-01

We show that the Hilbert space formed from a block spin renormalization construction of a cyclic quantum spin chain (based on the Temperley-Lieb algebra) does not support a chiral conformal field theory whose Hamiltonian generates translation on the circle as a continuous limit of the rotations on the lattice.

On the role of calcium ions in the regulation of glycogenolysis in mouse brain cortical slices.

PubMed

Ververken, D; Van Veldhoven, P; Proost, C; Carton, H; De Wulf, H

1982-05-01

Using mouse brain cortical slices, we investigated the relative roles of cyclic AMP and of calcium ions as the intracellular messengers for the activation of glycogen phosphorylase (EC 2.4.1.1; alpha-1,4-glucan:orthophosphate glucosyltransferase) induced by noradrenaline and by depolarization. Activation of phosphorylase by 100 microM noradrenaline is mediated by beta-adrenergic receptors and does not require the copresence of adenosine. The role of the concomitant small increase in cyclic AMP is questioned. Short-term treatment with EGTA or LaCl3 abolishes the noradrenaline activation of phosphorylase, pointing to a critical role of extracellular calcium. Depolarization by 25 mM K+ or 100 microM veratridine produces a rapid and large (fourfold) activation of phosphorylase. Only veratridine increases the cyclic AMP levels; exogenous adenosine deaminase essentially blocks this cyclic AMP accumulation but not the phosphorylase activation. A half-maximal activation of phosphorylase occurs at about 12 mM K+. Addition of EGTA or LaCl3 reduces the effect of both depolarizations to a slight and transient activation of phosphorylase. These results indicate that activation of glycogen phosphorylase by K+ or veratridine occurs by a cyclic AMP-independent and calcium-dependent mechanism. The calcium dependency of brain phosphorylase kinase renders this kinase the prime target enzyme for regulation of glycogenolysis by calcium ions.

High-temperature low cycle fatigue behavior of a gray cast iron

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

Fan, K.L., E-mail: 12klfan@tongji.edu.cn; He, G.Q.; She, M.

The strain controlled low cycle fatigue properties of the studied gray cast iron for engine cylinder blocks were investigated. At the same total strain amplitude, the low cycle fatigue life of the studied material at 523 K was higher than that at 423 K. The fatigue behavior of the studied material was characterized as cyclic softening at any given total strain amplitude (0.12%–0.24%), which was attributed to fatigue crack initiation and propagation. Moreover, this material exhibited asymmetric hysteresis loops due to the presence of the graphite lamellas. Transmission electron microscopy analysis suggested that cyclic softening was also caused by themore » interactions of dislocations at 423 K, such as cell structure in ferrite, whereas cyclic softening was related to subgrain boundaries and dislocation climbing at 523 K. Micro-analysis of specimen fracture appearance was conducted in order to obtain the fracture characteristics and crack paths for different strain amplitudes. It showed that the higher the temperature, the rougher the crack face of the examined gray cast iron at the same total strain amplitude. Additionally, the microcracks were readily blunted during growth inside the pearlite matrix at 423 K, whereas the microcracks could easily pass through pearlite matrix along with deflection at 523 K. The results of fatigue experiments consistently showed that fatigue damage for the studied material at 423 K was lower than that at 523 K under any given total strain amplitude. - Highlights: • The low cycle fatigue behavior of the HT250 for engine cylinder blocks was investigated. • TEM investigations were conducted to explain the cyclic deformation response. • The low cycle fatigue cracks of HT250 GCI were studied by SEM. • The fatigue life of the examined material at 523 K is higher than that at 423 K.« less

Cyclic stretching of soft substrates induces spreading and growth

PubMed Central

Cui, Yidan; Hameed, Feroz M.; Yang, Bo; Lee, Kyunghee; Pan, Catherine Qiurong; Park, Sungsu; Sheetz, Michael

2015-01-01

In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. To determine whether transient forces can substitute for a rigid matrix, we stretched soft pillar arrays. Surprisingly, 1–5% cyclic stretching over a frequency range of 0.01–10 Hz caused spreading and stress fibre formation (optimum 0.1 Hz) that persisted after 4 h of stretching. Similarly, stretching increased cell growth rates on soft pillars comparative to rigid substrates. Of possible factors linked to fibroblast growth, MRTF-A (myocardin-related transcription factor-A) moved to the nucleus in 2 h of cyclic stretching and reversed on cessation; but YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading, stress fibre formation and growth. PMID:25704457

Low cycle fatigue behavior of a ferritic reactor pressure vessel steel

NASA Astrophysics Data System (ADS)

Sarkar, Apu; Kumawat, Bhupendra K.; Chakravartty, J. K.

2015-07-01

The cyclic stress-strain response and the low cycle fatigue (LCF) behavior of 20MnMoNi55 pressure vessel steel were studied. Tensile strength and LCF properties were examined at room temperature (RT) using specimens cut from rolling direction of a rolled block. The fully reversed strain-controlled LCF tests were conducted at a constant total strain rate with different axial strain amplitude levels. The cyclic strain-stress relationships and the strain-life relationships were obtained through the test results, and related LCF parameters of the steel were calculated. The studied steel exhibits cyclic softening behavior. Furthermore, analysis of stabilized hysteresis loops showed that the steel exhibits non-Masing behavior. Complementary scanning electron microscopy examinations were also carried out on fracture surfaces to reveal dominant damage mechanisms during crack initiation, propagation and fracture. Multiple crack initiation sites were observed on the fracture surface. The investigated LCF behavior can provide reference for pressure vessel life assessment and fracture mechanisms analysis.

Numerical Modeling of Earthquake-Induced Landslide Using an Improved Discontinuous Deformation Analysis Considering Dynamic Friction Degradation of Joints

NASA Astrophysics Data System (ADS)

Huang, Da; Song, Yixiang; Cen, Duofeng; Fu, Guoyang

2016-12-01

Discontinuous deformation analysis (DDA) as an efficient technique has been extensively applied in the dynamic simulation of discontinuous rock mass. In the original DDA (ODDA), the Mohr-Coulomb failure criterion is employed as the judgment principle of failure between contact blocks, and the friction coefficient is assumed to be constant in the whole calculation process. However, it has been confirmed by a host of shear tests that the dynamic friction of rock joints degrades. Therefore, the friction coefficient should be gradually reduced during the numerical simulation of an earthquake-induced rockslide. In this paper, based on the experimental results of cyclic shear tests on limestone joints, exponential regression formulas are fitted for dynamic friction degradation, which is a function of the relative velocity, the amplitude of cyclic shear displacement and the number of its cycles between blocks with an edge-to-edge contact. Then, an improved DDA (IDDA) is developed by implementing the fitting regression formulas and a modified removing technique of joint cohesion, in which the cohesion is removed once the `sliding' or `open' state between blocks appears for the first time, into the ODDA. The IDDA is first validated by comparing with the theoretical solutions of the kinematic behaviors of a sliding block on an inclined plane under dynamic loading. Then, the program is applied to model the Donghekou landslide triggered by the 2008 Wenchuan earthquake in China. The simulation results demonstrate that the dynamic friction degradation of joints has great influences on the runout and velocity of sliding mass. Moreover, the friction coefficient possesses higher impact than the cohesion of joints on the kinematic behaviors of the sliding mass.

Effects of Nitric Oxide on Voltage-Gated K⁺ Currents in Human Cardiac Fibroblasts through the Protein Kinase G and Protein Kinase A Pathways but Not through S-Nitrosylation.

PubMed

Bae, Hyemi; Choi, Jeongyoon; Kim, Young-Won; Lee, Donghee; Kim, Jung-Ha; Ko, Jae-Hong; Bang, Hyoweon; Kim, Taeho; Lim, Inja

2018-03-12

This study investigated the expression of voltage-gated K⁺ (K V ) channels in human cardiac fibroblasts (HCFs), and the effect of nitric oxide (NO) on the K V currents, and the underlying phosphorylation mechanisms. In reverse transcription polymerase chain reaction, two types of K V channels were detected in HCFs: delayed rectifier K⁺ channel and transient outward K⁺ channel. In whole-cell patch-clamp technique, delayed rectifier K⁺ current (I K ) exhibited fast activation and slow inactivation, while transient outward K⁺ current (I to ) showed fast activation and inactivation kinetics. Both currents were blocked by 4-aminopyridine. An NO donor, S -nitroso- N -acetylpenicillamine (SNAP), increased the amplitude of I K in a concentration-dependent manner with an EC 50 value of 26.4 µM, but did not affect I to . The stimulating effect of SNAP on I K was blocked by pretreatment with 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or by KT5823. 8-bromo-cyclic GMP stimulated the I K . The stimulating effect of SNAP on I K was also blocked by pretreatment with KT5720 or by SQ22536. Forskolin and 8-bromo-cyclic AMP each stimulated I K . On the other hand, the stimulating effect of SNAP on I K was not blocked by pretreatment of N -ethylmaleimide or by DL-dithiothreitol. Our data suggest that NO enhances I K , but not I to , among K V currents of HCFs, and the stimulating effect of NO on I K is through the PKG and PKA pathways, not through S -nitrosylation.

Novel Conjugated Polymers Prepared by Direct (Hetero) arylation: An Eco-Friendly Tool for Organic Electronics.

PubMed

Liu, Fuchuan; Zhang, Yangqian; Wang, Hang; Zhang, Shiming

2018-02-13

The phthalimide (PhI) moiety has been attracting more attention as an excellent acceptor building block in donor-acceptor (D-A) conjugated polymers. In this paper; three D-A conjugated polymers with or without thiocarbonyl moieties are successfully prepared by the direct (hetero)-arylation polymerization (DHAP), which is an atom efficient and facile synthetic strategy to obtain polymer materials. Compared with the traditional carbon-carbon coupling reactions, this method possesses more advantages, including: fewer synthetic steps, avoidance of the preparation of the organometallic reagents, higher atom economy and fewer toxic byproducts, better compatibility with chemically sensitive functional groups and so on. All three of these designed PhI-based polymers exhibited favourable optoelectronic and thermal performance. The optical, thermodynamic and electrochemical properties of the synthesized polymers were systematically investigated using ultraviolet-visible (UV-vis) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and cyclic voltammetry (CV). The results of these three polymers indicated that thionation of the carbonyl was a highly effective methods to improve the properties of PhI-based polymers; and provided impetus for the development of thionated PhI derivatives for organic electronic applications.

High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

PubMed

Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

2016-05-01

The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour. © 2015 THE AUTHORS MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

Access to enhanced differences in Marcus-Hush and Butler-Volmer electron transfer theories by systematic analysis of higher order AC harmonics.

PubMed

Stevenson, Gareth P; Baker, Ruth E; Kennedy, Gareth F; Bond, Alan M; Gavaghan, David J; Gillow, Kathryn

2013-02-14

The potential-dependences of the rate constants associated with heterogeneous electron transfer predicted by the empirically based Butler-Volmer and fundamentally based Marcus-Hush formalisms are well documented for dc cyclic voltammetry. However, differences are often subtle, so, presumably on the basis of simplicity, the Butler-Volmer method is generally employed in theoretical-experimental comparisons. In this study, the ability of Large Amplitude Fourier Transform AC Cyclic Voltammetry to distinguish the difference in behaviour predicted by the two formalisms has been investigated. The focus of this investigation is on the difference in the profiles of the first to sixth harmonics, which are readily accessible when a large amplitude of the applied ac potential is employed. In particular, it is demonstrated that systematic analysis of the higher order harmonic responses in suitable kinetic regimes provides predicted deviations of Marcus-Hush from Butler-Volmer behaviour to be established from a single experiment under conditions where the background charging current is minimal.

Cyclic di-GMP regulation of the bvg-repressed genes and the orphan response regulator RisA in Bordetella pertussis

USDA-ARS?s Scientific Manuscript database

Expression of Bordetella pertussis virulence factors is activated by the BvgAS two-component system. Under modulating growth conditions BvgAS indirectly represses another set of genes through the action of BvgR, a bvg-activated protein. BvgR blocks activation of the response regulator RisA which is ...

Energy transfer within self-assembled cyclic multichromophoric arrays based on orthogonally arranged donor-acceptor building blocks.

PubMed

Karakostas, Nikolaos; Kaloudi-Chantzea, Antonia; Martinou, Elisabeth; Seintis, Kostas; Pitterl, Florian; Oberacher, Herbert; Fakis, Mihalis; Kallitsis, Joannis K; Pistolis, George

2015-01-01

We herein present the coordination-driven supramolecular synthesis and photophysics of a [4+4] and a [2+2] assembly, built up by alternately collocated donor-acceptor chromophoric building blocks based, respectively, on the boron dipyrromethane (Bodipy) and perylene bisimide dye (PBI). In these multichromophoric scaffolds, the intensely absorbing/emitting dipoles of the Bodipy subunit are, by construction, cyclically arranged at the corners and aligned perpendicular to the plane formed by the closed polygonal chain comprising the PBI units. Steady-state and fs time-resolved spectroscopy reveal the presence of efficient energy transfer from the vertices (Bodipys) to the edges (PBIs) of the polygons. Fast excitation energy hopping - leading to a rapid excited state equilibrium among the low energy perylene-bisimide chromophores - is revealed by fluorescence anisotropy decays. The dynamics of electronic excitation energy hopping between the PBI subunits was approximated on the basis of a theoretical model within the framework of Förster energy transfer theory. All energy-transfer processes are quantitatively describable with Förster theory. The influence of structural deformations and orientational fluctuations of the dipoles in certain kinetic schemes is discussed.

C-FSCV: Compressive Fast-Scan Cyclic Voltammetry for Brain Dopamine Recording.

PubMed

Zamani, Hossein; Bahrami, Hamid Reza; Chalwadi, Preeti; Garris, Paul A; Mohseni, Pedram

2018-01-01

This paper presents a novel compressive sensing framework for recording brain dopamine levels with fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode. Termed compressive FSCV (C-FSCV), this approach compressively samples the measured total current in each FSCV scan and performs basic FSCV processing steps, e.g., background current averaging and subtraction, directly with compressed measurements. The resulting background-subtracted faradaic currents, which are shown to have a block-sparse representation in the discrete cosine transform domain, are next reconstructed from their compressively sampled counterparts with the block sparse Bayesian learning algorithm. Using a previously recorded dopamine dataset, consisting of electrically evoked signals recorded in the dorsal striatum of an anesthetized rat, the C-FSCV framework is shown to be efficacious in compressing and reconstructing brain dopamine dynamics and associated voltammograms with high fidelity (correlation coefficient, ), while achieving compression ratio, CR, values as high as ~ 5. Moreover, using another set of dopamine data recorded 5 minutes after administration of amphetamine (AMPH) to an ambulatory rat, C-FSCV once again compresses (CR = 5) and reconstructs the temporal pattern of dopamine release with high fidelity ( ), leading to a true-positive rate of 96.4% in detecting AMPH-induced dopamine transients.

The development of a portable ultrahigh vacuum chamber via silicon block.

PubMed

Chuang, Ho-Chiao; Huang, Chia-Shiuan

2014-05-01

This paper describes a nonmetallic, light weight portable chamber for ultra-high vacuum (UHV) applications. The chamber consists of a processed silicon block anodically bonding five polished Pyrex glass windows and a Pyrex glass adapter, without using any screws, bolts or vacuum adhesives. The design features provide an alternative chamber for UHV applications which require nonmetallic components. We have cyclically baked the chamber up to 180 °C for 160 h and have achieved an ultimate pressure of 1.4 × 10(-9) Torr (limited by our pumping station), with no leak detected. Both Pyrex glass windows and Pyrex glass adapter have been used successfully.

Some fast elliptic solvers on parallel architectures and their complexities

NASA Technical Reports Server (NTRS)

Gallopoulos, E.; Saad, Y.

1989-01-01

The discretization of separable elliptic partial differential equations leads to linear systems with special block tridiagonal matrices. Several methods are known to solve these systems, the most general of which is the Block Cyclic Reduction (BCR) algorithm which handles equations with nonconstant coefficients. A method was recently proposed to parallelize and vectorize BCR. In this paper, the mapping of BCR on distributed memory architectures is discussed, and its complexity is compared with that of other approaches including the Alternating-Direction method. A fast parallel solver is also described, based on an explicit formula for the solution, which has parallel computational compelxity lower than that of parallel BCR.

Some fast elliptic solvers on parallel architectures and their complexities

NASA Technical Reports Server (NTRS)

Gallopoulos, E.; Saad, Youcef

1989-01-01

The discretization of separable elliptic partial differential equations leads to linear systems with special block triangular matrices. Several methods are known to solve these systems, the most general of which is the Block Cyclic Reduction (BCR) algorithm which handles equations with nonconsistant coefficients. A method was recently proposed to parallelize and vectorize BCR. Here, the mapping of BCR on distributed memory architectures is discussed, and its complexity is compared with that of other approaches, including the Alternating-Direction method. A fast parallel solver is also described, based on an explicit formula for the solution, which has parallel computational complexity lower than that of parallel BCR.

Variation of the uniaxial tensile behavior of ultrafine-grained pure aluminum after cyclic pre-deformation

NASA Astrophysics Data System (ADS)

Yan, Ying; Chen, Li-jia; Zhang, Guo-qiang; Han, Dong; Li, Xiao-wu

2018-06-01

To explore the influence of cyclic pre-deformation on the mechanical behavior of ultrafine-grained (UFG) materials with a high stacking fault energy (SFE), UFG Al processed by equal-channel angular pressing (ECAP) was selected as a target material and its tensile behavior at different pre-cyclic levels D ( D = N i / N f, where N i and N f are the applied cycles and fatigue life at a constant stress amplitude of 50 MPa, respectively) along with the corresponding microstructures and deformation features were systematically studied. The cyclic pre-deformation treatment on the ECAPed UFG Al led to a decrease in flow stress, and a stress quasi-plateau stage was observed after yielding for all of the different-state UFG Al samples. The yield strength σ YS, ultimate tensile strength σ UTS, and uniform strain ɛ exhibited a strong dependence on D when D ≤ 20%; however, when D was in the range from 20% to 50%, no obvious change in mechanical properties was observed. The micro-mechanism for the effect of cyclic pre-deformation on the tensile properties of the ECAPed UFG Al was revealed and compared with that of ECAPed UFG Cu through the observations of deformation features and microstructures.

Clinical safety and effectiveness of transversus abdominis plane (TAP) block in post-operative analgesia: a systematic review and meta-analysis.

PubMed

Ma, Ning; Duncan, Joanna K; Scarfe, Anje J; Schuhmann, Susanne; Cameron, Alun L

2017-06-01

Transversus abdominis plane (TAP) blocks can provide analgesia postoperatively for a range of surgeries. Abundant clinical trials have assessed TAP block showing positive analgesic effects. This systematic review assesses safety and effectiveness outcomes of TAP block in all clinical settings, comparing with both active (standard care) and inactive (placebo) comparators. PubMed, EMBASE, The Cochrane Library and the University of York CRD databases were searched. RCTs were screened for their eligibility and assessed for risk of bias. Meta-analyses were performed on available data. TAP block showed an equivalent safety profile to all comparators in the incidence of nausea (OR = 1.07) and vomiting (OR = 0.81). TAP block was more effective in reducing morphine consumption [MD = 13.05, 95% CI (8.33, 51.23)] and in delaying time to first analgesic request [MD = 123.49, 95% CI (48.59, 198.39)]. Postoperative pain within 24 h was reduced or at least equivalent in TAP block compared to its comparators. Therefore, TAP block is a safe and effective procedure compared to standard care, placebo and other analgesic techniques. Further research is warranted to investigate whether the TAP block technique can be improved by optimizing dose and technique-related factors.

Cyclic stress effect on stress corrosion cracking of duplex stainless steel in chloride and caustic solutions

NASA Astrophysics Data System (ADS)

Yang, Di

Duplex stainless steel (DSS) is a dual-phase material with approximately equal volume amount of austenite and ferrite. It has both great mechanical properties (good ductility and high tensile/fatigue strength) and excellent corrosion resistance due to the mixture of the two phases. Cyclic loadings with high stress level and low frequency are experienced by many structures. However, the existing study on corrosion fatigue (CF) study of various metallic materials has mainly concentrated on relatively high frequency range. No systematic study has been done to understand the ultra-low frequency (˜10-5 Hz) cyclic loading effect on stress corrosion cracking (SCC) of DSSs. In this study, the ultra-low frequency cyclic loading effect on SCC of DSS 2205 was studied in acidified sodium chloride and caustic white liquor (WL) solutions. The research work focused on the environmental effect on SCC of DSS 2205, the cyclic stress effect on strain accumulation behavior of DSS 2205, and the combined environmental and cyclic stress effect on the stress corrosion crack initiation of DSS 2205 in the above environments. Potentiodynamic polarization tests were performed to investigate the electrochemical behavior of DSS 2205 in acidic NaCl solution. Series of slow strain rate tests (SSRTs) at different applied potential values were conducted to reveal the optimum applied potential value for SCC to happen. Room temperature static and cyclic creep tests were performed in air to illustrate the strain accumulation effect of cyclic stresses. Test results showed that cyclic loading could enhance strain accumulation in DSS 2205 compared to static loading. Moreover, the strain accumulation behavior of DSS 2205 was found to be controlled by the two phases of DSS 2205 with different crystal structures. The B.C.C. ferrite phase enhanced strain accumulation due to extensive cross-slips of the dislocations, whereas the F.C.C. austenite phase resisted strain accumulation due to cyclic strain hardening. Cyclic SSRTs were performed under the conditions that SCC occurs in sodium chloride and WL solutions. Test results show that cyclic stress facilitated crack initiations in DSS 2205. Stress corrosion cracks initiated from the intermetallic precipitates in acidic chloride environment, and the cracks initiated from austenite phase in WL environment. Cold-working has been found to retard the crack initiations induced by cyclic stresses.

Definition of Two Angiogenic Pathways by Distinct α_v Integrins

NASA Astrophysics Data System (ADS)

Friedlander, Martin; Brooks, Peter C.; Shaffer, Robert W.; Kincaid, Christine M.; Varner, Judith A.; Cheresh, David A.

1995-12-01

Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-α depended on α_vβ_3, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-α, or phorbol ester depended on α_vβ_5. Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by α_vβ_5 but not by α_vβ_3.

Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP phosphodiesterase Eal in response to antibiotic exposure and diffusible signal factor-mediated cell-cell signaling.

PubMed

de Souza, Alessandra A; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M; Lindow, Steven E

2013-06-01

Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.

Experimental Investigation on the Fatigue Mechanical Properties of Intermittently Jointed Rock Models Under Cyclic Uniaxial Compression with Different Loading Parameters

NASA Astrophysics Data System (ADS)

Liu, Yi; Dai, Feng; Dong, Lu; Xu, Nuwen; Feng, Peng

2018-01-01

Intermittently jointed rocks, widely existing in many mining and civil engineering structures, are quite susceptible to cyclic loading. Understanding the fatigue mechanism of jointed rocks is vital to the rational design and the long-term stability analysis of rock structures. In this study, the fatigue mechanical properties of synthetic jointed rock models under different cyclic conditions are systematically investigated in the laboratory, including four loading frequencies, four maximum stresses, and four amplitudes. Our experimental results reveal the influence of the three cyclic loading parameters on the mechanical properties of jointed rock models, regarding the fatigue deformation characteristics, the fatigue energy and damage evolution, and the fatigue failure and progressive failure behavior. Under lower loading frequency or higher maximum stress and amplitude, the jointed specimen is characterized by higher fatigue deformation moduli and higher dissipated hysteresis energy, resulting in higher cumulative damage and lower fatigue life. However, the fatigue failure modes of jointed specimens are independent of cyclic loading parameters; all tested jointed specimens exhibit a prominent tensile splitting failure mode. Three different crack coalescence patterns are classified between two adjacent joints. Furthermore, different from the progressive failure under static monotonic loading, the jointed rock specimens under cyclic compression fail more abruptly without evident preceding signs. The tensile cracks on the front surface of jointed specimens always initiate from the joint tips and then propagate at a certain angle with the joints toward the direction of maximum compression.

Sub-Camera Calibration of a Penta-Camera

NASA Astrophysics Data System (ADS)

Jacobsen, K.; Gerke, M.

2016-03-01

Penta cameras consisting of a nadir and four inclined cameras are becoming more and more popular, having the advantage of imaging also facades in built up areas from four directions. Such system cameras require a boresight calibration of the geometric relation of the cameras to each other, but also a calibration of the sub-cameras. Based on data sets of the ISPRS/EuroSDR benchmark for multi platform photogrammetry the inner orientation of the used IGI Penta DigiCAM has been analyzed. The required image coordinates of the blocks Dortmund and Zeche Zollern have been determined by Pix4Dmapper and have been independently adjusted and analyzed by program system BLUH. With 4.1 million image points in 314 images respectively 3.9 million image points in 248 images a dense matching was provided by Pix4Dmapper. With up to 19 respectively 29 images per object point the images are well connected, nevertheless the high number of images per object point are concentrated to the block centres while the inclined images outside the block centre are satisfying but not very strongly connected. This leads to very high values for the Student test (T-test) of the finally used additional parameters or in other words, additional parameters are highly significant. The estimated radial symmetric distortion of the nadir sub-camera corresponds to the laboratory calibration of IGI, but there are still radial symmetric distortions also for the inclined cameras with a size exceeding 5μm even if mentioned as negligible based on the laboratory calibration. Radial and tangential effects of the image corners are limited but still available. Remarkable angular affine systematic image errors can be seen especially in the block Zeche Zollern. Such deformations are unusual for digital matrix cameras, but it can be caused by the correlation between inner and exterior orientation if only parallel flight lines are used. With exception of the angular affinity the systematic image errors for corresponding cameras of both blocks have the same trend, but as usual for block adjustments with self calibration, they still show significant differences. Based on the very high number of image points the remaining image residuals can be safely determined by overlaying and averaging the image residuals corresponding to their image coordinates. The size of the systematic image errors, not covered by the used additional parameters, is in the range of a square mean of 0.1 pixels corresponding to 0.6μm. They are not the same for both blocks, but show some similarities for corresponding cameras. In general the bundle block adjustment with a satisfying set of additional parameters, checked by remaining systematic errors, is required for use of the whole geometric potential of the penta camera. Especially for object points on facades, often only in two images and taken with a limited base length, the correct handling of systematic image errors is important. At least in the analyzed data sets the self calibration of sub-cameras by bundle block adjustment suffers from the correlation of the inner to the exterior calibration due to missing crossing flight directions. As usual, the systematic image errors differ from block to block even without the influence of the correlation to the exterior orientation.

Agonist-induced glycogenolysis in rabbit retinal slices and cultures.

PubMed Central

Ghazi, H.; Osborne, N. N.

1989-01-01

1. The effects of different putative retinal transmitters and/or modulators on glycogenolysis in rabbit retinal slices and in retinal Müller cell cultures were examined. 2. Incubation of rabbit retinal slices or primary retinal cultures (either 3-5 day-old or 25-30 day-old) in a buffer solution containing [3H]-glucose resulted in the accumulation of newly synthesized [3H]-glycogen. 3. Noradrenaline (NA), isoprenaline, vasoactive intestinal peptide (VIP), 5-hydroxytryptamine (5-HT) and 8-hydroxy-dipropylaminetetralin (8-OH-DPAT) stimulated the hydrolysis of this newly formed 3H-polymer. The potency order of maximal stimulations was: VIP greater than NA greater than isoprenaline greater than 5-HT greater than 8-OH-DPAT. 4. The putative retinal transmitters, dopamine, gamma-aminobutyric acid (GABA), glycine and taurine and the muscarinic agonist carbachol (CCh) had no effect on [3H]-glycogen content. 5. The glycogenolytic effects of NA/isoprenaline and 5-HT/8-OH-DPAT appear to be mediated by beta-adrenoceptors and 5-HT1 receptors (possibly 5-HT1A), respectively while the VIP-induced response involved another receptor subtype. 6. Agonists which mediated [3H]-glycogen hydrolysis also stimulated an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation. Both responses are blocked to a similar extent by the same antagonists and so are probably mediated via the same receptor subtypes. Moreover, dibutyryl cyclic AMP (db cyclic AMP) promoted tritiated glycogen breakdown in the three retinal preparations. 7. Not all receptors linked to cyclic AMP production however promote glycogenolysis. Dopamine and apomorphine stimulated cyclic AMP formation via D1-receptors without influencing glycogenolysis. These receptors are exclusively associated with neurones. PMID:2568145

Random versus Blocked Practice in Treatment for Childhood Apraxia of Speech

ERIC Educational Resources Information Center

Maas, Edwin; Farinella, Kimberly A.

2012-01-01

Purpose: To compare the relative effects of random vs. blocked practice schedules in treatment for childhood apraxia of speech (CAS). Although there have been repeated suggestions in the literature to use random practice in CAS treatment, no systematic studies exist that have directly compared random with blocked practice in this population.…

Alterations in ovarian follicular progesterone secretion by elevated exposures to the drinking water disinfection by-product dibromoacetic acid: examination of the potential site(s) of impact along the steroidogenic pathway

EPA Science Inventory

Previous data from our laboratory indicated that the drinking water disinfection by-product, dibromoacetic acid (DBA), when applied in vitro to rat preovulatory follicles at a concentration consistent with blood levels found to disrupt estrous cyclicity, was able to block the sti...

Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s bearing functionalizable carbonate building blocks: II. Enzymatic biodegradation and in vitro biocompatibility assay.

PubMed

Yang, Jing; Tian, Weisheng; Li, Qiaobo; Li, Yang; Cao, Amin

2004-01-01

In a previous study, we have reported chemical synthesis of novel aliphatic poly(butylene succinate-co-cyclic carbonate) P(BS-co-CC)s bearing various functionalizable carbonate building blocks, and this work will continue to present our new studies on their enzymatic degradation and in vitro cell biocompatibility assay. First, enzymatic degradation of the novel P(BS-co-CC) film samples was investigated with two enzymes of lipase B Candida Antartic (Novozyme 435) and lipase Porcine Pancreas PPL, and it was revealed that copolymerizing linear poly(butylene succinate) PBS with a functionalizable carbonate building block could remarkably accelerate the enzymatic degradation of a synthesized product P(BS-co-CC), and its biodegradation behavior was found to strongly depend on the overall impacts of several important factors as the cyclic carbonate (CC) comonomer structure and molar content, molar mass, thermal characteristics, morphology, the enzyme-substrate specificity, and so forth. Further, the biodegraded residual film samples and water-soluble enzymatic degradation products were allowed to be analyzed by means of proton nuclear magnetic resonance (1H NMR), gel permeation chromatograph (GPC), differential scanning calorimeter (DSC), attenuated total reflection FTIR (ATR-FTIR), scanning electron microscope (SEM), and liquid chromatograph-mass spectrometry (LC-MS). On the experimental evidences, an exo-type mechanism of enzymatic chain hydrolysis preferentially occurring in the noncrystalline domains was suggested for the synthesized new P(BS-co-CC) film samples. With regard to their cell biocompatibilities, an assay with NIH 3T3 mouse fibroblast cell was conducted using the novel synthesized P(BS-co-CC) films as substrates with respect to the cell adhesion and proliferation, and these new biodegradable P(BS-co-CC) samples were found to exhibit as low cell toxicity as the PLLA control, particularly the two samples of poly(butylene succinate-co-18.7 mol % dimethyl trimethylene carbonate) P(BS-co-18.7 mol % DMTMC) and poly(butylene succinate-co-21.9 mol % 5-benzyloxy trimethylene carbonate) P(BS-co-21.9 mol % BTMC) were interestingly found to show much better cell biocompatibilities than the PLLA reference.

Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers

PubMed Central

2017-01-01

Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block. PMID:28994585

Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers.

PubMed

van Genabeek, Bas; Lamers, Brigitte A G; de Waal, Bas F M; van Son, Martin H C; Palmans, Anja R A; Meijer, E W

2017-10-25

Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.

Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation.

PubMed

Steenberg, J; Møller, A M

2018-06-01

Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Method and structure for skewed block-cyclic distribution of lower-dimensional data arrays in higher-dimensional processor grids

DOEpatents

Chatterjee, Siddhartha [Yorktown Heights, NY; Gunnels, John A [Brewster, NY

2011-11-08

A method and structure of distributing elements of an array of data in a computer memory to a specific processor of a multi-dimensional mesh of parallel processors includes designating a distribution of elements of at least a portion of the array to be executed by specific processors in the multi-dimensional mesh of parallel processors. The pattern of the designating includes a cyclical repetitive pattern of the parallel processor mesh, as modified to have a skew in at least one dimension so that both a row of data in the array and a column of data in the array map to respective contiguous groupings of the processors such that a dimension of the contiguous groupings is greater than one.

Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action.

PubMed Central

D'Costa, M A; Angel, A

1975-01-01

The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis. Images PMID:162783

Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas

PubMed Central

Yago, Maria D; Tapia, Jose A; Salido, Gines M; Adeghate, Ernest; Juma, Lubna M O; Martinez-Victoria, Emilio; Mañas, Mariano; Singh, Jaipaul

2002-01-01

The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3′5′ cyclic monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked amylase secretion, tritiated choline ([3H]-choline) release and on intracellular free calcium concentration ([Ca2+]i) in the isolated rat pancreas were investigated.Electrical field stimulation (EFS; 10 Hz) and ACh (1×10−5 M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1×10−5 M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1×10−6 M) abolished the secretory effect of EFS.Either SNP (1×10−3 M) or 8-Br-cyclic GMP (1×10−4 M) inhibited amylase secretion compared to basal. Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP had no significant effect on the amylase response to ACh. When extracellular Ca2+ concentration ([Ca2+]o) was elevated from 2.56 mM to 5.12 mM, SNP failed to inhibit the response to EFS.EFS stimulated the release of 3H from pancreatic segments preloaded with [3H]-choline. Either SNP or 8-Br-cyclic GMP had no effect on basal 3H release but significantly reduced the EFS-evoked response.In fura-2 loaded acinar cells, SNP elicited a small decrease in [Ca2+]i compared to basal and had no effect on the ACh-induced [Ca2+]i peak response.Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas. PMID:11976267

Purine 3':5'-cyclic nucleotides with the nucleobase in a syn orientation: cAMP, cGMP and cIMP.

PubMed

Řlepokura, Katarzyna Anna

2016-06-01

Purine 3':5'-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3':5'-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3':5'-cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3':5'-cyclic phosphate 0.3-hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3':5'-cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H11N5O7P(-)·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H10N4O7P(-)·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP(-) in (IV) and cIMP(-) in (V)] are syn conformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib-H...Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn-anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter-nucleotide contacts in (I)-(V) have been systematized in terms of the chemical groups involved. All five structures display three-dimensional hydrogen-bonded networks.

MnO2-GO double-shelled sulfur (S@MnO2@GO) as a cathode for Li-S batteries with improved rate capability and cyclic performance

NASA Astrophysics Data System (ADS)

Huang, Xingkang; Shi, Keying; Yang, Joseph; Mao, George; Chen, Junhong

2017-07-01

Sulfur cathodes have attracted much attention recently because of their high energy density and power density. However, sulfur possesses very poor electrical conductivity, and lithium polysulfides, resulting from the lithiation of sulfur, are prone to dissolving into electrolytes, which leads to the loss of active materials and poor cyclic performance of the sulfur cathodes. Here we report an MnO2-graphene oxide (GO) double-shelled sulfur (S@MnO2@GO) with improved rate capability and cyclic performance, in which we propose a new reaction using sulfur-reducing KMnO4 to produce MnO2 that covers the surface of the excess sulfur in situ. The resulting MnO2 with honeycomb-like morphology provides excellent voids for storing polysulfides. The outermost GO was assembled to block the open pores of MnO2, thereby minimizing the opportunity for polysulfides to leach into the electrolytes. The GO significantly improved the electrical conductivity of the sulfur cathode, and the S@MnO2@GO exhibited excellent rate capability and long cycle life.

Application of nondestructive testing in cyclic fatigue evaluation of endodontic Ni-Ti rotary instruments.

PubMed

Li, Uei-Ming; Shin, Chow-Shing; Lan, Wan-Hong; Lin, Chun-Pin

2006-06-01

The purpose of this study was to investigate the application of nondestructive testing in cyclic fatigue evaluation of endodontic ProFile nickel-titanium (NiTi) rotary instruments. As-received ProFile instruments were made to rotate freely in sloped metal blocks by a contra-angle handpiece mounted on a testing machine. Rotation was interrupted periodically, and the instrument removed and engaged onto a device to monitor its stiffness by using two strain gauges in four different directions. This monitoring method has the potential to be developed into a convenient, nondestructive turnkey system that allows in situ assessment of the integrity of NiTi instruments in the clinic. Upon fracture, which was indicated by a change in instrument stiffness, the fractured surface would be examined under a scanning electron microscope. Microscopic evaluation indicated a small area of fatigue fracture with a large area of final ductile fracture, whereby the latter was the major cyclic failure mode. Based on the results of this study, we concluded that a potential nondestructive integrity assessment method for NiTi rotary instruments was developed.

Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway in the antinociceptive action of ketorolac.

PubMed

Lázaro-Ibáñez, G G; Torres-López, J E; Granados-Soto, V

2001-08-24

The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at the peripheral level.

Untemplated nonenzymatic polymerization of 3',5'cGMP: a plausible route to 3',5'-linked oligonucleotides in primordia.

PubMed

Šponer, Judit E; Šponer, Jiří; Giorgi, Alessandra; Di Mauro, Ernesto; Pino, Samanta; Costanzo, Giovanna

2015-02-19

The high-energy 3',5' phosphodiester linkages conserved in 3',5' cyclic GMPs offer a genuine solution for monomer activation required by the transphosphorylation reactions that could lead to the emergence of the first simple oligonucleotide sequences on the early Earth. In this work we provide an in-depth characterization of the effect of the reaction conditions on the yield of the polymerization reaction of 3',5' cyclic GMPs both in aqueous environment as well as under dehydrating conditions. We show that the threshold temperature of the polymerization is about 30 °C lower under dehydrating conditions than in solution. In addition, we present a plausible exergonic reaction pathway for the polymerization reaction, which involves transient formation of anionic centers at the O3' positions of the participating riboses. We suggest that excess Na(+) cations inhibit the polymerization reaction because they block the anionic mechanism via neutralizing the negatively charged O3'. Our experimental findings are compatible with a prebiotic scenario, where gradual desiccation of the environment could induce polymerization of 3',5' cyclic GMPs synthesized in liquid.

Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

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

Suzuki, Nobuhiro; Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602; Yamazaki, Yasuo

2008-10-01

The structures of pseudechetoxin and pseudecin suggest that both proteins bind to cyclic nucleotide-gated ion channels in a manner in which the concave surface occludes the pore entrance. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine-rich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinitiesmore » on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn{sup 2+}-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn{sup 2+} ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn{sup 2+} binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.« less

Engine-driven preparation of curved root canals: measuring cyclic fatigue and other physical parameters.

PubMed

Peters, Ove A; Kappeler, Stefan; Bucher, Willi; Barbakow, Fred

2002-04-01

An increasing number of engine-driven rotary systems are marketed to shape root canals. Although these systems may improve the quality of canal preparations, the risk for instrument fracture is also increased. Unfortunately, the stresses generated in rotary instruments when shaping curved root canals have not been adequately studied. Consequently, the aim of an ongoing project was to develop a measurement platform that could more accurately detail physical parameters generated in a simulated clinical situation. Such a platform was constructed by fitting a torque-measuring device between the rotating endodontic instrument and the motor driving it. Apically directed force and instrument insertion depth were also recorded. Additional devices were constructed to assess cyclic fatigue and static fracture loads. The current pilot study evaluated GT rotary instruments during the shaping of curved canals in plastic blocks as well as "ISO 3630-1 torque to fracture" and number of rotations required for fatigue fracture. Results indicated that torques in excess of 40 Nmm were generated by rotary GT-Files, a significantly higher figure than static fracture loads (less than 13 Nmm for the size 20. 12 GT-File). Furthermore, the number of rotations needed to shape simulated canals with a 5 mm radius of curvature in plastic blocks was 10 times lower than the number of rotations needed to fracture instruments in a "cyclic fatigue test". Apical forces were always greater than 1 N, and in some specimens, scores of 8 N or more were recorded. Further studies are required using extracted natural teeth, with their wide anatomical variation, in order to reduce the incidence of fracture of rotary instruments. In this way, the clinical potential of engine-driven rotary instruments to safely prepare curved canals can be fully appreciated.

Beta-tricalcium phosphate plugs for press-fit fixation in ACL reconstruction--a mechanical analysis in bovine bone.

PubMed

Mayr, Hermann O; Hube, Robert; Bernstein, Anke; Seibt, Alexander B; Hein, Werner; von Eisenhart-Rothe, Ruediger

2007-06-01

The goal of this study was to test fixation properties of microporous pure beta-tricalcium phosphate (TCP) plugs (porosity 40%) for press-fit fixation of the ACL graft using patellar tendons with and without bone blocks. We set out to establish whether it is possible, in this way, to obtain results comparable with those of interference screw fixation of bone-tendon-bone (BTB) grafts in terms of cyclic loading and load-to-failure. In a bovine model 30 ACL grafts were fixed in tibial drill holes, divided into three groups: 10 BTB grafts fixed with TCP press-fit plugs (7x25 mm), 10 pure patellar tendon grafts with TCP press-fit plugs (7x25 mm), and 10 BTB grafts with metal interference screws (7x25 mm). All grafts were tested by cyclic loading (50-200 N) and loaded until failure in a tensiometer. Under cyclic loading one interference screw fixation failed. None of the TCP plug fixations failed. After 1500 cycles the displacement of the graft in the drill hole for BTB fixed with screws was 3.6+/-7.8 mm, for BTB/TCP plugs 1.6+/-3.4 mm, and for the pure tendon/TCP grafts 1.4+/-0.4 mm. Regarding cyclic loading the pure tendon/TCP system was significantly superior to BTB (p=0.007). The load-to-failure for the BTB/interference screw group was 908+/-539 N with a stiffness of 94+/-36 N/mm, 936+/-245 N for the BTB/TCP cylinder group with a stiffness of 98+/-12 N/mm, and 673+/-159 N for the pure tendon/TCP group with a stiffness of 117+/-9 N/mm. In terms of pull-out load the BTB/TCP system was significantly better than the pure tendon/TCP group (p=0.011). However, pure tendon/TCP grafts achieved significantly greater stiffness (p=0.002) than the BTB system. Press-fit fixation with microporous pure beta-TCP plugs of BTB grafts or patellar tendon grafts without bone blocks for ACL reconstruction leads to primary stability comparable with that achieved by fixation with metal interference screws in case of BTB grafts.

Sphenopalatine ganglion: block, radiofrequency ablation and neurostimulation - a systematic review.

PubMed

Ho, Kwo Wei David; Przkora, Rene; Kumar, Sanjeev

2017-12-28

Sphenopalatine ganglion is the largest collection of neurons in the calvarium outside of the brain. Over the past century, it has been a target for interventional treatment of head and facial pain due to its ease of access. Block, radiofrequency ablation, and neurostimulation have all been applied to treat a myriad of painful syndromes. Despite the routine use of these interventions, the literature supporting their use has not been systematically summarized. This systematic review aims to collect and summarize the level of evidence supporting the use of sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were reviewed for studies on sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Studies included in this review were compiled and analyzed for their treated medical conditions, study design, outcomes and procedural details. Studies were graded using Oxford Center for Evidence-Based Medicine for level of evidence. Based on the level of evidence, grades of recommendations are provided for each intervention and its associated medical conditions. Eighty-three publications were included in this review, of which 60 were studies on sphenopalatine ganglion block, 15 were on radiofrequency ablation, and 8 were on neurostimulation. Of all the studies, 23 have evidence level above case series. Of the 23 studies, 19 were on sphenopalatine ganglion block, 1 study on radiofrequency ablation, and 3 studies on neurostimulation. The rest of the available literature was case reports and case series. The strongest evidence lies in using sphenopalatine ganglion block, radiofrequency ablation and neurostimulation for cluster headache. Sphenopalatine ganglion block also has evidence in treating trigeminal neuralgia, migraines, reducing the needs of analgesics after endoscopic sinus surgery and reducing pain associated with nasal packing removal after nasal operations. Overall, sphenopalatine ganglion is a promising target for treating cluster headache using blocks, radiofrequency ablation and neurostimulation. Sphenopalatine ganglion block also has some evidence supporting its use in a few other conditions. However, most of the controlled studies were small and without replications. Further controlled studies are warranted to replicate and expand on these previous findings.

(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

PubMed Central

Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH. PMID:22916194

(S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.

PubMed

Zhang, Hao; Yu, Huan; Wang, Xia; Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

Evidence for a possible neurotransmitter/neuromodulator role of tyramine on the locust oviducts.

PubMed

Donini, Andrew; Lange, Angela B

2004-04-01

Visualization of the tyraminergic innervation of the oviducts was demonstrated by immunohistochemistry, and the presence of tyramine was confirmed using high-performance liquid chromatography coupled to electrochemical detection. Oviducts incubated in high-potassium saline released tyramine in a calcium-dependent manner. Stimulation of the oviducal nerves also resulted in tyramine release, suggesting that tyramine might function as a neurotransmitter/neuromodulator at the locust oviducts. Tyramine decreased the basal tension, and also attenuated proctolin-induced contractions in a dose-dependent manner over a range of doses between 10(-7) and 10(-4) M. Low concentrations of tyramine attenuated forskolin-stimulated cyclic AMP levels in a dose-dependent manner. This effect was not blocked by yohimbine. High concentrations of tyramine increased basal cyclic AMP levels of locust oviducts in a dose-dependent manner; however, the increases in cyclic AMP were only evident at the highest concentrations tested, 5 x 10(-5) and 10(-4) M tyramine. The tyramine-induced increase in cyclic AMP shared a similar pharmacological profile with the octopamine-induced increase in cyclic AMP. Tyramine increased the amplitude of excitatory junction potentials at low concentrations while hyperpolarizing the membrane potential by 2-5 mV. A further increase in the amplitude of the excitatory junction potentials and the occurrence of an active response was seen upon washing tyramine from the preparation. These results suggest that tyramine can activate at least three different endogenous receptors on the locust oviducts a putative tyramine receptor at low concentrations, a different tyramine receptor to inhibit muscle contraction, and an octopamine receptor at high concentrations.

Detecting seasonal and cyclical trends in agricultural runoff water quality-hypothesis tests and block bootstrap power analysis.

PubMed

Uddameri, Venkatesh; Singaraju, Sreeram; Hernandez, E Annette

2018-02-21

Seasonal and cyclic trends in nutrient concentrations at four agricultural drainage ditches were assessed using a dataset generated from a multivariate, multiscale, multiyear water quality monitoring effort in the agriculturally dominant Lower Rio Grande Valley (LRGV) River Watershed in South Texas. An innovative bootstrap sampling-based power analysis procedure was developed to evaluate the ability of Mann-Whitney and Noether tests to discern trends and to guide future monitoring efforts. The Mann-Whitney U test was able to detect significant changes between summer and winter nutrient concentrations at sites with lower depths and unimpeded flows. Pollutant dilution, non-agricultural loadings, and in-channel flow structures (weirs) masked the effects of seasonality. The detection of cyclical trends using the Noether test was highest in the presence of vegetation mainly for total phosphorus and oxidized nitrogen (nitrite + nitrate) compared to dissolved phosphorus and reduced nitrogen (total Kjeldahl nitrogen-TKN). Prospective power analysis indicated that while increased monitoring can lead to higher statistical power, the effect size (i.e., the total number of trend sequences within a time-series) had a greater influence on the Noether test. Both Mann-Whitney and Noether tests provide complementary information on seasonal and cyclic behavior of pollutant concentrations and are affected by different processes. The results from these statistical tests when evaluated in the context of flow, vegetation, and in-channel hydraulic alterations can help guide future data collection and monitoring efforts. The study highlights the need for long-term monitoring of agricultural drainage ditches to properly discern seasonal and cyclical trends.

Phenotype Overlap in Xylella fastidiosa Is Controlled by the Cyclic Di-GMP Phosphodiesterase Eal in Response to Antibiotic Exposure and Diffusible Signal Factor-Mediated Cell-Cell Signaling

PubMed Central

de Souza, Alessandra A.; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M.

2013-01-01

Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3′-5′)-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates. PMID:23542613

Dynamic room temperature precipitation during cyclic deformation of an Al-Zn-Mg-Cu alloy

NASA Astrophysics Data System (ADS)

Hutchinson, C. R.; de Geuser, F.; Deschamps, A.

The effect of pre-straining on a precipitation heat treatment is a well-chartered area and is relevant to a number of Al alloy manufacturing processes. When straining and precipitation occur concurrently, the situation is less clear. This may arise during creep, fatigue or elevated temperature forming operations. Straining introduces dislocations and strain-induced vacancies that may enhance nucleation and growth processes but the dislocations may also shear and/or cause precipitate dissolution. This study reports a systematic characterization of precipitation during room temperature cyclic deformation of the AA7050 (Al-Zn-Mg-Cu) alloy. The mechanical response is monitored using plastic strain controlled cyclic deformation tests and the precipitation state is characterized using small angle x-ray scattering. It is shown that the precipitate volume fraction increases with the number of deformation cycles and is well correlated with the hardening increment observed but the mean precipitate radii remains relatively constant during cycling at 4-5A.

Improved global prediction of 300 nautical mile mean free air anomalies

NASA Technical Reports Server (NTRS)

Cruz, J. Y.

1982-01-01

Current procedures used for the global prediction of 300nm mean anomalies starting from known values of 1 deg by 1 deg mean anomalies yield unreasonable prediction results when applied to 300nm blocks which have a rapidly varying gravity anomaly field and which contain relatively few observed 60nm blocks. Improvement of overall 300nm anomaly prediction is first achieved by using area-weighted as opposed to unweighted averaging of the 25 generated 60nm mean anomalies inside the 300nm block. Then, improvement of prediction over rough 300nm blocks is realized through the use of fully known 1 deg by 1 deg mean elevations, taking advantage of the correlation that locally exists between 60nm mean anomalies and 60nm mean elevations inside the 300nm block. An improved prediction model which adapts itself to the roughness of the local anomaly field is found to be the model of Least Squares Collocation with systematic parameters, the systematic parameter being the slope b which is a type of Bouguer slope expressing the correlation that locally exists between 60nm mean anomalies and 60nm mean elevations.

State-dependent block of CNG channels by dequalinium.

PubMed

Rosenbaum, Tamara; Gordon-Shaag, Ariela; Islas, León D; Cooper, Jeremy; Munari, Mika; Gordon, Sharona E

2004-03-01

Cyclic nucleotide-gated (CNG) ion channels are nonselective cation channels with a high permeability for Ca(2+). Not surprisingly, they are blocked by a number of Ca(2+) channel blockers including tetracaine, pimozide, and diltiazem. We studied the effects of dequalinium, an extracellular blocker of the small conductance Ca(2+)-activated K(+) channel. We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV. Here we examined block by dequalinium at a broad range of voltages in both CNGA1 and CNGA2 channels. We found that dequalinium block was mildly state dependent for both channels, with the affinity for closed channels 3-5 times higher than that for open channels. Mutations in the S4-S5 linker did not alter the affinity of open channels for dequalinium, but increased the affinity of closed channels by 10-20-fold. The state-specific effect of these mutations raises the question of whether/how the S4-S5 linker alters the binding of a blocker within the ion permeation pathway.

Photoaffinity labelling of cyclic GMP-inhibited phosphodiesterase (PDE III) in human and rat platelets and rat tissues: effects of phosphodiesterase inhibitors.

PubMed

Tang, K M; Jang, E K; Haslam, R J

1994-06-15

Ultraviolet irradiation of human platelet cytosol in the presence of 32P-labelled cyclic GMP (cGMP) can specifically label 110, 80, 55, 49 and 38 kDa proteins; the 110 kDa species is the subunit of cGMP-inhibited phosphodiesterase (PDE III) and the 80 kDa species that of cGMP-dependent protein kinase (Tang et al., 1993, Biochem. J. 294, 329). We have now shown that although photolabelling of platelet PDE III was inhibited by unlabelled cGMP, 8-bromo-cGMP and cyclic AMP (cAMP), it was not affected by phosphorothioate analogues of these cyclic nucleotides. Specific concentration-dependent inhibitions of the photolabelling of PDE III were observed with the following PDE inhibitors: trequinsin (IC50 = 13 +/- 2 nM), lixazinone (IC50 = 22 +/- 4 nM), milrinone (IC50 = 56 +/- 12 nM), cilostamide (IC50 = 70 +/- 9 nM), siguazodan (IC50 = 117 +/- 29 nM) and 3-isobutyl 1-methylxanthine (IBMX) (IC50 = 3950 +/- 22 nM). Thus, measurements of the inhibitory effects of compounds on the photolabelling of platelet PDE III provide a simple quantitative means of investigating their actions at a molecular level that avoids the need to purify the enzyme. Photolabelling of rat platelet lysate or rat heart homogenate by [32P]cGMP showed that the 110 kDa PDE III present in human material was replaced by a 115 kDa protein, labelling of which was also blocked by PDE III inhibitors. Heart and other rat tissues contained much less of this putative 115 kDa PDE III than rat platelets. In contrast, the 80 kDa protein was labelled much less in platelets than in many other rat tissue homogenates (e.g., heart, aorta, uterus and lung). Thus, comparison of the relative amounts of specific photolabelled proteins in different cells may provide an indication of different patterns of cyclic nucleotide action. We compared the abilities of phosphodiesterase inhibitors to block the photolabelling of PDE III in human platelet cytosol and to increase the iloprost-stimulated accumulation of cAMP in intact platelets. Whereas trequinsin (EC50 = 19 +/- 3 nM), lixazinone (EC50 = 122 +/- 8 nM), milrinone (EC50 = 5320 +/- 970 nM) and siguazodan (EC50 = 18880 +/- 3110 nM) all increased platelet cAMP to the same maximum extent, cilostamide and IBMX increased cAMP further, indicating that they inhibited a PDE isozyme in addition to PDE III.

Investigating the Effects of an Experimental Approach to Comprehension Instruction within a Literacy Clinic

ERIC Educational Resources Information Center

Ortlieb, Evan; McDowell, F. D.

2015-01-01

Reading comprehension levels of elementary students have not significantly improved in the 21st century and as a result, the need for systematic and intensive reading interventions is as high as ever. Literacy clinics are an ideal setting for struggling readers to experience success through the implementation of a cyclical approach to individual…

Interactive communication channel

NASA Astrophysics Data System (ADS)

Chan, R. H.; Mann, M. R.; Ciarrocchi, J. A.

1985-10-01

Discussed is an interactive communications channel (ICC) for providing a digital computer with high-performance multi-channel interfaces. Sixteen full duplex channels can be serviced in the ICC with the sequence or scan pattern being programmable and dependent upon the number or channels and their speed. A channel buffer system is used for line interface, and character exchange. The channel buffer system is on a byte basis. The ICC performs frame start and frame end functions, bit stripping and bit stuffing. Data is stored in a memory in block format (256 bytes maximum) by a program control and the ICC maintains byte address information and a block byte count. Data exchange with a memory is made by cycle steals. Error detection is also provided for using a cyclic redundancy check technique.

Benzene oxidation at diamond electrodes: comparison of microcrystalline and nanocrystalline diamonds.

PubMed

Pleskov, Yu V; Krotova, M D; Elkin, V V; Varnin, V P; Teremetskaya, I G; Saveliev, A V; Ralchenko, V G

2012-08-27

A comparative study of benzene oxidation at boron-doped diamond (BDD) and nitrogenated nanocrystalline diamond (NCD) anodes in 0.5 M K(2)SO(4) aqueous solution is conducted by using cyclic voltammetry and electrochemical impedance spectroscopy. It is shown by measurements of differential capacitance and anodic current that during the benzene oxidation at the BDD electrode, adsorption of a reaction intermediate occurs, which partially blocks the electrode surface and lowers the anodic current. At the NCD electrode, benzene is oxidized concurrently with oxygen evolution, a (quinoid) intermediate being adsorbed at the electrode. The adsorption and the electrode surface blocking are reflected in the impedance-frequency and impedance-potential complex-plane plots. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nitroxide-mediated radical ring-opening copolymerization: chain-end investigation and block copolymer synthesis.

PubMed

Delplace, Vianney; Harrisson, Simon; Tardy, Antoine; Gigmes, Didier; Guillaneuf, Yohann; Nicolas, Julien

2014-02-01

Well-defined, degradable copolymers are successfully prepared by nitroxide-mediated radical ring opening polymerization (NMrROP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or methyl methacrylate (MMA), a small amount of acrylonitrile (AN) and cyclic ketene acetals (CKAs) of different structures. Phosphorous nuclear magnetic resonance allows in-depth chain-end characterization and gives crucial insights into the nature of the copoly-mer terminal sequences and the living chain fractions. By using a small library of P(OEGMA-co-AN-co-CKA) and P(MMA-co-AN-co-CKA) as macroinitiators, chain extensions with styrene are performed to furnish (amphiphilic) block copolymers comprising a degradable segment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SU-E-T-33: A Feasibility-Seeking Algorithm Applied to Planning of Intensity Modulated Proton Therapy: A Proof of Principle Study

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

Penfold, S; Casiraghi, M; Dou, T

2015-06-15

Purpose: To investigate the applicability of feasibility-seeking cyclic orthogonal projections to the field of intensity modulated proton therapy (IMPT) inverse planning. Feasibility of constraints only, as opposed to optimization of a merit function, is less demanding algorithmically and holds a promise of parallel computations capability with non-cyclic orthogonal projections algorithms such as string-averaging or block-iterative strategies. Methods: A virtual 2D geometry was designed containing a C-shaped planning target volume (PTV) surrounding an organ at risk (OAR). The geometry was pixelized into 1 mm pixels. Four beams containing a subset of proton pencil beams were simulated in Geant4 to provide themore » system matrix A whose elements a-ij correspond to the dose delivered to pixel i by a unit intensity pencil beam j. A cyclic orthogonal projections algorithm was applied with the goal of finding a pencil beam intensity distribution that would meet the following dose requirements: D-OAR < 54 Gy and 57 Gy < D-PTV < 64.2 Gy. The cyclic algorithm was based on the concept of orthogonal projections onto half-spaces according to the Agmon-Motzkin-Schoenberg algorithm, also known as ‘ART for inequalities’. Results: The cyclic orthogonal projections algorithm resulted in less than 5% of the PTV pixels and less than 1% of OAR pixels violating their dose constraints, respectively. Because of the abutting OAR-PTV geometry and the realistic modelling of the pencil beam penumbra, complete satisfaction of the dose objectives was not achieved, although this would be a clinically acceptable plan for a meningioma abutting the brainstem, for example. Conclusion: The cyclic orthogonal projections algorithm was demonstrated to be an effective tool for inverse IMPT planning in the 2D test geometry described. We plan to further develop this linear algorithm to be capable of incorporating dose-volume constraints into the feasibility-seeking algorithm.« less

Influence of cyclical fatigue on torsional fracture morphology in endodontic instruments.

PubMed

Lopreite, Gustavo; Basilaki, Jorge; Hecht, Pedro

2013-01-01

Cyclical fatigue may influence the appearance and propagation of the type of fracture of an endodontic instrument. The aim of this study was to assess the influence of cyclic fatigue on morphological features of torsional fracture in Pathfile nickel-titanium rotary instruments for surgical preparation in endodontics. Thirty new Pathfile instruments (Dentsply- Maillefer. Ballaigues-Switzerland) diameter .13 and taper .02 were randomly divided into 5 groups (n = 6). Twenty-four of them were subject to cyclical fatigue by continuous rotation using a stainless steel cylinder with internal bore 0.5 mm, length 25 mm, with a curve of 45 degrees and radius 8 mm at 5 mm from the tip, at 300 rpm and 1 Ncm torque for different times: A: 15 sec, B: 75 sec, C: 150 sec and D: 300 sec, while the fifth group was kept as a control (group N). As a second step, the instruments were rotated at 2 rpm and 1 Ncm torque, with their apical 3 mm fixed in a resin block until they suffered torsional fracture. The fracture surfaces were analyzed using a conventional high-vacuum scanning electron microscope (Phillips mod. 515) at 400x. All instruments had ductile fracture areas of different sizes. The ductile fracture areas were measured as percentages of the total area of the instrument by means of Golden Ratio (Softonic) software for measuring images. The data obtained were analyzed statistically using one-way variance analysis followed by Tukey's multiple comparison test. There were significant differences among groups regarding cyclic fatigue time and fragile fracture area (P < .001). Comparison of percentages shows five significant differences between N/C; N/D; A/D; C/N and C/A. No other comparison was significant. It is concluded that the increase in cyclical fatigue to which the rotating PathFile instrument is subject significantly increases the percentage of ductile fracture area produced by torsion.

Stretch-Induced Hypertrophy Activates NFkB-Mediated VEGF Secretion in Adult Cardiomyocytes

PubMed Central

Leychenko, Anna; Konorev, Eugene; Jijiwa, Mayumi; Matter, Michelle L.

2011-01-01

Hypertension and myocardial infarction are associated with the onset of hypertrophy. Hypertrophy is a compensatory response mechanism to increases in mechanical load due to pressure or volume overload. It is characterized by extracellular matrix remodeling and hypertrophic growth of adult cardiomyocytes. Production of Vascular Endothelial Growth Factor (VEGF), which acts as an angiogenic factor and a modulator of cardiomyocyte function, is regulated by mechanical stretch. Mechanical stretch promotes VEGF secretion in neonatal cardiomyocytes. Whether this effect is retained in adult cells and the molecular mechanism mediating stretch-induced VEGF secretion has not been elucidated. Our objective was to investigate whether cyclic mechanical stretch induces VEGF secretion in adult cardiomyocytes and to identify the molecular mechanism mediating VEGF secretion in these cells. Isolated primary adult rat cardiomyocytes (ARCMs) were subjected to cyclic mechanical stretch at an extension level of 10% at 30 cycles/min that induces hypertrophic responses. Cyclic mechanical stretch induced a 3-fold increase in VEGF secretion in ARCMs compared to non-stretch controls. This increase in stretch-induced VEGF secretion correlated with NFkB activation. Cyclic mechanical stretch-mediated VEGF secretion was blocked by an NFkB peptide inhibitor and expression of a dominant negative mutant IkBα, but not by inhibitors of the MAPK/ERK1/2 or PI3K pathways. Chromatin immunoprecipitation assays demonstrated an interaction of NFkB with the VEGF promoter in stretched primary cardiomyocytes. Moreover, VEGF secretion is increased in the stretched myocardium during pressure overload-induced hypertrophy. These findings are the first to demonstrate that NFkB activation plays a role in mediating VEGF secretion upon cyclic mechanical stretch in adult cardiomyocytes. Signaling by NFkB initiated in response to cyclic mechanical stretch may therefore coordinate the hypertrophic response in adult cardiomyocytes. Elucidation of this novel mechanism may provide a target for developing future pharmacotherapy to treat hypertension and heart disease. PMID:22174951

Cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments in artificial canals.

PubMed

Higuera, Oscar; Plotino, Gianluca; Tocci, Luigi; Carrillo, Gabriela; Gambarini, Gianluca; Jaramillo, David E

2015-06-01

The purpose of this study was to evaluate the cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments. A total of 45 nickel-titanium instruments were tested and divided into 3 experimental groups (n = 15): group 1, WaveOne Primary instruments; group 2, Reciproc R25 instruments; and group 3, Twisted File (TF) Adaptive M-L1 instruments. The instruments were then subjected to cyclic fatigue test on a static model consisting of a metal block with a simulated canal with 60° angle of curvature and a 5-mm radius of curvature. WaveOne Primary, Reciproc R25, and TF Adaptive instruments were activated by using their proprietary movements, WaveOne ALL, Reciproc ALL, and TF Adaptive, respectively. All instruments were activated until fracture occurred, and the time to fracture was recorded visually for each file with a 1/100-second chronometer. Mean number of cycles to failure and standard deviations were calculated for each group, and data were statistically analyzed (P < .05). Instruments were also observed through scanning electron microscopy to evaluate type of fracture. Cyclic fatigue resistance of Reciproc R25 and TF Adaptive M-L1 was significantly higher than that of WaveOne Primary (P = .009 and P = .002, respectively). The results showed no statistically significant difference between TF Adaptive M-L1 and Reciproc R25 (P = .686). Analysis of the fractured portion under scanning electron microscopy indicated that all instruments showed morphologic characteristics of ductile fracture that were due to accumulation of metal fatigue. No statistically significant differences were found between the instruments tested except for WaveOne Primary, which showed the lowest resistance to cyclic fatigue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of cyclic fatigue resistance of four different nickel-titanium rotary files with different cross-sectional designs and alloy properties.

PubMed

Kaval, Mehmet Emin; Capar, Ismail Davut; Ertas, Hüseyin; Sen, Bilge Hakan

2017-06-01

The purpose of the present study was to evaluate the cyclic fatigue resistance of F6 SkyTaper (Komet Brasseler, Lemgo, Germany), K3XF (SybronEndo, Orange, CA, USA), new generation OneShape (Micro Mega, Besancon, France) and TRUShape 3D conforming files (Dentsply Tulsa Dental Specialties, Tulsa, OK, USA). Ten instruments from each group were selected and allowed to rotate using a low-torque motor in a stainless steel block with 1.5 mm diameter, 3 mm radius of 60° angle of curvature at the manufacturer's recommended speed, and the number of cycles (NCF) from the beginning to the fracture was recorded. The data were analyzed using one-way ANOVA followed by post-hoc Tukey's test (P = 0.05). The ranking of the groups from the highest to the lowest NCF was as follows: F6 SkyTaper (959 ± 92), K3XF (725 ± 71), TRUShape (575 ± 84) and OneShape (289 ± 58). Statistically significant differences were detected between all groups (P < 0.05). Within the limitations of this study, F6 SkyTaper instruments presented the highest cyclic fatigue resistance among the tested instruments. The S-shaped cross-sectional design of F6 SkyTaper instruments could be the most important factor on the superior cyclic life span of these instruments. In endodontic practice, preferring the instruments with higher cyclic fatigue resistance would help to minimize the risk of instrument fractures; therefore especially during the preparation of curved canals, instruments with smaller core area and less cross-sectional metal mass, which could lead higher flexibility, can be proposed.

Synthesis of amphiphilic tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization directly initiating from cyclic precursors and their application as drug nanocarriers.

PubMed

Wan, Xuejuan; Liu, Tao; Liu, Shiyong

2011-04-11

We report on the facile synthesis of well-defined amphiphilic and thermoresponsive tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization (ROP) directly initiating from cyclic precursors, their self-assembling behavior in aqueous solution, and the application of micellar assemblies as controlled release drug nanocarriers. Starting from a trifunctional core molecule containing alkynyl, hydroxyl, and bromine moieties, alkynyl-(OH)-Br, macrocyclic poly(N-isopropylacrylamide) (c-PNIPAM) bearing a single hydroxyl functionality was prepared by atom transfer radical polymerization (ATRP), the subsequent end group transformation into azide functionality, and finally the intramacromolecular ring closure reaction via click chemistry. The target amphiphilic tadpole-shaped linear-cyclic diblock copolymer, (c-PNIPAM)-b-PCL, was then synthesized via the ROP of ε-caprolactone (CL) by directly initiating from the cyclic precursor. In aqueous solution at 20 °C, (c-PNIPAM)-b-PCL self-assembles into spherical micelles consisting of hydrophobic PCL cores and well-solvated coronas of cyclic PNIPAM segments. For comparison, linear diblock copolymer with comparable molecular weight and composition, (l-PNIPAM)-b-PCL, was also synthesized. It was found that the thermoresponsive coronas of micelles self-assembled from (c-PNIPAM)-b-PCL exhibit thermoinduced collapse and aggregation at a lower critical thermal phase transition temperature (T(c)) compared with those of (l-PNIPAM)-b-PCL. Temperature-dependent drug release profiles from the two types of micelles of (c-PNIPAM)-b-PCL and (l-PNIPAM)-b-PCL loaded with doxorubicin (Dox) were measured, and the underlying mechanism for the observed difference in releasing properties was proposed. Moreover, MTT assays revealed that micelles of (c-PNIPAM)-b-PCL are almost noncytotoxic up to a concentration of 1.0 g/L, whereas at the same polymer concentration, micelles loaded with Dox lead to ∼60% cell death. Overall, chain topologies of thermoresponsive block copolymers, that is, (c-PNIPAM)-b-PCL versus (l-PNIPAM)-b-PCL, play considerable effects on the self-assembling and thermal phase transition properties and their functions as controlled release drug nanocarriers.

Decision Making under the Adamha Block Grant: Four Case Studies.

ERIC Educational Resources Information Center

Hudson, Christopher G.; Dubey, Sumati N.

1986-01-01

Investigated whether block grants improve decision making through the decentralization of control of social programs to state governments. Found that department bureaucrats have sought to protect the new flexibility from encroachment by elected officials through the rationalization and systematization of decision-making procedures. (Author/ABB)

Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

PubMed Central

Nicholson, Graham M.; Lewis, Richard J.

2006-01-01

Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

Supramolecular macrocycles reversibly assembled by Te…O chalcogen bonding

PubMed Central

Ho, Peter C.; Szydlowski, Patrick; Sinclair, Jocelyn; Elder, Philip J. W.; Kübel, Joachim; Gendy, Chris; Lee, Lucia Myongwon; Jenkins, Hilary; Britten, James F.; Morim, Derek R.; Vargas-Baca, Ignacio

2016-01-01

Organic molecules with heavy main-group elements frequently form supramolecular links to electron-rich centres. One particular case of such interactions is halogen bonding. Most studies of this phenomenon have been concerned with either dimers or infinitely extended structures (polymers and lattices) but well-defined cyclic structures remain elusive. Here we present oligomeric aggregates of heterocycles that are linked by chalcogen-centered interactions and behave as genuine macrocyclic species. The molecules of 3-methyl-5-phenyl-1,2-tellurazole 2-oxide assemble a variety of supramolecular aggregates that includes cyclic tetramers and hexamers, as well as a helical polymer. In all these aggregates, the building blocks are connected by Te…O–N bridges. Nuclear magnetic resonance spectroscopic experiments demonstrate that the two types of annular aggregates are persistent in solution. These self-assembled structures form coordination complexes with transition-metal ions, act as fullerene receptors and host small molecules in a crystal. PMID:27090355

Synthesis and immobilization of Ag(0) nanoparticles on diazonium modified electrodes: SECM and cyclic voltammetry studies of the modified interfaces.

PubMed

Noël, Jean-Marc; Zigah, Dodzi; Simonet, Jacques; Hapiot, Philippe

2010-05-18

A versatile method was used to prepare modified surfaces on which metallic silver nanoparticles are immobilized on an organic layer. The preparation method takes advantage, on one hand, of the activated reactivity of some alkyl halides with Ag-Pd alloys to produce metallic silver nanoparticles and, on the other hand, of the facile production of an anchoring polyphenyl acetate layer by the electrografting of substituted diazonium salts on carbon surfaces. Transport properties inside such modified layers were investigated by cyclic voltammetry, scanning electrochemical microscopy (SECM) in feedback mode, and conducting AFM imaging for characterizing the presence and nature of the conducting pathways. The modification of the blocking properties of the surface (or its conductivity) was found to vary to a large extent on the solvents used for surface examination (H(2)O, CH(2)Cl(2), and DMF).

Transversus Abdominis Plane Block for Post Hysterectomy Pain: A Systematic Review and Meta-Analysis.

PubMed

Bacal, Vanessa; Rana, Urvi; McIsaac, Daniel I; Chen, Innie

2018-04-30

The objective of this study was to address the efficacy of transversus abdominis plane (TAP) blocks in pain management among women who undergo elective hysterectomy for benign pathology in both open and minimally invasive surgeries. We performed a systematic review by searching for bibliographic citations from Medline, Embase and Cochrane Library. MeSH headings for TAP blocks and hysterectomy were combined and restricted to the English language. We included RCTs comparing TAP blocks to placebo or no block in patients who underwent elective hysterectomy. Pain was measured using a visual analog score (VAS) on a scale of 0-100. We calculated pooled mean differences in VAS and total morphine consumption at 2 and 24 hours by performing a random effects meta-analysis. Fourteen studies met the inclusion criteria, comprising 855 participants. At 2 hours, mean VAS scores for patients who underwent TAP blocks were significantly lower after both total abdominal hysterectomy (TAH) (mean difference -14.97 [CI: -20.35- -9.59]) and total laparoscopic hysterectomy (TLH) (-18.16 [CI: -34.78- -1.53]) compared to placebo or no block. Pain scores at 24 hours for patients who underwent TAPB were significantly lower after both TAH (-10.09 [CI: -17.35- -2.83]) and TLH (-9.12 [CI: -18.12- -0.13]) compared to placebo or no block. Mean difference in morphine consumption was -9.53 mg (CI -15.43- -3.63) for TAH and -3.15 mg (CI: -8.41- 2.12) for TLH. In conclusion, TAP blocks provide significant postoperative early and delayed pain control compared to placebo or no block among women who undergo hysterectomy. There was reduced morphine consumption among patients who underwent TAH, but not after TLH. Copyright © 2018. Published by Elsevier Inc.

Data-Dependent Fingerprints for Wireless Device Authentication

DTIC Science & Technology

2014-05-20

enhanced when using a modulation based on orthogonal frequency division multiplexing ( OFDM ) that has a large range of signal levels. However, in...at 70 MHz. The radios use OFDM with 64-point FFT block sizes for transmission so that the bandwidth is divided into Nd = 64 data and Nc = 5 cyclic...τℓTs) (1) where Ts is the OFDM symbol period (and therefore discrete-time sampling period) and L is the number of multipaths in the channel with

Interference from related actions in spoken word production: Behavioural and fMRI evidence.

PubMed

de Zubicaray, Greig; Fraser, Douglas; Ramajoo, Kori; McMahon, Katie

2017-02-01

Few investigations of lexical access in spoken word production have investigated the cognitive and neural mechanisms involved in action naming. These are likely to be more complex than the mechanisms involved in object naming, due to the ways in which conceptual features of action words are represented. The present study employed a blocked cyclic naming paradigm to examine whether related action contexts elicit a semantic interference effect akin to that observed with categorically related objects. Participants named pictures of intransitive actions to avoid a confound with object processing. In Experiment 1, body-part related actions (e.g., running, walking, skating, hopping) were named significantly slower compared to unrelated actions (e.g., laughing, running, waving, hiding). Experiment 2 employed perfusion functional Magnetic Resonance Imaging (fMRI) to investigate the neural mechanisms involved in this semantic interference effect. Compared to unrelated actions, naming related actions elicited significant perfusion signal increases in frontotemporal cortex, including bilateral inferior frontal gyrus (IFG) and hippocampus, and decreases in bilateral posterior temporal, occipital and parietal cortices, including intraparietal sulcus (IPS). The findings demonstrate a role for temporoparietal cortex in conceptual-lexical processing of intransitive action knowledge during spoken word production, and support the proposed involvement of interference resolution and incremental learning mechanisms in the blocked cyclic naming paradigm. Copyright © 2017 Elsevier Ltd. All rights reserved.

A hammerhead ribozyme allows synthesis of a new form of the Tetrahymena ribozyme homogeneous in length with a 3' end blocked for transesterification.

PubMed Central

Grosshans, C A; Cech, T R

1991-01-01

The L-21 Scal form of the Tetrahymena ribozyme acts as a sequence-specific endonuclease. This ribozyme has a homogeneous 5' end but a somewhat heterogeneous 3' end, as is typical of RNA synthesized by transcription in vitro. To produce a more homogeneous ribozyme for both structural and enzymological studies, a hammerhead ribozyme was inserted at the 3' end of the Tetrahymena ribozyme. During transcription the hammerhead moiety self-cleaves to produce the L-21 A Tetrahymena ribozyme, which ends at A410 with a 2',3'-cyclic phosphate terminus. The new ribozyme has endoribonuclease activity equivalent to that of L-21 Scal under conditions where binding of substrate is rate-limiting, as well as under conditions where chemical cleavage by guanosine is rate-limiting. However, the L-21 A has lost activity in oligo(C) disproportionation (e.g., 2 pC5----pC4 + pC6), consistent with the previous proposal that this reaction occurs predominantly through a covalent ribozyme-substrate intermediate involving the 3'-terminal hydroxyl group of the ribozyme. Formation of such an intermediate would be prevented by the 2',3'-cyclic phosphate terminus. Thus the L-21 A ribozyme has simplified enzymatic activity, being fully active as an endonuclease but blocked for disproportionation. Images PMID:1650453

Initial Skill Acquisition of Handrim Wheelchair Propulsion: A New Perspective.

PubMed

Vegter, Riemer J K; de Groot, Sonja; Lamoth, Claudine J; Veeger, Dirkjan Hej; van der Woude, Lucas H V

2014-01-01

To gain insight into cyclic motor learning processes, hand rim wheelchair propulsion is a suitable cyclic task, to be learned during early rehabilitation and novel to almost every individual. To propel in an energy efficient manner, wheelchair users must learn to control bimanually applied forces onto the rims, preserving both speed and direction of locomotion. The purpose of this study was to evaluate mechanical efficiency and propulsion technique during the initial stage of motor learning. Therefore, 70 naive able-bodied men received 12-min uninstructed wheelchair practice, consisting of three 4-min blocks separated by 2 min rest. Practice was performed on a motor-driven treadmill at a fixed belt speed and constant power output relative to body mass. Energy consumption and the kinetics of propulsion technique were continuously measured. Participants significantly increased their mechanical efficiency and changed their propulsion technique from a high frequency mode with a lot of negative work to a longer-slower movement pattern with less power losses. Furthermore a multi-level model showed propulsion technique to relate to mechanical efficiency. Finally improvers and non-improvers were identified. The non-improving group was already more efficient and had a better propulsion technique in the first block of practice (i.e., the fourth minute). These findings link propulsion technique to mechanical efficiency, support the importance of a correct propulsion technique for wheelchair users and show motor learning differences.

Short-Block Protograph-Based LDPC Codes

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Samuel; Jones, Christopher

2010-01-01

Short-block low-density parity-check (LDPC) codes of a special type are intended to be especially well suited for potential applications that include transmission of command and control data, cellular telephony, data communications in wireless local area networks, and satellite data communications. [In general, LDPC codes belong to a class of error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels.] The codes of the present special type exhibit low error floors, low bit and frame error rates, and low latency (in comparison with related prior codes). These codes also achieve low maximum rate of undetected errors over all signal-to-noise ratios, without requiring the use of cyclic redundancy checks, which would significantly increase the overhead for short blocks. These codes have protograph representations; this is advantageous in that, for reasons that exceed the scope of this article, the applicability of protograph representations makes it possible to design highspeed iterative decoders that utilize belief- propagation algorithms.

Application of the self-diagnosis composite into concrete structure

NASA Astrophysics Data System (ADS)

Matsubara, Hideaki; Shin, Soon-Gi; Okuhara, Yoshiki; Nomura, Hiroshi; Yanagida, Hiroaki

2001-04-01

The function and performance of the self-diagnosis composites embedded in mortar/concrete blocks and concrete piles were investigated by bending tests and electrical resistance measurements. Carbon powder (CP) and carbon fiber (CF) were introduced in glass fiber reinforced plastics composites to obtain electrical conductivity. The CP composite has commonly good performances in various bending tests of block and pile specimens, comparing to the CF composite. The electrical resistance of the CP composite increases in a small strain to response remarkably micro-crack formation at about 200 (mu) strain and to detect well to smaller deformations before the crack formation. The CP composite possesses a continuous resistance change up to a large strain level near the final fracture of concrete structures reinforced by steel bars. The cyclic bending tests showed that the micro crack closed at unloading state was able to be evaluated from the measurement of residual resistance. It has been concluded that the self- diagnosis composite is fairly useful for the measurement of damage and fracture in concrete blocks and piles.

Fuel-Mediated Transient Clustering of Colloidal Building Blocks.

PubMed

van Ravensteijn, Bas G P; Hendriksen, Wouter E; Eelkema, Rienk; van Esch, Jan H; Kegel, Willem K

2017-07-26

Fuel-driven assembly operates under the continuous influx of energy and results in superstructures that exist out of equilibrium. Such dissipative processes provide a route toward structures and transient behavior unreachable by conventional equilibrium self-assembly. Although perfected in biological systems like microtubules, this class of assembly is only sparsely used in synthetic or colloidal analogues. Here, we present a novel colloidal system that shows transient clustering driven by a chemical fuel. Addition of fuel causes an increase in hydrophobicity of the building blocks by actively removing surface charges, thereby driving their aggregation. Depletion of fuel causes reappearance of the charged moieties and leads to disassembly of the formed clusters. This reassures that the system returns to its initial, equilibrium state. By taking advantage of the cyclic nature of our system, we show that clustering can be induced several times by simple injection of new fuel. The fuel-mediated assembly of colloidal building blocks presented here opens new avenues to the complex landscape of nonequilibrium colloidal structures, guided by biological design principles.

Prediction of the solubility of cucurbitacin drugs in self-associating poly(ethylene oxide)-b-poly(alpha-benzyl carboxylate epsilon-caprolactone) block copolymer with different tacticities using molecular dynamics simulation.

PubMed

Patel, Sarthak K; Lavasanifar, Afsaneh; Choi, Phillip

2010-01-01

Molecular dynamics (MD) simulation was used to investigate the solubility of two hydrophobic drugs Cucurbitacin B (CuB) and Cucurbitacin I (CuI) in poly(ethylene oxide)-b-poly(alpha-benzyl carboxylate epsilon-caprolactone) (PEO-b-PBCL) block copolymers with different tacticities. In particular, di-block copolymer with three different tacticities viz. PEO-b-iPBCL, PEO-b-sPBCL, and PEO-b-aPBCL were used. The solubility was quantified by calculating the corresponding Flory-Huggins interaction parameters (chi) using random binary mixture models with 10wt% of drug. The tacticity of the di-block copolymer was found to influence significantly the solubility of two drugs in it. In particular, based on MD simulation results, only PEO-b-sPBCL exhibited solubility while the other two did not. Given the fact that the drugs were shown to be soluble in PEO-b-PBCL experimentally, it is predicted that the tacticity of the di-block copolymer synthesized in experiment is syndiotactic. This predication matches well with the dominant ring opening polymerization of cyclic lactones to syndiotactic polymers by stannous octoate as catalyst used to prepare PEO-b-PBCL block copolymers in our previous experiments. The simulation results showed that the solubility of the drugs in PEO-b-sPBCL is attributed to the favorable intra-molecular interaction of the di-block copolymer and favorable intermolecular interaction between the di-block copolymer and the drugs. Radial distribution function analysis provides useful insights into the nature and type of the intermolecular interactions.

Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

PubMed

Meredith, Frances L; Benke, Tim A; Rennie, Katherine J

2012-12-01

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I(h)) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs(+) (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I(h) was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I(h) was -123 mV, which shifted to -114 mV in the presence of cAMP. Activation of I(h) was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at -139 mV). Activation speeded up significantly (τ=136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I(h) could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I(h) was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin-Huxley type ionic conductances, removal of I(h) similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.

Pulsed electromagnetic fields dosing impacts postoperative pain in breast reduction patients.

PubMed

Taylor, Erin M; Hardy, Krista L; Alonso, Amanda; Pilla, Arthur A; Rohde, Christine H

2015-01-01

Pulsed electromagnetic fields (PEMF) reduce postoperative pain and narcotic requirements in breast augmentation, reduction, and reconstruction patients. PEMF enhances both calmodulin-dependent nitric oxide and/or cyclic guanosine monophosphate signaling and phosphodiesterase activity, which blocks cyclic guanosine monophosphate. The clinical effect of these competing responses on PEMF dosing is not known. Two prospective, nonrandomized, active cohorts of breast reduction patients, with 15 min PEMF per 2 h; "Q2 (active)", and 5 min PEMF per 20 min; "5/20 (active)", dosing regimens were added to a previously reported double-blind clinical study wherein 20 min PEMF per 4 h, "Q4 (active)", dosing significantly accelerated postoperative pain reduction compared with Q4 shams. Postoperative visual analog scale pain scores and narcotic use were compared with results from the previous study. Visual analog scale scores at 24 h were 43% and 35% of pain at 1 h in the Q4 (active) and Q2 (active) cohorts, respectively (P < 0.01). Pain at 24 h in the 5/20 (active) cohort was 87% of pain at 1 h, compared with 74% in the Q4 (sham) cohort (P = 0.451). Concomitantly, narcotic usage in the 5/20 (active) and Q4 (sham) cohorts was not different (P = 0.478), and 2-fold higher than the Q4 (active) and Q2 (active) cohorts (P < 0.02). This prospective study shows Q4/Q2, but not 5/20 PEMF dosing, accelerated postoperative pain reduction compared with historical shams. The 5/20 (active) regimen increases NO 4-fold faster than the Q4 (active) regimen, possibly accelerating phosphodiesterase inhibition of cyclic guanosine monophosphate sufficiently to block the PEMF effect. This study helps define the dosing limits of clinically useful PEMF signals. Copyright © 2015 Elsevier Inc. All rights reserved.

Inhibition of muscarinic receptor-induced inositol phospholipid hydrolysis by caffeine, beta-adrenoceptors and protein kinase C in intestinal smooth muscle.

PubMed Central

Prestwich, S A; Bolton, T B

1995-01-01

1. The effects of caffeine, isoprenaline, dibutyryl cyclic AMP, isobutylmethylxanthine (IBMX), 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-oleoyl-2-acetylglycerol (OAG), (protein kinase C (PKC) activators), 2-methoxy verapamil (D600), thapsigargin and ryanodine on muscarinic acetylcholine receptor (AChR)-stimulated inositol phospholipid hydrolysis were studied in smooth muscle fragments from the longitudinal layer of the small intestine of the guinea-pig. 2. Incubation of the fragments with the muscarinic agonist, carbachol (CCh) (100 microM) resulted in rapid increases in the levels of all the inositol phosphate isomers with maximal increases in the [3H]-inositol (1,4,5) trisphosphate ([3H]-Ins(1,4,5)P3) isomer occurring 10 s following incubation. 3. The beta-adrenoceptor agonist, isoprenaline (10 microM) and dibutyryl cyclic AMP (10 microM), a membrane permeant analogue of cyclic AMP both reduced the CCh stimulation, but not the basal levels of [3H]-inositol phosphates. This inhibition by dibutyryl cyclic AMP was enhanced in the presence of the phosphodiesterase inhibitor, IBMX. CCh inhibited the isoprenaline-induced increases in the levels of cyclic AMP and this was via a pertussi toxin (PTX)-sensitive G-protein mechanism. 4. TPA (1 microM) and OAG (100 microM) a 1,2-diacylglycerol (DAG) analogue both reduced the CCh-induced increases in [3H]-inositol phosphates levels but neither affected basal values nor the basal levels of cyclic AMP. 5. D600 (10 microM), which blocks voltage-dependent Ca2+ channels, also reduced the CCh-stimulated levels of [3H]-inositol phosphates suggesting that some of the agonist-induced increases are due to a potentiating effect of Ca2+ entering the cell. 6. Caffeine (0.5-30 mM) significantly inhibited both the basal and CCh-induced increases in all the [3H]-inositol phosphate isomers. Its inhibitory action was not due to increases in cyclic AMP since caffeine had no effect on the levels of cyclic AMP at concentrations up to 30 mM. 7. Incubation with thapsigargin (1 microM) and ryanodine (10 microM) had no effect on either basal or CCh-induced inositol phospholipid hydrolysis or cyclic AMP levels. 8. The results indicate a reciprocal inhibition by beta-adrenoceptors and muscarinic AChRs of their effects on cyclic AMP and inositol phosphate levels respectively. Ca2+ entering the cell (but not the action of ryanodine or thapsigargin) potentiates while caffeine inhibits muscarinic AChR-induced rises in inositol phosphate levels. Diacylglycerols may exert a negative feedback inhibition on inositol phosphate production. PMID:7537591

De novo design of molecular architectures by evolutionary assembly of drug-derived building blocks.

PubMed

Schneider, G; Lee, M L; Stahl, M; Schneider, P

2000-07-01

An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which were obtained by a straightforward fragmentation procedure applied to 36,000 known drugs. Eleven reaction schemes were implemented for both fragmentation and building block assembly. This combination of drug-derived building blocks and a restricted set of reaction schemes proved to be a key for the automatic development of novel, synthetically tractable structures. In a cyclic optimization process, molecular architectures were generated from a parent structure by virtual synthesis, and the best structure of a generation was selected as the parent for the subsequent TOPAS cycle. Similarity measures were used to define 'fitness', based on 2D-structural similarity or topological pharmacophore distance between the template molecule and the variants. The concept of varying library 'diversity' during a design process was consequently implemented by using adaptive variant distributions. The efficiency of the design algorithm was demonstrated for the de novo construction of potential thrombin inhibitors mimicking peptide and non-peptide template structures.

Sildenafil and Phosphodiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumor Cells to Doxorubicin

DTIC Science & Technology

2010-07-01

were blocked for 30 min in PBS with gelatin . The chamber slide basket was then removed before incubation with primary antibody. 53BP1 primary antibody...then incubated with fluorescein-conjugated secondary antibody in PBS with gelatin for 1 h. Following this 1 h of incubation, slides were washed 3 9 5...properties of cancer drugs. J Pharmacol Toxicol Methods 54(3):313–319 28. Essayan DM (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin

Voltammetric behavior of Mammeisin (MA) at a glassy carbon electrode and its interaction with Bovine Serum Albumin (BSA).

PubMed

Leuna, Jules-Blaise Mabou; Sop, Sergeot Kungo; Makota, Suzanne; Njanja, Evangeline; Ebelle, Thiery Christophe; Azebaze, Anatole Guy; Ngameni, Emmanuel; Nassi, Achille

2018-02-01

The electrochemical oxidation of Mammeisin (MA) was studied in a solution containing acetone and 0.1M phosphate buffer +0.1M KCl (pH=5.3) at a glassy carbon electrode (GCE), using cyclic (CV) and square wave voltammetry (SWV). MA showed a quasi-reversible process, which is pH dependent and that involves the exchange of two electrons and two protons. The oxidation product was adsorbed by the electrode surface to form a film that blocks active sites over repetitive cyclic. Moreover, the interaction of MA and bovine serum albumin (BSA) was studied by CV and SWV at different pHs (5.4, 7.2, 9.5). As a result of the affinity binding with BSA, electrochemically inactive complex was formed. In addition, the oxidation potential of MA in the presence of BSA depends on the pH. The diffusion coefficients of both free and bound MA were estimated from the cyclic voltammetry data using the method developed by Randles-Sevich (D f =9.85×10 -5 cm 2 s -1 and D b =1.27×10 -9 cm 2 s -1 ) and the binding constant of MA-BSA complex, K=3.47×10 2 Lmol -1 , was obtained. Copyright © 2017. Published by Elsevier B.V.

Spontaneous and persistent currents in superconductive and mesoscopic structures (Review)

NASA Astrophysics Data System (ADS)

Kulik, I. O.

2004-07-01

We briefly review aspects of superconductive persistent currents in Josephson junctions of the S/I/S, S/O/S and S/N/S types, focusing on the origin of jumps in the current versus phase dependences, and discuss in more detail the persistent and the "spontaneous" currents in Aharonov-Bohm mesoscopic and nanoscopic (macromolecular) structures. A fixed-number-of-electrons mesoscopic or macromolecular conducting ring is shown to be unstable against structural transformation removing spatial symmetry (in particular, azimuthal periodicity) of its electron-lattice Hamiltonian. In the case when the transformation is blocked by strong coupling to an external azimuthally symmetric environment, the system becomes bistable in its electronic configuration at a certain number of electrons. Under such a condition, the persistent current has a nonzero value even at an (almost) zero applied Aharonov-Bohm flux and results in very high magnetic susceptibility dM/dH at small nonzero fields, followed by an oscillatory dependence at larger fields. We tentatively assume that previously observed oscillatory magnetization in cyclic metallo-organic molecules by Gatteschi et al. can be attributed to persistent currents. If this proves correct, it may present an opportunity for (and, more generally, macromolecular cyclic structures may suggest the possibility of) engineering quantum computational tools based on the Aharonov-Bohm effect in ballistic nanostructures and macromolecular cyclic aggregates.

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

PubMed

Shnitko, Tatiana A; Mace, Kyla D; Sullivan, Kaitlin M; Martin, W Kyle; Andersen, Elizabeth H; Williams Avram, Sarah K; Johns, Josephine M; Robinson, Donita L

2017-12-01

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

A systematic coarse-graining strategy for semi-dilute copolymer solutions: from monomers to micelles.

PubMed

Capone, Barbara; Coluzza, Ivan; Hansen, Jean-Pierre

2011-05-18

A systematic coarse-graining procedure is proposed for the description and simulation of AB diblock copolymers in selective solvents. Each block is represented by a small number, n(A) or n(B), of effective segments or blobs, containing a large number of microscopic monomers. n(A) and n(B) are unequivocally determined by imposing that blobs do not, on average, overlap, even if complete copolymer coils interpenetrate (semi-dilute regime). Ultra-soft effective interactions between blobs are determined by a rigorous inversion procedure in the low concentration limit. The methodology is applied to an athermal copolymer model where A blocks are ideal (theta solvent), B blocks self-avoiding (good solvent), while A and B blocks are mutually avoiding. The model leads to aggregation into polydisperse spherical micelles beyond a critical micellar concentration determined by Monte Carlo simulations for several size ratios f of the two blocks. The simulations also provide accurate estimates of the osmotic pressure and of the free energy of the copolymer solutions over a wide range of concentrations. The mean micellar aggregation numbers are found to be significantly lower than those predicted by an earlier, minimal two-blob representation (Capone et al 2009 J. Phys. Chem. B 113 3629).

Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton

PubMed Central

Parker, William H.; Rhea, Elizabeth Meredith; Qu, Zhi-Chao; Hecker, Morgan R.

2016-01-01

Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ∼30%. In human umbilical vein endothelial cells, this occurred at what are likely physiologic intracellular ascorbate concentrations. In so doing, ascorbate decreased measures of oxidative stress and also flattened the cells to increase cell-to-cell contact. Inhibition of downstream cyclic AMP-dependent proteins via protein kinase A did not prevent ascorbate from tightening the endothelial permeability barrier, whereas inhibition of Epac1 did block the ascorbate effect. Although Epac1 was required, its mediator Rap1 was not activated. Furthermore, ascorbate acutely stabilized microtubules during depolymerization induced by colchicine and nocodazole. Over several days in culture, ascorbate also increased the amount of stable acetylated α-tubulin. Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to α-tubulin. These results suggest that physiologic ascorbate concentrations tighten the endothelial permeability barrier in unstimulated cells by stabilizing microtubules in a manner downstream of cyclic AMP that might be due both to increasing nitric oxide availability and to scavenging of reactive oxygen or nitrogen species. PMID:27605450

Highly efficient peptide formation from N-acetylaminoacyl-AMP anhydride and free amino acid

NASA Technical Reports Server (NTRS)

Mullins, D. W., Jr.; Lacey, J. C., Jr.

1983-01-01

The kinetics of formation of the N-blocked dipeptide, N-acetylglycylglycine, from N-acetylglycyl adenylate anhydride and glycine in aqueous solution at 25 C, and at various PH's are reported. The reaction is of interest in that over a physiologically relevant pH range (6-8), peptide synthesis proceeds more rapidly than hydrolysis, even at those pH's at which this compound becomes increasingly susceptible to base-catalyzed hydrolysis. Under similar conditions, the corresponding unblocked aminoacyl adenylate anhydrides are considerably more unstable, and undergo appreciable hydrlysis in the presence of free amino acid. Because N-blocked aminoacyl adenylate anhydrides serve as model compounds of peptidyl adenylate anhydrides, these results suggest that primitive amino acid polymerization systems may have operated by cyclic reactivation of the peptidyl carboxyl group, rather than that of the incoming amino acid.

Direct and Dry Deposited Single-Walled Carbon Nanotube Films Doped with MoO(x) as Electron-Blocking Transparent Electrodes for Flexible Organic Solar Cells.

PubMed

Jeon, Il; Cui, Kehang; Chiba, Takaaki; Anisimov, Anton; Nasibulin, Albert G; Kauppinen, Esko I; Maruyama, Shigeo; Matsuo, Yutaka

2015-07-01

Organic solar cells have been regarded as a promising electrical energy source. Transparent and conductive carbon nanotube film offers an alternative to commonly used ITO in photovoltaics with superior flexibility. This communication reports carbon nanotube-based indium-free organic solar cells and their flexible application. Direct and dry deposited carbon nanotube film doped with MoO(x) functions as an electron-blocking transparent electrode, and its performance is enhanced further by overcoating with PSS. The single-walled carbon nanotube organic solar cell in this work shows a power conversion efficiency of 6.04%. This value is 83% of the leading ITO-based device performance (7.48%). Flexible application shows 3.91% efficiency and is capable of withstanding a severe cyclic flex test.

Mechanical Behavior and Microcrack Development in Nominally Dry Synthetic Salt-rock During Cyclic Loading

NASA Astrophysics Data System (ADS)

Ding, J.; Chester, F. M.; Chester, J. S.; Zhu, C.; Shen, X.; Arson, C. F.

2016-12-01

Synthetic salt-rock is produced through uniaxial consolidation of sieved granular salt (0.3-0.355 mm grain diam.) at 75-107 MPa pressure and 100-200 0 C for 15 min duration, to produce low porosity (3%-6%) aggregates. Based on microstructural observations, consolidation mechanisms are grain rearrangement, intragranular plastic flow, and minor microfracture and recrystallization. Following consolidation, the salt-rock is deformed by cyclic, triaxial loading at room temperature and 4 MPa confining pressure to investigate microfracture development, closure and healing effects on elastic properties and flow strength. Load cycles are performed within the elastic regime, up to yielding, and during steady ductile flow. The mechanical properties are determined using an internal load cell and strain gages bonded to the samples. Elastic properties vary systematically during deformation reflecting cracking and pore and grain shape changes. Between triaxial load cycles, samples are held at isostatic loads for durations up to one day to determine healing rates and strength recovery; a change in mechanical behavior is observed when significant healing is induced. The microstructures of all samples are characterized before and after cyclic loading using optical microscopy. The consolidation and cyclic triaxial tests, and optical microscopy investigations, are conducted in a controlled low-humidity environment to ensure nominally dry conditions. The microstructures of samples from different stages of cyclic triaxial deformation indicate that intracrystalline plasticity, accompanied by minor recovery by recrystallization, is dominant; but, grain-boundary crack opening also becomes significant. Grain-boundary microcracks have preferred orientations that are sub-parallel to the load axis. The stress-strain behavior correlates with microcrack fabrics and densities during cyclic loading. These experiments are used to both inform and test continuum damage mechanics models of salt-rock deformation in the semibrittle domain, as well as to help design and optimize salt-rock storage facilities.

Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[99mTc(CO)3]+: effect of cyclization on tumor-seeking properties.

PubMed

Raposinho, Paula D; Xavier, Catarina; Correia, João D G; Falcão, Soraia; Gomes, Paula; Santos, Isabel

2008-03-01

Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the 99mTc-labeled cyclic peptide betaAla-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 with that of the linear analog betaAla-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of betaAla, and the resulting pz-peptide conjugates were reacted with the fac-[99mTc(CO)3]+ moiety. The 99mTc(CO)3-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic 99mTc(CO)3-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear 99mTc(CO)3-pz-peptide presented lower values for both cellular internalization and tumor uptake. Receptor blocking studies with the potent (Nle4,DPhe7)-alphaMSH agonist demonstrated the specificity of the radioconjugates to MC1R (74.8 and 44.5% reduction of tumor uptake at 4 h after injection for cyclic and linear radioconjugates, respectively).

Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.

PubMed

Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

2003-04-07

A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-NH(2) and Penta-c[Asp-5-ClAtc-DPhe-Cit-Trp-Lys]-NH(2) which are potent hMC4R agonists and are either inactive or weak partial agonists (not tested for their antagonist activities) in hMC1R, hMC3R and hMC5R agonist assays.

Role of structural H 2O in TiO 2 nanotubes in enhancing Pt/C direct ethanol fuel cell anode electro-catalysts

NASA Astrophysics Data System (ADS)

Song, Huanqiao; Qiu, Xinping; Guo, Daojun; Li, Fushen

TiO 2 nanotubes (TNTs) with different structural water were obtained by heat treatment under different temperatures. The role of the structural water in TNTs co-catalyzing ethanol oxidation with Pt/C catalyst was studied systematically. Electrochemical studies using cyclic voltammetry and CO stripping voltammetry indicated that more structural water in TNTs was favorable for improving the tolerance of Pt/C to poisoning species; while chronoamperometry curves and repeated cyclic voltammograms showed that slightly less structural water in TNTs actually led to higher catalytic activity and better stability of Pt/C catalysts for ethanol oxidation. This strange result has been analyzed and was ascribed to the appropriate balance of bi-functional mechanism and ethanol transfer in the catalyst layer with less structural water.

Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: A meta-analysis.

PubMed

Yan, Zeng; Chen, Zong; Ma, Chuangen

2017-07-01

Postoperative pain control after total shoulder arthroplasty (TSA) can be challenging. Liposomal bupivacaine and interscalene nerve block are 2 common pain control protocol for TSA patients. However, whether liposomal bupivacaine was superior than interscalene nerve block was unknown. This meta-analysis aimed to illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain control in patients undergoing TSA. In May 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, and 2 weeks, total morphine consumption at 24 hours, and the length of hospital stay. Software of Stata 12.0 was used for pooling the final outcomes. Five clinical studies with 573 patients (liposomal bupivacaine group = 239, interscalene nerve block group = 334) were ultimately included in the meta-analysis. There was no significant difference between the VAS at 4 hours, 8 hours, and 2 weeks between liposomal bupivacaine group and interscalene nerve block group (P > .05). Compared with interscalene nerve block group, liposomal bupivacaine was associated with a reduction of VAS score at 12 hours, 24 hours by appropriately 3.31 points and 6.42 points respectively on a 100-point VAS. Furthermore, liposomal bupivacaine was associated with a significantly reduction of the length of hospital stay by appropriately by 0.16 days compared with interscalene nerve block group. Current meta-analysis indicates that compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and the length of hospital stay. However, studies with more patients and better-designed methods are needed to establish the optimal regimen and the safety of liposomal bupivacaine in TSA patients.

Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty

PubMed Central

Yan, Zeng; Chen, Zong; Ma, Chuangen

2017-01-01

Abstract Background: Postoperative pain control after total shoulder arthroplasty (TSA) can be challenging. Liposomal bupivacaine and interscalene nerve block are 2 common pain control protocol for TSA patients. However, whether liposomal bupivacaine was superior than interscalene nerve block was unknown. This meta-analysis aimed to illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain control in patients undergoing TSA. Methods: In May 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, and 2 weeks, total morphine consumption at 24 hours, and the length of hospital stay. Software of Stata 12.0 was used for pooling the final outcomes. Results: Five clinical studies with 573 patients (liposomal bupivacaine group = 239, interscalene nerve block group = 334) were ultimately included in the meta-analysis. There was no significant difference between the VAS at 4 hours, 8 hours, and 2 weeks between liposomal bupivacaine group and interscalene nerve block group (P > .05). Compared with interscalene nerve block group, liposomal bupivacaine was associated with a reduction of VAS score at 12 hours, 24 hours by appropriately 3.31 points and 6.42 points respectively on a 100-point VAS. Furthermore, liposomal bupivacaine was associated with a significantly reduction of the length of hospital stay by appropriately by 0.16 days compared with interscalene nerve block group. Conclusion: Current meta-analysis indicates that compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and the length of hospital stay. However, studies with more patients and better-designed methods are needed to establish the optimal regimen and the safety of liposomal bupivacaine in TSA patients. PMID:28682872

Data-Driven Correlation Analysis Between Observed 3D Fatigue-Crack Path and Computed Fields from High-Fidelity, Crystal-Plasticity, Finite-Element Simulations

NASA Astrophysics Data System (ADS)

Pierson, Kyle D.; Hochhalter, Jacob D.; Spear, Ashley D.

2018-05-01

Systematic correlation analysis was performed between simulated micromechanical fields in an uncracked polycrystal and the known path of an eventual fatigue-crack surface based on experimental observation. Concurrent multiscale finite-element simulation of cyclic loading was performed using a high-fidelity representation of grain structure obtained from near-field high-energy x-ray diffraction microscopy measurements. An algorithm was developed to parameterize and systematically correlate the three-dimensional (3D) micromechanical fields from simulation with the 3D fatigue-failure surface from experiment. For comparison, correlation coefficients were also computed between the micromechanical fields and hypothetical, alternative surfaces. The correlation of the fields with hypothetical surfaces was found to be consistently weaker than that with the known crack surface, suggesting that the micromechanical fields of the cyclically loaded, uncracked microstructure might provide some degree of predictiveness for microstructurally small fatigue-crack paths, although the extent of such predictiveness remains to be tested. In general, gradients of the field variables exhibit stronger correlations with crack path than the field variables themselves. Results from the data-driven approach implemented here can be leveraged in future model development for prediction of fatigue-failure surfaces (for example, to facilitate univariate feature selection required by convolution-based models).

[Diagnostic strategies for endometriosis: CNGOF-HAS Endometriosis Guidelines].

PubMed

Bourdel, N; Chauvet, P; Canis, M

2018-03-01

In this chapter we have examined the possibilities of screening endometriosis, both in the general population as well as in the target population. We then proposed decision trees, for primary and secondary care. Currently, there is not enough data in the literature to develop or organize a screening test for endometriosis. Screening for endometriosis is not recommended in the general population (level A). There is also no evidence to support systematic screening in a population with genetic risk factors (endometriosis in a relative), or with other clinical risk factors (increased menstrual volume, short cycles, early menarche) (level A). However, it is possible to propose a decision tree for the management of chronic pelvic pain symptoms (dysmenorrhea, dyspareunia, non-menstrual pelvic pain). The search for symptoms suggestive of endometriosis (intense dysmenorrhea [visual analogue scale >7/10, frequent abstention, resistance to level 1 analgesics], infertility) should be systematic. The search for localizing symptoms of deep endometriosis (deep dyspareunia, cyclic defecation pain, cyclic urinary signs) enables to orient the patient to second line evaluation. We propose a decision tree for second and third line evaluations, according to the suspicion and/or the discovery of deep lesions with specific locations, or the suspicion of superficial lesions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Sensitivity of polycrystal plasticity to slip system kinematic hardening laws for Al 7075-T6

DOE PAGES

Hennessey, Conor; Castelluccio, Gustavo M.; McDowell, David L.

2017-02-01

The prediction of formation and early growth of microstructurally small fatigue cracks requires use of constitutive models that accurately estimate local states of stress, strain, and cyclic plastic strain. However, few research efforts have attempted to systematically consider the sensitivity of overall cyclic stress-strain hysteresis and higher order mean stress relaxation and plastic strain ratcheting responses introduced by the slip system back-stress formulation in crystal plasticity, even for face centered cubic (FCC) crystal systems. This paper explores the performance of two slip system level kinematic hardening models using a finite element crystal plasticity implementation as a User Material Subroutine (UMAT)more » within ABAQUS, with fully implicit numerical integration. The two kinematic hardening formulations aim to reproduce the cyclic deformation of polycrystalline Al 7075-T6 in terms of both macroscopic cyclic stress-strain hysteresis loop shape, as well as ratcheting and mean stress relaxation under strain- or stress-controlled loading with mean strain or stress, respectively. The first formulation is an Armstrong-Frederick type hardening-dynamic recovery law for evolution of the back stress. This approach is capable of reproducing observed deformation under completely reversed uniaxial loading conditions, but overpredicts the rate of cyclic ratcheting and associated mean stress relaxation. The second formulation corresponds to a multiple back stress Ohno-Wang type hardening law with nonlinear dynamic recovery. The adoption of this back stress evolution law greatly improves the capability to model experimental results for polycrystalline specimens subjected to cycling with mean stress or strain. As a result, the relation of such nonlinear dynamic recovery effects are related to slip system interactions with dislocation substructures.« less

Sensitivity of polycrystal plasticity to slip system kinematic hardening laws for Al 7075-T6

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

Hennessey, Conor; Castelluccio, Gustavo M.; McDowell, David L.

The prediction of formation and early growth of microstructurally small fatigue cracks requires use of constitutive models that accurately estimate local states of stress, strain, and cyclic plastic strain. However, few research efforts have attempted to systematically consider the sensitivity of overall cyclic stress-strain hysteresis and higher order mean stress relaxation and plastic strain ratcheting responses introduced by the slip system back-stress formulation in crystal plasticity, even for face centered cubic (FCC) crystal systems. This paper explores the performance of two slip system level kinematic hardening models using a finite element crystal plasticity implementation as a User Material Subroutine (UMAT)more » within ABAQUS, with fully implicit numerical integration. The two kinematic hardening formulations aim to reproduce the cyclic deformation of polycrystalline Al 7075-T6 in terms of both macroscopic cyclic stress-strain hysteresis loop shape, as well as ratcheting and mean stress relaxation under strain- or stress-controlled loading with mean strain or stress, respectively. The first formulation is an Armstrong-Frederick type hardening-dynamic recovery law for evolution of the back stress. This approach is capable of reproducing observed deformation under completely reversed uniaxial loading conditions, but overpredicts the rate of cyclic ratcheting and associated mean stress relaxation. The second formulation corresponds to a multiple back stress Ohno-Wang type hardening law with nonlinear dynamic recovery. The adoption of this back stress evolution law greatly improves the capability to model experimental results for polycrystalline specimens subjected to cycling with mean stress or strain. As a result, the relation of such nonlinear dynamic recovery effects are related to slip system interactions with dislocation substructures.« less

Interventions for postoperative pain in children: An overview of systematic reviews.

PubMed

Boric, Krste; Dosenovic, Svjetlana; Jelicic Kadic, Antonia; Batinic, Marijan; Cavar, Marija; Urlic, Marjan; Markovina, Nikolina; Puljak, Livia

2017-09-01

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti-inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non-Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children. © 2017 John Wiley & Sons Ltd.

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns.

PubMed

Viswanathan, Jayalakshmi; Rémy, Florence; Bacon-Macé, Nadège; Thorpe, Simon J

2016-01-01

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10- and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may strongly depend on individual attention and auditory discrimination abilities.

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns

PubMed Central

Viswanathan, Jayalakshmi; Rémy, Florence; Bacon-Macé, Nadège; Thorpe, Simon J.

2016-01-01

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10− and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may strongly depend on individual attention and auditory discrimination abilities. PMID:27932941

Does Abutment Collar Length Affect Abutment Screw Loosening After Cyclic Loading?

PubMed

Siadat, Hakimeh; Pirmoazen, Salma; Beyabanaki, Elaheh; Alikhasi, Marzieh

2015-07-01

A significant vertical space that is corrected with vertical ridge augmentation may necessitate selection of longer abutments, which would lead to an increased vertical cantilever. This study investigated the influence of different abutment collar heights on single-unit dental implant screw-loosening after cyclic loading. Fifteen implant-abutment assemblies each consisted of an internal hexagonal implant were randomly assigned to 3 groups: Group1, consisting of 5 abutments with 1.5 mm gingival height (GH); Group2, 5 abutments with 3.5 mm GH; and Group3, 5 abutments with 5.5 mm GH. Each specimen was mounted in transparent auto-polymerizing acrylic resin block, and the abutment screw was tightened to 35 Ncm with an electric torque wrench. After 5 minutes, initial torque loss (ITL) was recorded for all specimens. Metal crowns were fabricated with 45° occlusal surface and were placed on the abutments. A cyclic load of 75 N and frequency of 1 Hz were applied perpendicular to the long axis of each specimen. After 500 000 cycles, secondary torque loss (STL) was recorded. One-way ANOVA analysis was used to evaluate the effects of abutment collar height before and after cyclic loading. One-way ANOVA showed that ITL among the groups was not significantly different (P = .52), while STL was significantly different among the groups (P = .008). Post-hoc Tukey HSD tests showed that STL values were significantly different between the abutments with 1.5 mm GH (Group1) and with 5.5 mm GH (Group3) (P = .007). A paired comparison t-test showed that cyclic loading significantly influenced the STL in comparison with the ITL in each group. Within the limitations of this study, it can be concluded that increase in height of the abutment collar could adversely affect the torque loss of the abutment screw.

A Deep Machine Learning Method for Classifying Cyclic Time Series of Biological Signals Using Time-Growing Neural Network.

PubMed

Gharehbaghi, Arash; Linden, Maria

2017-10-12

This paper presents a novel method for learning the cyclic contents of stochastic time series: the deep time-growing neural network (DTGNN). The DTGNN combines supervised and unsupervised methods in different levels of learning for an enhanced performance. It is employed by a multiscale learning structure to classify cyclic time series (CTS), in which the dynamic contents of the time series are preserved in an efficient manner. This paper suggests a systematic procedure for finding the design parameter of the classification method for a one-versus-multiple class application. A novel validation method is also suggested for evaluating the structural risk, both in a quantitative and a qualitative manner. The effect of the DTGNN on the performance of the classifier is statistically validated through the repeated random subsampling using different sets of CTS, from different medical applications. The validation involves four medical databases, comprised of 108 recordings of the electroencephalogram signal, 90 recordings of the electromyogram signal, 130 recordings of the heart sound signal, and 50 recordings of the respiratory sound signal. Results of the statistical validations show that the DTGNN significantly improves the performance of the classification and also exhibits an optimal structural risk.

A comparative study of Si-containing electrolyte additives for lithium ion battery: Which one is better and why is it better

NASA Astrophysics Data System (ADS)

Wang, Kang; Xing, Lidan; Zhu, Yunmin; Zheng, Xiongwen; Cai, Dandan; Li, Weishan

2017-02-01

Influence of two Si-containing electrolyte additives, tris(trimethylsilyl)borate (TMSB) and tris(trimethylsilyl)phosphate (TMSP), on the cyclic stability of high voltage LiNi0.5Mn1.5O4 electrode has been systematically studied in this work. The capacity retention of LiNi0.5Mn1.5O4 cycling in STD (1M LiPF6/EC: EMC = 3:7), TMSB- and TMSP-containing electrolytes is 23%, 85% and 71% after 600 cycles at 1C rate, respectively, revealing that the ability of TMSB on improving the cyclic performance of LiNi0.5Mn1.5O4 is superior to that of TMSP. Experimental and theoretical characterizations show that the preferential reaction of both TMSB and TMSP generates thin and uniform film on LiNi0.5Mn1.5O4 surface, which effectively suppress the continuous oxidation reaction of electrolyte. While the film generated from TMSB, which contains B and Si-rich compounds, shows better ability on restraining the growth of interfacial resistance during cycling, resulting in better cyclic stability of LiNi0.5Mn1.5O4 than that of TMSP.

Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1.

PubMed

Durek, Thomas; Cromm, Philipp M; White, Andrew M; Schroeder, Christina I; Kaas, Quentin; Weidmann, Joachim; Ahmad Fuaad, Abdullah; Cheneval, Olivier; Harvey, Peta J; Daly, Norelle L; Zhou, Yang; Dellsén, Anita; Österlund, Torben; Larsson, Niklas; Knerr, Laurent; Bauer, Udo; Kessler, Horst; Cai, Minying; Hruby, Victor J; Plowright, Alleyn T; Craik, David J

2018-04-26

Ultrastable cyclic peptide frameworks offer great potential for drug design due to their improved bioavailability compared to their linear analogues. Using the sunflower trypsin inhibitor-1 (SFTI-1) peptide scaffold in combination with systematic N-methylation of the grafted pharmacophore led to the identification of novel subtype selective melanocortin receptor (MCR) agonists. Multiple bicyclic peptides were synthesized and tested toward their activity at MC1R and MC3-5R. Double N-methylated compound 18 showed a p K i of 8.73 ± 0.08 ( K i = 1.92 ± 0.34 nM) and a pEC 50 of 9.13 ± 0.04 (EC 50 = 0.75 ± 0.08 nM) at the human MC1R and was over 100 times more selective for MC1R. Nuclear magnetic resonance structural analysis of 18 emphasized the role of peptide bond N-methylation in shaping the conformation of the grafted pharmacophore. More broadly, this study highlights the potential of cyclic peptide scaffolds for epitope grafting in combination with N-methylation to introduce receptor subtype selectivity in the context of peptide-based drug discovery.

Fatigue behavior of highly porous titanium produced by powder metallurgy with temporary space holders.

PubMed

Özbilen, Sedat; Liebert, Daniela; Beck, Tilmann; Bram, Martin

2016-03-01

Porous titanium cylinders were produced with a constant amount of temporary space holder (70 vol.%). Different interstitial contents were achieved by varying the starting powders (HDH vs. gas atomized) and manufacturing method (cold compaction without organic binders vs. warm compaction of MIM feedstocks). Interstitial contents (O, C, and N) as a function of manufacturing were measured by chemical analysis. Samples contained 0.34-0.58 wt.% oxygen, which was found to have the greatest effect on mechanical properties. Quasi-static mechanical tests under compression at low strain rate were used for reference and to define parameters for cyclic compression tests. Not unexpectedly, increased oxygen content increased the yield strength of the porous titanium. Cyclic compression fatigue tests were conducted using sinusoidal loading in a servo-hydraulic testing machine. Increased oxygen content was concomitant with embrittlement of the titanium matrix, resulting in significant reduction of compression cycles before failure. For samples with 0.34 wt.% oxygen, R, σ(min) and σ(max) were varied systematically to estimate the fatigue limit (~4 million cycles). Microstructural changes induced by cyclic loading were then characterized by optical microscopy, SEM and EBSD. Copyright © 2015 Elsevier B.V. All rights reserved.

Micropatterned ferrocenyl monolayers covalently bound to hydrogen-terminated silicon surfaces: effects of pattern size on the cyclic voltammetry and capacitance characteristics.

PubMed

Fabre, Bruno; Pujari, Sidharam P; Scheres, Luc; Zuilhof, Han

2014-06-24

The effect of the size of patterns of micropatterned ferrocene (Fc)-functionalized, oxide-free n-type Si(111) surfaces was systematically investigated by electrochemical methods. Microcontact printing with amine-functionalized Fc derivatives was performed on a homogeneous acid fluoride-terminated alkenyl monolayer covalently bound to n-type H-terminated Si surfaces to give Fc patterns of different sizes (5 × 5, 10 × 10, and 20 × 20 μm(2)), followed by backfilling with n-butylamine. These Fc-micropatterned surfaces were characterized by static water contact angle measurements, ellipsometry, X-ray photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy (IRRAS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The charge-transfer process between the Fc-micropatterned and underlying Si interface was subsequently studied by cyclic voltammetry and capacitance. By electrochemical studies, it is evident that the smallest electroactive ferrocenyl patterns (i.e., 5 × 5 μm(2) squares) show ideal surface electrochemistry, which is characterized by narrow, perfectly symmetric, and intense cyclic voltammetry and capacitance peaks. In this respect, strategies are briefly discussed to further improve the development of photoswitchable charge storage microcells using the produced redox-active monolayers.

Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis.

PubMed

Collins, Angela C; Cai, Haocheng; Li, Tuo; Franco, Luis H; Li, Xiao-Dong; Nair, Vidhya R; Scharn, Caitlyn R; Stamm, Chelsea E; Levine, Beth; Chen, Zhijian J; Shiloh, Michael U

2015-06-10

Activation of the DNA-dependent cytosolic surveillance pathway in response to Mycobacterium tuberculosis infection stimulates ubiquitin-dependent autophagy and inflammatory cytokine production, and plays an important role in host defense against M. tuberculosis. However, the identity of the host sensor for M. tuberculosis DNA is unknown. Here we show that M. tuberculosis activated cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor protein stimulator of interferon genes (STING) to induce type I interferons and other cytokines. cGAS localized with M. tuberculosis in mouse and human cells and in human tuberculosis lesions. Knockdown or knockout of cGAS in human or mouse macrophages blocked cytokine production and induction of autophagy. Mice deficient in cGAS were more susceptible to lethality caused by infection with M. tuberculosis. These results demonstrate that cGAS is a vital innate immune sensor of M. tuberculosis infection. Copyright © 2015 Elsevier Inc. All rights reserved.

The cyclic fatigue behavior of adhesive joints

NASA Astrophysics Data System (ADS)

Kinloch, A. J.; Toh, T.

1995-06-01

In the last six months we have: (1) Concentrated our efforts on the fatigue failure of carbon-fiber PEEK/AFl63 lap joints, and in particular we have started to predict the life time of single-lap joints under cyclic fatigue loading. The analysis is based on data obtained from double cantilever beam (DCB) fracture mechanics tests; (2) Further, we have been successful in measuring the rate of crack growth in lap joints during fatigue fracture using ultrasonic scanning; (3) Preliminary test data on the static fracture of glass-fiber reinforced poly(phenylene sulphide) (PPS)/AF163 joints have also been studied; and (4) A comparison has been made in computing the critical strain energy release rate G(sub c) for the glass-fiber PPS/AF163 joints based on the compliance method, beam theory and corrected beam theory. The last method accounts for large non-linear deflections and the associated crack root rotations along with the necessary corrections for the increase in stiffness introduced by the presence of end blocks.

Molecular interaction study of commercial cyclic peptides and MERS-COV papain-like protease as novel drug candidate for MERS-COV

NASA Astrophysics Data System (ADS)

Nasution, M. A. F.; Azzuhdi, M. G.; Tambunan, U. S. F.

2017-07-01

Middle-east respiratory syndrome coronavirus (MERS-CoV) has become the current outbreak, MERS-CoV infection results in illness at the respiratory system, digestive, and even lead to death with an average mortality caused by MERS-CoV infection reaches 50 %. Until now, there is not any effective vaccine or drug to ward off MERS-CoV infection. Papain-like protease (PLpro) is responsible for cleavage of a nonstructural protein that is essential for viral maturation. Inhibition of PLpro with a ligand will block the cleavage process of nonstructural protein, thus reduce the infection of MERS-CoV. Through of bioinformatics study with molecular docking and binding interaction analysis of commercial cyclic peptides, aldosterone secretion inhibiting factor (1-35) (bovine) was obtained as an inhibitor for PLpro. Thus, aldosterone secretion inhibiting factor (1-35) (bovine) has a potential as a novel candidate drug for treating MERS-CoV.

Evolution of Akaganeite in Rust Layers Formed on Steel Submitted to Wet/Dry Cyclic Tests

PubMed Central

Ye, Wei; Song, Xiaoping; Ma, Yuantai; Li, Ying

2017-01-01

The evolution of akaganeite in rust layers strongly impacts the atmospheric corrosion behavior of steel during long-term exposure; however, the factors affecting the evolution of akaganeite and its mechanism of formation are vague. In this work, wet-dry cyclic corrosion tests were conducted to simulate long-term exposure. Quantitative X-ray diffraction analysis was employed to analyze variations in the relative amounts of akaganeite; scanning electron microscopy and electron probe microanalysis were used to study the migration of relevant elements in the rust layer, which could help elucidate the mechanism of akaganeite evolution. The results indicate that the fraction of akaganeite tends to decrease as the corrosion process proceeded, which is a result of the decrease in the amount of soluble chloride available and the ability of the thick rust layer to block the migration of relevant ions. This work also explores the location of akaganeite formation within the rust layer. PMID:29099061

Hydroperoxide Traces in Common Cyclic Ethers as Initiators for Controlled RAFT Polymerizations.

PubMed

Eggers, Steffen; Abetz, Volker

2018-04-01

Herein, a reversible addition-fragmentation chain transfer (RAFT) polymerization is introduced for reactive monomers like N-acryloylpyrrolidine or N,N-dimethylacrylamide working without a conventional radical initiator. As a very straightforward proof of principle, the method takes advantage of the usually inconvenient radical-generating hydroperoxide contaminations in cyclic ethers like tetrahydrofuran or 1,4-dioxane, which are very common solvents in polymer sciences. The polymerizations are surprisingly well controlled and the polymers can be extended with a second block, indicating their high livingness. "Solvent-initiated" RAFT polymerizations hence prove to be a feasible access to tailored materials with minimal experimental effort and standard laboratory equipment, only requiring the following ingredients: hydroperoxide-contaminated solvent, monomer, and RAFT agent. In other respects, however, the potential coinitiating ability of the used solvent is to be considered when investigating the kinetics of RAFT polymerizations or aiming for the synthesis of high-livingness polymers, e.g., multiblock copolymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner

PubMed Central

Pai, Vaibhav P.; Willocq, Valerie; Pitcairn, Emily J.; Lemire, Joan M.; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A.

2017-01-01

ABSTRACT Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels (Ih currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal, Lefty, and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. PMID:28818840

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

PubMed

Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

2017-10-15

Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

Comparison of analgesic interventions for traumatic rib fractures: a systematic review and meta-analysis.

PubMed

Peek, Jesse; Smeeing, Diederik P J; Hietbrink, Falco; Houwert, Roderick M; Marsman, Marije; de Jong, Mirjam B

2018-02-06

Many studies report on outcomes of analgesic therapy for (suspected) traumatic rib fractures. However, the literature is inconclusive and diverse regarding the management of pain and its effect on pain relief and associated complications. This systematic review and meta-analysis summarizes and compares reduction of pain for the different treatment modalities and as secondary outcome mortality during hospitalization, length of mechanical ventilation, length of hospital stay, length of intensive care unit stay (ICU) and complications such as respiratory, cardiovascular, and/or analgesia-related complications, for four different types of analgesic therapy: epidural analgesia, intravenous analgesia, paravertebral blocks and intercostal blocks. PubMed, EMBASE and CENTRAL databases were searched to identify comparative studies investigating epidural, intravenous, paravertebral and intercostal interventions for traumatic rib fractures, without restriction for study type. The search strategy included keywords and MeSH or Emtree terms relating blunt chest trauma (including rib fractures), analgesic interventions, pain management and complications. A total of 19 papers met our inclusion criteria and were finally included in this systematic review. Significant differences were found in favor of epidural analgesia for the reduction of pain. No significant differences were observed between epidural analgesia, intravenous analgesia, paravertebral blocks and intercostal blocks, for the secondary outcomes. Results of this study show that epidural analgesia provides better pain relief than the other modalities. No differences were observed for secondary endpoints like length of ICU stay, length of mechanical ventilation or pulmonary complications. However, the quality of the available evidence is low, and therefore, preclude strong recommendations.

A Dual-Mode Bioreactor System for Tissue Engineered Vascular Models.

PubMed

Bono, N; Meghezi, S; Soncini, M; Piola, M; Mantovani, D; Fiore, Gianfranco Beniamino

2017-06-01

In the past decades, vascular tissue engineering has made great strides towards bringing engineered vascular tissues to the clinics and, in parallel, obtaining in-lab tools for basic research. Herein, we propose the design of a novel dual-mode bioreactor, useful for the fabrication (construct mode) and in vitro stimulation (culture mode) of collagen-based tubular constructs. Collagen-based gels laden with smooth muscle cells (SMCs) were molded directly within the bioreactor culture chamber. Based on a systematic characterization of the bioreactor culture mode, constructs were subjected to 10% cyclic strain at 0.5 Hz for 5 days. The effects of cyclic stimulation on matrix re-arrangement and biomechanical/viscoelastic properties were examined and compared vs. statically cultured constructs. A thorough comparison of cell response in terms of cell localization and expression of contractile phenotypic markers was carried out as well. We found that cyclic stimulation promoted cell-driven collagen matrix bi-axial compaction, enhancing the mechanical strength of strained samples with respect to static controls. Moreover, cyclic strain positively affected SMC behavior: cells maintained their contractile phenotype and spread uniformly throughout the whole wall thickness. Conversely, static culture induced a noticeable polarization of cell distribution to the outer rim of the constructs and a sharp reduction in total cell density. Overall, coupling the use of a novel dual-mode bioreactor with engineered collagen-gel-based tubular constructs demonstrated to be an interesting technology to investigate the modulation of cell and tissue behavior under controlled mechanically conditioned in vitro maturation.

Semiclassical Virasoro blocks from AdS 3 gravity

DOE PAGES

Hijano, Eliot; Kraus, Per; Perlmutter, Eric; ...

2015-12-14

We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in [1], evaluated in locally AdS 3 geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block — in which two external operators become parametrically heavy — as a certain scattering process involving higher spin gauge fields in AdS 3; thismore » approach highlights the chiral nature of Virasoro blocks. Finally, these techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.« less

Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

NASA Technical Reports Server (NTRS)

Lin, Shu; Rhee, Dojun

1996-01-01

This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

Immunosuppressants: tools to investigate the physiological role of cytokines.

PubMed

Quesniaux, V F

1993-11-01

The cyclic peptide Cyclosporine A (CsA) is best known as the immunosuppressive drug which has revolutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL-2 at the level of transcription factor modulation. The structurally unrelated immunosuppressant FK 506 acts on the same pathway and blocks cytokine gene expression. In contrast, rapamycin, a structural analogue of FK 506, interferes with the immune response at a different level, by blocking the response induced by cytokines such as IL-2. Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the sole IL-2-mediated responses involved in the immune response. For instance, CsA and FK 506 inhibit the transcription of IL-3, IL-4, IFN gamma, TNF alpha or GM-CSF by activated T cells, and rapamycin has been shown to block the response to various growth factors such as IL-3, IL-4 or IL-6. Here, we recap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us about the physiological role of cytokines for hematopoiesis.

Characterization of toxin-producing cyanobacteria by using an oligonucleotide probe containing a tandemly repeated heptamer.

PubMed Central

Rouhiainen, L; Sivonen, K; Buikema, W J; Haselkorn, R

1995-01-01

Cyanobacteria produce toxins that kill animals. The two main classes of cyanobacterial toxins are cyclic peptides that cause liver damage and alkaloids that block nerve transmission. Many toxin-producing strains from Finnish lakes were brought into axenic culture, and their toxins were characterized. Restriction fragment length polymorphism analysis, probing with a short tandemly repeated DNA sequence found at many locations in the chromosome of Anabaena sp. strain PCC 7120, distinguishes hepatotoxic Anabaena isolates from neurotoxin-producing strains and from Nostoc spp. PMID:7592362

Clonidine prevents enhancement of spinal sympathetic transmission by phosphodiesterase inhibitors.

PubMed

Franz, D N; Madsen, P W

1982-02-12

Preganglionic sympathetic discharges, evoked by cervical stimulation in spinal cats, were rapidly and markedly enhanced for 1-2 h by aminophylline or isobutylmethylxanthine. Clonidine depressed intraspinal transmission and prevented enhancement by the xanthines; alpha 2-receptor antagonists blocked the effect of clonidine and not only restored but also markedly prolonged the enhancement by the xanthines. The results suggest that the excitability of sympathetic preganglionic neurons is regulated by cyclic AMP through activation of different subtypes of adrenergic receptors that are either positively or negatively coupled to adenylate cyclase.

Transversus abdominal plane block for postoperative analgesia: a systematic review and meta-analysis of randomized-controlled trials.

PubMed

Brogi, Etrusca; Kazan, Roy; Cyr, Shantale; Giunta, Francesco; Hemmerling, Thomas M

2016-10-01

The transversus abdominal plane (TAP) block has been described as an effective pain control technique after abdominal surgery. We performed a systematic review and meta-analysis of randomized-controlled trials (RCTs) to account for the increasing number of TAP block studies appearing in the literature. The primary outcome we examined was the effect of TAP block on the postoperative pain score at six, 12, and 24 hr. The secondary outcome was 24-hr morphine consumption. We searched the United States National Library of Medicine database, the Excerpta Medica database, and the Cochrane Central Register of Controlled Clinical Studies and identified RCTs focusing on the analgesic efficacy of TAP block compared with a control group [i.e., placebo, epidural analgesia, intrathecal morphine (ITM), and ilioinguinal nerve block after abdominal surgery]. Meta-analyses were performed on postoperative pain scores at rest at six, 12, and 24 hr (visual analogue scale, 0-10) and on 24-hr opioid consumption. In the 51 trials identified, compared with placebo, TAP block reduced the VAS for pain at six hours by 1.4 (95% confidence interval [CI], -1.9 to -0.8; P < 0.001), at 12 hr by 2.0 (95% CI, -2.7 to -1.4; P < 0.001), and at 24 hr by 1.2 (95% CI, -1.6 to -0.8; P < 0.001). Similarly, compared with placebo, TAP block reduced morphine consumption at 24 hr after surgery (mean difference, -14.7 mg; 95% CI, -18.4 to -11.0; P < 0.001). We observed this reduction in pain scores and morphine consumption in the TAP block group after gynecological surgery, appendectomy, inguinal surgery, bariatric surgery, and urological surgery. Nevertheless, separate analysis of the studies comparing ITM with TAP block revealed that ITM seemed to have a greater analgesic efficacy. The TAP block can play an important role in the management of pain after abdominal surgery by reducing both pain scores and 24-hr morphine consumption. It may have particular utility when neuraxial techniques or opioids are contraindicated.

Phase response curves for models of earthquake fault dynamics

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

Franović, Igor, E-mail: franovic@ipb.ac.rs; Kostić, Srdjan; Perc, Matjaž

We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge-Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how themore » profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period.« less

New paleomagnetic data from the Wadi Abyad crustal section and their implications for the rotation history of the Oman ophiolite

NASA Astrophysics Data System (ADS)

Meyer, Matthew; Morris, Antony; Anderson, Mark; MacLeod, Chris

2015-04-01

The Oman ophiolite is an important natural laboratory for understanding the construction of oceanic crust at fast spreading axes and its subsequent tectonic evolution. Previous paleomagnetic research in lavas of the northern ophiolitic blocks (Perrin et al., 2000) has demonstrated substantial clockwise intraoceanic tectonic rotations. Paleomagnetic data from lower crustal sequences in the southern blocks, however, have been more equivocal due to complications arising from remagnetization, and have been used to infer that clockwise rotations seen in the north are internal to the ophiolite rather than regionally significant (Weiler, 2000). Here we demonstrate the importance and advantages of sampling crustal transects in the ophiolite in order to understand the nature and variability in magnetization directions. By systematically sampling the lower crustal sequence exposed in Wadi Abyad (Rustaq block) we resolve for the first time in a single section a pattern of remagnetized lowermost gabbros and retention of earlier magnetizations by uppermost gabbros and the overlying dyke-rooting zone. Results are supported by a positive fold test that shows that remagnetization of lower gabbros occurred prior to the Campanian structural disruption of the Moho. NW-directed remagnetized remanences in the lower units are consistent with those used by Weiler (2000) to infer lack of significant rotation of the southern blocks and to argue, therefore, that rotation of the northern blocks was internal to the ophiolite. In contrast, E/ENE-directed remanences in the uppermost levels of Wadi Abyad imply large, clockwise rotation of the Rustaq block, of a sense and magnitude consistent with intraoceanic rotations inferred from extrusive sections in the northern blocks. We conclude that without the control provided by systematic crustal sampling, the potential for different remanence directions being acquired at different times may lead to erroneous tectonic interpretation.

Structural evolution of self-ordered alumina tapered nanopores with 100 nm interpore distance

NASA Astrophysics Data System (ADS)

Li, Juan; Li, Congshan; Gao, Xuefeng

2011-10-01

We in-detail investigated the profile evolution processes of highly ordered alumina under the cyclic treatment of mild anodizing of aluminum foils in oxalic acid followed by etching in phosphoric acid. With the cyclic times increasing, the profiles of nanopores were gradually evolved into the parabola-like, trumpet-like and conical shape. Although the inserted etching itself nearly had no impact on the growth rate of the nanopores due to the rapid recovering of thinned barrier layer at the initial stage of next anodizing, overmuch etching could bring apparent side effects such as wall-breaking, thinning and taper-removing from the top down. The anodizing and etching kinetics and their synergetic effects in modulating different aspect ratios and open sizes of conical pores were studied systematically. These findings are helpful to tailor high-quality anodic alumina taper-pores with tunable profiles.

Effect of Magnesium Ion on the Zinc Electrodeposition from Acidic Sulfate Electrolyte

NASA Astrophysics Data System (ADS)

Tian, Lin; Xie, Gang; Yu, Xiao-Hua; Li, Rong-Xing; Zeng, Gui-Sheng

2012-02-01

The effects of Mg2+ ion on the zinc electrodeposition were systematically investigated in sulfuric acid solution through the characterizations of current efficiency (CE), power consumption (PC), deposit morphology, cathodic polarization, and cyclic voltammetry. The results demonstrate that there is no significant influence on CE and PC in the Mg2+ concentration range of 1 to 10 g L-1, but with a drastic decrease of the CE and rapid increase of PC at Mg2+ ion concentration above 15 g L-1. Based on the morphology observation and polarization curves, the presence of Mg2+ ions could also induce the coarse surface on the electrodeposited zinc accompanying the enhancement of the cathodic polarization, which becomes more distinct at a high concentration above 15 g L-1. Furthermore, hydrogen evolution could be promoted with the existence of Mg2+ ions according to cyclic voltammograms.

Superelastic SMA U-shaped dampers with self-centering functions

NASA Astrophysics Data System (ADS)

Wang, Bin; Zhu, Songye

2018-05-01

As high-performance metallic materials, shape memory alloys (SMAs) have been investigated increasingly by the earthquake engineering community in recent years, because of their remarkable self-centering (SC) and energy-dissipating capabilities. This paper systematically presents an experimental study on a novel superelastic SMA U-shaped damper (SMA-UD) with SC function under cyclic loading. The mechanical properties, including strength, SC ability, and energy-dissipating capability with varying loading amplitudes and strain rates are evaluated. Test results show that excellent and stable flag-shaped hysteresis loops are exhibited in multiple loading cycles. Strain rate has a negligible effect on the cyclic behavior of the SMA-UD within the dynamic frequency range of typical interest in earthquake engineering. Furthermore, a numerical investigation is performed to understand the mechanical behavior of the SMA-UD. The numerical model is calibrated against the experimental results with reasonable accuracy. Then, the stress–strain states with different phase transformations are also discussed.

Analysis of a Multi-Flap Control System for a Swashplateless Rotor

NASA Technical Reports Server (NTRS)

Sekula, Martin K.; Wilbur, Matthew L.

2011-01-01

An analytical study was conducted examining the feasibility of a swashplateless rotor controlled through two trailing edge flaps (TEF), where the cyclic and collective controls were provided by separate TEFs. This analysis included a parametric study examining the impact of various design parameters on TEF deflections. Blade pitch bearing stiffness; blade pitch index; and flap chord, span, location, and control function of the inboard and outboard flaps were systematically varied on a utility-class rotorcraft trimmed in steady level flight. Gradient-based optimizations minimizing flap deflections were performed to identify single- and two-TEF swashplateless rotor designs. Steady, forward and turning flight analyses suggest that a two-TEF swashplateless rotor where the outboard flap provides cyclic control and inboard flap provides collective control can reduce TEF deflection requirements without a significant impact on power, compared to a single-TEF swashplateless rotor design.

Effects of Vitex agnus and Flaxseed on cyclic mastalgia: A randomized controlled trial.

PubMed

Mirghafourvand, Mojgan; Mohammad-Alizadeh-Charandabi, Sakineh; Ahmadpour, Parivash; Javadzadeh, Yousef

2016-02-01

Evidence on the effect of Vitex agnus and Flaxseed on cyclical mastalgia is not enough. This study aimed to assess the efficacy of V. agnus and Flaxseed on cyclical mastalgia. This randomized controlled trial was conducted on 159 women referred to health centers of Tabriz, Iran. Subjects were allocated into three groups (n=53 per group) using block randomization. Group I received 25g daily Flaxseed powder and placebo of V. agnus; group II received daily 3.2-4.8mg V. agnus tablet and placebo of Flaxseed and control group received both placebo. Nominal day breast pain was applied at baseline, first, and second month after the intervention. Data was analyzed using general linear model. There was no statistical significant difference between the three groups in terms of socio-demographic characteristics and baseline values. The breast pain improved significantly in both intervention groups during the first and second month after intervention. Mean NDBP score was significantly lower than that in the control group at the first month after the intervention in the Flaxseed [adjusted mean difference: -3.1 (95% CI: -4.2 to -2.0)] and V. agnus groups [-3.3 (-4.3 to -2.2)] and the second month after the intervention in Flaxseed [-7.0 (-8.1 to -5.9)] and V. agnus groups [-6.4 (-7.5 to -5.3)]. Flaxseed and V. agnus are effective in short-term period in decreasing cyclical mastalgia. However, further studies are needed to examine the long-term effectiveness and sustainability of the effects after stopping the treatment in order to decide whether these alternative treatments are suitable to treat mastalgia or not. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin

PubMed Central

Furumai, Ryohei; Komatsu, Yasuhiko; Nishino, Norikazu; Khochbin, Saadi; Yoshida, Minoru; Horinouchi, Sueharu

2001-01-01

Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar concentrations. The HDAC1 inhibition by CHAP1 was reversible as it was by TSA, in contrast to the irreversible inhibition by TPX. CHAP with an aliphatic chain length of five, which corresponded to that of acetylated lysine, was stronger than those with other lengths. These results suggest that TPX is a substrate mimic and that the replacement of the epoxyketone with the hydroxamic acid converted TPX to an inhibitor chelating the zinc like TSA. Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited these HDACs to a similar extent. HDAC6 inhibition by TPX at a high concentration was reversible, probably because HDAC6 is not alkylated by TPX. We further synthesized the counterparts of all known naturally occurring cyclic tetrapeptides containing the epoxyketone. HDAC1 was highly sensitive to all these CHAPs much more than HDAC6, indicating that the structure of the cyclic tetrapeptide framework affects the target enzyme specificity. These results suggest that CHAP is a unique lead to develop isoform-specific HDAC inhibitors. PMID:11134513

Fatigue resistance and microleakage of CAD/CAM ceramic and composite molar crowns.

PubMed

Kassem, Amr S; Atta, Osama; El-Mowafy, Omar

2012-01-01

The aim of this study was to determine effect of compressive cyclic loading on fatigue resistance and microleakage of monolithic CAD/CAM molar ceramic and composite crowns. Thirty-two extracted molars were prepared to receive CEREC crowns according to manufacturer's guidelines using a special paralleling device (Parallel-A-Prep). Sixteen feldspathic ceramic crowns (VITABLOCS Mark II) (VMII) and 16 resin-composite crowns (Paradigm-MZ100 blocks) (PMZ) were milled using a CEREC-3D machine. Eight crowns of each group were cemented to their respective teeth using self-etching resin cement (Panavia-F-2.0) (PAN), and eight were cemented using self-adhesive resin cement (RelyX-Unicem-Clicker) (RXU). Following storage for 1 week in water, specimens were subjected to uniaxial compressive cyclic loading in an Instron testing machine at 12 Hz for 1,000,000 cycles. Load was applied at the central fossa, and the cycle range was 60-600 N. Specimens were then subjected to microleakage testing. Data were statistically analyzed using factorial ANOVA and Post Hoc (Tukey HSD) tests. All composite crowns survived compressive cyclic loading without fracture, while three ceramic crowns from the subgroup cemented with RXU developed surface cracks at the center of occlusal surfaces, extending laterally. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other three subgroups (p < 0.05). After 1,000,000 cycles of compressive cyclic loading, PMZ composite molar crowns were more fatigue-resistant than VMII ceramic crowns. Cement type had a significant effect on fatigue resistance of the ceramic crowns but not the composite ones. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other subgroups (p < 0.05). © 2011 by The American College of Prosthodontists.

The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

PubMed

Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

2016-01-01

The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels.

PubMed

Sartiani, Laura; Mannaioni, Guido; Masi, Alessio; Novella Romanelli, Maria; Cerbai, Elisabetta

2017-10-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain. Their role in heart rate, neuronal pacemaking, dendritic integration, learning and memory, and visual and pain perceptions has been extensively studied; these channels have been found also in some peripheral tissues, where their functions still need to be fully elucidated. Genetic defects and altered expression of HCN channels are linked to several pathologies, which makes these proteins attractive targets for translational research; at the moment only one drug (ivabradine), which specifically blocks the hyperpolarization-activated current, is clinically available. This review discusses current knowledge about HCN channels, starting from their biophysical properties, origin, and developmental features, to (patho)physiologic role in different tissues and pharmacological modulation, ending with their present and future relevance as drug targets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Discovery of a cAMP Deaminase That Quenches Cyclic AMP-Dependent Regulation

PubMed Central

Goble, Alissa M.; Feng, Youjun; Raushel, Frank M.; Cronan, John E.

2013-01-01

An enzyme of unknown function within the amidohydrolase superfamily was discovered to catalyze the hydrolysis of the universal second messenger, cyclic-3’, 5’-adenosine monophosphate (cAMP). The enzyme, which we have named CadD, is encoded by the human pathogenic bacterium Leptospira interrogans. Although CadD is annotated as an adenosine deaminase, the protein specifically deaminates cAMP to cyclic-3’, 5’-inosine monophosphate (cIMP) with a kcat/Km of 2.7 ± 0.4 × 105 M−1 s−1 and has no activity on adenosine, adenine, or 5’-adenosine monophosphate (AMP). This is the first identification of a deaminase specific for cAMP. Expression of CadD in Escherichia coli mimics the loss of adenylate cyclase in that it blocks growth on carbon sources that require the cAMP-CRP transcriptional activator complex for expression of the cognate genes. The cIMP reaction product cannot replace cAMP as the ligand for CRP binding to DNA in vitro and cIMP is a very poor competitor of cAMP activation of CRP for DNA binding. Transcriptional analyses indicate that CadD expression represses expression of several cAMP-CRP dependent genes. CadD adds a new activity to the cAMP metabolic network and may be a useful tool in intracellular study of cAMP-dependent processes. PMID:24074367

Excitation energy migration processes in various multi-porphyrin assemblies.

PubMed

Yang, Jaesung; Kim, Dongho

2012-08-13

The electronic interactions and excitation energy transfer (EET) processes of a variety of multi-porphyrin arrays with linear, cyclic and box architectures have been explored. Directly meso-meso linked linear arrays (Z(N)) exhibit strong excitonic coupling with an exciton coherence length of approximately 6 porphyrin units, while fused linear arrays (T(N)) exhibit extensive π-conjugation over the whole array. The excitonic coherence length in directly linked cyclic porphyrin rings (CZ(N)) was determined to be approximately 2.7 porphyrin units by simultaneous analysis of fluorescence intensities and lifetimes at the single-molecule level. By performing transient absorption (TA) and TA anisotropy decay measurements, the EET rates in m-phenylene linked cyclic porphyrin wheels C12ZA and C24ZB were determined to be 4 and 36 ps(-1), respectively. With increasing the size of C(N)ZA, the EET efficiencies decrease owing to the structural distortions that produce considerable non-radiative decay pathways. Finally, the EET rates of self-assembled porphyrin boxes consisting of directly linked diporphyrins, B1A, B2A and B3A, are 48, 98 and 361 ps(-1), respectively. The EET rates of porphyrin boxes consisting of alkynylene-bridged diporphyrins, B2B and B4B, depend on the conformation of building blocks (planar or orthogonal) rather than the length of alkynylene linkers.

Androgen Receptor Antagonism By Divalent Ethisterone Conjugates In Castrate-Resistant Prostate Cancer Cells

PubMed Central

Levine, Paul M.; Lee, Eugine; Greenfield, Alex; Bonneau, Richard; Logan, Susan K.; Garabedian, Michael J.; Kirshenbaum, Kent

2013-01-01

Sustained treatment of prostate cancer with Androgen Receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, new therapeutic regimens that target and modulate AR activity could prove beneficial. We previously introduced a versatile chemical platform to generate competitive and non-competitive multivalent peptoid oligomer conjugates that modulate AR activity. In particular, we identified a linear and a cyclic divalent ethisterone conjugate that exhibit potent anti-proliferative properties in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we characterize the mechanism of action of these compounds utilizing confocal microscopy, time-resolved fluorescence resonance energy transfer, chromatin immunoprecipitation, flow cytometry, and microarray analysis. The linear conjugate competitively blocks AR action by inhibiting DNA binding. In addition, the linear conjugate does not promote AR nuclear localization or co-activator binding. In contrast, the cyclic conjugate promotes AR nuclear localization and induces cell-cycle arrest, despite its inability to compete against endogenous ligand for binding to AR in vitro. Genome-wide expression analysis reveals that gene transcripts are differentially affected by treatment with the linear or cyclic conjugate. Although the divalent ethisterone conjugates share extensive chemical similarities, we illustrate that they can antagonize the AR via distinct mechanisms of action, establishing new therapeutic strategies for potential applications in AR pharmacology. PMID:22871957

The theory of cyclic voltammetry of electrochemically heterogeneous surfaces: comparison of different models for surface geometry and applications to highly ordered pyrolytic graphite.

PubMed

Ward, Kristopher R; Lawrence, Nathan S; Hartshorne, R Seth; Compton, Richard G

2012-05-28

The cyclic voltammetry at electrodes composed of multiple electroactive materials, where zones of one highly active material are distributed over a substrate of a second, less active material, is investigated by simulation. The two materials are assumed to differ in terms of their electrochemical rate constants towards any given redox couple. For a one-electron oxidation or reduction, the effect on voltammetry of the size and relative surface coverages of the zones as well as the rate constant of the slower zone are considered for systems where it is much slower than the rate constant of the faster zones. The occurrence of split peak cyclic voltammetry where two peaks are observed in the forward sweep, is studied in terms of the diffusional effects present in the system. A number of surface geometries are compared: specifically the more active zones are modelled as long, thin bands, as steps in the surface, as discs, and as rings (similar to a partially blocked electrode). Similar voltammetry for the band, step and ring models is seen but the disc geometry shows significant differences. Finally, the simulation technique is applied to the modelling of highly-ordered pyrolytic graphite (HOPG) surface and experimental conditions under which it may be possible to observe split peak voltammetry are predicted.

Phase transitions and thermal entanglement of the distorted Ising-Heisenberg spin chain: topology of multiple-spin exchange interactions in spin ladders

NASA Astrophysics Data System (ADS)

Arian Zad, Hamid; Ananikian, Nerses

2017-11-01

We consider a symmetric spin-1/2 Ising-XXZ double sawtooth spin ladder obtained from distorting a spin chain, with the XXZ interaction between the interstitial Heisenberg dimers (which are connected to the spins based on the legs via an Ising-type interaction), the Ising coupling between nearest-neighbor spins of the legs and rungs spins, respectively, and additional cyclic four-spin exchange (ring exchange) in the square plaquette of each block. The presented analysis supplemented by results of the exact solution of the model with infinite periodic boundary implies a rich ground state phase diagram. As well as the quantum phase transitions, the characteristics of some of the thermodynamic parameters such as heat capacity, magnetization and magnetic susceptibility are investigated. We prove here that among the considered thermodynamic and thermal parameters, solely heat capacity is sensitive versus the changes of the cyclic four-spin exchange interaction. By using the heat capacity function, we obtain a singularity relation between the cyclic four-spin exchange interaction and the exchange coupling between pair spins on each rung of the spin ladder. All thermal and thermodynamic quantities under consideration should be investigated by regarding those points which satisfy the singularity relation. The thermal entanglement within the Heisenberg spin dimers is investigated by using the concurrence, which is calculated from a relevant reduced density operator in the thermodynamic limit.

Reader's Block: A Systematic Review of Barriers to Adoption, Access and Use in E-Book User Studies

ERIC Educational Resources Information Center

Girard, Adam

2014-01-01

Introduction: This review of barriers to e-book use systematically identifies obstacles to engaging reading experiences. Through the use of an analytical framework, the users being studied, study setting, and methods used in previous work are described in order to identify promising areas for future research. Method: The method used is a…

How economic recessions and unemployment affect illegal drug use: A systematic realist literature review.

PubMed

Nagelhout, Gera E; Hummel, Karin; de Goeij, Moniek C M; de Vries, Hein; Kaner, Eileen; Lemmens, Paul

2017-06-01

Economic recessions may influence illegal drug use via different mechanisms, for example increased use due to more psychological distress or decreased use due to lower incomes and purchasing power. This paper reviews the literature on how economic recessions and unemployment affect the use of illegal drugs among adults. We conducted a systematic realist literature review, which is an explanatory method that aims to understand underlying mechanisms that connect an event to an outcome in a specific context. A systematic search was performed in EconLit, Embase, Medline, PsycINFO, SocIndex, and Web of Science for studies examining mechanisms explaining how recessions or unemployment affect illegal drug use. We synthesized 28 studies published between 1990 and 2015. Most evidence (17 studies) was found for the counter-cyclical mechanism that recessions and unemployment increase psychological distress, which increases drug use. Mainly supportive evidence for this mechanism was found in several high quality studies, in different contexts, and in a diverse number of countries and samples. In contrast, decreased income did not seem to decrease drug use (10 studies). Little evidence was available on the non-working time mechanism (4 studies) and the social exclusion mechanism (5 studies). Most of the studies that did examine these latter mechanisms confirmed the hypothesized counter-cyclical associations. The current evidence is in line with the hypothesis that drug use increases in times of recession because unemployment increases psychological distress which increases drug use. During times of recession, psychological support for those who lost their job and are vulnerable to drug use (relapse) is likely to be important. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Dichloro-Cycloazatriphosphane: The Missing Link between N2 P2 and P4 Ring Systems in the Systematic Development of NP Chemistry.

PubMed

Bresien, Jonas; Hinz, Alexander; Schulz, Axel; Suhrbier, Tim; Thomas, Max; Villinger, Alexander

2017-10-20

A dichloro-cycloazatriphosphane that incorporates a cyclic NP 3 backbone could be synthesized using knowledge gained from the chemistry of N 2 P 2 and P 4 ring systems. It fills the gap between the congeneric compounds [ClP(μ-NR)] 2 and [ClP(μ-PR)] 2 (R=sterically demanding substituent), and thus contributes to the systematic development of nitrogen-phosphorus chemistry in general. The title compound was studied with respect to its formation via a labile aminodiphosphene, which readily underwent different rearrangement reactions depending on the solvent. All compounds were fully characterized by experimental and computational methods. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A drift experiment to assess the influence of wind on recovery of oiled seabirds on St Paul Island, Alaska

USGS Publications Warehouse

Flint, Paul L.; Fowler, A.C.

1998-01-01

We used wooden blocks to estimate the proportion of oiled seabird carcasses that were likely to be recovered on beaches of St Paul Island, Alaska following a near-shore oil spill. We released a total of 302 blocks 6 km north of the island in 1997 at the site of a 17 II 1996 oil spill. We used a paired design and released half the blocks when the winds were onshore and released the second half when the winds were offshore. We systematically searched beaches after the second release to recover blocks. We recovered 93 of 152 (61%) blocks released when winds were onshore but only 1 of 150 (0.7%) blocks released when winds were offshore. Given that winds following the 1996 spill were offshore, we conclude that most birds killed at sea following the 1996 spill were likely not recovered on beaches.

On complexity of trellis structure of linear block codes

NASA Technical Reports Server (NTRS)

Lin, Shu

1990-01-01

The trellis structure of linear block codes (LBCs) is discussed. The state and branch complexities of a trellis diagram (TD) for a LBC is investigated. The TD with the minimum number of states is said to be minimal. The branch complexity of a minimal TD for a LBC is expressed in terms of the dimensions of specific subcodes of the given code. Then upper and lower bounds are derived on the number of states of a minimal TD for a LBC, and it is shown that a cyclic (or shortened cyclic) code is the worst in terms of the state complexity among the LBCs of the same length and dimension. Furthermore, it is shown that the structural complexity of a minimal TD for a LBC depends on the order of its bit positions. This fact suggests that an appropriate permutation of the bit positions of a code may result in an equivalent code with a much simpler minimal TD. Boolean polynomial representation of codewords of a LBC is also considered. This representation helps in study of the trellis structure of the code. Boolean polynomial representation of a code is applied to construct its minimal TD. Particularly, the construction of minimal trellises for Reed-Muller codes and the extended and permuted binary primitive BCH codes which contain Reed-Muller as subcodes is emphasized. Finally, the structural complexity of minimal trellises for the extended and permuted, and double-error-correcting BCH codes is analyzed and presented. It is shown that these codes have relatively simple trellis structure and hence can be decoded with the Viterbi decoding algorithm.

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

PubMed

Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

2016-03-15

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scalable video transmission over Rayleigh fading channels using LDPC codes

NASA Astrophysics Data System (ADS)

Bansal, Manu; Kondi, Lisimachos P.

2005-03-01

In this paper, we investigate an important problem of efficiently utilizing the available resources for video transmission over wireless channels while maintaining a good decoded video quality and resilience to channel impairments. Our system consists of the video codec based on 3-D set partitioning in hierarchical trees (3-D SPIHT) algorithm and employs two different schemes using low-density parity check (LDPC) codes for channel error protection. The first method uses the serial concatenation of the constant-rate LDPC code and rate-compatible punctured convolutional (RCPC) codes. Cyclic redundancy check (CRC) is used to detect transmission errors. In the other scheme, we use the product code structure consisting of a constant rate LDPC/CRC code across the rows of the `blocks' of source data and an erasure-correction systematic Reed-Solomon (RS) code as the column code. In both the schemes introduced here, we use fixed-length source packets protected with unequal forward error correction coding ensuring a strictly decreasing protection across the bitstream. A Rayleigh flat-fading channel with additive white Gaussian noise (AWGN) is modeled for the transmission. The rate-distortion optimization algorithm is developed and carried out for the selection of source coding and channel coding rates using Lagrangian optimization. The experimental results demonstrate the effectiveness of this system under different wireless channel conditions and both the proposed methods (LDPC+RCPC/CRC and RS+LDPC/CRC) outperform the more conventional schemes such as those employing RCPC/CRC.

A Systematic Review of Serum Biomarkers Anti-Cyclic Citrullinated Peptide and Rheumatoid Factor as Tests for Rheumatoid Arthritis

PubMed Central

Taylor, Peter; Gartemann, Juliane; Hsieh, Jeanie; Creeden, James

2011-01-01

This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients. PMID:21915375

Reductive ring closure methodology toward heteroacenes bearing a dihydropyrrolo[3,2-b]pyrrole core: scope and limitation.

PubMed

Qiu, Li; Wang, Xiao; Zhao, Na; Xu, Shiliang; An, Zengjian; Zhuang, Xuhui; Lan, Zhenggang; Wen, Lirong; Wan, Xiaobo

2014-12-05

A newly developed reductive ring closure methodology to heteroacenes bearing a dihydropyrrolo[3,2-b]pyrrole core was systematically studied for its scope and limitation. The methodology involves (i) the cyclization of an o-aminobenzoic acid ester derivative to give an eight-membered cyclic dilactam, and (ii) the conversion of the dilactams into the corresponding diimidoyl chloride, which undergoes (iii) reductive ring closure to install the dihydropyrrolo[3,2-b]pyrrole core. The first step of the methodology plays the key role due to its substrate limitation, which suffers from the competition of oligomerization and hydrolysis. All the dilactams could successfully convert to the corresponding diimidoyl chlorides, most of which succeeded to give the dihydropyrrolo[3,2-b]pyrrole core. The influence of the substituents and the elongation of conjugated length on the photophysical properties of the obtained heteroacenes were then investigated systematically using UV-vis spectroscopy and cyclic voltammetry. It was found that chlorination and fluorination had quite a different effect on the photophysical properties of the heteroacene, and the ring fusing pattern also had a drastic influence on the band gap of the heteroacene. The successful preparation of a series of heteroacenes bearing a dihydropyrrolo[3,2-b]pyrrole core would provide a wide variety of candidates for further fabrication of organic field-effect transistor devices.

Systematic aging of commercial LiFePO4|Graphite cylindrical cells including a theory explaining rise of capacity during aging

NASA Astrophysics Data System (ADS)

Lewerenz, Meinert; Münnix, Jens; Schmalstieg, Johannes; Käbitz, Stefan; Knips, Marcus; Sauer, Dirk Uwe

2017-03-01

The contribution introduces a new theory explaining the capacity increase that is often observed in early stages of life of lithium-ion batteries. This reversible and SOC-depending capacity rise is explained by the passive electrode effect in this work. The theory assumes a slow, compensating flow of active lithium between the passive and the active part of the anode, where the passive part represents the geometric excess anode with respect to the cathode. The theory is validated using a systematic test of 50 cylindrical 8 Ah LiFePO4|Graphite battery cells analyzed during cyclic and calendaric aging. The cyclic aging has been performed symmetrically at 40 °C cell temperature, varying current rates and DODs. The calendar aging is executed at three temperatures and up to four SOCs. The aging is dominated by capacity fade while the increase of internal resistance is hardly influenced. Surprisingly shallow cycling between 45 and 55% SOC shows stronger aging than aging at higher DOD and tests at 4 C exhibit less aging than aging at lower C-rates. Aging mechanisms at 60 °C seem to deviate from those at 40 °C or lower. The data of this aging matrix is used for further destructive and non-destructive characterization in future contributions.

Personality Types in Adolescence: Change and Stability and Links with Adjustment and Relationships--A Five-Wave Longitudinal Study

ERIC Educational Resources Information Center

Meeus, Wim; Van de Schoot, Rens; Klimstra, Theo; Branje, Susan

2011-01-01

We examined change and stability of the 3 personality types identified by Block and Block (1980) and studied their links with adjustment and relationships. We used data from a 5-wave study of 923 early-to-middle and 390 middle-to-late adolescents, thereby covering the ages of 12-20 years. In Study 1, systematic evidence for personality change was…

Liposomal bupivacaine versus interscalene nerve block for pain control after total shoulder arthroplasty: A systematic review and meta-analysis.

PubMed

Wang, Kun; Zhang, Hong-Xia

2017-10-01

To illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain management after total shoulder arthroplasty. A systematic search was performed in Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Data on patients prepared for total shoulder arthroplasty in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) and opioid consumption. Fixed/random effect model was used according to the heterogeneity tested by I 2 statistic. Software of Stata 11.0 was used for pooling the final outcomes. Four randomized controlled trials (RCTs) including 510 patients met the inclusion criteria. The present meta-analysis indicated that there were no significant differences between groups in terms of VAS score at 12 h, 24 h, and 48 h (p > 0.05). No significant differences were found regarding to opioid consumption at postoperative 12 h, 24 h and 48 h (p > 0.05). Compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and opioid consumption. Higher quality RCTs are required for further research. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

TEST SYSTEM FOR EVALUATING SPENT NUCLEAR FUEL BENDING STIFFNESS AND VIBRATION INTEGRITY

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

Wang, Jy-An John; Wang, Hong; Bevard, Bruce Balkcom

2013-01-01

Transportation packages for spent nuclear fuel (SNF) must meet safety requirements specified by federal regulations. For normal conditions of transport, vibration loads incident to transport must be considered. This is particularly relevant for high-burnup fuel (>45 GWd/MTU). As the burnup of the fuel increases, a number of changes occur that may affect the performance of the fuel and cladding in storage and during transportation. The mechanical properties of high-burnup de-fueled cladding have been previously studied by subjecting defueled cladding tubes to longitudinal (axial) tensile tests, ring-stretch tests, ring-compression tests, and biaxial tube burst tests. The objective of this study ismore » to investigate the mechanical properties and behavior of both the cladding and the fuel in it under vibration/cyclic loads similar to the sustained vibration loads experienced during normal transport. The vibration loads to SNF rods during transportation can be characterized by dynamic, cyclic, bending loads. The transient vibration signals in a specified transport environment can be analyzed, and frequency, amplitude and phase components can be identified. The methodology being implemented is a novel approach to study the vibration integrity of actual SNF rod segments through testing and evaluating the fatigue performance of SNF rods at defined frequencies. Oak Ridge National Laboratory (ORNL) has developed a bending fatigue system to evaluate the response of the SNF rods to vibration loads. A three-point deflection measurement technique using linear variable differential transformers is used to characterize the bending rod curvature, and electromagnetic force linear motors are used as the driving system for mechanical loading. ORNL plans to use the test system in a hot cell for SNF vibration testing on high burnup, irradiated fuel to evaluate the pellet-clad interaction and bonding on the effective lifetime of fuel-clad structure bending fatigue performance. Technical challenges include pure bending implementation, remote installation and detachment of the SNF test specimen, test specimen deformation measurement, and identification of a driving system suitable for use in a hot cell. Surrogate test specimens have been used to calibrate the test setup and conduct systematic cyclic tests. The calibration and systematic cyclic tests have been used to identify test protocol issues prior to implementation in the hot cell. In addition, cyclic hardening in unidirectional bending and softening in reverse bending were observed in the surrogate test specimens. The interface bonding between the surrogate clad and pellets was found to impact the bending response of the surrogate rods; confirming this behavior in the actual spent fuel segments will be an important aspect of the hot cell test implementation,« less

Diagnosis and treatment of posterior sacroiliac complex pain: a systematic review with comprehensive analysis of the published data.

PubMed

King, Wade; Ahmed, Shihab U; Baisden, Jamie; Patel, Nileshkumar; Kennedy, David J; Duszynski, Belinda; MacVicar, John

2015-02-01

To assess the evidence on the validity of sacral lateral branch blocks and the effectiveness of sacral lateral branch thermal radiofrequency neurotomy in managing sacroiliac complex pain. Systematic review with comprehensive analysis of all published data. Six reviewers searched the literature on sacral lateral branch interventions. Each assessed the methodologies of studies found and the quality of the evidence presented. The outcomes assessed were diagnostic validity and effectiveness of treatment for sacroiliac complex pain. The evidence found was appraised in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of evaluating scientific evidence. The searches yielded two primary publications on sacral lateral branch blocks and 15 studies of the effectiveness of sacral lateral branch thermal radiofrequency neurotomy. One study showed multisite, multidepth sacral lateral branch blocks can anesthetize the posterior sacroiliac ligaments. Therapeutic studies show sacral lateral branch thermal radiofrequency neurotomy can relieve sacroiliac complex pain to some extent. The evidence of the validity of these blocks and the effectiveness of this treatment were rated as moderate in accordance with the GRADE system. The literature on sacral lateral branch interventions is sparse. One study demonstrates the face validity of multisite, multidepth sacral lateral branch blocks for diagnosis of posterior sacroiliac complex pain. Some evidence of moderate quality exists on therapeutic procedures, but it is insufficient to determine the indications and effectiveness of sacral lateral branch thermal radiofrequency neurotomy, and more research is required. Wiley Periodicals, Inc.

Pattern interpolation in thin films of lamellar, symmetric copolymers on nano-patterned substrates

NASA Astrophysics Data System (ADS)

Detcheverry, Francois; Nagpal, Umang; Liu, Guoliang; Nealey, Paul; de Pablo, Juan

2009-03-01

A molecular model of block copolymer systems is used to conduct a systematic study of the morphologies that arise when thin films of symmetric, lamellar forming block copolymer materials are deposited on nanopatterned surfaces. Over 500 distinct cases are considered. It is found that, in general, three distinct morphologies can arise depending on the strength of the substrate-polymer interactions, the film thickness, and the period of the substrate pattern. The relative stability of those morphologies is determined by direct calculation of the free energy differences. The dynamic propensity of those morphologies to emerge is examined by careful analysis of simulated trajectories. The results of this systematic study are used to interpret recent experimental data for films of polystyrene-PMMA copolymers on chemically nanopatterned surfaces.

Kinematic Effects of Nickel-Titanium Instruments with Reciprocating or Continuous Rotation Motion: A Systematic Review of In Vitro Studies.

PubMed

Ahn, So-Yeon; Kim, Hyeon-Cheol; Kim, Euiseong

2016-07-01

This review aimed to compare the kinematic effect of nickel-titanium instruments with reciprocating and continuous rotation motion for cyclic fatigue resistance, shaping ability, apical debris extrusion, and dentinal defects or cracks. Articles were selected for inclusion in this review if they fulfilled all of the following criteria: described in vitro studies performed on either extracted human teeth or an artificial canal model, assessed both reciprocating and rotary instruments, compared reciprocating files and rotary files for the kinematics of files, and evaluated reciprocating and rotary files regarding the aim of this study. The electronic search was undertaken in MEDLINE, Cochrane database, and manual searches, including journals, reference lists, and other reviews. Twelve studies were chosen for cyclic fatigue, 19 studies for shaping ability, 14 studies for apical debris extrusion, and 13 studies for dentinal defects or cracks. Most of the studies showed that reciprocating motion had a higher resistance to cyclic fatigue. Nine studies from the shaping studies reported less canal transportation by using the reciprocating motion than the continuous rotation. The reciprocating instruments tended to extrude more dentin debris than the continuous rotating instruments, but many of the studies showed conflicting results. In addition, 2 studies from the defects or cracks studies claimed the reciprocating motion produced more dentinal defects than the continuous rotating motion. Instruments with reciprocating motion seemed to have better resistance to cyclic fatigue with less canal transportation tendency than the instruments with continuous rotating motion. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Pain Management After Outpatient Shoulder Arthroscopy: A Systematic Review of Randomized Controlled Trials.

PubMed

Warrender, William J; Syed, Usman Ali M; Hammoud, Sommer; Emper, William; Ciccotti, Michael G; Abboud, Joseph A; Freedman, Kevin B

2017-06-01

Effective postoperative pain management after shoulder arthroscopy is a critical component to recovery, rehabilitation, and patient satisfaction. This systematic review provides a comprehensive overview of level 1 and level 2 evidence regarding postoperative pain management for outpatient arthroscopic shoulder surgery. Systematic review. We performed a systematic review of the various modalities reported in the literature for postoperative pain control after outpatient shoulder arthroscopy and analyzed their outcomes. Analgesic regimens reviewed include regional nerve blocks/infusions, subacromial/intra-articular injections or infusions, cryotherapy, and oral medications. Only randomized control trials with level 1 or level 2 evidence that compared 2 or more pain management modalities or placebo were included. We excluded studies without objective measures to quantify postoperative pain within the first postoperative month, subjective pain scale measurements, or narcotic consumption as outcome measures. A combined total of 40 randomized control trials met our inclusion criteria. Of the 40 included studies, 15 examined nerve blocks, 4 studied oral medication regimens, 12 studied subacromial infusion, 8 compared multiple modalities, and 1 evaluated cryotherapy. Interscalene nerve blocks (ISBs) were found to be the most effective method to control postoperative pain after shoulder arthroscopy. Increasing concentrations, continuous infusions, and patient-controlled methods can be effective for more aggressively controlling pain. Dexamethasone, clonidine, intrabursal oxycodone, and magnesium have all been shown to successfully improve the duration and adequacy of ISBs when used as adjuvants. Oral pregabalin and etoricoxib administered preoperatively have evidence supporting decreased postoperative pain and increased patient satisfaction. On the basis of the evidence in this review, we recommend the use of ISBs as the most effective analgesic for outpatient arthroscopic shoulder surgery.

Code Optimization Techniques

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

MAGEE,GLEN I.

Computers transfer data in a number of different ways. Whether through a serial port, a parallel port, over a modem, over an ethernet cable, or internally from a hard disk to memory, some data will be lost. To compensate for that loss, numerous error detection and correction algorithms have been developed. One of the most common error correction codes is the Reed-Solomon code, which is a special subset of BCH (Bose-Chaudhuri-Hocquenghem) linear cyclic block codes. In the AURA project, an unmanned aircraft sends the data it collects back to earth so it can be analyzed during flight and possible flightmore » modifications made. To counter possible data corruption during transmission, the data is encoded using a multi-block Reed-Solomon implementation with a possibly shortened final block. In order to maximize the amount of data transmitted, it was necessary to reduce the computation time of a Reed-Solomon encoding to three percent of the processor's time. To achieve such a reduction, many code optimization techniques were employed. This paper outlines the steps taken to reduce the processing time of a Reed-Solomon encoding and the insight into modern optimization techniques gained from the experience.« less

Conductivities of the ionic complexes of two cyclic polyethers

NASA Technical Reports Server (NTRS)

Fielder, W. L.; Odonnell, P. M.

1975-01-01

The conductivities of the solid potassium thiocyanate complex of both dicyclohexyl-18-crown-6 and dibenzo-18-crown-6 were measured at 300K (27 C). Saturated aqueous potassium thiocyanate and graphite were used as ion-transporting and ion-blocking electrodes, respectively. The ionic conductivity predominated for both samples, but it was many orders of magnitude smaller than the value previously reported. The ionic conductivity of the dicyclohexyl complex (the better conductor) was 0.000003 ohm/cm. Crown complexes, in general, do not appear promising as potassium ion solid electrolytes contrary to claims in the patent literature.

Integrated Technology Rotor Methodology Assessment Workshop Held in Moffett Field, California on 21-22 Jun 1983

DTIC Science & Technology

1988-06-01

Fuseaje mode%, 6/un/im NA 10 10 10 6/10 6/9 6/10 6/10 4/0 NA rigid body / elastic Aerodynamics on NA NA NA NA NA CP CP CP CP NA NA fuselage Pylon CP PR GDOF... motions were cyclic and body modes using the moving-block allowed to decay freely. The body pitch and roll analysis. A complete discussion of the model...conditions. Quick-acting and slow- o acting (self-centering) snubbers were intalled to 0 0 arrest the fuselage motion divergences or co lock 0 0 out body

Thermotropic nanostructured gels with complex hierarchical structure and two gelling components for water shut-off and enhance of oil recovery

NASA Astrophysics Data System (ADS)

Altunina, L. K.; Kuvshinov, I. V.; Kuvshinov, V. A.; Kozlov, V. V.; Stasyeva, L. A.

2017-12-01

This work presents the results of laboratory and field tests of thermotropic composition MEGA with two simultaneously acting gelling components, polymer and inorganic. The composition is intended for improving oil recovery and water shut-off at oilfields developed by thermal flooding, and cyclic-steam stimulated oil production wells. The composition forms an in-situ "gel-in-gel" system with improved structural-mechanical properties, using reservoir or carrier fluid heat for gelling. The gel blocks water breakthrough into producing wells and redistribute fluid flows, thus increasing the oil recovery factor.

An electrochemical study of natural and chemically controlled eumelanin

NASA Astrophysics Data System (ADS)

Xu, Ri; Prontera, Carmela Tania; Di Mauro, Eduardo; Pezzella, Alessandro; Soavi, Francesca; Santato, Clara

2017-12-01

Eumelanin is the most common form of the pigment melanin in the human body, with functions including antioxidant behavior, metal chelation, and free radical scavenging. This biopigment is of interest for biologically derived batteries and supercapacitors. In this work, we characterized the voltammetric properties of chemically controlled eumelanins produced from 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) building blocks, namely, DHI-melanin, DHICA-melanin, and natural eumelanin, extracted from the ink sac of cuttlefish, Sepia melanin. Eumelanin electrodes were studied for their cyclic voltammetric properties in acidic buffers including Na+, K+, NH4+, and Cu2+ ions.

Solid-phase synthesis and structure-activity relationships of novel biarylethers as melanin-concentrating hormone receptor-1 antagonists.

PubMed

Ma, Vu; Bannon, Anthony W; Baumgartner, Jamie; Hale, Clarence; Hsieh, Faye; Hulme, Christopher; Rorrer, Kirk; Salon, John; van Staden, Carlo; Tempest, Paul

2006-10-01

Melanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic neuropeptide. The action of MCH on feeding is thought to involve the activation of its respective G protein-coupled receptor MCH-R1. Consequently, antagonists that block MCH regulated MCH-R1 activity may provide a viable approach to the treatment of diet-induced obesity. This communication reports the discovery of a novel MCH-R1 receptor antagonist, the biarylether 7, identified through high throughput screening. The solid-phase synthesis and structure-activity relationship of related analogs is described.

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

PubMed Central

2010-01-01

Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin) may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin). Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs) phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and endothelial nitric oxide synthase (eNOS) expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP-eNOS/NO-cyclic GMP pathway, resulting in inhibition of the PLCγ2-PKC-p38 MAPK-TxA2 cascade, and finally inhibition of platelet aggregation. PMID:20525309

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

cAMP is an essential signal in the induction of antibody production by B cells but inhibits helper function of T cells.

PubMed

Gilbert, K M; Hoffmann, M K

1985-09-01

Dibutyryl cAMP and IL 1 were found to stimulate antigen-specific and polyclonal antibody production when added together to cultures of highly purified B cells. We propose that IL 1 and an elevation in cytoplasmic cAMP represent minimal signal requirements for B cell activation. In contrast to its effect on B cells, dibutyryl cAMP inhibited helper T cell activity. Cyclic AMP suppressed the production of IL 2 and T cell replacing factor (TRF) by T cells and thus abrogated the ability of helper T cells to enhance SRBC-specific antibody production by B cells. Cyclic AMP did not inhibit the generation by T cells of B cell growth factor (BCGF). BCGF, not normally detected in Con A supernatant, was found in the culture supernatant of spleen cells that were stimulated with Con A in the presence of cAMP. Our findings indicate that cAMP blocks the production of an inhibitor of BCGF activity. cAMP had no effect on the production by macrophages of IL 1.

Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williaes, B. A.

1983-01-01

It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

Palmyramide A, a Cyclic Depsipeptide from a Palmyra Atoll Collection of the Marine Cyanobacterium Lyngbya majuscula

PubMed Central

Taniguchi, Masatoshi; Nunnery, Joshawna K.; Engene, Niclas; Esquenazi, Eduardo; Byrum, Tara; Dorrestein, Pieter C.; Gerwick, William H.

2010-01-01

Bioassay-guided fractionation of the extract of a consortium of a marine cyanobacterium and a red alga (Rhodophyta) led to the discovery of a novel compound, palmyramide A, along with the known compounds curacin D and malyngamide C. The planar structure of palmyramide A was determined by one- and two-dimensional NMR studies and mass spectrometry. Palmyramide A is a cyclic depsipeptide which features an unusual arrangement of three amino acids and three hydroxy acids; one of the hydroxy acids is the rare 2,2-dimethyl-3-hydroxyhexanoic acid unit (Dmhha). The absolute configurations of the six residues were determined by Marfey’s analysis, chiral HPLC analysis and GC/MS analysis of the hydrolysate. Morphological and phylogenetic studies revealed the sample to be composed of a Lyngbya majuscula-Centroceras sp. association. MALDI-imaging analysis of the cultured L. majuscula indicated that it was the true producer of this new depsipeptide. Pure palmyramide A showed sodium channel blocking activity in neuro-2a cells and cytotoxic activity in H-460 human lung carcinoma cells. PMID:19839606

Pyrazine as a building block for molecular architectures with PtII.

PubMed

Willermann, Michael; Mulcahy, Clodagh; Sigel, Roland K O; Cerdà, Marta Morell; Freisinger, Eva; Sanz Miguel, Pablo J; Roitzsch, Michael; Lippert, Bernhard

2006-03-06

A series of pyrazine (pz) complexes containing cis-(NH(3))(2)Pt(II), (tmeda)Pt(II) (tmeda = N,N,N',N'-tetramethylethylenediamine), and trans-(NH(3))(2)Pt(II) entities have been prepared and characterized by X-ray crystallography and/or 1H NMR spectroscopy. In these compounds, the pz ligands act as monodentate (1-3) or bidentate bridging ligands (4-7). Three variants of the latter case are described: a dinuclear complex [Pt(II)]2 (4b), a cyclic tetranuclear [Pt(II)](4) complex (5), and a trinuclear mixed-metal complex [Pt2Ag] (7). Mono- and bidentate binding modes are readily differentiated by 1H NMR spectroscopy, and the assignment of pz protons in the case of monodentate coordination is aided by the observation of (195)Pt satellites. Formation of the open molecular box cis-[{(NH3)2Pt(pz)}4](NO3)8.3.67H2O (5) from cis-(NH3)2Pt(II) and pz follows expectations of the "molecular library approach" for the generation of a cyclic tetramer.

A new and selective cycle for dehydrogenation of linear and cyclic alkanes under mild conditions using a base metal.

PubMed

Solowey, Douglas P; Mane, Manoj V; Kurogi, Takashi; Carroll, Patrick J; Manor, Brian C; Baik, Mu-Hyun; Mindiola, Daniel J

2017-11-01

Selectively converting linear alkanes to α-olefins under mild conditions is a highly desirable transformation given the abundance of alkanes as well as the use of olefins as building blocks in the chemical community. Until now, this reaction has been primarily the remit of noble-metal catalysts, despite extensive work showing that base-metal alkylidenes can mediate the reaction in a stoichiometric fashion. Here, we show how the presence of a hydrogen acceptor, such as the phosphorus ylide, when combined with the alkylidene complex (PNP)Ti=CH t Bu(CH 3 ) (PNP=N[2-P(CHMe 2 ) 2 -4-methylphenyl] 2 - ), catalyses the dehydrogenation of cycloalkanes to cyclic alkenes, and linear alkanes with chain lengths of C 4 to C 8 to terminal olefins under mild conditions. This Article represents the first example of a homogeneous and selective alkane dehydrogenation reaction using a base-metal titanium catalyst. We also propose a unique mechanism for the transfer dehydrogenation of hydrocarbons to olefins and discuss a complete cycle based on a combined experimental and computational study.

A new and selective cycle for dehydrogenation of linear and cyclic alkanes under mild conditions using a base metal

NASA Astrophysics Data System (ADS)

Solowey, Douglas P.; Mane, Manoj V.; Kurogi, Takashi; Carroll, Patrick J.; Manor, Brian C.; Baik, Mu-Hyun; Mindiola, Daniel J.

2017-11-01

Selectively converting linear alkanes to α-olefins under mild conditions is a highly desirable transformation given the abundance of alkanes as well as the use of olefins as building blocks in the chemical community. Until now, this reaction has been primarily the remit of noble-metal catalysts, despite extensive work showing that base-metal alkylidenes can mediate the reaction in a stoichiometric fashion. Here, we show how the presence of a hydrogen acceptor, such as the phosphorus ylide, when combined with the alkylidene complex (PNP)Ti=CHtBu(CH3) (PNP=N[2-P(CHMe2)2-4-methylphenyl]2-), catalyses the dehydrogenation of cycloalkanes to cyclic alkenes, and linear alkanes with chain lengths of C4 to C8 to terminal olefins under mild conditions. This Article represents the first example of a homogeneous and selective alkane dehydrogenation reaction using a base-metal titanium catalyst. We also propose a unique mechanism for the transfer dehydrogenation of hydrocarbons to olefins and discuss a complete cycle based on a combined experimental and computational study.

Cyclic GMP-mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice.

PubMed

Lueptow, Lindsay M; Zhan, Chang-Guo; O'Donnell, James M

2016-02-01

Cyclic nucleotide phosphodiesterase-2 (PDE2) is a potential therapeutic target for the treatment of cognitive dysfunction. Using the object recognition test (ORT), this study assessed the effects of two PDE2 inhibitors, Bay 60-7550 and ND7001, on learning and memory, and examined underlying mechanisms. To assess the role of PDE2 inhibition on phases of memory, Bay 60-7550 (3 mg/kg) was administered: 30 min prior to training; 0, 1, or 3 h after training; or 30 min prior to recall testing. To assess cyclic nucleotide involvement in PDE2 inhibitor-enhanced memory consolidation, either the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg; intraperitoneal (IP)), soluble guanylyl cyclase inhibitor 1H-[-1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 20 mg/kg; IP), protein kinase G inhibitor KT5823 (2.5 μg; intracerebroventricular (ICV)), or protein kinase A inhibitor H89 (1 μg; ICV) was administered 30 min prior to the PDE2 inhibitor Bay 60-7550 (3 mg/kg) or ND7001 (3 mg/kg). Changes in the phosphorylation of 3'5'-cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) at Ser-133 and vasodilator-stimulated phosphoprotein (VASP) at Ser-239 were determined to confirm activation of cAMP and 3'5'-cyclic guanosine monophosphate (cGMP) signaling. Bay 60-7550 (3 mg/kg) enhanced memory of mice in the ORT when given 30 min prior to training, immediately after training, or 30 min prior to recall. Inhibitors of the cGMP pathway blocked the memory-enhancing effects of both Bay 60-7550 (3 mg/kg) and ND7001 (3 mg/kg) on early consolidation processes. Bay 60-7550 (3 mg/kg) enhanced phosphorylation of CREB and VASP, both targets of cGMP-dependent protein kinase (PKG). These results confirm a potential of PDE2, or components of its signaling pathway, as a therapeutic target for drug discovery focused on restoring memory function.

Measurement of impulsive choice in rats: Same and alternate form test-retest reliability and temporal tracking

PubMed Central

Peterson, Jennifer R.; Hill, Catherine C.; Kirkpatrick, Kimberly

2016-01-01

Impulsive choice is typically measured by presenting smaller-sooner (SS) versus larger-later (LL) rewards, with biases towards the SS indicating impulsivity. The current study tested rats on different impulsive choice procedures with LL delay manipulations to assess same-form and alternate-form test-retest reliability. In the systematic-GE procedure (Green & Estle, 2003), the LL delay increased after several sessions of training; in the systematic-ER procedure (Evenden & Ryan, 1996), the delay increased within each session; and in the adjusting-M procedure (Mazur, 1987), the delay changed after each block of trials within a session based on each rat’s choices in the previous block. In addition to measuring choice behavior, we also assessed temporal tracking of the LL delays using the median times of responding during LL trials. The two systematic procedures yielded similar results in both choice and temporal tracking measures following extensive training, whereas the adjusting procedure resulted in relatively more impulsive choices and poorer temporal tracking. Overall, the three procedures produced acceptable same form test-retest reliability over time, but the adjusting procedure did not show significant alternate form test-retest reliability with the other two procedures. The results suggest that systematic procedures may supply better measurements of impulsive choice in rats. PMID:25490901

Mutations in the Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL) Confer Multidrug Resistance.

PubMed

LaMonte, Gregory; Lim, Michelle Yi-Xiu; Wree, Melanie; Reimer, Christin; Nachon, Marie; Corey, Victoria; Gedeck, Peter; Plouffe, David; Du, Alan; Figueroa, Nelissa; Yeung, Bryan; Bifani, Pablo; Winzeler, Elizabeth A

2016-07-05

Mutations in the Plasmodium falciparum cyclic amine resistance locus (PfCARL) are associated with parasite resistance to the imidazolopiperazines, a potent class of novel antimalarial compounds that display both prophylactic and transmission-blocking activity, in addition to activity against blood-stage parasites. Here, we show that pfcarl encodes a protein, with a predicted molecular weight of 153 kDa, that localizes to the cis-Golgi apparatus of the parasite in both asexual and sexual blood stages. Utilizing clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene introduction of 5 variants (L830V, S1076N/I, V1103L, and I1139K), we demonstrate that mutations in pfcarl are sufficient to generate resistance against the imidazolopiperazines in both asexual and sexual blood-stage parasites. We further determined that the mutant PfCARL protein confers resistance to several structurally unrelated compounds. These data suggest that PfCARL modulates the levels of small-molecule inhibitors that affect Golgi-related processes, such as protein sorting or membrane trafficking, and is therefore an important mechanism of resistance in malaria parasites. Several previous in vitro evolution studies have implicated the Plasmodium falciparum cyclic amine resistance locus (PfCARL) as a potential target of imidazolopiperazines, potent antimalarial compounds with broad activity against different parasite life cycle stages. Given that the imidazolopiperazines are currently being tested in clinical trials, understanding their mechanism of resistance and the cellular processes involved will allow more effective clinical usage. Copyright © 2016 LaMonte et al.

Cyclic nucleotides induce long-term augmentation of glutamate-activated chloride current in molluscan neurons.

PubMed

Bukanova, Julia V; Solntseva, Elena I; Skrebitsky, Vladimir G

2005-12-01

1. Literature data indicate that serotonin induces the long-term potentiation of glutamate (Glu) response in molluscan neurons. The aim of present work was to elucidate whether cyclic nucleotides can cause the same effect. 2. Experiments were carried out on isolated neurons of the edible snail (Helix pomatia) using a two-microelectrode voltage-clamp method. 3. In the majority of the cells examined, the application of Glu elicited a Cl- -current. The reversal potential (Er) of this current lied between -35 and -55 mV in different cells. 4. Picrotoxin, a blocker of Cl- -channels, suppressed this current equally on both sides of Er. Furosemide, an antagonist of both Cl- -channels and the Na+/K+/Cl- -cotransporter, had a dual effect on Glu-response: decrease in conductance, and shift of Er to negative potentials. 5. A short-term (2 min) cell treatment with 8-Br-cAMP or 8-Br-cGMP caused long-term (up to 30 min) change in Glu-response. At a holding potential of -60 mV, which was close to the resting level, an increase in Glu-activated inward current was observed. This potentiation seems to be related to the right shift of Er of Glu-activated Cl- -current rather than to the increase in conductance of Cl- -channels. The blocking effect of picrotoxin rested after 8-Br-cAMP treatment. 6. The change in the Cl- -homeostasis as a possible mechanism for the observed effect of cyclic nucleotides is discussed.

Resolving writer's block.

PubMed Central

Huston, P.

1998-01-01

PROBLEM BEING ADDRESSED: Writer's block, or a distinctly uncomfortable inability to write, can interfere with professional productivity. OBJECTIVE OF PROGRAM: To identify writer's block and to outline suggestions for its early diagnosis, treatment, and prevention. MAIN COMPONENTS OF PROGRAM: Once the diagnosis has been established, a stepwise approach to care is recommended. Mild blockage can be resolved by evaluating and revising expectations, conducting a task analysis, and giving oneself positive feedback. Moderate blockage can be addressed by creative exercises, such as brainstorming and role-playing. Recalcitrant blockage can be resolved with therapy. Writer's block can be prevented by taking opportunities to write at the beginning of projects, working with a supportive group of people, and cultivating an ongoing interest in writing. CONCLUSIONS: Writer's block is a highly treatable condition. A systematic approach can help to alleviate anxiety, build confidence, and give people the information they need to work productively. PMID:9481467

Distribution and abundance of birds wintering in Maryland, 1988-1993

USGS Publications Warehouse

Hatfield, J.S.; Ricciardi, S.A.; Gough, G.A.; Bystrak, D.; Droege, S.; Robbins, C.S.

1994-01-01

A winter bird survey was conducted throughout Maryland, primarily by volunteers, during the 6 winters of 1988 to 1993 between the dates of 10 Jan and 10 Feb. The state of Maryland is covered by 1231 blocks (9.5 sq. miles each), each comprising one-sixth of the standard U.S.G.S. 7.5 minute topographic quadrangle, and 548 of these blocks (44.5%) were surveyed for winter birds. Blocks were chosen in a systematic pattern with eventually almost every other block in the state having been surveyed as of Feb, 1993. Volunteers conducted each 4-hour survey by walking a 4-6 mile route chosen by the volunteer to sample habitats in proportion to their availability in the block. Surveys began around sunrise (~7:30 a.m.) and all birds seen or heard during the 4 hours were recorded on data sheets. The data were then used to create maps representing the distribution and relative abundance of each species of wintering bird found in at least 10 blocks in the state.

Plastic Fibre Reinforced Soil Blocks as a Sustainable Building Material

NASA Astrophysics Data System (ADS)

Prasad, C. K. Subramania; Nambiar, E. K. Kunhanandan; Abraham, Benny Mathews

2012-10-01

Solid waste management, especially the huge quantity of waste plastics, is one of the major environmental concerns nowadays. Their employability in block making in the form of fibres, as one of the methods of waste management, can be investigated through a fundamental research. This paper highlights the salient observations from a systematic investigation on the effect of embedded fibre from plastic waste on the performance of stabilised mud blocks. Stabilisation of the soil was done by adding cement, lime and their combination. Plastic fibre in chopped form from carry bags and mineral water bottles were added (0.1% & 0.2% by weight of soil) as reinforcement. The blocks were tested for density, and compressive strength, and observed failure patterns were analysed. Blocks with 0.1% of plastic fibres showed an increase in strength of about 3 to 10%. From the observations of failure pattern it can be concluded that benefits of fibre reinforcement includes both improved ductility in comparison with raw blocks and inhibition of crack propogation after its initial formation.

The application of GPS precise point positioning technology in aerial triangulation

NASA Astrophysics Data System (ADS)

Yuan, Xiuxiao; Fu, Jianhong; Sun, Hongxing; Toth, Charles

In traditional GPS-supported aerotriangulation, differential GPS (DGPS) positioning technology is used to determine the 3-dimensional coordinates of the perspective centers at exposure time with an accuracy of centimeter to decimeter level. This method can significantly reduce the number of ground control points (GCPs). However, the establishment of GPS reference stations for DGPS positioning is not only labor-intensive and costly, but also increases the implementation difficulty of aerial photography. This paper proposes aerial triangulation supported with GPS precise point positioning (PPP) as a way to avoid the use of the GPS reference stations and simplify the work of aerial photography. Firstly, we present the algorithm for GPS PPP in aerial triangulation applications. Secondly, the error law of the coordinate of perspective centers determined using GPS PPP is analyzed. Thirdly, based on GPS PPP and aerial triangulation software self-developed by the authors, four sets of actual aerial images taken from surveying and mapping projects, different in both terrain and photographic scale, are given as experimental models. The four sets of actual data were taken over a flat region at a scale of 1:2500, a mountainous region at a scale of 1:3000, a high mountainous region at a scale of 1:32000 and an upland region at a scale of 1:60000 respectively. In these experiments, the GPS PPP results were compared with results obtained through DGPS positioning and traditional bundle block adjustment. In this way, the empirical positioning accuracy of GPS PPP in aerial triangulation can be estimated. Finally, the results of bundle block adjustment with airborne GPS controls from GPS PPP are analyzed in detail. The empirical results show that GPS PPP applied in aerial triangulation has a systematic error of half-meter level and a stochastic error within a few decimeters. However, if a suitable adjustment solution is adopted, the systematic error can be eliminated in GPS-supported bundle block adjustment. When four full GCPs are emplaced in the corners of the adjustment block, then the systematic error is compensated using a set of independent unknown parameters for each strip, the final result of the bundle block adjustment with airborne GPS controls from PPP is the same as that of bundle block adjustment with airborne GPS controls from DGPS. Although the accuracy of the former is a little lower than that of traditional bundle block adjustment with dense GCPs, it can still satisfy the accuracy requirement of photogrammetric point determination for topographic mapping at many scales.

New Paleomagnetic Data from the Wadi Abyad Crustal Section and their Implications for the Rotation History of the Oman Ophiolite

NASA Astrophysics Data System (ADS)

Meyer, M.; Morris, A.; Anderson, M.; MacLeod, C. J.

2014-12-01

The Oman ophiolite is an important natural laboratory for understanding the construction of oceanic crust at fast spreading axes and its subsequent tectonic evolution. Previous paleomagnetic research in lavas of the northern ophiolitic blocks (Perrin et al., 2000, Mar. Geophys. Res.) has demonstrated substantial clockwise intraoceanic tectonic rotations. Paleomagnetic data from lower crustal sequences in the southern blocks, however, have been more equivocal due to complications arising from remagnetization, and have been used to infer that clockwise rotations seen in the north are internal to the ophiolite rather than regionally significant (Weiler, 2000, Mar. Geophys. Res.). Here we demonstrate the importance and advantages of sampling crustal transects in the ophiolite in order to understand the nature and variability in magnetization directions. By systematically sampling the lower crustal sequence exposed in Wadi Abyad (Rustaq block) we resolve for the first time in a single section a pattern of remagnetized lowermost gabbros and retention of earlier magnetizations by uppermost gabbros and the overlying dyke-rooting zone. Results are supported by a positive fold test that shows that remagnetization of lower gabbros occurred prior to the Campanian structural disruption of the Moho. NW-directed remagnetized remanences in the lower units are consistent with those used by Weiler (2000, Mar. Geophys. Res.) to infer lack of significant rotation of the southern blocks and to argue, therefore, that rotation of the northern blocks was internal to the ophiolite. In contrast, E/ENE-directed remanences in the uppermost levels of Wadi Abyad imply a large, clockwise rotation of the Rustaq block, of a sense and magnitude consistent with intraoceanic rotations inferred from extrusive sections in the northern blocks. We conclude that without the control provided by systematic crustal sampling, the potential for different remanence directions being acquired at different times may lead to erroneous tectonic interpretation.

The effect of parturition induction treatment on interval to calving, calving ease, postpartum uterine health, and resumption of ovarian cyclicity in beef heifers.

PubMed

Šavc, Miha; Kenny, David A; Beltman, Marijke E

2016-05-01

The aim of this study was to compare the effects of two parturition induction protocols with a nontreated control group, on interval to calving, calving ease, postpartum uterine health, and ovarian cyclicity in beef heifers. At Day 285 of gestation, 81 crossbred recipient beef heifers carrying purebred Simmental fetuses, were blocked by live-weight, body condition score, expected calving date and fetal sex, and assigned to one of three groups: (1) control (CON; no induction treatment, n = 29); (2) induction with corticosteroids (CORT; n = 27); or (3) induction with corticosteroids plus prostaglandin (CORT + PG; n = 25). Interval from induction to calving in hours and calving ease on a scale of 1 to 5 were recorded. Vaginal mucus samples were collected on Day 21 and Day 42 after calving (Day 0) by means of a Metricheck and scored on a scale of 0 to 3. Reproductive tract examinations were conducted on Day 21 and Day 42 after calving, and uterine cytology samples were obtained on Day 21. A positive cytologic sample was defined as greater than 18% neutrophils in the sample obtained via a cytobrush technique. Cows were considered to have resumed ovarian cyclicity if the presence of the CL was confirmed. Data were analyzed using the Mixed (normally distributed data) and Genmod (nonparametric data) procedures of SAS (v. 9.3). The interval from treatment to calving was longer (P < 0.0001) for CON (161.9 ± 15.12 hours) animals compared with CORT (39.7 ± 11.64 hours) or CORT + PG (32.6 ± 12.10 hours), which did not differ. Treatment did not affect calving difficulty score. There was also no difference in incidence of retained placenta between the three groups. At Day 21 postpartum, cytology score tended to be higher for both induced groups (48%) compared with the control animals (24%), but this was not the case for vaginal mucus score (CON 52%, CORT 70%, and CORT + PG 52%). A higher proportion of CON had an involuted uterus by Day 21 postpartum (69%) compared with both induced groups (CORT 48%, CORT + PG 32%). Day 21 ovarian cyclicity was higher in both CON (52%) and CORT (59%) compared with CORT + PG (29%). By Day 42, there was no difference in ovarian cyclicity or uterine involution between CON and CORT; however, a positive relationship was observed between uterine involution score on Day 21 and return to cyclicity on Day 42 in these two groups. There was a negative relationship between uterine involution score and return to cyclicity in the CORT + PG group, and these animals were slower (P < 0.05) to resume cyclicity by Day 42 with a larger proportion animals having evidence of having resumed postpartum ovarian cyclicity in both CON (P = 0.03) and CORT compared with CORT + PG on Day 42. In conclusion, the use of corticosteroid-based treatments is an effective strategy to advance parturition in full term dams and does not have a negative effect on calving progress or dam health. However, when prostaglandin is also included in the protocol, these treatments may lead to greater delay in uterine involution with increased chance of uterine infection and slower resumption of ovarian cyclicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Suprascapular and Interscalene Nerve Block for Shoulder Surgery: A Systematic Review and Meta-analysis.

PubMed

Hussain, Nasir; Goldar, Ghazaleh; Ragina, Neli; Banfield, Laura; Laffey, John G; Abdallah, Faraj W

2017-12-01

Interscalene block provides optimal shoulder surgery analgesia, but concerns over its associated risks have prompted the search for alternatives. Suprascapular block was recently proposed as an interscalene block alternative, but evidence of its comparative analgesic effect is conflicting. This meta-analysis compares the analgesic effect and safety of suprascapular block versus interscalene block for shoulder surgery. Databases were searched for randomized trials comparing interscalene block with suprascapular block for shoulder surgery. Postoperative 24-h cumulative oral morphine consumption and the difference in the area under curve for pooled rest pain scores were designated as primary outcomes. Analgesic and safety outcomes, particularly block-related and respiratory complications, were evaluated as secondary outcomes. Results were pooled using random-effects modeling. Data from 16 studies (1,152 patients) were analyzed. Interscalene block and suprascapular block were not different in 24-h morphine consumption. The difference in area under the curve of pain scores for the 24-h interval favored interscalene block by 1.1 cm/h, but this difference was not clinically important. Compared with suprascapular block, interscalene block reduced postoperative pain but not opioid consumption during recovery room stay by a weighted mean difference (95% CI) of 1.5 cm (0.6 to 2.5 cm; P < 0.0001). Pain scores were not different at any other time. In contrast, suprascapular block reduced the odds of block-related and respiratory complications. This review suggests that there are no clinically meaningful analgesic differences between suprascapular block and interscalene block except for interscalene block providing better pain control during recovery room stay; however, suprascapular block has fewer side effects. These findings suggest that suprascapular block may be considered an effective and safe interscalene block alternative for shoulder surgery.

Shaping Crystal-Crystal Phase Transitions

NASA Astrophysics Data System (ADS)

Du, Xiyu; van Anders, Greg; Dshemuchadse, Julia; Glotzer, Sharon

Previous computational and experimental studies have shown self-assembled structure depends strongly on building block shape. New synthesis techniques have led to building blocks with reconfigurable shape and it has been demonstrated that building block reconfiguration can induce bulk structural reconfiguration. However, we do not understand systematically how this transition happens as a function of building block shape. Using a recently developed ``digital alchemy'' framework, we study the thermodynamics of shape-driven crystal-crystal transitions. We find examples of shape-driven bulk reconfiguration that are accompanied by first-order phase transitions, and bulk reconfiguration that occurs without any thermodynamic phase transition. Our results suggest that for well-chosen shapes and structures, there exist facile means of bulk reconfiguration, and that shape-driven bulk reconfiguration provides a viable mechanism for developing functional materials.

Proposal for a new definition of congenital complete atrioventricular block.

PubMed

Brucato, A; Jonzon, A; Friedman, D; Allan, L D; Vignati, G; Gasparini, M; Stein, J I; Montella, S; Michaelsson, M; Buyon, J

2003-01-01

The classic old definition of congenital heart block by Yater (1929) is still generally accepted: 'Heart block established in a young patient. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis'. However, other definitions are used. We systematically reviewed 1825 cases from 38 separate studies. We conclude that complete AV blocks detected in utero in the absence of structural abnormalities differ from blocks detected later in life with respect to pathogenesis (they are generally associated with maternal anti-Ro/SSA antibodies), poorer childhood prognosis, increased risk of developing late-onset dilated cardiomyopathy, different maternal clinical features and increased risk of recurrence in future pregnancies. For these reasons we propose a new modern definition of congenital complete AV block which might be acceptable to cardiologists, rheumatologists, pediatricians and obstetricians: 'an AV block is defined as congenital if it is diagnosed in utero, at birth or within the neonatal period (0-27 days after birth)'.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

PubMed

Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam

2015-11-15

The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins. Because of their extreme toxicity and history of weaponization, the BoNTs are regarded as potential biowarfare/bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than intensive care; therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was evaluated in a FRET assay for its ability to inhibit BoNT/A light chain (Balc). CPI was found to be highly potent, exhibiting a Ki of 12.3 nM with full-length Balc448 and 39.2 nM using a truncated crystallizable form of the light chain (Balc424). Cocrystallization studies revealed that in the Balc424-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn(2+) binding region involved in catalysis. This differs from linear peptide inhibitors described to date which block only the latter. Published by Elsevier Ltd.

Nursing regimens: effects on body condition, return to postpartum ovarian cyclicity in Santa Ines ewes, and performance of lambs.

PubMed

Ascari, I J; Alves, A C; Pérez, J R O; Lima, R R; Garcia, I F F; Nogueira, G P; Junqueira, F B; Castro, T R; Aziani, W L B; Alves, N G

2013-08-01

The effects of nursing regimens on the body condition, onset of ovarian cyclicity postpartum and weaning weight of lambs were assessed in Santa Ines ewes. Thirty-two ewes were blocked according to parity, number of lambs, and body weight at lambing and within each block randomly allocated to treatments: continuous nursing (CN), controlled nursing (CN2) with two daily feedings for an hour after the 10th day postpartum, or early weaning (EW) with total separation from the lambs after the 10th day. The animals were evaluated from the 12th day postpartum until the first estrus or until 60th day. The dry matter and nutrients intake did not differ among treatments (P>0.05) but did differ over time (P<0.01). The weight, body condition score, serum concentrations of non-esterified fatty acids and prolactin, the percentages of ewes in estrus, of ewes that ovulated within 60th day and had ovulation silent, the period from lambing to estrus, ovulation and follicle with a diameter ≥5mm and the maximum follicular diameter did not differ (P>0.05) among the treatments. The percentage of ovulation until 30th day was greater (P<0.05) in the EW group. The percentage of short luteal phases was higher in the CN2 and EW groups (P=0.07) and normal luteal phases were higher in the CN group (P=0.01). Lamb weight weaning was lower in the EW group (P<0.05). It is possible to use CN to obtain lambing periods less than eight months in Santa Ines ewes, with the advantages of simpler management and higher lamb weaning weights. Copyright © 2013 Elsevier B.V. All rights reserved.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: insights from x-ray crystallography

DOE PAGES

Kumaran, D.; Adler, M.; Levit, M.; ...

2015-10-17

The seven antigenically distinct serotypes (A to G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins: the heavy chain is responsible for neurospecific binding, internalization and translocation, and the light chain is responsible for substrate cleavage. Because of their extreme toxicity and prior history of weaponization, the BoNTs are considered to be potential bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than critical care;more » therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was synthesized and found to inhibit BoNT/A light chain (Balc) with high affinity. When tested in a cell-free Förster resonance excitation transfer (FRET) assay, CPI-1 was found to have a K i of 13.9 nM using full-length Balc448 and 42.1 nM using a truncated crystallizable form of light chain (Balc424). Co-crystallization of CPI-1 with Balc424 revealed that in the Balc-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn 2+ binding region involved in catalysis. This is in contrast to linear peptide inhibitors described to date which block only the latter« less

Lexical selection in the semantically blocked cyclic naming task: the role of cognitive control and learning

PubMed Central

Crowther, Jason E.; Martin, Randi C.

2014-01-01

Studies of semantic interference in language production have provided evidence for a role of cognitive control mechanisms in regulating the activation of semantic competitors during naming. The present study investigated the relationship between individual differences in cognitive control abilities, for both younger and older adults, and the degree of semantic interference in a blocked cyclic naming task. We predicted that individuals with lower working memory capacity (as measured by word span), lesser ability to inhibit distracting responses (as measured by Stroop interference), and a lesser ability to resolve proactive interference (as measured by a recent negatives task) would show a greater increase in semantic interference in naming, with effects being larger for older adults. Instead, measures of cognitive control were found to relate to specific indices of semantic interference in the naming task, rather than overall degree of semantic interference, and few interactions with age were found, with younger and older adults performing similarly. The increase in naming latencies across naming trials within a cycle was negatively correlated with word span for both related and unrelated conditions, suggesting a strategy of narrowing response alternatives based upon memory for the set of item names. Evidence for a role of inhibition in response selection was obtained, as Stroop interference correlated positively with the change in naming latencies across cycles for the related, but not unrelated, condition. In contrast, recent negatives interference correlated negatively with the change in naming latencies across unrelated cycles, suggesting that individual differences in this tap the degree of strengthening of links in a lexical network based upon prior exposure. Results are discussed in terms of current models of lexical selection and consequences for word retrieval in more naturalistic production. PMID:24478675

Landslide initiation in saprolite and colluvium in southern Brazil: Field and laboratory observations

NASA Astrophysics Data System (ADS)

Lacerda, Willy A.

2007-06-01

The weathering of granitic and gneissic rocks in tropical regions can reach depths of more than 100 m. In southeast Brazil there are situations where landslide initiation depends on the fluctuation of the groundwater level, on the impact of falling rocks and on intense rainfall, causing superficial slides. The fluctuation of groundwater induces cyclical variations of the pore water pressure, and consequently of the effective stresses. This variation causes cyclic expansion and contraction of the structure of the saprolitic soil, weakening the imbrication of grains and loss of the cementation that may exist. This could be called a "fatigue" phenomenon. The practical effect is the lowering of the Mohr shear strength envelope, and a sudden rupture of the soil at a lower groundwater level than that which would be compatible with the intact soil strength properties, initiating a landslide. Another situation arises during intense rains, when a rock slab or a rock block detaches from the uppermost parts of a slope. This occurs where steep rock outcrops exhibit relief joints or where residual blocks of granite roll down the slope, impacting the compressible, saturated colluvial soil overlying the saprolitic soil. The sudden increase of pore pressure can liquefy the soil. Finally, another mechanism is that of the advance of a saturation front in a steep slope of unsaturated saprolitic soil, reaching a depth below the root zone. The loss of the cohesion due to suction, without the beneficial contribution of the roots to the shearing strength, causes a sudden slide. During extreme rain episodes literally hundreds of such superficial slides, reaching 1 to 3 m in depth, occur in a given basin. The concentrated runoff that flows along the surface of the thalweg of the basin carries this soil in a muddy state, and a debris flow ensues.

Pain Management After Outpatient Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials.

PubMed

Secrist, Eric S; Freedman, Kevin B; Ciccotti, Michael G; Mazur, Donald W; Hammoud, Sommer

2016-09-01

Effective pain management after anterior cruciate ligament (ACL) reconstruction improves patient satisfaction and function. To collect and evaluate the available evidence from randomized controlled trials (RCTs) on pain control after ACL reconstruction. Systematic review. A systematic literature review was performed using PubMed, Medline, Google Scholar, UpToDate, Cochrane Reviews, CINAHL, and Scopus following PRISMA guidelines (July 2014). Only RCTs comparing a method of postoperative pain control to another method or placebo were included. A total of 77 RCTs met inclusion criteria: 14 on regional nerve blocks, 21 on intra-articular injections, 4 on intramuscular/intravenous injections, 12 on multimodal regimens, 6 on oral medications, 10 on cryotherapy/compression, 6 on mobilization, and 5 on intraoperative techniques. Single-injection femoral nerve blocks provided superior analgesia to placebo for up to 24 hours postoperatively; however, this also resulted in a quadriceps motor deficit. Indwelling femoral catheters utilized for 2 days postoperatively provided superior analgesia to a single-injection femoral nerve block. Local anesthetic injections at the surgical wound site or intra-articularly provided equivalent analgesia to regional nerve blocks. Continuous-infusion catheters of a local anesthetic provided adequate pain relief but have been shown to cause chondrolysis. Cryotherapy improved analgesia compared to no cryotherapy in 4 trials, while in 4 trials, ice water and water at room temperature provided equivalent analgesic effects. Early weightbearing decreased pain compared to delayed weightbearing. Oral gabapentin given preoperatively and oral zolpidem given for the first week postoperatively each decreased opioid consumption as compared to placebo. Ibuprofen reduced pain compared to acetaminophen. Oral ketorolac reduced pain compared to hydrocodone-acetaminophen. Regional nerve blocks and intra-articular injections are both effective forms of analgesia. Cryotherapy-compression appears to be beneficial, provided that intra-articular temperatures are sufficiently decreased. Early mobilization reduces pain symptoms. Gabapentin, zolpidem, ketorolac, and ibuprofen decrease opioid consumption. Despite the vast amount of high-quality evidence on this topic, further research is needed to determine the optimal multimodal approach that can maximize recovery while minimizing pain and opioid consumption. These results provide the best available evidence from RCTs on pain control regimens after ACL reconstruction. © 2015 The Author(s).

The laccase-like reactivity of manganese oxide nanomaterials for pollutant conversion: rate analysis and cyclic voltammetry.

PubMed

Wang, Xinghao; Liu, Jiaoqin; Qu, Ruijuan; Wang, Zunyao; Huang, Qingguo

2017-08-10

Nanostructured manganese oxides, e.g. MnO 2 , have shown laccase-like catalytic activities, and are thus promising for pollutant oxidation in wastewater treatment. We have systematically compared the laccase-like reactivity of manganese oxide nanomaterials of different crystallinity, including α-, β-, γ-, δ-, and ɛ-MnO 2 , and Mn 3 O 4 , with 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and 17β-estradiol (E2) as the probing substrates. The reaction rate behaviors were examined with regard to substrate oxidation and oxygen reduction to evaluate the laccase-like catalysis of the materials, among which γ-MnO 2 exhibits the best performance. Cyclic voltammetry (CV) was employed to assess the six MnO x nanomaterials, and the results correlate well with their laccase-like catalytic activities. The findings help understand the mechanisms of and the factors controlling the laccase-like reactivity of different manganese oxides nanomaterials, and provide a basis for future design and application of MnO x -based catalysts.

Effect of moisture on the fatigue behavior of graphite/epoxy composite laminates

NASA Technical Reports Server (NTRS)

Ramani, S. V.; Nelson, H. G.

1979-01-01

The form of the moisture distribution in the specimen (gradient and flat profile) was considered to establish the influence of accelerated moisture conditioning on fatigue behavior. For the gradient specimens having an average moisture content of 1.4 percent, fatigue life was reduced by a factor of 8 at all stress levels investigated. Corresponding reduction in fatigue life for the flat moisture profile specimens at the same average moisture content was comparatively smaller, being about a factor of 5 from the value in dry specimens. X-ray radiographic analysis of damage accumulation in compression-compression fatigue revealed interlaminar cracking to be the dominant mode of failure responsible for the observed enhanced cyclic degradation of moisture-conditioned specimens. This finding was corroborated by the observed systematic reduction in interlaminar shear strength as a function of moisture content, which, in turn, increased the propensity for delamination under cyclic compressive loads. Residual strength measurements on cycled specimens indicated significant strength reductions at long lives, particularly in moisture conditioned specimens.

Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

NASA Astrophysics Data System (ADS)

Sidera, Mireia; Fletcher, Stephen P.

2015-11-01

Csp2-Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2-Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2-Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

THE ANALYSIS OF THE TIME-SERIES FLUCTUATION OF WATER DEMAND FOR THE SMALL WATER SUPPLY BLOCK

NASA Astrophysics Data System (ADS)

Koizumi, Akira; Suehiro, Miki; Arai, Yasuhiro; Inakazu, Toyono; Masuko, Atushi; Tamura, Satoshi; Ashida, Hiroshi

The purpose of this study is to define one apartment complex as "the water supply block" and to show the relationship between the amount of water supply for an apartment house and its time series fluctuation. We examined the observation data which were collected from 33 apartment houses. The water meters were installed at individual observation points for about 20 days in Tokyo. This study used Fourier analysis in order to grasp the irregularity in a time series data. As a result, this paper demonstrated that the smaller the amount of water supply became, the larger irregularity the time series fluctuation had. We also found that it was difficult to describe the daily cyclical pattern for a small apartment house using the dominant periodic components which were obtained from a Fourier spectrum. Our research give useful information about the design for a directional water supply system, as to making estimates of the hourly fluctuation and the maximum daily water demand.

Oxidations of N-(3-indoleethyl) cyclic aliphatic amines by horseradish peroxidase: the indole ring binds to the enzyme and mediates electron-transfer amine oxidation.

PubMed

Ling, Ke-Qing; Li, Wen-Shan; Sayre, Lawrence M

2008-01-23

Although oxidations of aromatic amines by horseradish peroxidase (HRP) are well-known, typical aliphatic amines are not substrates of HRP. In this study, the reactions of N-benzyl and N-methyl cyclic amines with HRP were found to be slow, but reactions of N-(3-indoleethyl) cyclic amines were 2-3 orders of magnitude faster. Analyses of pH-rate profiles revealed a dominant contribution to reaction by the amine-free base forms, the only species found to bind to the enzyme. A metabolic study on a family of congeneric N-(3-indoleethyl) cyclic amines indicated competition between amine and indole oxidation pathways. Amine oxidation dominated for the seven- and eight-membered azacycles, where ring size supports the change in hybridization from sp3 to sp2 that occurs upon one-electron amine nitrogen oxidation, whereas only indole oxidation was observed for the six-membered ring congener. Optical difference spectroscopic binding data and computational docking simulations suggest that all the arylalkylamine substrates bind to the enzyme through their aromatic termini with similar binding modes and binding affinities. Kinetic saturation was observed for a particularly soluble substrate, consistent with an obligatory role of an enzyme-substrate complexation preceding electron transfer. The significant rate enhancements seen for the indoleethylamine substrates suggest the ability of the bound indole ring to mediate what amounts to medium long-range electron-transfer oxidation of the tertiary amine center by the HRP oxidants. This is the first systematic investigation to document aliphatic amine oxidation by HRP at rates consistent with normal metabolic turnover, and the demonstration that this is facilitated by an auxiliary electron-rich aromatic ring.

Magmatic Processes at Kilauea Volcano Revealed by the Puu Oo Eruption

NASA Astrophysics Data System (ADS)

Garcia, M. O.; Marske, J. P.; Pietruszka, A. P.; Rhodes, J. M.; Norman, M. D.; Eiler, J.

2008-12-01

The ongoing Puu Oo eruption (1983 to present) provides an unprecedented opportunity to probe the crustal and mantle magmatic processes beneath Kilauea volcano. Here we present Pb, Sr, Nd and O isotope ratios, major- and trace-element abundances, olivine compositions, and petrography data for Puu Oo lavas an compare them to the Kilauea historical record. Crustal processes are dominated by olivine fractionation and accumulation with minor clinopyroxene fractionation, and to a lesser extent and only periodically when eruption rates decrease, by crustal contamination. Systematic variations in Sr isotope ratios, incompatible trace element ratios, and MgO-normalized major elements document remarkable changes in parental magma compositions delivered to Puu Oo. Inflections in some trends correlate broadly with increasing intermediate depth earthquakes under the Kilauea's summit and to changes in eruption rate. Thus, volcanic events are influenced by melting and transport processes. One surprising feature is the systematic trend of Puu Oo rock compositions away from and beyond typical historical Kilauea compositions towards those of lavas from neighboring Mauna Loa volcano. The source for this component in Puu Oo lavas is a hybrid with about equal mixtures of historical Kilauea and Mauna Loa end members. The Puu Oo lava trend continues the cyclic pattern of compositional variation that extends back over 1000 years. Similar trends are also recorded on a coarser scale in HSDP lavas. These patterns of cyclic compositional variation are important for understanding melting processes in Hawaiian and other volcanoes.

An Adaptive Mesh Algorithm: Mesh Structure and Generation

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

Scannapieco, Anthony J.

2016-06-21

The purpose of Adaptive Mesh Refinement is to minimize spatial errors over the computational space not to minimize the number of computational elements. The additional result of the technique is that it may reduce the number of computational elements needed to retain a given level of spatial accuracy. Adaptive mesh refinement is a computational technique used to dynamically select, over a region of space, a set of computational elements designed to minimize spatial error in the computational model of a physical process. The fundamental idea is to increase the mesh resolution in regions where the physical variables are represented bymore » a broad spectrum of modes in k-space, hence increasing the effective global spectral coverage of those physical variables. In addition, the selection of the spatially distributed elements is done dynamically by cyclically adjusting the mesh to follow the spectral evolution of the system. Over the years three types of AMR schemes have evolved; block, patch and locally refined AMR. In block and patch AMR logical blocks of various grid sizes are overlaid to span the physical space of interest, whereas in locally refined AMR no logical blocks are employed but locally nested mesh levels are used to span the physical space. The distinction between block and patch AMR is that in block AMR the original blocks refine and coarsen entirely in time, whereas in patch AMR the patches change location and zone size with time. The type of AMR described herein is a locally refi ned AMR. In the algorithm described, at any point in physical space only one zone exists at whatever level of mesh that is appropriate for that physical location. The dynamic creation of a locally refi ned computational mesh is made practical by a judicious selection of mesh rules. With these rules the mesh is evolved via a mesh potential designed to concentrate the nest mesh in regions where the physics is modally dense, and coarsen zones in regions where the physics is modally sparse.« less

Semi-automatic spray pyrolysis deposition of thin, transparent, titania films as blocking layers for dye-sensitized and perovskite solar cells.

PubMed

Krýsová, Hana; Krýsa, Josef; Kavan, Ladislav

2018-01-01

For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO 2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO 2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20-200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO 2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO 2 films. The blocking properties of the as-deposited TiO 2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO 2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells.

Generation and Characterization of Monoclonal Antibodies against a Cyclic Variant of Hepatitis C Virus E2 Epitope 412-422

PubMed Central

Sandomenico, Annamaria; Leonardi, Antonio; Berisio, Rita; Sanguigno, Luca; Focà, Giuseppina; Focà, Annalia; Ruggiero, Alessia; Doti, Nunzianna; Muscariello, Livio; Barone, Daniela; Farina, Claudio; Owsianka, Ania; Vitagliano, Luigi

2016-01-01

ABSTRACT The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for virus entry into hepatocytes. A conserved region of E2 encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical for virus entry, is recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt a β-hairpin conformation when bound to neutralizing monoclonal antibodies (MAbs) AP33 and HCV1. We therefore generated new mouse MAbs that were able to bind to a cyclic peptide containing E2 residues 412 to 422 (C-epitope I) but not to the linear counterpart. These MAbs bound to purified E2 with affinities of about 50 nM, but they were unable to neutralize virus infection. Structural analysis of the complex between C-epitope I and one of our MAbs (C2) showed that the Trp420 side chain is largely buried in the combining site and that the Asn417 side chain, which is glycosylated in E2 and solvent exposed in other complexes, is slightly buried upon C2 binding. Also, the orientation of the cyclic peptide in the antibody-combining site is rotated by 180° compared to the orientations of the other complexes. All these structural features, however, do not explain the lack of neutralization activity. This is instead ascribed to the high degree of selectivity of the new MAbs for the cyclic epitope and to their inability to interact with the epitope in more flexible and extended conformations, which recent data suggest play a role in the mechanisms of neutralization escape. IMPORTANCE Hepatitis C virus (HCV) remains a major health care burden, affecting almost 3% of the global population. The conserved epitope comprising residues 412 to 423 of the viral E2 glycoprotein is a valid vaccine candidate because antibodies recognizing this region exhibit potent neutralizing activity. This epitope adopts a β-hairpin conformation when bound to neutralizing MAbs. We explored the potential of cyclic peptides mimicking this structure to elicit anti-HCV antibodies. MAbs that specifically recognize a cyclic variant of the epitope bind to soluble E2 with a lower affinity than other blocking antibodies and do not neutralize virus. The structure of the complex between one such MAb and the cyclic epitope, together with new structural data showing the linear peptide bound to neutralizing MAbs in extended conformations, suggests that the epitope displays a conformational flexibility that contributes to neutralization escape. Such features can be of major importance for the design of epitope-based anti-HCV vaccines. PMID:26819303

Transversus abdominis plane block using a short-acting local anesthetic for postoperative pain after laparoscopic colorectal surgery: a systematic review and meta-analysis.

PubMed

Oh, Tak Kyu; Lee, Se-Jun; Do, Sang-Hwan; Song, In-Ae

2018-02-01

Transversus abdominis plane (TAP) block using a short-acting local anesthetic as part of multimodal analgesia is efficient in various abdominal surgeries, including laparoscopic surgery. However, information regarding its use in laparoscopic colorectal surgery is still limited and sometimes controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether TAP block using a short-acting anesthetic has a positive postoperative analgesic outcome in patients who have undergone laparoscopic colorectal surgery. We searched for studies comparing the postoperative pain outcome after laparoscopic colorectal surgery between patients who received TAP block and a control group (placebo or no treatment). Outcome measures were early pain at rest (numeric rating scale [NRS] score at 0-2 h postoperatively), late pain at movement (NRS score at 24 h postoperatively), late pain at rest (NRS score at 24 h postoperatively), and postoperative opioid consumption (up to 24 h postoperatively). We used a random-effects model for the meta-analysis and Egger's regression test to detect publication bias. We included six studies involving 452 patients (224 in the TAP block group, 228 in the control group). Early and late pain scores at movement were significantly different between the TAP block and control groups (standardized mean difference: - 0.695, P < 0.0001 for early pain and - 0.242, P = 0.029 for late pain). There was no significant difference between the TAP block and control groups in early pain at rest (P = 0.475), late pain at rest (P = 0.826), and postoperative opioid consumption (P = 0.257). The TAP block using a short-acting anesthetic had a significant effect on the postoperative pain outcome in the early (0-2 h) and late (24 h) period at movement. However, it did not have a significant effect on the postoperative pain outcome in the early (0-2 h) and late (24 h) periods at rest after laparoscopic surgery.

Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Singh, Vijay; Derby, Richard; Fellows, Bert; Falco, Frank J E; Datta, Sukdeb; Smith, Howard S; Hirsch, Joshua A

2009-01-01

Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain. Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients. To provide evidence-based clinical practice guidelines for diagnostic interventional techniques. Best evidence synthesis. Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all. The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3. Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation of systematic reviews and guidelines. These guidelines include the evaluation of evidence for diagnostic interventional procedures in managing chronic spinal pain and recommendations. However, these guidelines do not constitute inflexible treatment recommendations. These guidelines also do not represent a "standard of care."

Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN.

PubMed

Haseneen, Nadia A; Vaday, Gayle G; Zucker, Stanley; Foda, Hussein D

2003-03-01

High-volume mechanical ventilation leads to ventilator-induced lung injury. This type of lung injury is accompanied by an increased release and activation of matrix metalloproteinases (MMPs). To investigate the mechanism leading to the increased MMP release, we systematically studied the effect of mechanical stretch on human microvascular endothelial cells isolated from the lung. We exposed cells grown on collagen 1 BioFlex plates to sinusoidal cyclic stretch at 0.5 Hz using the Flexercell system with 17-18% elongation of cells. After 4 days of cell stretching, conditioned media and cell lysate were collected and analyzed by gelatin, casein, and reverse zymograms as well as Western blotting. RT-PCR of mRNA extracted from stretched cells was performed. Our results show that 1) cyclic stretch led to increased release and activation of MMP-2 and MMP-1; 2) the activation of MMP-2 was accompanied by an increase in membrane type-1 MMP (MT1-MMP) and inhibited by a hydroxamic acid-derived inhibitor of MMPs (Prinomastat, AG3340); and 3) the MMP-2 release and activation were preceded by an increase in production of extracellular MMP inducer (EMMPRIN). These results suggest that cyclic mechanical stretch leads to MMP-2 activation through an MT1-MMP mechanism. EMMPRIN may play an important role in the release and activation of MMPs during lung injury.

Systematic approach to in-depth understanding of photoelectrocatalytic bacterial inactivation mechanisms by tracking the decomposed building blocks.

PubMed

Sun, Hongwei; Li, Guiying; Nie, Xin; Shi, Huixian; Wong, Po-Keung; Zhao, Huijun; An, Taicheng

2014-08-19

A systematic approach was developed to understand, in-depth, the mechanisms involved during the inactivation of bacterial cells using photoelectrocatalytic (PEC) processes with Escherichia coli K-12 as the model microorganism. The bacterial cells were found to be inactivated and decomposed primarily due to attack from photogenerated H2O2. Extracellular reactive oxygen species (ROSs), such as H2O2, may penetrate into the bacterial cell and cause dramatically elevated intracellular ROSs levels, which would overwhelm the antioxidative capacity of bacterial protective enzymes such as superoxide dismutase and catalase. The activities of these two enzymes were found to decrease due to the ROSs attacks during PEC inactivation. Bacterial cell wall damage was then observed, including loss of cell membrane integrity and increased permeability, followed by the decomposition of cell envelope (demonstrated by scanning electronic microscope images). One of the bacterial building blocks, protein, was found to be oxidatively damaged due to the ROSs attacks, as well. Leakage of cytoplasm and biomolecules (bacterial building blocks such as proteins and nucleic acids) were evident during prolonged PEC inactivation process. The leaked cytoplasmic substances and cell debris could be further degraded and, ultimately, mineralized with prolonged PEC treatment.

Surface monolayers of well-defined amphiphilic block copolymer composed of poly(acrylic acid) or poly(oxyethylene) and poly(styrene). Interpolymer complexation at the air-water interface

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

Niwa, Masazo; Hayashi, Takehiro; Higashi, Nobuyuki

1990-01-01

Amphiphilic block polymers (2,3) composed of poly(acrylic acid) (PAA) or poly(oxyethylene) (POE) and chain length controlled poly(styrene) (PSt) have been prepared by using a catalytic system of tribromomethyl-terminated oligomer and manganese carbonyl. All the amphiphilic materials formed well-behaved surface monolayers, and the II-A curves for them expanded systematically with an increase of the PSt chain length.

Simulation of a 3D Turbulent Wavy Channel based on the High-order WENO Scheme

NASA Astrophysics Data System (ADS)

Tsai, Bor-Jang; Chou, Chung-Chyi; Tsai, Yeong-Pei; Chuang, Ying Hung

2018-02-01

Passive interest turbulent drag reduction, effective means to improve air vehicle fuel consumption costs. Most turbulent problems happening to the nature and engineering applications were exactly the turbulence problem frequently caused by one or more turbulent shear flows. This study was operated with incompressible 3-D channels with cyclic wavy boundary to explore the physical properties of turbulence flow. This research measures the distribution of average velocity, instant flowing field shapes, turbulence and pressure distribution, etc. Furthermore, the systematic computation and analysis for the 3-D flow field was also implemented. It was aimed to clearly understand the turbulence fields formed by wavy boundary of tube flow. The purpose of this research is to obtain systematic structural information about the turbulent flow field and features of the turbulence structure are discussed.

The systematic change of metamorphism along the Dabie-Sulu-Hongseong-Odesan collision belt between the North and South China blocks

NASA Astrophysics Data System (ADS)

Oh, C. W.

2013-12-01

As a last step of formation of the Pangea supercontinent, the North China block collided with the South China block during Permo-Triassic time forming the Oinling-Dabie-Sulu collision belt which was identified by the finding of ultrahigh- and high-P/T eclogites along the belt. After the Qiling-Dabie-Sulu collision belt was found, the continuation of the collision belt into Korean Peninsula became a hot issue. Although the Imjingang belt in Korean Peninsula was suggested as an extension of the belt, no evidence of collision belt such as eclogite and ophiolite, was found. Whereas recent studies on Korean Peninsula reveal that Triassic eclogite (ca. > 230 Ma) formed in the Hongseong area and Triassic post collision igneous rocks (with ca. 230 Ma intrusion ages) occurred throughout the Gyeonggi Massif locating to the north of the line connecting the Hongseong, Yangpyeong and Odesan areas. These new findings derive the tectonic model in which the Permo-Triassic Qinling-Dabie-Sulu collision belt between the North and South China blocks extends into the Hongseong-Yangpyeong-Odesan collision belt in Korean Peninsula. The belt may be further extended into the late Paleozoic subduction complex in the Yanji belt in North Korea through the Paleozoic subduction complex in the inner part of SW Japan. The collision had started from Korea at ca. 250 Ma and propagated towards China. The collision completed during late Triassic. The metamorphic conditions systematically change along the collision belt; ultrahigh-temperature metamorphism occurred in the Odesan area (at 245-230Ma; 9.0-10.6 kbar, 915-1160°C), high-P/T metamorphism in the Hongseong area (17.0-21.9 kbar, 835-860°C) and ultrahigh-pressure metamorphism in the Dabie and Sulu belts (30-40 kbar, 680-880°C). This systematic increasing peak pressure condition and decreasing peak temperature condition towards west, may be due to the increase in the depth of slab break-off towards west, which might be related to the increase of the amounts of subducted ocecnic slab towards west. The wide distribution of Permo-Triassic arc-related granitoids in the Yeongnam Massif, southern part of Korean Peninsula and in the southern part of the South China block, indicate the Permo-Triassic subduction along the southern boundary of the South China block which may be due to compression caused by the Permo-Triassic collision between the North and South China blocks. The collision belt divides the Gyeonggi Massif into two parts; the northern and southern parts can be correlated to the North and South China blocks, respectively. The Ogcheon metamorphic belt which locates between the Gyeonggi and Youngnam Massifs in Korean Peninsula, can be correlated to the Nanhua rift which formed at 760 Ma and separated the South China blocks into the Yantze and Cathaysia cratons. In that case, the southern Gyeonggi Massif and Yeongnam Massif can be correlated to the Yangtze and Cathaysia cratons in the South China block, respectively. Recently Neoproterozoic igneous complex which was metamorphosed by the late Silurian intermediate-P/T and early Devonian ultrahigh temperature metamorphism, are recognized in the Hongseong area. These metamorphisms indicate the possibility of Middle Paleozoic collision of Neoproterozoic microcontinent with the northern margin of the South China block.

Re-Evaluation of the Lower San Fernando Dam; Report 2: Examination of the Post-Earthquake Slide of February 9, 1971

DTIC Science & Technology

1989-09-01

CA TION • i . , . ; .n ; -",~ ] .:p’ . M ,. .)] ,- .,%e r5 4 : 1h ,.’<>ikI t l , . ll th , h . .a ... •MI ’,~ ~FP/.’ - : ’ . . 1,0. . . ,, . n~ ’E...Sands in M z 7 1/2 Earthquakes (after Seed et al., 1985) 82 Figure 5-8 Comparison of Results of Laboratory Cyclic Load Tests with Data Determined From... m ) beyond the toe of the dam. The block of soil which contained the toe of the dam moved about 150 ft (46 m ) into the reservoir. Data from

Efficient quantum circuits for dense circulant and circulant like operators

PubMed Central

Zhou, S. S.

2017-01-01

Circulant matrices are an important family of operators, which have a wide range of applications in science and engineering-related fields. They are, in general, non-sparse and non-unitary. In this paper, we present efficient quantum circuits to implement circulant operators using fewer resources and with lower complexity than existing methods. Moreover, our quantum circuits can be readily extended to the implementation of Toeplitz, Hankel and block circulant matrices. Efficient quantum algorithms to implement the inverses and products of circulant operators are also provided, and an example application in solving the equation of motion for cyclic systems is discussed. PMID:28572988

Proceedings of the International Conference on Cyclic Nucleotides, Calcium and Protein Phosphorylation (6th) Held in Bethesda, Maryland on September 2-7, 1986. Advances in Second Messenger and Phosphorprotein Research. Volume 21A. Abstracts Volume

DTIC Science & Technology

1988-11-16

oxoireamorine. Oxotremorine inhibited Ach release for a shorter duration. The ACh release-inhibition induced by 50 PH Aech-M was only acutely blocked...and the partial agonist oxotresorine in the presence of 59K of Lit. Carbacbol showed a 10-fold lover ECS0-value (3.7liM) and oxotremorine a 3-fold...however, only a decrease in the maximal response was seen. In both tissues, the maximal, response of the partial agonist oxotremorine was suppressed

Phase transitions and magnetization of the mixed-spin Ising–Heisenberg double sawtooth frustrated ladder

NASA Astrophysics Data System (ADS)

Arian Zad, Hamid; Ananikian, Nerses

2018-04-01

The mixed spin-(1,1/2) Ising–Heisenberg double sawtooth ladder containing a mixture of both spin-1 and spin-1/2 nodal atoms, and the spin-1/2 interstitial dimers are approximately solved by the transfer-matrix method. Here, we study in detail the ground-state phase diagrams, also influences of the bilinear exchange coupling on the rungs and cyclic four-spin exchange interaction in square plaquette of each block on the magnetization and magnetic susceptibility of the suggested ladder at low temperature. Such a double sawtooth ladder may be found in a Shastry-Sutherland lattice-type. In spite of the spin ordering of odd and even blocks being different from each other, due to the commutation relation between all different block Hamiltonians, phase diagrams, magnetization behavior and thermodynamic properties of the model are the same for odd and even blocks. We show that at low temperature, both exchange couplings can change the quality and quantity of the magnetization plateaus versus the magnetic field changes. Specially, we find a new magnetization plateau M/Ms= 5/6 for this model. Besides, we examine the magnetic susceptibility and specific heat of the model in detail. It is proven that behaviors of the magnetization and the magnetic susceptibility coincide at low temperature. The specific heat displays diverse temperature dependencies, which include a Schottky-type peak at a special temperature interval. We observe that with increase of the bilinear exchange coupling on the rungs, second peak temperature dependence grows.

Characterization and Structural Analysis of a Novel exo-Type Enzyme Acting on β-1,2-Glucooligosaccharides from Parabacteroides distasonis.

PubMed

Shimizu, Hisaka; Nakajima, Masahiro; Miyanaga, Akimasa; Takahashi, Yuta; Tanaka, Nobukiyo; Kobayashi, Kaito; Sugimoto, Naohisa; Nakai, Hiroyuki; Taguchi, Hayao

2018-05-25

β-1,2-Glucan is a polysaccharide produced mainly by some Gram-negative bacteria as a symbiosis and infectious factor. We recently identified endo-β-1,2-glucanase from Chitinophaga pinensis ( CpSGL) as an enzyme comprising a new family. Here, we report the characteristics and crystal structure of a CpSGL homologue from Parabacteroides distasonis, an intestinal bacterium (BDI_3064 protein), which exhibits distinctive properties of known β-1,2-glucan-degrading enzymes. BDI_3064 hydrolyzed linear β-1,2-glucan and β-1,2-glucooligosaccharides with degrees of polymerization (DPs) of ≥4 to produce sophorose specifically but did not hydrolyze cyclic β-1,2-glucan. This result indicates that BDI_3064 is a new exo-type enzyme. BDI_3064 also produced sophorose from β-1,2-glucooligosaccharide analogues that have a modified reducing end, indicating that BDI_3064 acts on its substrates from the nonreducing end. The crystal structure showed that BDI_3064 possesses additional N-terminal domains 1 and 2, unlike CpSGL. Superimposition of BDI_3064 and CpSGL complexed with ligands showed that R93 in domain 1 overlapped subsite -3 in CpSGL. Docking analysis involving a β-1,2-glucooligosaccharide with DP4 showed that R93 completely blocks the nonreducing end of the docked β-1,2-glucooligosaccharide. This indicates that BDI_3064 employs a distinct mechanism of recognition at the nonreducing end of substrates to act as an exo-type enzyme. Thus, we propose 2-β-d-glucooligosaccharide sophorohydrolase (nonreducing end) as a systematic name for BDI_3064.

Buta-1,3-diyne-Based π-Conjugated Polymers for Organic Transistors and Solar Cells

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

Eckstein, Brian J.; Melkonyan, Ferdinand S.; Zhou, Nanjia

We report the synthesis and characterization of new alkyl-substituted 1,4-di(thiophen-2-yl)buta-1,3-diyne (R-DTB) donor building blocks, based on the -C≡C-C≡C- conjugative pathway, and their incorporation with thienyl-diketopyrrolopyrrole (R'-TDPP) acceptor units into π-conjugated PTDPP-DTB polymers (P1-P4). The solubility of the new polymers strongly depends on the DTB and DPP solubilizing (R and R', respectively) substituents. Thus, solution processable and high molecular weight PDPP-DTB polymers are achieved for P3 (R = n-C12H25, R' = 2- butyloctyl) and P4 (R = 2-ethylhexyl, R' = 2-butyloctyl). Systematic studies of P3 and P4 physicochemical properties are carried using optical spectroscopy, cyclic voltammetry, and thermal analysis, revealing characteristicmore » features of the dialkynyl motif. For the first time, optoelectronic devices (OFETs, OPVs) are fabricated with 1,3-butadiyne containing organic semiconductors. OFET hole mobilities and record OPV power conversion efficiencies for acetylenic organic materials approach 0.1 cm2/(V s) and 4%, respectively, which can be understood from detailed thin-film morphology and microstructural characterization using AFM, TEM, XRD, and GIWAXS methodologies. Importantly, DTB-based polymers (P3 and P4) exhibit, in addition to stabilization of frontier molecular orbitals and to -C≡C-C≡C- relief of steric torsions, discrete morphological pliability through thermal annealing and processing additives. The advantageous materials properties and preliminary device performance reported here demonstrate the promise of 1,3-butadiyne-based semiconducting polymers.« less

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

PubMed

Baker, David A; Stewart, Lindsay B; Large, Jonathan M; Bowyer, Paul W; Ansell, Keith H; Jiménez-Díaz, María B; El Bakkouri, Majida; Birchall, Kristian; Dechering, Koen J; Bouloc, Nathalie S; Coombs, Peter J; Whalley, David; Harding, Denise J; Smiljanic-Hurley, Ela; Wheldon, Mary C; Walker, Eloise M; Dessens, Johannes T; Lafuente, María José; Sanz, Laura M; Gamo, Francisco-Javier; Ferrer, Santiago B; Hui, Raymond; Bousema, Teun; Angulo-Barturén, Iñigo; Merritt, Andy T; Croft, Simon L; Gutteridge, Winston E; Kettleborough, Catherine A; Osborne, Simon A

2017-09-05

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC 50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC 50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

Catalytic allylic oxidation of internal alkenes to a multifunctional chiral building block

NASA Astrophysics Data System (ADS)

Bayeh, Liela; Le, Phong Q.; Tambar, Uttam K.

2017-07-01

The stereoselective oxidation of hydrocarbons is one of the most notable advances in synthetic chemistry over the past fifty years. Inspired by nature, enantioselective dihydroxylations, epoxidations and other oxidations of unsaturated hydrocarbons have been developed. More recently, the catalytic enantioselective allylic carbon-hydrogen oxidation of alkenes has streamlined the production of pharmaceuticals, natural products, fine chemicals and other functional materials. Allylic functionalization provides a direct path to chiral building blocks with a newly formed stereocentre from petrochemical feedstocks while preserving the olefin functionality as a handle for further chemical elaboration. Various metal-based catalysts have been discovered for the enantioselective allylic carbon-hydrogen oxidation of simple alkenes with cyclic or terminal double bonds. However, a general and selective allylic oxidation using the more common internal alkenes remains elusive. Here we report the enantioselective, regioselective and E/Z-selective allylic oxidation of unactivated internal alkenes via a catalytic hetero-ene reaction with a chalcogen-based oxidant. Our method enables non-symmetric internal alkenes to be selectively converted into allylic functionalized products with high stereoselectivity and regioselectivity. Stereospecific transformations of the resulting multifunctional chiral building blocks highlight the potential for rapidly converting internal alkenes into a broad range of enantioenriched structures that can be used in the synthesis of complex target molecules.

An in situ carbonization-replication method to synthesize mesostructured WO3/C composite as nonprecious-metal anode catalyst in PEMFC.

PubMed

Cui, Xiangzhi; Hua, Zile; Wei, Chenyang; Shu, Zhu; Zhang, Liangxia; Chen, Hangrong; Shi, Jianlin

2013-02-01

A meostructured WO(3)/C composite with crystalline framework and high electric conductivity has been synthesized by a new in situ carbonization-replication route using the block copolymer (poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)) present in situ in the pore channels of mesoporous silica template as carbon source. X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, thermogravimetry differential thermal analysis, and N(2) adsorption techniques were adopted for the structural characterization. Cyclic voltammetry, chronoamperometry, and single-cell test for hydrogen electrochemical oxidation were adopted to characterize the electrochemical activities of the mesoporous WO(3)/C composite. The carbon content and consequent electric conductivity of these high-surface-area (108-130 m(2) g(-1)) mesostructured WO(3)/C composite materials can be tuned by variation of the duration of heat treatment, and the composites exhibited high and stable electrochemical catalytic activity. The single-cell test results indicated that the mesostructured WO(3)/C composites showed clear electrochemical catalytic activity toward hydrogen oxidation at 25 °C, which makes them potential non-precious-metal anode catalysts in proton exchange membrane fuel cell. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lesions to the left lateral prefrontal cortex impair decision threshold adjustment for lexical selection.

PubMed

Anders, Royce; Riès, Stéphanie; Van Maanen, Leendert; Alario, F-Xavier

Patients with lesions in the left prefrontal cortex (PFC) have been shown to be impaired in lexical selection, especially when interference between semantically related alternatives is increased. To more deeply investigate which computational mechanisms may be impaired following left PFC damage due to stroke, a psychometric modelling approach is employed in which we assess the cognitive parameters of the patients from an evidence accumulation (sequential information sampling) modelling of their response data. We also compare the results to healthy speakers. Analysis of the cognitive parameters indicates an impairment of the PFC patients to appropriately adjust their decision threshold, in order to handle the increased item difficulty that is introduced by semantic interference. Also, the modelling contributes to other topics in psycholinguistic theory, in which specific effects are observed on the cognitive parameters according to item familiarization, and the opposing effects of priming (lower threshold) and semantic interference (lower drift) which are found to depend on repetition. These results are developed for the blocked-cyclic picture naming paradigm, in which pictures are presented within semantically homogeneous (HOM) or heterogeneous (HET) blocks, and are repeated several times per block. Overall, the results are in agreement with a role of the left PFC in adjusting the decision threshold for lexical selection in language production.

A compendium of cyclic sugar amino acids and their carbocyclic and heterocyclic nitrogen analogues.

PubMed

Risseeuw, Martijn; Overhand, Mark; Fleet, George W J; Simone, Michela I

2013-10-01

This compendium focuses on functionalised sugar amino acids (SAAs) and their 3- to 6-membered nitrogen heterocyclic and carbocyclic analogues. The main benefit of using SAAs and their related nitrogen and carbon congeners in the production of peptidomimetics and glycomimetics is that their properties can be readily altered via modification of their ring size, chemical manipulation of their numerous functional groups and fine-tuning of the stereochemical arrangement of their ring substituents. These building blocks provide access to hydrophilic and hydrophobic peptide isosteres whose physical properties allow entry to a region of chemotherapeutic space which is still under-explored by medicinal chemists. These building blocks are also important in providing amino acids whose inherent conformational bias leads to predisposition to secondary structure upon oligomerisation in relatively short sequences. These foldamers, particularly those containing ω-amino acids, provide an additional opportunity to expand access to the control of structures by artificial peptides. The synthesis and biological evaluation of these building blocks in glycomimetics and peptidomimetics systems keep expanding the reach of the glycosciences to the medical sciences, provide a greater outlook onto the wide range of cellular functions of saccharides and their derivatives involved and greater insight into the nature of oligosaccharide and protein folding.

Flexible strategy for immobilizing redox-active compounds using in situ generation of diazonium salts. Investigations of the blocking and catalytic properties of the layers.

PubMed

Noël, Jean-Marc; Sjöberg, Béatrice; Marsac, Rémi; Zigah, Dodzi; Bergamini, Jean-François; Wang, Aifang; Rigaut, Stéphane; Hapiot, Philippe; Lagrost, Corinne

2009-11-03

A versatile two-step method is developed to covalently immobilize redox-active molecules onto carbon surfaces. First, a robust anchoring platform is grafted onto surfaces by electrochemical reduction of aryl diazonium salts in situ generated. Depending on the nature of the layer termini, -COOH or -NH(2), a further chemical coupling involving ferrocenemethylamine or ferrocene carboxylic acid derivatives leads to the covalent binding of ferrocene centers. The chemical strategy using acyl chloride activation is efficient and flexible, since it can be applied either to surface-reactive end groups or to reactive species in solution. Cyclic voltammetry analyses point to the covalent binding of ferrocene units restricted to the upper layers of the underlying aryl films, while AFM measurements show a lost of compactness of the layers after the chemical attachment of ferrocene centers. The preparation conditions of the anchoring layers were found to determine the interfacial properties of the resulted ferrocenyl-modified electrodes. The ferrocene units promoted effective redox mediation providing that the free redox probes are adequately chosen (i.e., vs size/formal potential) and the underlying layers exhibit strong blocking properties. For anchoring films with weaker blocking effect, the coexistence of two distinct phenomena, redox mediation and ET at pinholes could be evidenced.

Reversible Nerve Conduction Block Using Kilohertz Frequency Alternating Current

PubMed Central

Kilgore, Kevin L.; Bhadra, Niloy

2013-01-01

Objectives The features and clinical applications of balanced-charge kilohertz frequency alternating currents (KHFAC) are reviewed. Preclinical studies of KHFAC block have demonstrated that it can produce an extremely rapid and reversible block of nerve conduction. Recent systematic analysis and experimentation utilizing KHFAC block has resulted in a significant increase in interest in KHFAC block, both scientifically and clinically. Materials and Methods We review the history and characteristics of KHFAC block, the methods used to investigate this type of block, the experimental evaluation of block, and the electrical parameters and electrode designs needed to achieve successful block. We then analyze the existing clinical applications of high frequency currents, comparing the early results with the known features of KHFAC block. Results Although many features of KHFAC block have been characterized, there is still much that is unknown regarding the response of neural structures to rapidly fluctuating electrical fields. The clinical reports to date do not provide sufficient information to properly evaluate the mechanisms that result in successful or unsuccessful treatment. Conclusions KHFAC nerve block has significant potential as a means of controlling nerve activity for the purpose of treating disease. However, early clinical studies in the use of high frequency currents for the treatment of pain have not been designed to elucidate mechanisms or allow direct comparisons to preclinical data. We strongly encourage the careful reporting of the parameters utilized in these clinical studies, as well as the development of outcome measures that could illuminate the mechanisms of this modality. PMID:23924075

Identifying seasonal and temporal trends in the pressures experienced by hospitals related to unscheduled care.

PubMed

Walker, N J; Van Woerden, H C; Kiparoglou, V; Yang, Y

2016-07-26

As part of an electronic dashboard operated by Public Health Wales, senior managers at hospitals in Wales report daily "escalation" scores which reflect management opinion on the pressure a hospital is experiencing and ability to meet ongoing demand with respect to unscheduled care. An analysis was undertaken of escalation scores returned for 18 hospitals in Wales between the years 2006 and 2014 inclusive, with a view to identifying systematic temporal patterns in pressure experienced by hospitals in relation to unscheduled care. Exploratory data analysis indicated the presence of within-year cyclicity in average daily scores over all hospitals. In order to quantify this cyclicity, a Generalised Linear Mixed Model was fitted which incorporated a trigonometric function (sine and cosine) to capture within-year change in escalation. In addition, a 7-level categorical day of the week effect was fitted as well as a 3-level categorical Christmas holiday variable based on patterns observed in exploration of the raw data. All of the main effects investigated were found to be statistically significant. Firstly, significant differences emerged in terms of overall pressure reported by individual hospitals. Furthermore, escalation scores were found to vary systematically within-year in a wave-like fashion for all hospitals (but not between hospitals) with the period of highest pressure consistently observed to occur in winter and lowest pressure in summer. In addition to this annual variation, pressure reported by hospitals was also found to be influenced by day of the week (low at weekends, high early in the working week) and especially low over the Christmas period but high immediately afterwards. Whilst unpredictable to a degree, quantifiable pressure experienced by hospitals can be anticipated according to models incorporating systematic temporal patterns. In the context of finite resources for healthcare services, these findings could optimise staffing schedules and inform resource utilisation.

Insight into the growth dynamics and systematic affinities of the Late Cretaceous Gargantuavis from bone microstructure

NASA Astrophysics Data System (ADS)

Chinsamy, Anusuya; Buffetaut, Eric; Canoville, Aurore; Angst, Delphine

2014-05-01

Enigmatic avialan remains of Gargantuavis philoinos from the Ibero-Armorican island of the Late Cretaceous European archipelago (Southern France) led to a debate concerning its taxonomic affinities. Here, we show that the bone microstructure of Gargantuavis resembles that of Apteryx, the extinct emeids and Megalapteryx from New Zealand, and indicates that like these slow-growing terrestrial birds, it took several years to attain skeletal maturity. Our findings suggest that the protracted cyclical growth in these ornithurines may have been in response to insular evolution.

Transforming information from silicon testing and design characterization into numerical data sets for yield learning

NASA Astrophysics Data System (ADS)

Yang, Thomas; Shen, Yang; Zhang, Yifan; Sweis, Jason; Lai, Ya-Chieh

2017-03-01

Silicon testing results are regularly collected for a particular lot of wafers to study yield loss from test result diagnostics. Product engineers will analyze the diagnostic results and perform a number of physical failure analyses to detect systematic defects which cause yield loss for these sets of wafers in order to feedback the information to process engineers for process improvements. Most of time, the systematic defects that are detected are major issues or just one of the causes for the overall yield loss. This paper will present a working flow for using design analysis techniques combined with diagnostic methods to systematically transform silicon testing information into physical layout information. A new set of the testing results are received from a new lot of wafers for the same product. We can then correlate all the diagnostic results from different periods of time to check which blocks or nets have been highlighted or stop occurring on the failure reports in order to monitor process changes which impact the yield. The design characteristic analysis flow is also implemented to find 1) the block connections on a design that have failed electrical test or 2) frequently used cells that been highlighted multiple times.

Bundle Block Adjustment of Airborne Three-Line Array Imagery Based on Rotation Angles

PubMed Central

Zhang, Yongjun; Zheng, Maoteng; Huang, Xu; Xiong, Jinxin

2014-01-01

In the midst of the rapid developments in electronic instruments and remote sensing technologies, airborne three-line array sensors and their applications are being widely promoted and plentiful research related to data processing and high precision geo-referencing technologies is under way. The exterior orientation parameters (EOPs), which are measured by the integrated positioning and orientation system (POS) of airborne three-line sensors, however, have inevitable systematic errors, so the level of precision of direct geo-referencing is not sufficiently accurate for surveying and mapping applications. Consequently, a few ground control points are necessary to refine the exterior orientation parameters, and this paper will discuss bundle block adjustment models based on the systematic error compensation and the orientation image, considering the principle of an image sensor and the characteristics of the integrated POS. Unlike the models available in the literature, which mainly use a quaternion to represent the rotation matrix of exterior orientation, three rotation angles are directly used in order to effectively model and eliminate the systematic errors of the POS observations. Very good experimental results have been achieved with several real datasets that verify the correctness and effectiveness of the proposed adjustment models. PMID:24811075

Bundle block adjustment of airborne three-line array imagery based on rotation angles.

PubMed

Zhang, Yongjun; Zheng, Maoteng; Huang, Xu; Xiong, Jinxin

2014-05-07

In the midst of the rapid developments in electronic instruments and remote sensing technologies, airborne three-line array sensors and their applications are being widely promoted and plentiful research related to data processing and high precision geo-referencing technologies is under way. The exterior orientation parameters (EOPs), which are measured by the integrated positioning and orientation system (POS) of airborne three-line sensors, however, have inevitable systematic errors, so the level of precision of direct geo-referencing is not sufficiently accurate for surveying and mapping applications. Consequently, a few ground control points are necessary to refine the exterior orientation parameters, and this paper will discuss bundle block adjustment models based on the systematic error compensation and the orientation image, considering the principle of an image sensor and the characteristics of the integrated POS. Unlike the models available in the literature, which mainly use a quaternion to represent the rotation matrix of exterior orientation, three rotation angles are directly used in order to effectively model and eliminate the systematic errors of the POS observations. Very good experimental results have been achieved with several real datasets that verify the correctness and effectiveness of the proposed adjustment models.

A systematic evaluation of prevalence and diagnostic accuracy of sacroiliac joint interventions.

PubMed

Simopoulos, Thomas T; Manchikanti, Laxmaiah; Singh, Vijay; Gupta, Sanjeeva; Hameed, Haroon; Diwan, Sudhir; Cohen, Steven P

2012-01-01

The contributions of the sacroiliac joint to low back and lower extremity pain have been a subject of considerable debate and research. It is generally accepted that 10% to 25% of patients with persistent mechanical low back pain below L5 have pain secondary to sacroiliac joint pathology. However, no single historical, physical exam, or radiological feature can definitively establish a diagnosis of sacroiliac joint pain. Based on present knowledge, a proper diagnosis can only be made using controlled diagnostic blocks. The diagnosis and treatment of sacroiliac joint pain continue to be characterized by wide variability and a paucity of the literature. To evaluate the accuracy of diagnostic sacroiliac joint interventions. A systematic review of diagnostic sacroiliac joint interventions. Methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to December 2011, and manual searches of the bibliographies of known primary and review articles. In this evaluation we utilized controlled local anesthetic blocks using at least 50% pain relief as the reference standard. The evidence is good for the diagnosis of sacroiliac joint pain utilizing controlled comparative local anesthetic blocks. The prevalence of sacroiliac joint pain is estimated to range between 10% and 62% based on the setting; however, the majority of analyzed studies suggest a point prevalence of around 25%, with a false-positive rate for uncontrolled blocks of approximately 20%. The evidence for provocative testing to diagnose sacroiliac joint pain was fair. The evidence for the diagnostic accuracy of imaging is limited. The limitations of this systematic review include a paucity of literature, variations in technique, and variable criterion standards for the diagnosis of sacroiliac joint pain. Based on this systematic review, the evidence for the diagnostic accuracy of sacroiliac joint injections is good, the evidence for provocation maneuvers is fair, and evidence for imaging is limited.

Synthesis of most polyene natural product motifs using just twelve building blocks and one coupling reaction

PubMed Central

Woerly, Eric M.; Roy, Jahnabi; Burke, Martin D.

2014-01-01

The inherent modularity of polypeptides, oligonucleotides, and oligosaccharides has been harnessed to achieve generalized building block-based synthesis platforms. Importantly, like these other targets, most small molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled the synthesis of a wide range of polyene frameworks covering all of this natural product chemical space, and first total syntheses of the polyene natural products asnipyrone B, physarigin A, and neurosporaxanthin β-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach for making small molecules in the laboratory. PMID:24848233

Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA.

PubMed

Guo, Shicheng; Diep, Dinh; Plongthongkum, Nongluk; Fung, Ho-Lim; Zhang, Kang; Zhang, Kun

2017-04-01

Adjacent CpG sites in mammalian genomes can be co-methylated owing to the processivity of methyltransferases or demethylases, yet discordant methylation patterns have also been observed, which are related to stochastic or uncoordinated molecular processes. We focused on a systematic search and investigation of regions in the full human genome that show highly coordinated methylation. We defined 147,888 blocks of tightly coupled CpG sites, called methylation haplotype blocks, after analysis of 61 whole-genome bisulfite sequencing data sets and validation with 101 reduced-representation bisulfite sequencing data sets and 637 methylation array data sets. Using a metric called methylation haplotype load, we performed tissue-specific methylation analysis at the block level. Subsets of informative blocks were further identified for deconvolution of heterogeneous samples. Finally, using methylation haplotypes we demonstrated quantitative estimation of tumor load and tissue-of-origin mapping in the circulating cell-free DNA of 59 patients with lung or colorectal cancer.

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

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

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

DOE PAGES

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

2017-01-27

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

2D photonic crystal complete band gap search using a cyclic cellular automaton refination

NASA Astrophysics Data System (ADS)

González-García, R.; Castañón, G.; Hernández-Figueroa, H. E.

2014-11-01

We present a refination method based on a cyclic cellular automaton (CCA) that simulates a crystallization-like process, aided with a heuristic evolutionary method called differential evolution (DE) used to perform an ordered search of full photonic band gaps (FPBGs) in a 2D photonic crystal (PC). The solution is proposed as a combinatorial optimization of the elements in a binary array. These elements represent the existence or absence of a dielectric material surrounded by air, thus representing a general geometry whose search space is defined by the number of elements in such array. A block-iterative frequency-domain method was used to compute the FPBGs on a PC, when present. DE has proved to be useful in combinatorial problems and we also present an implementation feature that takes advantage of the periodic nature of PCs to enhance the convergence of this algorithm. Finally, we used this methodology to find a PC structure with a 19% bandgap-to-midgap ratio without requiring previous information of suboptimal configurations and we made a statistical study of how it is affected by disorder in the borders of the structure compared with a previous work that uses a genetic algorithm.

Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide.

PubMed

Li, Yue; McRobb, Lucinda S; Khachigian, Levon M

2016-10-01

Percutaneous coronary intervention is widely used for the treatment of coronary artery disease; however, significant challenges such as restenosis remain. Key to solving these problems is to inhibit smooth muscle cell activation while enhancing re-endothelialization. Early growth response-1 (Egr-1) is a transcription factor that regulates vascular smooth muscle cell (SMC) proliferation and migration through its control of an array of downstream genes. A "cocktail" of vascular endothelial growth factor (VEGF)-A, VEGF-D and cyclic RGD was tested for its ability to inhibit neointima formation and accelerate re-endothelialization following balloon injury to carotid arteries of rats. In vitro, the cocktail stimulated endothelial cell growth yet inhibited smooth muscle cell growth. In vivo, cocktail-treated injured arteries exhibited reduced intimal thickening by >50% (P<0.05). It increased both re-endothelialization and endothelial nitric oxide synthase (NOS) expression. Cocktail reduced Egr-1 expression, an effect blocked by the NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) that also prevented cocktail inhibition of neointima inhibition. This combination may potentially be useful for the treatment of restenosis with concomitant stimulation of revascularization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cyclic AMP regulates formation of mammary epithelial acini in vitro

PubMed Central

Nedvetsky, Pavel I.; Kwon, Sang-Ho; Debnath, Jayanta; Mostov, Keith E.

2012-01-01

Epithelial cells form tubular and acinar structures notable for a hollow lumen. In three-dimensional culture utilizing MCF10A mammary epithelial cells, acini form due to integrin-dependent polarization and survival of cells contacting extracellular matrix (ECM), and the apoptosis of inner cells of acini lacking contact with the ECM. In this paper, we report that cyclic AMP (cAMP)-dependent protein kinase A (PKA) promotes acinus formation via two mechanisms. First, cAMP accelerates redistribution of α6-integrin to the periphery of the acinus and thus facilitates the polarization of outer acinar cells. Blocking of α6-integrin function by inhibitory antibody prevents cAMP-dependent polarization. Second, cAMP promotes the death of inner cells occupying the lumen. In the absence of cAMP, apoptosis is delayed, resulting in perturbed luminal clearance. cAMP-dependent apoptosis is accompanied by a posttranscriptional PKA-dependent increase in the proapoptotic protein Bcl-2 interacting mediator of cell death. These data demonstrate that cAMP regulates lumen formation in mammary epithelial cells in vitro, both through acceleration of polarization of outer cells and apoptosis of inner cells of the acinus. PMID:22675028

Synthesis of protein in intestinal cells exposed to cholera toxin

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

Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

1987-11-01

The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells andmore » Chinese hamster ovary cells exposed to cholera toxin. An increase in (/sup 3/H) leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of (/sup 35/S) methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed.« less

Introduction of pre-etch deposition techniques in EUV patterning

NASA Astrophysics Data System (ADS)

Xiang, Xun; Beique, Genevieve; Sun, Lei; Labonte, Andre; Labelle, Catherine; Nagabhirava, Bhaskar; Friddle, Phil; Schmitz, Stefan; Goss, Michael; Metzler, Dominik; Arnold, John

2018-04-01

The thin nature of EUV (Extreme Ultraviolet) resist has posed significant challenges for etch processes. In particular, EUV patterning combined with conventional etch approaches suffers from loss of pattern fidelity in the form of line breaks. A typical conventional etch approach prevents the etch process from having sufficient resist margin to control the trench CD (Critical Dimension), minimize the LWR (Line Width Roughness), LER (Line Edge Roughness) and reduce the T2T (Tip-to-Tip). Pre-etch deposition increases the resist budget by adding additional material to the resist layer, thus enabling the etch process to explore a wider set of process parameters to achieve better pattern fidelity. Preliminary tests with pre-etch deposition resulted in blocked isolated trenches. In order to mitigate these effects, a cyclic deposition and etch technique is proposed. With optimization of deposition and etch cycle time as well as total number of cycles, it is possible to open the underlying layers with a beneficial over etch and simultaneously keep the isolated trenches open. This study compares the impact of no pre-etch deposition, one time deposition and cyclic deposition/etch techniques on 4 aspects: resist budget, isolated trench open, LWR/LER and T2T.

Vitamin E and organic selenium for broilers from 22 to 42 days old: performance and carcass traits.

PubMed

Albuquerque, Daniel M N; Lopes, João B; Ferraz, Maíra S; Ribeiro, Mabell N; Silva, Sandra R G; Costa, Elvânia M S; Lima, Daniela C P; Ferreira, Jefferson D M; Gomes, Pedro E B; Lopes, Jackelline C O

2017-01-01

This study was conducted to evaluate the effect of vitamin E and selenium on performance, viability, productive efficiency, and yields of carcass, major cuts, and organs of broilers from 22 to 42 days submitted to cyclic-heat stress. The experimental design was randomized blocks, in a 2 × 3 factorial arrangement with two levels of selenium (0.1 and 0.3 mg/kg) and three levels of vitamin E (300, 400, and 500 mg/kg), plus a control treatment. Animals were submitted to a natural condition of high cyclic temperature. Organic selenium levels of 0.1 and 0.3 mg/kg associated with 300, 400, and 500 mg/kg of vitamin E were tested. The level of vitamin E did not affect the performance or production efficiency of broilers in the period from 22 to 33 days and 22 to 42 days. However, the selenium inclusion level of 0.3 mg/kg improved the viability in both phases. The yields of carcass, major cuts, intestine, and heart were not influenced by the levels of selenium and vitamin E, whereas abdominal fat for the selenium level 0.1 mg/kg decreased linearly with the inclusion in vitamin E.

Newer regional analgesia interventions (fascial plane blocks) for breast surgeries: Review of literature.

PubMed

Garg, Rakesh; Bhan, Swati; Vig, Saurabh

2018-04-01

Surgical resection of the primary tumour with axillary dissection is one of the main modalities of breast cancer treatment. Regional blocks have been considered as one of the modalities for effective perioperative pain control. With the advent of ultrasound, newer interventions such as fascial plane blocks have been reported for perioperative analgesia in breast surgeries. Our aim is to review the literature for fascial plane blocks for analgesia in breast surgeries. The research question for initiating the review was 'What are the reported newer regional anaesthesia techniques (fascial plane blocks) for female patients undergoing breast surgery and their analgesic efficacy?.' The participants, intervention, comparisons, outcomes and study design were followed. Due to the paucity of similar studies and heterogeneity, the assessment of bias, systematic review or pooled analysis/meta-analysis was not feasible. Of the 989 manuscripts, the present review included 28 manuscripts inclusive of all types of published manuscripts. 15 manuscripts directly related to the administration of fascial plane blocks for breast surgery across all type of study designs and cases were reviewed for the utility of fascial plane blocks in breast surgeries. Interfascial blocks score over regional anaesthetic techniques such as paravertebral block as they have no risk of sympathetic blockade, intrathecal or epidural spread which may lead to haemodynamic instability and prolonged hospital stay. This review observed that no block effectively covers the whole of breast and axilla, thus a combination of blocks should be used depending on the site of incision and extent of surgical resection.

Experimental, numerical, and analytical studies on the seismic response of steel-plate concrete (SC) composite shear walls

NASA Astrophysics Data System (ADS)

Epackachi, Siamak

The seismic performance of rectangular steel-plate concrete (SC) composite shear walls is assessed for application to buildings and mission-critical infrastructure. The SC walls considered in this study were composed of two steel faceplates and infill concrete. The steel faceplates were connected together and to the infill concrete using tie rods and headed studs, respectively. The research focused on the in-plane behavior of flexure- and flexure-shear-critical SC walls. An experimental program was executed in the NEES laboratory at the University at Buffalo and was followed by numerical and analytical studies. In the experimental program, four large-size specimens were tested under displacement-controlled cyclic loading. The design variables considered in the testing program included wall thickness, reinforcement ratio, and slenderness ratio. The aspect ratio (height-to-length) of the four walls was 1.0. Each SC wall was installed on top of a re-usable foundation block. A bolted baseplate to RC foundation connection was used for all four walls. The walls were identified to be flexure- and flexure-shear critical. The progression of damage in the four walls was identical, namely, cracking and crushing of the infill concrete at the toes of the walls, outward buckling and yielding of the steel faceplates near the base of the wall, and tearing of the faceplates at their junctions with the baseplate. A robust finite element model was developed in LS-DYNA for nonlinear cyclic analysis of the flexure- and flexure-shear-critical SC walls. The DYNA model was validated using the results of the cyclic tests of the four SC walls. The validated and benchmarked models were then used to conduct a parametric study, which investigated the effects of wall aspect ratio, reinforcement ratio, wall thickness, and uniaxial concrete compressive strength on the in-plane response of SC walls. Simplified analytical models, suitable for preliminary analysis and design of SC walls, were developed, validated, and implemented in MATLAB. Analytical models were proposed for monotonic and cyclic simulations of the in-plane response of flexure- and flexure-shear-critical SC wall piers. The model for cyclic analysis was developed by modifying the Ibarra-Krawinler Pinching (IKP) model. The analytical models were verified using the results of the parametric study and validated using the test data.

Sampling error in timber surveys

Treesearch

Austin Hasel

1938-01-01

Various sampling strategies are evaluated for efficiency in an interior ponderosa pine forest. In a 5760 acre tract, efficiency was gained by stratifying into quarter acre blocks and sampling randomly from within. A systematic cruise was found to be superior for volume estimation.

Design study and performance analysis of a high-speed multistage variable-geometry fan for a variable cycle engine

NASA Technical Reports Server (NTRS)

Sullivan, T. J.; Parker, D. E.

1979-01-01

A design technology study was performed to identify a high speed, multistage, variable geometry fan configuration capable of achieving wide flow modulation with near optimum efficiency at the important operating condition. A parametric screening study of the front and rear block fans was conducted in which the influence of major fan design features on weight and efficiency was determined. Key design parameters were varied systematically to determine the fan configuration most suited for a double bypass, variable cycle engine. Two and three stage fans were considered for the front block. A single stage, core driven fan was studied for the rear block. Variable geometry concepts were evaluated to provide near optimum off design performance. A detailed aerodynamic design and a preliminary mechanical design were carried out for the selected fan configuration. Performance predictions were made for the front and rear block fans.

Fabrication of Ordered Nanopattern by using ABC Triblock Copolymer with Salt in Toluene.

PubMed

Huang, Hailiang; Zhong, Benbin; Zu, Xihong; Luo, Hongsheng; Lin, Wenjing; Zhang, Minghai; Zhong, Yazhou; Yi, Guobin

2017-08-15

Ordered nanopatterns of triblock copolymer polystyrene-block-poly(2-vinylpyridine)-block- poly (ethylene oxide)(PS-b-P2VP-b-PEO) have been achieved by the addition of lithium chloride (LiCl). The morphological and structural evolution of PS-b-P2VP-b-PEO/LiCl thin films were systematically investigated by varying different experimental parameters, including the treatment for polymer solution after the addition of LiCl, the time scale of ultrasonic treatment and the molar ratio of Li + ions to the total number of oxygen atoms (O) in PEO block and the nitrogen atoms (N) in P2VP block. When toluene was used as the solvent for LiCl, ordered nanopattern with cylinders or nanostripes could be obtained after spin-coating. The mechanism of nanopattern transformation was related to the loading of LiCl in different microdomains.

Using research literature to develop a perceptual retraining treatment protocol.

PubMed

Neistadt, M E

1994-01-01

Treatment protocols derived from research literature can help therapists provide more rigorous treatment and more systematic assessment of client progress. This study applied research findings about the influence of task, subject, and feedback parameters on adult performance with block designs to an occupational therapy treatment protocol for parquetry block assembly--an activity occupational therapists use to remediate constructional deficits. Task parameter research suggests that parquetry tasks can be graded according to the features of the design cards, with cards having all block boundaries drawn in being easier than those with some block boundaries omitted. Subject parameter findings suggest that clients' lesions and initial constructional competence can influence their approaches to parquetry tasks. Feedback parameter research suggests that a combination of perceptual and planning cues is most effective for parquetry tasks. Methods to help clients transfer constructional skills from parquetry to functional tasks are also discussed.

Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction.

PubMed

Woerly, Eric M; Roy, Jahnabi; Burke, Martin D

2014-06-01

The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled both the synthesis of a wide range of polyene frameworks that covered all of this natural-product chemical space and the first total syntheses of the polyene natural products asnipyrone B, physarigin A and neurosporaxanthin b-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach to making small molecules in the laboratory.

Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction

NASA Astrophysics Data System (ADS)

Woerly, Eric M.; Roy, Jahnabi; Burke, Martin D.

2014-06-01

The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled both the synthesis of a wide range of polyene frameworks that covered all of this natural-product chemical space and the first total syntheses of the polyene natural products asnipyrone B, physarigin A and neurosporaxanthin β-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach to making small molecules in the laboratory.

Structural Benchmark Testing of Superalloy Lattice Block Subelements Completed

NASA Technical Reports Server (NTRS)

2004-01-01

Superalloy lattice block panels, which are produced directly by investment casting, are composed of thin ligaments arranged in three-dimensional triangulated trusslike structures (see the preceding figure). Optionally, solid panel face sheets can be formed integrally during casting. In either form, lattice block panels can easily be produced with weights less than 25 percent of the mass of a solid panel. Inconel 718 (IN 718) and MarM-247 superalloy lattice block panels have been developed under NASA's Ultra-Efficient Engine Technology Project and Higher Operating Temperature Propulsion Components Project to take advantage of the superalloys' high strength and elevated temperature capability with the inherent light weight and high stiffness of the lattice architecture (ref. 1). These characteristics are important in the future development of turbine engine components. Casting quality and structural efficiency were evaluated experimentally using small beam specimens machined from the cast and heat treated 140- by 300- by 11-mm panels. The matrix of specimens included samples of each superalloy in both open-celled and single-face-sheet configurations, machined from longitudinal, transverse, and diagonal panel orientations. Thirty-five beam subelements were tested in Glenn's Life Prediction Branch's material test machine at room temperature and 650 C under both static (see the following photograph) and cyclic load conditions. Surprisingly, test results exceeded initial linear elastic analytical predictions. This was likely a result of the formation of plastic hinges and redundancies inherent in lattice block geometry, which was not considered in the finite element models. The value of a single face sheet was demonstrated by increased bending moment capacity, where the face sheet simultaneously increased the gross section modulus and braced the compression ligaments against early buckling as seen in open-cell specimens. Preexisting flaws in specimens were not a discriminator in flexural, shear, or stiffness measurements, again because of redundant load paths available in the lattice block structure. Early test results are available in references 2 and 3; more complete analyses are scheduled for publication in 2004.

Rectus sheath and transversus abdominis plane blocks in children: a systematic review and meta-analysis of randomized trials.

PubMed

Hamill, James K; Rahiri, Jamie-Lee; Liley, Andrew; Hill, Andrew G

2016-04-01

The role of rectus sheath blocks (RSB) and transversus abdominis plane (TAP) blocks in pediatric surgery has not been well established. We aimed to determine if RSB and TAP blocks decrease postoperative pain and improve recovery in children. Duplicate searching of MEDLINE, EMBASE, Cochrane, Web of Science, and trial registries databases by two reviewers. Included were randomized trials in children on RSB or TAP block in abdominal operations, excluding inguinal procedures. Independent duplicate data extraction and quality assessment using a standardized form. Ten trials met inclusion criteria (n = 599), RSB in five and TAP block in five. A linear mixed effects model on patient level data from three trials showed nerve blocks lowered morphine requirements 6-8 h after surgery, -0.03 mg · kg(-1) (95% CI -0.05, -0.002). Pooled analysis of summary data showed nerve blocks lowered 0-10 scale pain scores immediately after the operation, -0.7 (95% CI -1.3, -0.1); lowered 4-16 scale pain scores, -2.0 (95% CI -2.3, -1.7); and delayed the time to first rescue analgesia, 17 min (95% CI 1.3, 33). Quality assessment showed some studies at moderate to high risk of bias. Abdominal wall blocks reduce pain and opiate use in children. We advise cautious interpretation of the results given the heterogeneity of studies. © 2016 John Wiley & Sons Ltd.

Simulation of fatigue damage in ferroelectric polycrystals under mechanical/electrical loading

NASA Astrophysics Data System (ADS)

Kozinov, S.; Kuna, M.

2018-07-01

The reliability of smart-structures made of ferroelectric ceramics is essentially reduced by the formation of cracks under the action of external electrical and/or mechanical loading. In the current research a numerical model for low-cycle fatigue in ferroelectric mesostructures is proposed. In the finite element simulations a combination of two user element routines is utilized. The first one is used to model a micromechanical ferroelectric domain switching behavior inside the grains. The second one is used to simulate fatigue damage of grain boundaries by a cohesive zone model (EMCCZM) based on an electromechanical cyclic traction-separation law (TSL). For numerical simulations a scanning electron microscope image of the ceramic's grain structure was digitalized and meshed. The response of this mesostructure to cyclic electrical or mechanical loading is systematically analyzed. As a result of the simulations, the distribution of electric potential, field, displacement and polarization as well as mechanical stresses and deformations inside the grains are obtained. At the grain boundaries, the formation and evolution of damage are analyzed until final failure and induced degradation of electric permittivity. It is found that the proposed model correctly mimics polycrystalline behavior during poling processes and progressive damage under cyclic electromechanical loading. To the authors' knowledge, it is the first model and numerical analysis of ferroelectric polycrystals taking into account both domain reorientation and cohesive modeling of intergranular fracture. It can help to understand failure mechanisms taking place in ferroelectrics during fatigue processes.

6-[3-(p-Tolyl­sulfonyl­amino)­prop­yl]diquino­thia­zine1

PubMed Central

Jeleń, Małgorzata; Shkurenko, Aleksander; Suwińska, Kinga; Pluta, Krystian; Morak-Młodawska, Beata

2013-01-01

In the title mol­ecule {systematic name: N-[3-(diquino[3,2-b;2′,3′-e][1,4]thia­zin-6-yl)prop­yl]-4-methyl­benzene­sulfon­amide}, C28H24N4O2S2, the penta­cyclic system is relatively planar [maximum deviation from the mean plane = 0.242 (1) Å]. The dihedral angle between two quinoline ring systems is 8.23 (2)° and that between the two halves of the 1,4-thia­zine ring is 5.68 (3)°. The conformation adopted by the 3-(p-tolyl­sulfonyl­amino)­propyl substituent allows for the formation of an intra­molecular N—H⋯N hydrogen bond and places the benzene ring of this substituent above one of the quinoline fragments of the penta­cyclic system. In the crystal, mol­ecules are arranged via π–π stacking inter­actions into (0-11) layers [centroid–centroid distances = 3.981 (1)–4.320 (1) Å for the rings in the penta­cyclic system and 3.645 (1) Å for the tolyl benzene rings]. In addition, mol­ecules are involved in weak C—H⋯O, which connect the layers, and C—H⋯S hydrogen bonds. The title compound shows promising anti­cancer activity against renal cancer cell line UO-31. PMID:23795128

Role of the S4-S5 linker in CNG channel activation.

PubMed

Kusch, Jana; Zimmer, Thomas; Holschuh, Jascha; Biskup, Christoph; Schulz, Eckhard; Nache, Vasilica; Benndorf, Klaus

2010-10-20

Cyclic nucleotide-gated (CNG) channels mediate sensory signal transduction in retinal and olfactory cells. The channels are activated by the binding of cyclic nucleotides to a cyclic nucleotide-binding domain (CNBD) in the C-terminus that is located at the intracellular side. The molecular events translating the ligand binding to the pore opening are still unknown. We investigated the role of the S4-S5 linker in the activation process by quantifying its interaction with other intracellular regions. To this end, we constructed chimeric channels in which the N-terminus, the S4-S5 linker, the C-linker, and the CNBD of the retinal CNGA1 subunit were systematically replaced by the respective regions of the olfactory CNGA2 subunit. Macroscopic concentration-response relations were analyzed, yielding the apparent affinity to cGMP and the Hill coefficient. The degree of functional coupling of intracellular regions in the activation gating was determined by thermodynamic double-mutant cycle analysis. We observed that all four intracellular regions, including the relatively short S4-S5 linker, are involved in controlling the apparent affinity of the channel to cGMP and, moreover, in determining the degree of cooperativity between the subunits, as derived from the Hill coefficient. The interaction energies reveal an interaction of the S4-S5 linker with both the N-terminus and the C-linker, but no interaction with the CNBD. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A systematic examination of the morphogenesis of calcium carbonate in the presence of a double-hydrophilic block copolymer.

PubMed

Cölfen, H; Qi, L

2001-01-05

In this paper, a systematic study of the influence of various experimental parameters on the morphology and size of CaCO3 crystals after room-temperature crystallization from water in the presence of poly(ethylene glycol)-block-poly(methacrylic acid) (PEG-b-PMAA) is presented. The pH of the solution, the block copolymer concentration, and the ratio [polymer]/[CaCO3] turned out to be important parameters for the morphogenesis of CaCO3, whereas a moderate increase of the ionic strength (0.016 M) had no influence. Depending on the experimental conditions, the crystal morphologies can be tuned from calcite rhombohedra via rods, ellipsoids or dumbbells to spheres. A morphology map is presented which allows the prediction of the crystal morphology from a combination of pH, and CaCO3 and polymer concentration. Morphologies reported in literature for the same system but under different crystallization conditions agree well with the predictions from the morphology map. A closer examination of the growth of polycrystalline macroscopic CaCO3 spheres by TEM and time-resolved dynamic light scattering showed that CaCO3 macrocrystals are formed from strings of aggregated amorphous nanoparticles and then recrystallize as dumbbell-shaped or spherical calcite macrocrystal.

Initial Mechanical Testing of Superalloy Lattice Block Structures Conducted

NASA Technical Reports Server (NTRS)

Krause, David L.; Whittenberger, J. Daniel

2002-01-01

The first mechanical tests of superalloy lattice block structures produced promising results for this exciting new lightweight material system. The testing was performed in-house at NASA Glenn Research Center's Structural Benchmark Test Facility, where small subelement-sized compression and beam specimens were loaded to observe elastic and plastic behavior, component strength levels, and fatigue resistance for hundreds of thousands of load cycles. Current lattice block construction produces a flat panel composed of thin ligaments arranged in a three-dimensional triangulated trusslike structure. Investment casting of lattice block panels has been developed and greatly expands opportunities for using this unique architecture in today's high-performance structures. In addition, advances made in NASA's Ultra-Efficient Engine Technology Program have extended the lattice block concept to superalloy materials. After a series of casting iterations, the nickel-based superalloy Inconel 718 (IN 718, Inco Alloys International, Inc., Huntington, WV) was successfully cast into lattice block panels; this combination offers light weight combined with high strength, high stiffness, and elevated-temperature durability. For tests to evaluate casting quality and configuration merit, small structural compression and bend test specimens were machined from the 5- by 12- by 0.5-in. panels. Linear elastic finite element analyses were completed for several specimen layouts to predict material stresses and deflections under proposed test conditions. The structural specimens were then subjected to room-temperature static and cyclic loads in Glenn's Life Prediction Branch's material test machine. Surprisingly, the test results exceeded analytical predictions: plastic strains greater than 5 percent were obtained, and fatigue lives did not depreciate relative to the base material. These assets were due to the formation of plastic hinges and the redundancies inherent in lattice block construction, which were not considered in the simplified computer models. The fatigue testing proved the value of redundancies since specimen strength was maintained even after the fracture of one or two ligaments. This ongoing test program is planned to continue through high-temperature testing. Also scheduled for testing are IN 718 lattice block panels with integral face sheets, as well as specimens cast from a higher temperature alloy. The initial testing suggests the value of this technology for large panels under low and moderate pressure loadings and for high-risk, damage-tolerant structures. Potential aeropropulsion uses for lattice blocks include turbine-engine actuated panels, exhaust nozzle flaps, and side panel structures.

Scaffold design of trivalent chelator heads dictates high-affinity and stable His-tagged protein labeling in vitro and in cellulo.

PubMed

Gatterdam, Karl; Joest, Eike F; Gatterdam, Volker; Tampé, Robert

2018-05-29

Small chemical/biological interaction pairs are at the forefront in tracing proteins' function and interaction at high signal-to-background ratio in cellular pathways. Pharma ventures have eager plans to develop trisNTA probes for in vitro and in vivo screening of His-tagged protein targets. However, the optimal design of scaffold, linker, and chelator head yet deserves systematic investigations to achieve highest affinity and kinetic stability for in vitro and especially cell applications. In this study, we report on a library of N-nitrilotriacetic acid (NTA) based multivalent chelator heads (MCHs) built up on linear, cyclic, and dendritic scaffolds and contrast these with regard to their binding affinity and stability for labeling of cellular His-tagged proteins. Furthermore, we assign a new approach for tracing cellular target proteins at picomolar probe concentrations in cells. Finally, we describe fundamental differences between the MCH scaffold and define a cyclic trisNTA chelator, which displays the highest affinity and kinetic stability of all reversible, low-molecular weight interaction pairs. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling the viscoplastic behavior of Inconel 718 at 1200 F

NASA Technical Reports Server (NTRS)

Abdel-Kader, M. S.; Eftis, J.; Jones, D. L.

1988-01-01

A large number of tests, including tensile, creep, fatigue, and creep-fatigue were performed to characterize the mechanical properties of Inconel 718 (a nickel based superalloy) at 1200 F, the operating temperature for turbine blades. In addition, a few attempts were made to model the behavior of Inconel 718 at 1200 F using viscoplastic theories. The Chaboche theory of viscoplasticity can model a wide variety of mechanical behavior, including monotonic, sustained, and cyclic responses of homogeneous, initially-isotropic, strain hardening (or softening) materials. It is shown how the Chaboche theory can be used to model the viscoplastic behavior of Inconel 718 at 1200 F. First, an algorithm was developed to systematically determine the material parameters of the Chaboche theory from uniaxial tensile, creep, and cyclic data. The algorithm is general and can be used in conjunction with similar high temperature materials. A sensitivity study was then performed and an optimal set of Chaboche's parameters were obtained. This study has also indicated the role of each parameter in modeling the response to different loading conditions.

Method and apparatus for removing unwanted reflections from an interferometer

NASA Technical Reports Server (NTRS)

Steimle, Lawrence J. (Inventor); Thiessen, David L. (Inventor)

1994-01-01

A device for eliminating unwanted reflections from refractive optical elements in an optical system is provided. The device operates to prevent desired multiple fringe patterns from being obscured by reflections from refractive elements positioned in proximity to a focal plane of the system. The problem occurs when an optical beam is projected into, and reflected back out of, the optical system. Surfaces of the refractive elements reflect portions of the beam which interfere with portions of the beam which are transmitted through the refractive elements. Interference between the reflected and transmitted portions of the beam produce multiple fringe sets which tend to obscure desired interference fringes. With the refractive optical element in close proximity to the focal plane of the system, the undesired reflected light reflects at an angle 180 degrees opposite from the desired transmitted beam. The device exploits the 180-degree offset, or rotational shear, of the undesired reflected light by providing an optical stop for blocking one-half of the cross-section of the test beam. By blocking one-half of the test beam, the undesired offset beam is blocked, while the returning transmitted beam passes into the optical system unaffected. An image is thereby produced from only the desired transmitted beam. In one configuration, the blocking device includes a semicircular aperture which is caused to rotate about the axis of the test beam. By rotating, all portions of the test beam are cyclically projected into the optical system to thereby produce a complete test image. The rotating optical stop is preferably caused to rotate rapidly to eliminate flicker in the resulting image.

Block Copolymer Patterns as Templates for the Electrocatalyzed Deposition of Nanostructures on Electrodes and for the Generation of Surfaces of Controlled Wettability.

PubMed

Chandaluri, Chanchayya Gupta; Pelossof, Gilad; Tel-Vered, Ran; Shenhar, Roy; Willner, Itamar

2016-01-20

ITO electrodes modified with a nanopatterned film of polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP, where the P2VP domains are quaternized with iodomethane, are used for selective deposition of redox-active materials. Electrochemical studies (cyclic voltammetry, Faradaic impedance measurements) indicate that the PS domains insulate the conductive surface toward redox labels in solution. In turn, the quaternized P2VP domains electrostatically attract negatively charged redox labels solubilized in the electrolyte solution, resulting in an effective electron transfer between the electrode and the redox label. This phenomenon is implemented for the selective deposition of the electroactive Prussian blue on the nanopatterned surface and for the electrochemical deposition of Au nanoparticles, modified with a monolayer of p-aminothiophenol/2-mercaptoethanesulfonic acid, on the quaternized P2VP domains. The patterned Prussian blue-modified surface enables controlling the wettability properties by the content of the electrochemically deposited Prussian blue. Controlled wettability is unattainable with the homopolymer-modified surface, attesting to the role of the nanopattern.

Formation of Methylamine and Ethylamine in Extraterrestrial Ices and Their Role as Fundamental Building Blocks of Proteinogenic α -amino Acids

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

Förstel, Marko; Bergantini, Alexandre; Maksyutenko, Pavlo

The –CH–NH{sub 2} moiety represents the fundamental building block of all proteinogenic amino acids, with the cyclic amino acid proline being a special case (–CH–NH– in proline). Exploiting a chemical retrosynthesis, we reveal that methylamine (CH{sub 3}NH{sub 2}) and/or ethylamine (CH{sub 3}CH{sub 2}NH{sub 2}) are essential precursors in the formation of each proteinogenic amino acid. In the present study we elucidate the abiotic formation of methylamine and ethylamine from ammonia (NH{sub 3}) and methane (CH{sub 4}) ices exposed to secondary electrons generated by energetic cosmic radiation in cometary and interstellar model ices. Our experiments show that methylamine and ethylamine aremore » crucial reaction products in irradiated ices composed of ammonia and methane. Using isotopic substitution studies we further obtain valuable information on the specific reaction pathways toward methylamine. The very recent identification of methylamine and ethylamine together with glycine in the coma of 67P/Churyumov–Gerasimenko underlines their potential to the extraterrestrial formation of amino acids.« less

α-Fluorovinyl Weinreb Amides and α- Fluoroenones from a Common Fluorinated Building Block

PubMed Central

Ghosh, Arun K.; Banerjee, Shaibal; Sinha, Saikat; Kang, Soon Bang; Zajc, Barbara

2009-01-01

Synthesis and reactivity of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfonyl)fluoroacetamide, a building block for Julia olefination, is reported. This reagent undergoes condensation reactions with aldehydes and cyclic ketones, to give α-fluorovinyl Weinreb amides. Olefination reactions proceed under mild, DBU-mediated conditions, or in the presence of NaH. DBU-mediated condensations proceed with either E or Z-selectivity, depending upon reaction conditions, whereas NaH-mediated reactions are ≥98% Z-stereoselective. Conversion of the Weinreb amide moiety in N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide to ketones, followed by oxidation, resulted in another set of olefination reagents, namely (1,3-benzothiazol-2-ylsulfonyl)fluoromethyl phenyl and propyl ketones. In the presence of DBU, these compounds react with aldehydes tested to give α-fluoroenones with high Z-selectivity. The use of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide as a common fluorinated intermediate in the synthesis of α-fluorovinyl Weinreb amides and α-fluoroenones has been demonstrated. Application of the Weinreb amide to α-fluoro allyl amine synthesis is also shown. PMID:19361189

Chemometric studies on potential larvicidal compounds against Aedes aegypti.

PubMed

Scotti, Luciana; Scotti, Marcus Tullius; Silva, Viviane Barros; Santos, Sandra Regina Lima; Cavalcanti, Sócrates C H; Mendonça, Francisco J B

2014-03-01

The mosquito Aedes aegypti (Diptera, Culicidae) is the vector of yellow and dengue fever. In this study, chemometric tools, such as, Principal Component Analysis (PCA), Consensus PCA (CPCA), and Partial Least Squares Regression (PLS), were applied to a set of fifty five active compounds against Ae. aegypti larvae, which includes terpenes, cyclic alcohols, phenolic compounds, and their synthetic derivatives. The calculations were performed using the VolSurf+ program. CPCA analysis suggests that the higher weight blocks of descriptors were SIZE/SHAPE, DRY, and H2O. The PCA was generated with 48 descriptors selected from the previous blocks. The scores plot showed good separation between more and less potent compounds. The first two PCs accounted for over 60% of the data variance. The best model obtained in PLS, after validation leave-one-out, exhibited q(2) = 0.679 and r(2) = 0.714. External prediction model was R(2) = 0.623. The independent variables having a hydrophobic profile were strongly correlated to the biological data. The interaction maps generated with the GRID force field showed that the most active compounds exhibit more interaction with the DRY probe.

Fatigue Life Estimation under Cumulative Cyclic Loading Conditions

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; McGaw, Michael A; Halford, Gary R.

1999-01-01

The cumulative fatigue behavior of a cobalt-base superalloy, Haynes 188 was investigated at 760 C in air. Initially strain-controlled tests were conducted on solid cylindrical gauge section specimens of Haynes 188 under fully-reversed, tensile and compressive mean strain-controlled fatigue tests. Fatigue data from these tests were used to establish the baseline fatigue behavior of the alloy with 1) a total strain range type fatigue life relation and 2) the Smith-Wastson-Topper (SWT) parameter. Subsequently, two load-level multi-block fatigue tests were conducted on similar specimens of Haynes 188 at the same temperature. Fatigue lives of the multi-block tests were estimated with 1) the Linear Damage Rule (LDR) and 2) the nonlinear Damage Curve Approach (DCA) both with and without the consideration of mean stresses generated during the cumulative fatigue tests. Fatigue life predictions by the nonlinear DCA were much closer to the experimentally observed lives than those obtained by the LDR. In the presence of mean stresses, the SWT parameter estimated the fatigue lives more accurately under tensile conditions than under compressive conditions.

BIPAD: A web server for modeling bipartite sequence elements

PubMed Central

Bi, Chengpeng; Rogan, Peter K

2006-01-01

Background Many dimeric protein complexes bind cooperatively to families of bipartite nucleic acid sequence elements, which consist of pairs of conserved half-site sequences separated by intervening distances that vary among individual sites. Results We introduce the Bipad Server [1], a web interface to predict sequence elements embedded within unaligned sequences. Either a bipartite model, consisting of a pair of one-block position weight matrices (PWM's) with a gap distribution, or a single PWM matrix for contiguous single block motifs may be produced. The Bipad program performs multiple local alignment by entropy minimization and cyclic refinement using a stochastic greedy search strategy. The best models are refined by maximizing incremental information contents among a set of potential models with varying half site and gap lengths. Conclusion The web service generates information positional weight matrices, identifies binding site motifs, graphically represents the set of discovered elements as a sequence logo, and depicts the gap distribution as a histogram. Server performance was evaluated by generating a collection of bipartite models for distinct DNA binding proteins. PMID:16503993

The Resolution Sensitivity of Northern Hemisphere Blocking in Four 25-km Atmospheric Global Circulation Models

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

Schiemann, Reinhard; Demory, Marie-Estelle; Shaffrey, Len C.

The aim of this study is to investigate if the representation of Northern Hemisphere blocking is sensitive to resolution in current-generation atmospheric global circulation models (AGCMs). An evaluation is thus conducted of how well atmospheric blocking is represented in four AGCMs whose horizontal resolution is increased from a grid spacing of more than 100 km to about 25 km. It is shown that Euro-Atlantic blocking is simulated overall more credibly at higher resolution (i.e., in better agreement with a 50-yr reference blocking climatology created from the reanalyses ERA-40 and ERA-Interim). The improvement seen with resolution depends on the season andmore » to some extent on the model considered. Euro-Atlantic blocking is simulated more realistically at higher resolution in winter, spring, and autumn, and robustly so across the model ensemble. The improvement in spring is larger than that in winter and autumn. Summer blocking is found to be better simulated at higher resolution by one model only, with little change seen in the other three models. The representation of Pacific blocking is not found to systematically depend on resolution. Despite the improvements seen with resolution, the 25-km models still exhibit large biases in Euro-Atlantic blocking. For example, three of the four 25-km models underestimate winter northern European blocking frequency by about one-third. The resolution sensitivity and biases in the simulated blocking are shown to be in part associated with the mean-state biases in the models' midlatitude circulation.« less

The Resolution Sensitivity of Northern Hemisphere Blocking in Four 25-km Atmospheric Global Circulation Models

DOE PAGES

Schiemann, Reinhard; Demory, Marie-Estelle; Shaffrey, Len C.; ...

2016-12-19

The aim of this study is to investigate if the representation of Northern Hemisphere blocking is sensitive to resolution in current-generation atmospheric global circulation models (AGCMs). An evaluation is thus conducted of how well atmospheric blocking is represented in four AGCMs whose horizontal resolution is increased from a grid spacing of more than 100 km to about 25 km. It is shown that Euro-Atlantic blocking is simulated overall more credibly at higher resolution (i.e., in better agreement with a 50-yr reference blocking climatology created from the reanalyses ERA-40 and ERA-Interim). The improvement seen with resolution depends on the season andmore » to some extent on the model considered. Euro-Atlantic blocking is simulated more realistically at higher resolution in winter, spring, and autumn, and robustly so across the model ensemble. The improvement in spring is larger than that in winter and autumn. Summer blocking is found to be better simulated at higher resolution by one model only, with little change seen in the other three models. The representation of Pacific blocking is not found to systematically depend on resolution. Despite the improvements seen with resolution, the 25-km models still exhibit large biases in Euro-Atlantic blocking. For example, three of the four 25-km models underestimate winter northern European blocking frequency by about one-third. The resolution sensitivity and biases in the simulated blocking are shown to be in part associated with the mean-state biases in the models' midlatitude circulation.« less

Semi-automatic spray pyrolysis deposition of thin, transparent, titania films as blocking layers for dye-sensitized and perovskite solar cells

PubMed Central

Krýsová, Hana; Kavan, Ladislav

2018-01-01

For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20–200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO2 films. The blocking properties of the as-deposited TiO2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells. PMID:29719764

Sugammadex for reversal of neuromuscular block after rapid sequence intubation: a systematic review and economic assessment†

PubMed Central

Chambers, D.; Paulden, M.; Paton, F.; Heirs, M.; Duffy, S.; Hunter, J. M.; Sculpher, M.; Woolacott, N.

2010-01-01

Summary Sugammadex 16 mg kg−1 can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a ‘can't intubate, can't ventilate’ (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment. PMID:20937718

"Saber" and "Conocer."

ERIC Educational Resources Information Center

Taylor, Kathy

1985-01-01

Attempts to redefine the meaning of the two Spanish verbs "saber" and "conocer" and explores some possible extralinguistic factors affecting their usage. Shows that "conocer" represents knowledge which is firsthand and that this type of knowledge is a building block for the more thorough, systematic knowledge represented by "saber." (SED)

Bit Error Probability for Maximum Likelihood Decoding of Linear Block Codes

NASA Technical Reports Server (NTRS)

Lin, Shu; Fossorier, Marc P. C.; Rhee, Dojun

1996-01-01

In this paper, the bit error probability P(sub b) for maximum likelihood decoding of binary linear codes is investigated. The contribution of each information bit to P(sub b) is considered. For randomly generated codes, it is shown that the conventional approximation at high SNR P(sub b) is approximately equal to (d(sub H)/N)P(sub s), where P(sub s) represents the block error probability, holds for systematic encoding only. Also systematic encoding provides the minimum P(sub b) when the inverse mapping corresponding to the generator matrix of the code is used to retrieve the information sequence. The bit error performances corresponding to other generator matrix forms are also evaluated. Although derived for codes with a generator matrix randomly generated, these results are shown to provide good approximations for codes used in practice. Finally, for decoding methods which require a generator matrix with a particular structure such as trellis decoding or algebraic-based soft decision decoding, equivalent schemes that reduce the bit error probability are discussed.

Measurement of Systematic Error Effects for a Sensitive Storage Ring EDM Polarimeter

NASA Astrophysics Data System (ADS)

Imig, Astrid; Stephenson, Edward

2009-10-01

The Storage Ring EDM Collaboration was using the Cooler Synchrotron (COSY) and the EDDA detector at the Forschungszentrum J"ulich to explore systematic errors in very sensitive storage-ring polarization measurements. Polarized deuterons of 235 MeV were used. The analyzer target was a block of 17 mm thick carbon placed close to the beam so that white noise applied to upstream electrostatic plates increases the vertical phase space of the beam, allowing deuterons to strike the front face of the block. For a detector acceptance that covers laboratory angles larger than 9 ^o, the efficiency for particles to scatter into the polarimeter detectors was about 0.1% (all directions) and the vector analyzing power was about 0.2. Measurements were made of the sensitivity of the polarization measurement to beam position and angle. Both vector and tensor asymmetries were measured using beams with both vector and tensor polarization. Effects were seen that depend upon both the beam geometry and the data rate in the detectors.

Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate the activity of NMDA receptors in hippocampal neurons.

PubMed

Zhang, Yanmin; Sheng, Hui; Qi, Jinshun; Ma, Bei; Sun, Jihu; Li, Shaofeng; Ni, Xin

2012-04-01

Glucocorticoids (GCs) have been demonstrated to act through both genomic and nongenomic mechanisms. The present study demonstrated that corticosterone rapidly suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured hippocampal neurons. The effect was maintained with corticosterone conjugated to bovine serum albumin and blocked by inhibition of G protein activity with intracellular GDP-β-S application. Corticosterone increased GTP-bound G(s) protein and cyclic AMP (cAMP) production, activated phospholipase Cβ(3) (PLC-β(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist, Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused a decrease in NMDA-evoked currents. Application of corticosterone partly reversed the inhibition of NMDA currents caused by blockage of AC and PKA. Intracerebroventricular administration of corticosterone significantly suppressed long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min in vivo, implicating the possibly physiological significance of rapid effects of GC on NMDA receptors. Taken together, our results indicate that GCs act on a putative G protein-coupled receptor to activate multiple signaling pathways in hippocampal neurons, and the rapid suppression of NMDA activity by GCs is dependent on PLC and downstream signaling.

A Fully Integrated Sensor SoC with Digital Calibration Hardware and Wireless Transceiver at 2.4 GHz

PubMed Central

Kim, Dong-Sun; Jang, Sung-Joon; Hwang, Tae-Ho

2013-01-01

A single-chip sensor system-on-a-chip (SoC) that implements radio for 2.4 GHz, complete digital baseband physical layer (PHY), 10-bit sigma-delta analog-to-digital converter and dedicated sensor calibration hardware for industrial sensing systems has been proposed and integrated in a 0.18-μm CMOS technology. The transceiver's building block includes a low-noise amplifier, mixer, channel filter, receiver signal-strength indicator, frequency synthesizer, voltage-controlled oscillator, and power amplifier. In addition, the digital building block consists of offset quadrature phase-shift keying (OQPSK) modulation, demodulation, carrier frequency offset compensation, auto-gain control, digital MAC function, sensor calibration hardware and embedded 8-bit microcontroller. The digital MAC function supports cyclic redundancy check (CRC), inter-symbol timing check, MAC frame control, and automatic retransmission. The embedded sensor signal processing block consists of calibration coefficient calculator, sensing data calibration mapper and sigma-delta analog-to-digital converter with digital decimation filter. The sensitivity of the overall receiver and the error vector magnitude (EVM) of the overall transmitter are −99 dBm and 18.14%, respectively. The proposed calibration scheme has a reduction of errors by about 45.4% compared with the improved progressive polynomial calibration (PPC) method and the maximum current consumption of the SoC is 16 mA. PMID:23698271

Osteosynthesis of partial rib osteotomy in a miniature pig model using human standard-sized magnesium plate/screw systems: Effect of cyclic deformation on implant integrity and bone healing.

PubMed

Schaller, Benoit; Saulacic, Nikola; Beck, Stefan; Imwinkelried, Thomas; Liu, Edwin Wei Yang; Nakahara, Ken; Hofstetter, Willy; Iizuka, Tateyuki

2017-06-01

Magnesium alloys are candidates for resorbable material in bone fixation. However, the degradation and performance of osteosynthesis plate/screw systems in vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human standard-sized magnesium plate/screw systems with or without plasma-electrolytic surface modifications in a miniature pig rib model. Of a total of 14 minipigs, six were implanted with coated magnesium WE43 six-hole plates/screws, six received magnesium uncoated plates/screws, and two received titanium osteosynthesis systems. The performance of the plate/screw fixation system on partially osteotomized 7th ribs was compared with that on intact 9th ribs. Radiological examinations were performed in vivo at 1, 4 and 8 weeks and after euthanasia at 12 and 24 weeks. After euthanasia the bone blocks were analyzed by computed tomography (CT), microfocus computed tomography (micro-CT), histology and histomorphometry. Follow-up post-surgery showed no trouble with wound healing. In vivo radiological examinations showed higher amounts of gas formation above the uncoated magnesium plates fixed on the partially osteotomized and intact ribs. CT scans showed no broken plates or implant displacement. The micro-CT examination demonstrated better surrounding bone properties around the coated than the uncoated magnesium implants 12 weeks after surgery. No negative influence of magnesium degradation on bone healing was observed with histological examinations. Plastic deformation during surgery and cyclic deformation did not affect the integrity of the used magnesium plates. This study showed promising results for the further development of coated magnesium plate/screw systems for bone fixation. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Wear at the titanium-titanium and the titanium-zirconia implant-abutment interface: a comparative in vitro study.

PubMed

Stimmelmayr, Michael; Edelhoff, Daniel; Güth, Jan-Frederik; Erdelt, Kurt; Happe, Arndt; Beuer, Florian

2012-12-01

The purpose of this study was to determine and measure the wear of the interface between titanium implants and one-piece zirconia abutments in comparison to titanium abutments. 6 implants were secured into epoxy resin blocks. The implant interface of these implants and 6 corresponding abutments (group Zr: three one-piece zirconia abutments; group Ti: three titanium abutments) were examined by a microscope and scanning electron micrograph (SEM). Also the implants and the abutments were scanned by 3D-Micro Computer Tomography (CT). The abutments were connected to the implants and cyclically loaded with 1,200,000 cycles at 100N in a two-axis fatigue testing machine. Afterwards, all specimens were unscrewed and the implants and abutments again were scanned by microscope, SEM and CT. The microscope and SEM images were compared, the CT data were superimposed and the wear was calculated by inspection software. The statistical analysis was carried out with an unpaired t-test. Abutment fracture or screw loosening was not observed during cyclical loading. Comparing the microscope and SEM images more wear was observed on the implants connected to zirconia abutments. The maximum wear on the implant shoulder calculated by the inspection software was 10.2μm for group Zr, and 0.7μm for group Ti. The influence of the abutment material on the measured wear was statistically significant (p≤0.001; Levene-test). Titanium implants showed higher wear at the implant interface following cyclic loading when connected to one-piece zirconia implant abutments compared to titanium abutments. The clinical relevance is not clear; hence damage of the internal implant connection could result in prosthetic failures up to the need of implant removal. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Disease-associated mutations in CNGB3 promote cytotoxicity in photoreceptor-derived cells

PubMed Central

Liu, Chunming; Sherpa, Tshering

2013-01-01

Purpose To determine if achromatopsia associated F525N and T383fsX mutations in the CNGB3 subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels increases susceptibility to cell death in photoreceptor-derived cells. Methods Photoreceptor-derived 661W cells were transfected with cDNA encoding wild-type (WT) CNGA3 subunits plus WT or mutant CNGB3 subunits, and incubated with the membrane-permeable CNG channel activators 8-(4-chlorophenylthio) guanosine 3′,5′-cyclic monophosphate (CPT-cGMP) or CPT-adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Cell viability under these conditions was determined by measuring lactate dehydrogenase release. Channel ligand sensitivity was calibrated by patch-clamp recording after expression of WT or mutant channels in Xenopus oocytes. Results Coexpression of CNGA3 with CNGB3 subunits containing F525N or T383fsX mutations produced channels exhibiting increased apparent affinity for CPT-cGMP compared to WT channels. Consistent with these effects, cytotoxicity in the presence of 0.1 μM CPT-cGMP was enhanced relative to WT channels, and the increase in cell death was more pronounced for the mutation with the largest gain-of-function effect on channel gating, F525N. Increased susceptibility to cell death was prevented by application of the CNG channel blocker L-cis-diltiazem. Increased cytotoxicity was also found to be dependent on the presence of extracellular calcium. Conclusions These results indicate a connection between disease-associated mutations in cone CNG channel subunits, altered CNG channel-activation properties, and photoreceptor cytotoxicity. The rescue of cell viability via CNG channel block or removal of extracellular calcium suggests that cytotoxicity in this model depends on calcium entry through hyperactive CNG channels. PMID:23805033

New insights into neurogenic cyclic motor activity in the isolated guinea-pig colon.

PubMed

Costa, M; Wiklendt, L; Keightley, L; Brookes, S J H; Dinning, P G; Spencer, N J

2017-10-01

The contents of the guinea pig distal colon consist of multiple pellets that move anally in a coordinated manner. This row of pellets results in continued distention of the colon. In this study, we have investigated quantitatively the features of the neurally dependent colonic motor patterns that are evoked by constant distension of the full length of guinea-pig colon. Constant distension was applied to the excised guinea-pig by high-resolution manometry catheters or by a series of hooks. Constant distension elicited regular Cyclic Motor Complexes (CMCs) that originated at multiple different sites along the colon and propagated in an oral or anal direction extending distances of 18.3±10.3 cm. CMCs were blocked by tetrodotoxin (TTX; 0.6 μ mol L -1 ), hexamethonium (100 μ mol L -1 ) or hyoscine (1 μ mol L -1 ). Application of TTX in a localized compartment or cutting the gut circumferentially disrupted the spatial continuity of CMCs. Localized smooth muscle contraction was not required for CMC propagation. Shortening the length of the preparations or disruption of circumferential pathways reduced the integrity and continuity of CMCs. CMCs are a distinctive neurally dependent cyclic motor pattern, that emerge with distension over long lengths of the distal colon. They do not require changes in muscle tension or contractility to entrain the neural activity underlying CMC propagation. CMCs are likely to play an important role interacting with the neuromechanical processes that time the propulsion of multiple natural pellets and may be particularly relevant in conditions of impaction or obstruction, where long segments of colon are simultaneously distended. © 2017 John Wiley & Sons Ltd.

Should we search Chinese biomedical databases when performing systematic reviews?

PubMed

Cohen, Jérémie F; Korevaar, Daniël A; Wang, Junfeng; Spijker, René; Bossuyt, Patrick M

2015-03-06

Chinese biomedical databases contain a large number of publications available to systematic reviewers, but it is unclear whether they are used for synthesizing the available evidence. We report a case of two systematic reviews on the accuracy of anti-cyclic citrullinated peptide for diagnosing rheumatoid arthritis. In one of these, the authors did not search Chinese databases; in the other, they did. We additionally assessed the extent to which Cochrane reviewers have searched Chinese databases in a systematic overview of the Cochrane Library (inception to 2014). The two diagnostic reviews included a total of 269 unique studies, but only 4 studies were included in both reviews. The first review included five studies published in the Chinese language (out of 151) while the second included 114 (out of 118). The summary accuracy estimates from the two reviews were comparable. Only 243 of the published 8,680 Cochrane reviews (less than 3%) searched one or more of the five major Chinese databases. These Chinese databases index about 2,500 journals, of which less than 6% are also indexed in MEDLINE. All 243 Cochrane reviews evaluated an intervention, 179 (74%) had at least one author with a Chinese affiliation; 118 (49%) addressed a topic in complementary or alternative medicine. Although searching Chinese databases may lead to the identification of a large amount of additional clinical evidence, Cochrane reviewers have rarely included them in their search strategy. We encourage future initiatives to evaluate more systematically the relevance of searching Chinese databases, as well as collaborative efforts to allow better incorporation of Chinese resources in systematic reviews.

Evaluation of blocking performance in ensemble seasonal integrations

NASA Astrophysics Data System (ADS)

Casado, M. J.; Doblas-Reyes, F. J.; Pastor, M. A.

2003-04-01

EVALUATION OF BLOCKING PERFOMANCE IN ENSEMBLE SEASONAL INTEGRATIONS M. J. Casado (1), F. J. Doblas-Reyes (2), A. Pastor (1) (1) I Instituto Nacional de Meteorología, c/Leonardo Prieto Castro,8,28071 ,Madrid,Spain, mjcasado@inm.es (2) ECMWF, Shinfield Park,RG2 9AX, Reading, UK, f.doblas-reyes@ecmwf.int Climate models have shown a robust inability to reliably predict blocking onset and frequency. This systematic error has been evaluated using multi-model ensemble seasonal integrations carried out in the framework of the Prediction Of climate Variations On Seasonal and interanual Timescales (PROVOST) project and compared to a blocking features assessment of the NCEP re-analyses. The PROVOST GCMs are able to adequately reproduce the spatial NCEP teleconnection patterns over the Northern Hemisphere, being notorious the great spatial correlation coefficient with some of the corresponding NCEP patterns. In spite of that, the different models show a consistent underestimation of blocking frequency which may impact on the ability to predict the seasonal amplitude of the leading modes of variability over the Northern Hemisphere.

The use of blocking screws with internal lengthening nail and reverse rule of thumb for blocking screws in limb lengthening and deformity correction surgery.

PubMed

Muthusamy, Saravanaraja; Rozbruch, S Robert; Fragomen, Austin T

2016-11-01

Internal lengthening nail (ILN) is a recent development in limb lengthening and deformity correction specialty. The ILN has the distinct advantage of combining acute deformity correction with gradual lengthening of bone. While using ILN, the short metaphyseal bone fragment may develop a deformity at the time of osteotomy and nail insertion or during bone lengthening because of the wide medullary canal. These deformities are typically predictable, and blocking screws (Poller screws) are helpful in these situations. This manuscript describes the common deformities that occur in femur and tibia with osteotomies at different locations while using ILN in antegrade and retrograde nailing technique. Also, a systematic approach to the appropriate use of blocking screws in these deformities is described. In addition, the "reverse rule of thumb" is introduced as a quick reference to determine the ideal location(s) and number of blocking screws. These principles are applicable to limb lengthening and deformity correction as well as fracture fixation using intramedullary nails.

Simulation of modern climate with the new version of the INM RAS climate model

NASA Astrophysics Data System (ADS)

Volodin, E. M.; Mortikov, E. V.; Kostrykin, S. V.; Galin, V. Ya.; Lykosov, V. N.; Gritsun, A. S.; Diansky, N. A.; Gusev, A. V.; Yakovlev, N. G.

2017-03-01

The INMCM5.0 numerical model of the Earth's climate system is presented, which is an evolution from the previous version, INMCM4.0. A higher vertical resolution for the stratosphere is applied in the atmospheric block. Also, we raised the upper boundary of the calculating area, added the aerosol block, modified parameterization of clouds and condensation, and increased the horizontal resolution in the ocean block. The program implementation of the model was also updated. We consider the simulation of the current climate using the new version of the model. Attention is focused on reducing systematic errors as compared to the previous version, reproducing phenomena that could not be simulated correctly in the previous version, and modeling the problems that remain unresolved.

Superconductivity in REO0.5F0.5BiS2 with high-entropy-alloy-type blocking layers

NASA Astrophysics Data System (ADS)

Sogabe, Ryota; Goto, Yosuke; Mizuguchi, Yoshikazu

2018-05-01

We synthesized new REO0.5F0.5BiS2 (RE: rare earth) superconductors with high-entropy-alloy-type (HEA-type) REO blocking layers. The lattice constant a systematically changed in the HEA-type samples with the RE concentration and the RE ionic radius. A sharp superconducting transition was observed in the resistivity measurements for all the HEA-type samples, and the transition temperature of the HEA-type samples was higher than that of typical REO0.5F0.5BiS2. The sharp superconducting transition and the enhanced superconducting properties of the HEA-type samples may indicate the effectiveness of the HEA states of the REO blocking layers in the REO0.5F0.5BiS2 system.

Management of lumbar zygapophysial (facet) joint pain

PubMed Central

Manchikanti, Laxmaiah; Hirsch, Joshua A; Falco, Frank JE; Boswell, Mark V

2016-01-01

AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back pain. METHODS: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including PubMed from 1966 onwards, Cochrane library, National Guideline Clearinghouse, clinicaltrials.gov, along with other sources including previous systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level I to level V. RESULTS: Across all databases, 16 high quality diagnostic accuracy studies were identified. In addition, multiple studies assessed the influence of multiple factors on diagnostic validity. In contrast to diagnostic validity studies, therapeutic efficacy trials were limited to a total of 14 randomized controlled trials, assessing the efficacy of intraarticular injections, facet or zygapophysial joint nerve blocks, and radiofrequency neurotomy of the innervation of the facet joints. The evidence for the diagnostic validity of lumbar facet joint nerve blocks with at least 75% pain relief with ability to perform previously painful movements was level I, based on a range of level I to V derived from a best evidence synthesis. For therapeutic interventions, the evidence was variable from level II to III, with level II evidence for lumbar facet joint nerve blocks and radiofrequency neurotomy for long-term improvement (greater than 6 mo), and level III evidence for lumbosacral zygapophysial joint injections for short-term improvement only. CONCLUSION: This review provides significant evidence for the diagnostic validity of facet joint nerve blocks, and moderate evidence for therapeutic radiofrequency neurotomy and therapeutic facet joint nerve blocks in managing chronic low back pain. PMID:27190760

Self-Assembled α-Fe2O3 mesocrystals/graphene nanohybrid for enhanced electrochemical capacitors.

PubMed

Yang, Shuhua; Song, Xuefeng; Zhang, Peng; Sun, Jing; Gao, Lian

2014-06-12

Self-assembled α-Fe2O3 mesocrystals/graphene nanohybrids have been successfully synthesized and have a unique mesocrystal porous structure, a large specific surface area, and high conductivity. Mesocrystal structures have recently attracted unparalleled attention owing to their promising application in energy storage as electrochemical capacitors. However, mesocrystal/graphene nanohybrids and their growth mechanism have not been clearly investigated. Here we show a facile fabrication of short rod-like α-Fe2O3 mesocrystals/graphene nanohybrids by self-assembly of FeOOH nanorods as the primary building blocks on graphene under hydrothermal conditions, accompanied and promoted by concomitant phase transition from FeOOH to α-Fe2O3. A systematic study of the formation mechanism is also presented. The galvanostatic charge/discharge curve shows a superior specific capacitance of the as-prepared α-Fe2O3 mesocrystals/graphene nanohybrid (based on total mass of active materials), which is 306.9 F g(-1) at 3 A g(-1) in the aqueous electrolyte under voltage ranges of up to 1 V. The nanohybrid with unique sufficient porous structure and high electrical conductivity allows for effective ion and charge transport in the whole electrode. Even at a high discharge current density of 10 A g(-1), the enhanced ion and charge transport still yields a higher capacitance (98.2 F g(-1)), exhibiting enhanced rate capability. The α-Fe2O3 mesocrystal/graphene nanohybrid electrode also demonstrates excellent cyclic performance, which is superior to previously reported graphene-based hematite electrode, suggesting it is highly stable as an electrochemical capacitor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of adrenal hormones and prostaglandins in the control of mouse thymocytes lysis.

PubMed

Durant, S; Seillan, C; Duval, D; Homo-Delarche, F

1984-01-01

The cytolytic actions of glucocorticoids and of agents increasing cyclic AMP were studied in vitro in thymocyte suspensions isolated from adrenalectomized or hydrocortisone-treated mice. Although considered as corticoresistant cells, the thymocytes isolated from hydrocortisone-treated mice were lysed to the same extent although more slowly in vitro by dexamethasone than whole thymocyte populations (i.e. corticosensitive cells). Moreover, these two cell populations were shown to contain comparable amounts of glucocorticoid receptors and to be almost equally sensitive to the metabolic effects of glucocorticoids when measured by inhibition of RNA and DNA synthesis. Studies performed with corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyrilcyclic AMP were also able to induce cell lysis and that, isoproterenol and dexamethasone exerted additive cytolytic action in vitro. In vivo experiments showed also an additive effect of steroids and isoproterenol on thymus atrophy. In contrast, cells isolated from hydrocortisone-treated animals were not sensitive to the cytotoxic action of prostaglandin E2, isoproterenol and dibutyril cyclic AMP. This difference between the two populations was not associated with any difference in the responsiveness of adenylate cyclase as determined following isoproterenol-induced accumulation of cyclic AMP. The cytolytic action of dexamethasone but also that of prostaglandin E2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis. Among the hypotheses proposed to explain the differences between in vitro and in vivo sensitivity of lymphoid cell to glucocorticoids, it was suggested that the drug may in vivo indirectly control the viability or the proliferation of thymocytes through the release of other mediators. We have shown that in vivo injection of hydrocortisone induces an accumulation of fatty acids in the whole thymus gland but not in the isolated thymocytes. Since exogenous fatty acids exert cytolytic actions on isolated thymocytes, we suggest that glucocorticoids may exert in vivo an indirect toxic action by promoting the release of fatty acids from adipose tissue or other sources.

Down-regulation of angiotensin II receptor subtypes and desensitization of cyclic GMP production in neuroblastoma N1E-115 cells.

PubMed

Reagan, L P; Ye, X; Maretzski, C H; Fluharty, S J

1993-01-01

Murine neuroblastoma N1E-115 cells possess membranous receptors for the octapeptide angiotensin II (AngII) whose density is substantially increased by in vitro differentiation. Incubation of differentiated N1E-115 cells with AngII produced a rapid decrease in receptor density, but did not alter the affinity of these receptors for either 125I-AngII or the high-affinity antagonist 125I-[Sarc1,Ile8]-AngII. This apparent down-regulation was dose related with an ED50 of 1 nM, and maximal decreases of approximately 90% were obtained with 100 nM AngII. Receptor loss from differentiated cell membranes was unaffected by incubations of membranes obtained from agonist-exposed cells with non-hydrolyzable analogues of GTP for 60 min at 37 degrees C to ensure dissociation of the ligand. Partial loss of AngII receptors was apparent within 5 min of agonist exposure, whereas maximal declines were not observed until 30 min. This temporal pattern resulted from a preferential decrease in the AT1 receptor subtype during the first 5 min, followed by a decline in both AT1 and AT2 receptors with longer periods of agonist exposure. The loss of membranous receptors was reversible with partial recovery observed after 4 h, and with nearly full recovery observed 18 h after exposure of the cells to AngII. However, the long-term recovery of receptor density was blocked by the protein synthesis inhibitor, cycloheximide. The heptapeptide angiotensin III produced a similar down-regulation of receptors, and the high-affinity antagonist [Sarc1,Thr8]-AngII blocked agonist-induced down-regulation. Finally, the apparent loss of cell surface AngII receptors decreased the ability of AngII to stimulate cyclic GMP production within intact N1E-115 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Informational Polymers and Nanomaterials from Ring-Opening Metathesis Polymerization

NASA Astrophysics Data System (ADS)

James, Carrie Rae

Inspired by naturally occurring polymers (DNA, polypeptides, polysaccharides, etc.) that can self-assemble on the nanoscale into complex, information-rich architectures, we have synthesized nucleic acid based polymers using ROMP. These polymers were synthesized using a graft-through strategy, whereby nucleic acids bearing a strained cyclic olefin were directly polymerized. This is the first example of the graft-through polymerization of nucleic acids. Our approach takes advantage of non-charged peptide nucleic acids (PNAs) as elements to incorporate into ROMP polymer backbones. PNA is a synthetic nucleic acid analogue known for its increased affinity and specificity for complementary DNA or RNA. To accomplish the graft-through polymerization of PNA, we conjugated PNA to strained cyclic olefins using solid phase peptide conjugation chemistry. These PNA monomers were then directly polymerized into homo and block copolymers forming brushes, or comb-like arrangements, of information. Block copolymer amphiphiles of these materials, where the PNA brush served as the hydrophilic portion, were capable of self-assembly into spherical nanoparticles (PNA NPs). These PNA NPs were then studied with respect to their ability to hybridize complementary DNA sequences, as well as their ability to undergo cellular internalization. PNA NPs consisting of densely packed brushes of nucleic acids possessed increased thermal stability when mixed with their complementary DNA sequence, indicating a greater DNA binding affinity over their unpolymerized PNA counterparts. In addition, by arranging the PNA into dense brushes at the surface of the nanoparticle, Cy5.5 labeled PNA NPs were able to undergo cellular internalization into HeLa cells without the need for an additional cellular delivery device. Importantly, cellular internalization of PNA has remained a significant challenge in the literature due to the neutrally charged amino-ethyl glycine backbone of PNA. Therefore, this represents a novel way of facilitating cellular uptake of PNA. This materials strategy represents the first direct polymerization of nucleic acids, and presents a novel method for arranging biological information on the nanoscale at high density in order to confer novel attributes.

Effect of fluoride dentifrice and casein phosphopeptide-amorphous calcium phosphate cream with and without fluoride in preventing enamel demineralization in a pH cyclic study.

PubMed

Sinfiteli, Priscila de Pinto; Coutinho, Thereza Christina Lopes; Oliveira, Patrícia Regina Almeida de; Vasques, Wesley Felisberto; Azevedo, Leandra Matos; Pereira, André Maues Brabo; Tostes, Monica Almeida

2017-01-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complexes are anticariogenic and capable of remineralizing the early stages of enamel lesions. The use of fluoride prevents dental decay and the association of CPP-ACP with fluoride can increase remineralization. To evaluate the effect of CPP-ACP and CPP-ACPF creams associated with a fluoride dentifrice to prevent enamel demineralization in a pH cyclic model. Previously selected by surface microhardness (SH) analysis, human enamel blocks (n = 56) were submitted to daily treatment with dentifrice in a pH-cycling model. The enamel blocks were divided into four groups; G1: Crest™ Cavity Protection - Procter & Gamble (1,100 ppmF of NaF); G2: Crest™ +MI Paste (MP) - Recaldent™ GC Corporation Tokyo, Japan); G3: Crest™ + MI Paste Plus (MPP) - Recaldent™ 900 ppm as NaF, GC Corporation Tokyo, Japan), and G4: control, saliva. Specimens were soaked alternatively in a demineralizing solution and in artificial saliva for 5 d. The fluoride dentifrice, with proportion of 1:3 (w/w), was applied three times for 60 s after the remineralization period. The undiluted MP and MPP creams were applied for 3 m/d. After cycling, SH was re-measured and cross section microhardness measurements were taken. The SH values observed for the groups G3 (257±70), G1 (205±70), and G2 (208±84) differed from the G4 group (98±110) (one-way ANOVA and Tukey's post hoc test). There were no differences between the groups G1xG2, G2xG3, and G1xG3 for demineralization inhibition. The percentage of volume mineral showed that, when applied with fluoride dentifrice, MPP was the most effective in preventing enamel demineralization at 50 µ from the outer enamel surface (Kruskal-Wallis and Mann Whitney p<0.05). Fluoride dentifrice associated with CPP-ACPF inhibited subsurface enamel demineralization.

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion

PubMed Central

Schwede, Frank; Chepurny, Oleg G.; Kaufholz, Melanie; Bertinetti, Daniela; Leech, Colin A.; Cabrera, Over; Zhu, Yingmin; Mei, Fang; Cheng, Xiaodong; Manning Fox, Jocelyn E.; MacDonald, Patrick E.; Genieser, Hans-G.; Herberg, Friedrich W.

2015-01-01

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In dynamic perifusion assays of human or rat islets, a step-wise increase of glucose concentration leads to biphasic insulin secretion, and under these conditions, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer, 4-acetoxybenzyl ester (Rp-8-Br-cAMPS-pAB) inhibits first-phase GSIS by up to 80%. Surprisingly, second-phase GSIS is inhibited to a much smaller extent (≤20%). Using luciferase, fluorescence resonance energy transfer, and bioluminescence resonance energy transfer assays performed in living cells, we validate that Rp-8-Br-cAMPS-pAB does in fact block cAMP-dependent protein kinase activation. Novel effects of Rp-8-Br-cAMPS-pAB to block the activation of cAMP-regulated guanine nucleotide exchange factors (Epac1, Epac2) are also validated using genetically encoded Epac biosensors, and are independently confirmed in an in vitro Rap1 activation assay using Rp-cAMPS and Rp-8-Br-cAMPS. Thus, in addition to revealing the cAMP dependence of first-phase GSIS from human and rat islets, these findings establish a pAB-based chemistry for the synthesis of highly membrane permeable prodrug derivatives of Rp-cAMPS that act with micromolar or even nanomolar potency to inhibit cAMP signaling in living cells. PMID:26061564

The Rae craton of Laurentia/Nuna: a tectonically unique entity providing critical insights into the concept of Precambrian supercontinental cyclicity

NASA Astrophysics Data System (ADS)

Bethune, K. M.

2015-12-01

Forming the nucleus of Laurentia/Nuna, the Rae craton contains rocks and structures ranging from Paleo/Mesoarchean to Mesoproterozoic in age and has long been known for a high degree of tectonic complexity. Recent work strongly supports the notion that the Rae developed independently from the Hearne; however, while the Hearne appears to have been affiliated with the Superior craton and related blocks of 'Superia', the genealogy of Rae is far less clear. A diagnostic feature of the Rae, setting it apart from both Hearne and Slave, is the high degree of late Neoarchean to early Paleoproterozoic reworking. Indeed, following a widespread 2.62-2.58 Ga granite bloom, the margins of Rae were subjected to seemingly continuous tectonism, with 2.55-2.50 Ga MacQuoid orogenesis in the east superseded by 2.50 to 2.28 Ga Arrowsmith orogenesis in the west. A recent wide-ranging survey of Hf isotopic ratios in detrital and magmatic zircons across Rae has demonstrated significant juvenile, subduction-related crustal production in this period. Following break-up at ca. 2.1 Ga, the Rae later became a tectonic aggregation point as the western and eastern margins transitioned back to convergent plate boundaries (Thelon-Taltson and Snowbird orogens) marking onset of the 2.0-1.8 Ga assembly of Nuna. The distinctive features of Rae, including orogenic imprints of MacQuoid and Arrowsmith vintage have now been identified in about two dozen cratonic blocks world-wide, substantiating the idea that the Rae cratonic family spawned from an independent earliest Paleoproterozoic landmass before its incorportation in Nuna. While critical tests remain to be made, including more reliable ground-truthing of proposed global correlations, these relationships strongly support the notion of supercontinental cyclicity in the Precambrian, including the Archean. They also challenge the idea of a globally quiescent period in the early Paleoproterozoic (2.45-2.2 Ga) in which plate tectonics slowed or shut down.

Development of experimental approach to examine U occurrence continuity over the extended area reconnoitory boreholes: Lostoin Block, West Khasi Hills district, Meghalaya (India).

PubMed

Kukreti, B M; Kumar, Pramod; Sharma, G K

2015-10-01

Exploratory drilling was undertaken in the Lostoin block, West Khasi Hills district of Meghalaya based on the geological extension to the major uranium deposit in the basin. Gamma ray logging of drilled boreholes shows considerable subsurface mineralization in the block. However, environmental and exploration related challenges such as climatic, logistic, limited core drilling and poor core recovery etc. in the block severely restricted the study of uranium exploration related index parameters for the block with a high degree confidence. The present study examines these exploration related challenges and develops an integrated approach using representative sampling of reconnoitory boreholes in the block. Experimental findings validate a similar geochemically coherent nature of radio elements (K, Ra and Th) in the Lostoin block uranium hosting environment with respect to the known block of Mahadek basin and uranium enrichment is confirmed by the lower U to Th correlation index (0.268) of hosting environment. A mineralized zone investigation in the block shows parent (refers to the actual parent uranium concentration at a location and not a secondary concentration such as the daughter elements which produce the signal from a total gamma ray measurement) favoring uranium mineralization. The confidence parameters generated under the present study have implications for the assessment of the inferred category of uranium ore in the block and setting up a road map for the systematic exploration of large uranium potential occurring over extended areas in the basin amid prevailing environmental and exploratory impediments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systematic review of patient history and physical examination to diagnose chronic low back pain originating from the facet joints.

PubMed

Maas, E T; Juch, J N S; Ostelo, R W J G; Groeneweg, J G; Kallewaard, J W; Koes, B W; Verhagen, A P; Huygen, F J P M; van Tulder, M W

2017-03-01

Patient history and physical examination are frequently used procedures to diagnose chronic low back pain (CLBP) originating from the facet joints, although the diagnostic accuracy is controversial. The aim of this systematic review is to determine the diagnostic accuracy of patient history and/or physical examination to identify CLBP originating from the facet joints using diagnostic blocks as reference standard. We searched MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Collaboration database from inception until June 2016. Two review authors independently selected studies for inclusion, extracted data and assessed the risk of bias. We calculated sensitivity and specificity values, with 95% confidence intervals (95% CI). Twelve studies were included, in which 129 combinations of index tests and reference standards were presented. Most of these index tests have only been evaluated in single studies with a high risk of bias. Four studies evaluated the diagnostic accuracy of the Revel's criteria combination. Because of the clinical heterogeneity, results were not pooled. The published sensitivities ranged from 0.11 (95% CI 0.02-0.29) to 1.00 (95% CI 0.75-1.00), and the specificities ranged from 0.66 (95% CI 0.46-0.82) to 0.91 (95% CI 0.83-0.96). Due to clinical heterogeneity, the evidence for the diagnostic accuracy of patient history and/or physical examination to identify facet joint pain is inconclusive. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. © 2016 European Pain Federation - EFIC®.

Polystyrene-block-poly(ethylene oxide) copolymers as templates for stacked, spherical large-mesopore silica coatings: dependence of silica pore size on the PS/PEO ratio

PubMed Central

Magnacca, Giuliana; Jadhav, Sushilkumar A; Scalarone, Dominique

2016-01-01

Summary Large-mesopore silica films with a narrow pore size distribution and high porosity have been obtained by a sol–gel reaction of a silicon oxide precursor (TEOS) and using polystyrene-block-poly(ethylene oxide) (PS-b-PEO) copolymers as templates in an acidic environment. PS-b-PEO copolymers with different molecular weight and composition have been studied in order to assess the effects of the block length on the pore size of the templated silica films. The changes in the morphology of the porous systems have been investigated by transmission electron microscopy and a systematic analysis has been carried out, evidencing the dependence between the hydrophilic/hydrophobic ratio of the two polymer blocks and the size of the final silica pores. The obtained results prove that by tuning the PS/PEO ratio, the pore size of the templated silica films can be easily and finely predicted. PMID:27826520

Building Blocks of Psychology: on Remaking the Unkept Promises of Early Schools.

PubMed

Gozli, Davood G; Deng, Wei Sophia

2018-03-01

The appeal and popularity of "building blocks", i.e., simple and dissociable elements of behavior and experience, persists in psychological research. We begin our assessment of this research strategy with an historical review of structuralism (as espoused by E. B. Titchener) and behaviorism (espoused by J. B. Watson and B. F. Skinner), two movements that held the assumption in their attempts to provide a systematic and unified discipline. We point out the ways in which the elementism of the two schools selected, framed, and excluded topics of study. After the historical review, we turn to contemporary literature and highlight the persistence of research into building blocks and the associated framing and exclusions in psychological research. The assumption that complex categories of human psychology can be understood in terms of their elementary components and simplest forms seems indefensible. In specific cases, therefore, reliance on the assumption requires justification. Finally, we review alternative strategies that bypass the commitment to building blocks.

New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.

PubMed

Brand, Thomas; Schindler, Roland

2017-12-01

The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.

PubMed

Perez, Dominique R; Smagley, Yelena; Garcia, Matthew; Carter, Mark B; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S; Sklar, Larry A; Chigaev, Alexandre

2016-06-07

Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.

Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion

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

Mukai, Atsushi; Hashimoto, Naohiro

2008-01-15

Multinucleated myotubes are formed by fusion of mononucleated myogenic progenitor cells (myoblasts) during terminal skeletal muscle differentiation. In addition, myoblasts fuse with myotubes, but terminally differentiated myotubes have not been shown to fuse with each other. We show here that an adenylate cyclase activator, forskolin, and other reagents that elevate intracellular cyclic AMP (cAMP) levels induced cell fusion between small bipolar myotubes in vitro. Then an extra-large myotube, designated a 'myosheet,' was produced by both primary and established mouse myogenic cells. Myotube-to-myotube fusion always occurred between the leading edge of lamellipodia at the polar end of one myotube and themore » lateral plasma membrane of the other. Forskolin enhanced the formation of lamellipodia where cAMP-dependent protein kinase (PKA) was accumulated. Blocking enzymatic activity or anchoring of PKA suppressed forskolin-enhanced lamellipodium formation and prevented fusion of multinucleated myotubes. Localized PKA activity was also required for fusion of mononucleated myoblasts. The present results suggest that localized PKA plays a pivotal role in the early steps of myogenic cell fusion, such as cell-to-cell contact/recognition through lamellipodium formation. Furthermore, the localized cAMP-PKA pathway might be involved in the specification of the fusion-competent areas of the plasma membrane in lamellipodia of myogenic cells.« less

Electrically and Thermally Conductive Carbon Fibre Fabric Reinforced Polymer Composites Based on Nanocarbons and an In-situ Polymerizable Cyclic Oligoester.

PubMed

Jang, Ji-Un; Park, Hyeong Cheol; Lee, Hun Su; Khil, Myung-Seob; Kim, Seong Yun

2018-05-16

There is growing interest in carbon fibre fabric reinforced polymer (CFRP) composites based on a thermoplastic matrix, which is easy to rapidly produce, repair or recycle. To expand the applications of thermoplastic CFRP composites, we propose a process for fabricating conductive CFRP composites with improved electrical and thermal conductivities using an in-situ polymerizable and thermoplastic cyclic butylene terephthalate oligomer matrix, which can induce good impregnation of carbon fibres and a high dispersion of nanocarbon fillers. Under optimal processing conditions, the surface resistivity below the order of 10 +10 Ω/sq, which can enable electrostatic powder painting application for automotive outer panels, can be induced with a low nanofiller content of 1 wt%. Furthermore, CFRP composites containing 20 wt% graphene nanoplatelets (GNPs) were found to exhibit an excellent thermal conductivity of 13.7 W/m·K. Incorporating multi-walled carbon nanotubes into CFRP composites is more advantageous for improving electrical conductivity, whereas incorporating GNPs is more beneficial for enhancing thermal conductivity. It is possible to fabricate the developed thermoplastic CFRP composites within 2 min. The proposed composites have sufficient potential for use in automotive outer panels, engine blocks and other mechanical components that require conductive characteristics.

Efficient entrapment of large and small compounds during vesiculation of intestinal microvilli.

PubMed Central

van Dommelen, F S; Hamer, C M; De Jonge, H R

1986-01-01

An efficient method is described permitting the encapsulation of membrane-impermeable compounds at the interior of intestinal microvilli during vesicle formation. Rat intestinal epithelial cells were isolated by high-frequency vibration and exposed transiently to iso-osmotic medium containing 5 mM-EDTA. Vesiculation of microvilli was effected by freeze-thawing instead of mechanical fragmentation or hypo-osmotic lysis. Solutes to be entrapped were mixed with the extracellular medium before freezing in liquid N2. Microvillous vesicles were isolated from thawed cell suspensions by Ca2+- or Mg2+-aggregation of contaminants and differential centrifugation. The yield, purity, orientation and transport properties of the vesicles were similar, or superior, to preparations described in the literature. A high loading efficiency was demonstrated for small impermeants (cyclic GMP, ATP, Arsenazo III) as well as proteins (albumin); in contrast, loading of isolated vesicles by hypo-osmotic shock was only partially effective (cyclic GMP, ATP) or ineffective (albumin). Entrapment of an ATP-regenerating system could partially block a Mg2+-dependent conversion of intravesicular ATP into ADP. No evidence was obtained for the contribution of a proton pump to the intrinsic Mg2+-ATPase of the vesicle. Potential applications of the vesicle-loading technique in studies of brush-border transport regulation by intramicrovillar factors are discussed. Images Fig. 1. Fig. 2. PMID:3024625

Essential role for cyclic-AMP responsive element binding protein 1 (CREB) in the survival of acute lymphoblastic leukemia.

PubMed

van der Sligte, Naomi E; Kampen, Kim R; ter Elst, Arja; Scherpen, Frank J G; Meeuwsen-de Boer, Tiny G J; Guryev, Victor; van Leeuwen, Frank N; Kornblau, Steven M; de Bont, Eveline S J M

2015-06-20

Acute lymphoblastic leukemia (ALL) relapse remains a leading cause of cancer related death in children, therefore, new therapeutic options are needed. Recently, we showed that a peptide derived from Cyclic-AMP Responsive Element Binding Protein (CREB) was highly phosphorylated in pediatric leukemias. In this study, we determined CREB phosphorylation and mRNA levels showing that CREB expression was significantly higher in ALL compared to normal bone marrow (phosphorylation: P < 0.0001, mRNA: P = 0.004). High CREB and phospho-CREB expression was correlated with a lower median overall survival in a cohort of 140 adult ALL patients. ShRNA mediated knockdown of CREB in ALL cell lines blocked leukemic cell growth by inducing cell cycle arrest and apoptosis. Gene expression array analysis showed downregulation of CREB target genes regulating cell proliferation and glucose metabolism and upregulation of apoptosis inducing genes. Similar to CREB knockdown, the CREB inhibitor KG-501 decreased leukemic cell viability and induced apoptosis in ALL cell lines, as well as primary T-ALL samples, with cases showing high phospho-CREB levels being more sensitive than those with lower phospho-CREB levels. Together, these in vitro findings support an important role for CREB in the survival of ALL cells and identify this transcription factor as a potential target for treatment.

Role of melatonin on diabetes-related metabolic disorders

PubMed Central

Espino, Javier; Pariente, José A; Rodríguez, Ana B

2011-01-01

Melatonin is a circulating hormone that is mainly released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3’,5’-cyclic adenosine monophosphate, 3’,5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals may be more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, blocking the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes. PMID:21860691

Designing Learning Environments to Teach Interactive Quantum Physics

ERIC Educational Resources Information Center

Puente, Sonia M. Gomez; Swagten, Henk J. M.

2012-01-01

This study aims at describing and analysing systematically an interactive learning environment designed to teach Quantum Physics, a second-year physics course. The instructional design of Quantum Physics is a combination of interactive lectures (using audience response systems), tutorials and self-study in unit blocks, carried out with small…

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2014 CFR

2014-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2012 CFR

2012-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

30 CFR 75.222 - Roof control plan-approval criteria.

Code of Federal Regulations, 2013 CFR

2013-07-01

... systems. (1) Systematic supplemental support should be installed throughout— (i) The tailgate entry of the first longwall panel prior to any mining; and (ii) In the proposed tailgate entry of each subsequent... should address— (i) Notification of miners that the travelway is blocked; (ii) Re-instruction of miners...

Cyclic nucleotide content of tobacco BY-2 cells.

PubMed

Richards, Helen; Das, Swadipa; Smith, Christopher J; Pereira, Louisa; Geisbrecht, Alan; Devitt, Nicola J; Games, David E; van Geyschem, Jan; Gareth Brenton, A; Newton, Russell P

2002-11-01

The cyclic nucleotide content of cultured tobacco bright yellow-2 (BY-2) cells was determined, after freeze-killing, perchlorate extraction and sequential chromatography, by radioimmunoassay. The identities of the putative cyclic nucleotides, adenosine 3',5'-cyclic monophosphate (cyclic AMP), guanosine 3',5'-cyclic monophosphate (cyclic GMP) and cytidine 3',5'-cyclic monophosphate (cyclic CMP) were unambiguously confirmed by tandem mass spectrometry. The potential of BY-2 cell cultures as a model system for future investigations of cyclic nucleotide function in higher plants is discussed.

Cyclic Nucleotide Monophosphates in Plants and Plant Signaling.

PubMed

Marondedze, Claudius; Wong, Aloysius; Thomas, Ludivine; Irving, Helen; Gehring, Chris

2017-01-01

Cyclic nucleotide monophosphates (cNMPs) and the enzymes that can generate them are of increasing interest in the plant sciences. Arguably, the major recent advance came with the release of the complete Arabidopsis thaliana genome that has enabled the systematic search for adenylate (ACs) or guanylate cyclases (GCs) and did eventually lead to the discovery of a number of GCs in higher plants. Many of these proteins have complex domain architectures with AC or GC centers moonlighting within cytosolic kinase domains. Recent reports indicated the presence of not just the canonical cNMPs (i.e., cAMP and cGMP), but also the noncanonical cCMP, cUMP, cIMP, and cdTMP in plant tissues, and this raises several questions. Firstly, what are the functions of these cNMPs, and, secondly, which enzymes can convert the substrate triphosphates into the respective noncanonical cNMPs? The first question is addressed here by comparing the reactive oxygen species (ROS) response of cAMP and cGMP to that elicited by the noncanonical cCMP or cIMP. The results show that particularly cIMP can induce significant ROS production. To answer, at least in part, the second question, we have evaluated homology models of experimentally confirmed plant GCs probing the substrate specificity by molecular docking simulations to determine if they can conceivably catalytically convert substrates other than ATP or GTP. In summary, molecular modeling and substrate docking simulations can contribute to the evaluation of cyclases for noncanonical cyclic mononucleotides and thereby further our understanding of the molecular mechanism that underlie cNMP-dependent signaling in planta.

Back to basics: The effects of block vs. interleaved trial administration on pro- and anti-saccade performance

PubMed Central

Zeligman, Liran; Zivotofsky, Ari Z.

2017-01-01

The pro and anti-saccade task (PAT) is a widely used tool in the study of overt and covert attention with promising potential role in neurocognitive and psychiatric assessment. However, specific PAT protocols can vary significantly between labs, potentially resulting in large variations in findings across studies. In light of recent calls towards a standardization of PAT the current study's objective was to systematically and purposely evaluate the effects of block vs. interleaved administration—a fundamental consideration—on PAT measures in a within subject design. Additionally, this study evaluated whether measures of a Posner-type cueing paradigm parallels measures of the PAT paradigm. As hypothesized, results indicate that PAT performance is highly susceptible to administration mode. Interleaved mode resulted in larger error rates not only for anti (blocks: M = 22%; interleaved: M = 42%) but also for pro-saccades (blocks: M = 5%; interleaved: M = 12%). This difference between block and interleaved administration was significantly larger in anti-saccades compared to pro-saccades and cannot be attributed to a 'speed/accuracy tradeoff'. Interleaved mode produced larger pro and anti-saccade differences in error rates while block administration produced larger latency differences. Results question the reflexive nature of pro-saccades, suggesting they are not purely reflexive. These results were further discussed and compared to previous studies that included within subject data of blocks and interleaved trials. PMID:28222173

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Vitagliano, A; Saccone, G; Noventa, M; Borini, A; Coccia, M E; Nardelli, G B; Saccardi, C; Bifulco, G; Litta, P S; Andrisani, A

2018-06-03

Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles. © 2018 Royal College of Obstetricians and Gynaecologists.

Berry phase in Heisenberg representation

NASA Technical Reports Server (NTRS)

Andreev, V. A.; Klimov, Andrei B.; Lerner, Peter B.

1994-01-01

We define the Berry phase for the Heisenberg operators. This definition is motivated by the calculation of the phase shifts by different techniques. These techniques are: the solution of the Heisenberg equations of motion, the solution of the Schrodinger equation in coherent-state representation, and the direct computation of the evolution operator. Our definition of the Berry phase in the Heisenberg representation is consistent with the underlying supersymmetry of the model in the following sense. The structural blocks of the Hamiltonians of supersymmetrical quantum mechanics ('superpairs') are connected by transformations which conserve the similarity in structure of the energy levels of superpairs. These transformations include transformation of phase of the creation-annihilation operators, which are generated by adiabatic cyclic evolution of the parameters of the system.

A calcium-permeable cGMP-activated cation conductance in hippocampal neurons

NASA Technical Reports Server (NTRS)

Leinders-Zufall, T.; Rosenboom, H.; Barnstable, C. J.; Shepherd, G. M.; Zufall, F.

1995-01-01

Whole-cell patch clamp recordings detected a previously unidentified cGMP-activated membrane conductance in cultured rat hippocampal neurons. This conductance is nonselectively permeable for cations and is completely but reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal cGMP-activated conductance was examined in detail, indicating that the underlying ion channels display a high relative permeability for Ca2+. The results indicate that hippocampal neurons contain a cGMP-activated membrane conductance that has some properties similar to the cyclic nucleotide-gated channels previously shown in sensory receptor cells and retinal neurons. In hippocampal neurons this conductance similarly could mediate membrane depolarization and Ca2+ fluxes in response to intracellular cGMP elevation.

Block Gauss elimination followed by a classical iterative method for the solution of linear systems

NASA Astrophysics Data System (ADS)

Alanelli, Maria; Hadjidimos, Apostolos

2004-02-01

In the last two decades many papers have appeared in which the application of an iterative method for the solution of a linear system is preceded by a step of the Gauss elimination process in the hope that this will increase the rates of convergence of the iterative method. This combination of methods has been proven successful especially when the matrix A of the system is an M-matrix. The purpose of this paper is to extend the idea of one to more Gauss elimination steps, consider other classes of matrices A, e.g., p-cyclic consistently ordered, and generalize and improve the asymptotic convergence rates of some of the methods known so far.

Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.

PubMed

Glanowska, Katarzyna M; Moenter, Suzanne M

2015-01-01

GnRH release in the median eminence (ME) is the central output for control of reproduction. GnRH processes in the preoptic area (POA) also release GnRH. We examined region-specific regulation of GnRH secretion using fast-scan cyclic voltammetry to detect GnRH release in brain slices from adult male mice. Blocking endoplasmic reticulum calcium reuptake to elevate intracellular calcium evokes GnRH release in both the ME and POA. This release is action potential dependent in the ME but not the POA. Locally applied kisspeptin induced GnRH secretion in both the ME and POA. Local blockade of inositol triphospate-mediated calcium release inhibited kisspeptin-induced GnRH release in the ME, but broad blockade was required in the POA. In contrast, kisspeptin-evoked secretion in the POA was blocked by local gonadotropin-inhibitory hormone, but broad gonadotropin-inhibitory hormone application was required in the ME. Although action potentials are required for GnRH release induced by pharmacologically-increased intracellular calcium in the ME and kisspeptin-evoked release requires inositol triphosphate-mediated calcium release, blocking action potentials did not inhibit kisspeptin-induced GnRH release in the ME. Kisspeptin-induced GnRH release was suppressed after blocking both action potentials and plasma membrane Ca(2+) channels. This suggests that kisspeptin action in the ME requires both increased intracellular calcium and influx from the outside of the cell but not action potentials. Local interactions among kisspeptin and GnRH processes in the ME could thus stimulate GnRH release without involving perisomatic regions of GnRH neurons. Coupling between action potential generation and hormone release in GnRH neurons is thus likely physiologically labile and may vary with region.

The angiotensin II type 1 receptor-neprilysin inhibitor LCZ696 blocked aldosterone synthesis in a human adrenocortical cell line.

PubMed

Miura, Shin-Ichiro; Suematsu, Yasunori; Matsuo, Yoshino; Tomita, Sayo; Nakayama, Asuka; Goto, Masaki; Arimura, Tadaaki; Kuwano, Takashi; Yahiro, Eiji; Saku, Keijiro

2016-11-01

A recent clinical study indicated that an angiotensin II (Ang II) type 1 (AT 1 ) receptor-neprilysin inhibitor (ARNi) designated LCZ696 (sacubitril/valsartan, as combined sodium complex) was superior to enalapril at reducing the risks of death and hospitalization due to heart failure. Therefore, we investigated the possible mechanisms of the beneficial effect of LCZ696, in which the inhibition of neprilysin enhances atrial natriuretic peptide (NP) or brain NP (ANP or BNP)-evoked signals that can block Ang II/AT 1 receptor-induced aldosterone (Ald) synthesis in human adrenocortical cells. The binding affinity of valsartan+LBQ657 (active moiety of sacubitril) to the AT 1 receptor was greater than that of valsartan alone in an AT 1 receptor-expressing human embryonic kidney cell-based assay. There was no difference in the dissociation from the AT 1 receptor between valsartan+LBQ657 and valsartan alone. In Ang II-sensitized human adrenocortical cells, ANP or BNP alone, but not LBQ657 or valsartan alone, significantly decreased Ald synthesis. The level of suppression of Ald synthesis by ANP or BNP with LBQ657 was greater than that by ANP or BNP without LBQ657. The suppression of ANP was blocked by inhibitors of regulator of G-protein signaling proteins and cyclic GMP-dependent protein kinase. The inhibition of neprilysin did not change the mRNA levels of the AT 1 receptor, ANP receptor A, regulator of G-protein signaling protein, renin or 3β-hydroxysteroid dehydrogenases. In conclusion, the inhibition of neprilysin by LBQ657 enhances the NP-evoked signals that can block Ang II/AT 1 receptor-induced Ald synthesis in human adrenocortical cells.

SEM analysis of ionizing radiation effects in an analog to digital converter /AD571/

NASA Technical Reports Server (NTRS)

Gauthier, M. K.; Perret, J.; Evans, K. C.

1981-01-01

The considered investigation is concerned with the study of the total-dose degradation mechanisms in an IIL analog to digital (A/D) converter. The A/D converter is a 10 digit device having nine separate functional units on the chip which encompass several hundred transistors and circuit elements. It was the objective of the described research to find the radiation sensitive elements by a systematic search of the devices on the LSI chip. The employed technique using a scanning electron microscope to determine the functional blocks of an integrated circuit which are sensitive to ionizing radiation and then progressively zeroing in on the soft components within those blocks, proved extremely successful on the AD571. Four functional blocks were found to be sensitive to radiation, including the Voltage Reference, DAC, IIL Clock, and IIL SAR.

Mapping magnetized geologic structures from space: The effect of orbital and body parameters

NASA Technical Reports Server (NTRS)

Schnetzler, C. C.; Taylor, P. T.; Langel, R. A.

1984-01-01

When comparing previous satellite magnetometer missions (such as MAGSAT) with proposed new programs (for example, Geopotential Research Mission, GRM) it is important to quantify the difference in scientific information obtained. The ability to resolve separate magnetic blocks (simulating geological units) is used as a parameter for evaluating the expected geologic information from each mission. The effect of satellite orbital altitude on the ability to resolve two magnetic blocks with varying separations is evaluated and quantified. A systematic, nonlinear, relationship exists between resolution and distance between magnetic blocks as a function of orbital altitude. The proposed GRM would provide an order-of-magnitude greater anomaly resolution than the earlier MAGSAT mission for widely separated bodies. The resolution achieved at any particular altitude varies depending on the location of the bodies and orientation.

Evolution of roughness during the pattern transfer of high-chi, 10nm half-pitch, silicon-containing block copolymer structures

NASA Astrophysics Data System (ADS)

Blachut, Gregory; Sirard, Stephen M.; Liang, Andrew; Mack, Chris A.; Maher, Michael J.; Rincon-Delgadillo, Paulina A.; Chan, Boon Teik; Mannaert, Geert; Vandenberghe, Geert; Willson, C. Grant; Ellison, Christopher J.; Hymes, Diane

2018-03-01

A pattern transfer study was conducted to monitor the evolution of roughness in sub-10 nm half-pitch lines generated by the directed self-assembly (DSA) of a high-chi, silicon-containing block copolymer, poly(4-trimethylsilylstyrene)-block-poly(4-methoxystyrene). Unbiased roughness measurements were used to characterize the roughness of the structures before and after pattern transfer into silicon nitride. Parameters of the reactive ion etch process used as a dry development were systematically modified to minimize undesired line walking created by the DSA pre-pattern and to determine their impacts on roughness. The results of this study indicate that an optimized dry development can mitigate the effects of pre-pattern inhomogeneity, and that both dry development and pattern transfer steps effect the roughness of the final structures.

Jamming by compressing a system of granular crosses

NASA Astrophysics Data System (ADS)

Zheng, Hu; Wang, Dong; Barés, Jonathan; Behringer, Robert

2017-06-01

A disordered stress-free granular packing can be jammed, transformed into a mechanically rigid structure, by increasing the density of particles or by applying shear deformation. The jamming behavior of systems made of 2D circular discs has been investigated in detail, but very little is known about jamming for non-spherical particles, and particularly, non-convex particles. Here, we perform an experimental study on jamming by compression of a system of quasi-2D granular crosses made of photo-elastic crosses. We measure the pressure evolution during cyclic compression and decompression. The Jamming packing fraction of these quasi-2D granular crosses is ϕJ ≃ 0.475, which is much smaller than the value ϕJ ≃ 0.84 for-2D granular disks. The packing fraction shifts systematically to higher values under compressive cycling, corresponding to systematic shifts in the stress-strain response curves. Associated with these shifts are rotations of the crosses, with minimal changes in their centers of mass.

Clinical audit in dentistry: From a concept to an initiation.

PubMed

Malleshi, Suchetha N; Joshi, Mahasweta; Nair, Soumya K; Ashraf, Irshad

2012-11-01

Clinical audit is a quality improvement process that aims to improve patient care through a systematic review of care against explicit criteria. It is a cyclic and multidisciplinary process which involves a series of steps from planning the audit through measuring the performance to implementing and sustaining the change. Although audit contains some facets of research, it is essential to understand the difference between the two. Auditing can be done right from the record maintaining, diagnosis and treatment and postoperative evaluation and follow-up. The immense potential of clinical audit can be utilized only when open-mindedness and innovativeness are encouraged and evidence-based work culture is cultivated.

Preparation of V-Doped LiFePO4/C as the Optimized Cathode Material for Lithium Ion Batteries.

PubMed

Sun, Pingping; Zhang, Haiyang; Shen, Kai; Fan, Qi; Xu, Qingyu

2015-04-01

LiFe1-x,Vx,PO4/C composites were synthesized by solid state reaction. The effect of carbon coating and V doping on the performance of LiFePO4 has been systematically investigated by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM), charge/discharge and cyclic voltammetry (CV) measurement. The results show that carbon coating and proper amount of V incorporation do not significantly change the host crystal structure of LiFePO4, while the electrochemical performance of LiFePO4 can be significantly improved. Particularly, the LiFe0.96V0.04PO4/C exhibits the best performance with a specific discharge capacity of 105.5 mA h/g at 5.0 C, 90.3 mA h/g at 10 C and 66.7 mA h/g at 30 C with stable cycle performance, which is significantly improved compared with the pure LiFePO4/C. The cyclic voltammograms result reveals that V doping could decrease the resistance of LiFePO4/C composite electrode drastically and improve its reversibility.

Influence of surface charge on the rate, extent, and structure of adsorbed Bovine Serum Albumin to gold electrodes.

PubMed

Beykal, Burcu; Herzberg, Moshe; Oren, Yoram; Mauter, Meagan S

2015-12-15

The objective of this work is to investigate the rate, extent, and structure of amphoteric proteins with charged solid surfaces over a range of applied potentials and surface charges. We use Electrochemical Quartz Crystal Microbalance with Dissipation Monitoring (E-QCM-D) to investigate the adsorption of amphoteric Bovine Serum Albumin (BSA) to a gold electrode while systematically varying the surface charge on the adsorbate and adsorbent by manipulating pH and applied potential, respectively. We also perform cyclic voltammetry-E-QCM-D on an adsorbed layer of BSA to elucidate conformational changes in response to varied applied potentials. We confirm previous results demonstrating that increasing magnitude of applied potential on the gold electrode is positively correlated with increasing mass adsorption when the protein and the surface are oppositely charged. On the other hand, we find that the rate of BSA adsorption is not governed by simple electrostatics, but instead depends on solution pH, an observation not well documented in the literature. Cyclic voltammetry with simultaneous E-QCM-D measurements suggest that BSA protein undergoes a conformational change as the surface potential varies. Copyright © 2015 Elsevier Inc. All rights reserved.

A simple theory of molecular organization in fullerene-containing liquid crystals

NASA Astrophysics Data System (ADS)

Peroukidis, S. D.; Vanakaras, A. G.; Photinos, D. J.

2005-10-01

Systematic efforts to synthesize fullerene-containing liquid crystals have produced a variety of successful model compounds. We present a simple molecular theory, based on the interconverting shape approach [Vanakaras and Photinos, J. Mater. Chem. 15, 2002 (2005)], that relates the self-organization observed in these systems to their molecular structure. The interactions are modeled by dividing each molecule into a number of submolecular blocks to which specific interactions are assigned. Three types of blocks are introduced, corresponding to fullerene units, mesogenic units, and nonmesogenic linkage units. The blocks are constrained to move on a cubic three-dimensional lattice and molecular flexibility is allowed by retaining a number of representative conformations within the block representation of the molecule. Calculations are presented for a variety of molecular architectures including twin mesogenic branch monoadducts of C60, twin dendromesogenic branch monoadducts, and conical (badminton shuttlecock) multiadducts of C60. The dependence of the phase diagrams on the interaction parameters is explored. In spite of its many simplifications and the minimal molecular modeling used (three types of chemically distinct submolecular blocks with only repulsive interactions), the theory accounts remarkably well for the phase behavior of these systems.

Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

PubMed Central

Broadus, Arthur E.; Kaminsky, Neil I.; Hardman, Joel G.; Sutherland, Earl W.; Liddle, Grant W.

1970-01-01

Kinetic parameters and the renal clearances of plasma adenosine 3′,5′-monophosphate (cyclic AMP) and guanosine 3′,5′-monophosphate (cyclic GMP) were evaluated in normal subjects using tritium-labeled cyclic nucleotides. Each tracer was administered both by single, rapid intravenous injection and by constant intravenous infusion, and the specific activities of the cyclic nucleotides in plasma and urine were determined. Both cyclic AMP and cyclic GMP were cleared from plasma by glomerular filtration. The kidney was found to add a variable quantity of endogenous cyclic AMP to the tubular urine, amounting to an average of approximately one-third of the total level of cyclic AMP excreted. Plasma was the source of virtually all of the cyclic GMP excreted. Plasma levels of the cyclic nucleotides appeared to be in dynamic steady state. The apparent volumes of distribution of both nucleotides exceeded extracellular fluid volume, averaging 27 and 38% of body weight for cyclic AMP and cyclic GMP, respectively. Plasma production rates ranged from 9 to 17 nmoles/min for cyclic AMP and from 7 to 13 nmoles/min for cyclic GMP. Plasma clearance rates averaged 668 ml/min for cyclic AMP and 855 ml/min for cyclic GMP. Approximately 85% of the elimination of the cyclic nucleotides from the circulation was due to extrarenal clearance. PMID:5480849

IMPLICIT DUAL CONTROL BASED ON PARTICLE FILTERING AND FORWARD DYNAMIC PROGRAMMING.

PubMed

Bayard, David S; Schumitzky, Alan

2010-03-01

This paper develops a sampling-based approach to implicit dual control. Implicit dual control methods synthesize stochastic control policies by systematically approximating the stochastic dynamic programming equations of Bellman, in contrast to explicit dual control methods that artificially induce probing into the control law by modifying the cost function to include a term that rewards learning. The proposed implicit dual control approach is novel in that it combines a particle filter with a policy-iteration method for forward dynamic programming. The integration of the two methods provides a complete sampling-based approach to the problem. Implementation of the approach is simplified by making use of a specific architecture denoted as an H-block. Practical suggestions are given for reducing computational loads within the H-block for real-time applications. As an example, the method is applied to the control of a stochastic pendulum model having unknown mass, length, initial position and velocity, and unknown sign of its dc gain. Simulation results indicate that active controllers based on the described method can systematically improve closed-loop performance with respect to other more common stochastic control approaches.

Sulfur-carbon nanocomposite cathodes improved by an amphiphilic block copolymer for high-rate lithium-sulfur batteries.

PubMed

Fu, Yongzhu; Su, Yu-Sheng; Manthiram, Arumugam

2012-11-01

A sulfur-carbon nanocomposite consisting of a commercial high-surface-area carbon (i.e., Black Pearls 2000, BET surface area >1000 m² g⁻¹) and sulfur has been synthesized by an in situ deposition method. The nanocomposite is in the form of agglomerated nanoparticles, with the micropores within the carbon filled with sulfur and the mesopores on the carbon surface almost completely covered by sulfur. The BET surface area of the nanocomposite containing a sulfur content of 63.5 wt % is significantly reduced to only 40 m² g⁻¹. Cathodes containing the nanocomposite and Pluronic F-127 block copolymer, which partially replaces the polyvinylidene fluoride binder, were prepared and evaluated in lithium cells by cyclic voltammetry and galvanostatic cycling. The nanocomposite cathodes with the copolymer show improved electrochemical stability and cyclability. The Pluronic copolymer helps retain a uniform nanocomposite structure within the electrodes, improving the electrochemical contact, which was manifested by scanning electron microscopy and electrochemical impedance spectroscopy. The sulfur-Black Pearls nanocomposite with the Pluronic copolymer as an additive in the electrodes is promising for high-rate rechargeable lithium-sulfur batteries.

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow

NASA Technical Reports Server (NTRS)

Papadaki, M.; Tilton, R. G.; Eskin, S. G.; McIntire, L. V.

1998-01-01

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

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

NASA Astrophysics Data System (ADS)

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

1991-02-01

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

Octopamine and tyramine regulate the activity of reproductive visceral muscles in the adult female blood-feeding bug, Rhodnius prolixus.

PubMed

Hana, Sam; Lange, Angela B

2017-05-15

The role of octopamine and tyramine in regulating spontaneous contractions of reproductive tissues was examined in the female Rhodnius prolixus Octopamine decreased the amplitude of spontaneous contractions of the oviducts and reduced RhoprFIRFa-induced contractions in a dose-dependent manner, whereas tyramine only reduced the RhoprFIRFa-induced contractions. Both octopamine and tyramine decreased the frequency of spontaneous bursal contractions and completely abolished the contractions at 5×10 -7  mol l -1 and above. Phentolamine, an octopamine receptor antagonist, attenuated the inhibition induced by octopamine on the oviducts and the bursa. Octopamine also increased the levels of cAMP in the oviducts, and this effect was blocked by phentolamine. Dibutyryl cyclic AMP mimicked the effects of octopamine by reducing the frequency of bursal contractions, suggesting that the octopamine receptor may act by an Octβ receptor. The tyramine receptor antagonist yohimbine failed to block the inhibition of contractions induced by tyramine on the bursa, suggesting that tyramine may be acting on the Octβ receptor in the bursa. © 2017. Published by The Company of Biologists Ltd.

3-D dumbbell-like LiNi1/3Mn1/3Co1/3O2 cathode materials assembled with nano-building blocks for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Ryu, Won-Hee; Lim, Sung-Jin; Kim, Won-Keun; Kwon, HyukSang

2014-07-01

Dumbbell-like microsphere carbonate precursors including multi-transition metal components (Ni1/3Mn1/3Co1/3CO3) assembled with nano-building blocks were synthesized by urea-assisted solvo/hydrothermal method, and layered cathode materials (LiNi1/3Mn1/3Co1/3O2) were subsequently prepared using the similarly shaped carbonate precursors for Li-ion batteries. For the synthesis of hierarchical microsphere structures, the partial addition of viscous organic solvent (e.g. ethylene glycol) in aqueous solution played a crucial role, not only in suppressing the sudden particle growth but also in regulating the directional crystallization of carbonate particles on the surface. The dumbbell-like LiNi1/3Mn1/3Co1/3O2 assembled with nanocubes prepared via the urea-assisted solvo/hydrothermal method exhibited better electrochemical characteristics, such as initial discharge capacity, cyclic performance, and rate-capability as a cathode material of Li-ion batteries, compared with the LiNi1/3Mn1/3Co1/3O2 materials prepared via the conventional co-precipitation method.

Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons.

PubMed

Wang, Rui; Li, Yu-Hua; Xu, Ying; Li, Ying-Bo; Wu, Hong-Li; Guo, Hao; Zhang, Jian-Zhao; Zhang, Jing-Jie; Pan, Xue-Yang; Li, Xue-Jun

2010-02-01

Curcumin is a major constituent of curcuma longa, a traditional medicine used to manage mental disorders effectively in China. The neuroprotective effects of curcumin have been demonstrated in our previous studies. In the present research, we confirmed this effect by showing that curcumin application promoted the viability of cultured rodent cortical neurons. Moreover, when neurons were pretreated with tyrosine kinase B (TrkB) antibody, known to inhibit the activity of brain-derived neurotrophic factor (BDNF), the protective effect of curcumin was blocked. Additionally, treatment of curcumin increased BDNF and phosphor-TrkB and both of these enhancements can be suppressed by ERK and PI-3K inhibitors. The administration of curcumin led to increased levels of phosphor-ERK and AKT, which were each blocked by MAPK and PI-3K inhibitors. Furthermore, the curcumin-induced increase in phosphorylated cyclic AMP response element binding protein (CREB), which has been implicated as a possible mediator of antidepressant actions, was prevented by MAPK and PI-3K inhibitors. Therefore, we hypothesize the neuroprotection of curcumin might be mediated via BDNF/TrkB-MAPK/PI-3K-CREB signaling pathway. Copyright 2009. Published by Elsevier Inc.

Comparison of local anesthetics for digital nerve blocks: a systematic review.

PubMed

Vinycomb, Toby I; Sahhar, Lukas J

2014-04-01

To evaluate the time to onset of anesthesia, duration of anesthesia, and pain on injection of local anesthetics. A systematic search of the English literature was performed of the Medline, Cochrane Central Register of Controlled Trials, The Allied and Complementary Medicine Database (AMED), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. The study selection process was adapted from the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, and 6 articles were complied with the study inclusion criteria. Six studies (335 nerve blocks) were included in our final analysis measuring 6 local anesthetic preparations (lidocaine, lidocaine with epinephrine, bupivacaine, bupivacaine with epinephrine, lidocaine with bupivacaine, and ropivacaine). Lidocaine demonstrated the shortest mean onset of anesthesia (3.1 min) and bupivacaine the longest (7.6 min). Lidocaine also demonstrated the shortest mean duration of anesthesia (1.8 h) and ropivacaine the longest mean duration (21.5 h). Lidocaine with epinephrine demonstrated the least mean pain on injection (26 mm on a visual analog scale) and bupivacaine with epinephrine the most mean pain (53 mm). Lidocaine with epinephrine provides a good short-term anesthesia and may reduce the risk of injury or complication while the finger in still anesthetized. Bupivacaine with lidocaine provides good long-term anesthesia and may reduce the need for postprocedural anesthesia. Ropivacaine likely provides the longest duration of anesthesia but the absence of epinephrine means a tourniquet must be used to create a bloodless field and thus is contraindicated in some procedures such as flexor tendon repairs where active testing may be required. Lidocaine with epinephrine, bupivacaine with epinephrine, and ropivacaine all provide benefits in digital nerve blocks. The surgeon may choose the most appropriate local anesthetic or combination of local anesthetics based on the procedure to be undertaken and the postoperative requirements. Therapeutic II. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Hydrogen bonds and twist in cellulose microfibrils.

PubMed

Kannam, Sridhar Kumar; Oehme, Daniel P; Doblin, Monika S; Gidley, Michael J; Bacic, Antony; Downton, Matthew T

2017-11-01

There is increasing experimental and computational evidence that cellulose microfibrils can exist in a stable twisted form. In this study, atomistic molecular dynamics (MD) simulations are performed to investigate the importance of intrachain hydrogen bonds on the twist in cellulose microfibrils. We systematically enforce or block the formation of these intrachain hydrogen bonds by either constraining dihedral angles or manipulating charges. For the majority of simulations a consistent right handed twist is observed. The exceptions are two sets of simulations that block the O2-O6' intrachain hydrogen bond, where no consistent twist is observed in multiple independent simulations suggesting that the O2-O6' hydrogen bond can drive twist. However, in a further simulation where exocyclic group rotation is also blocked, right-handed twist still develops suggesting that intrachain hydrogen bonds are not necessary to drive twist in cellulose microfibrils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative pain management: a meta-analysis.

PubMed

Hain, E; Maggiori, L; Prost À la Denise, J; Panis, Y

2018-04-01

Transversus abdominis plane (TAP) block is a locoregional anaesthesia technique of growing interest in abdominal surgery. However, its efficacy following laparoscopic colorectal surgery is still debated. This meta-analysis aimed to assess the efficacy of TAP block after laparoscopic colorectal surgery. All comparative studies focusing on TAP block after laparoscopic colorectal surgery have been systematically identified through the MEDLINE database, reviewed and included. Meta-analysis was performed according to the Mantel-Haenszel method for random effects. End-points included postoperative opioid consumption, morbidity, time to first bowel movement and length of hospital stay. A total of 13 studies, including 7 randomized controlled trials, were included, comprising a total of 600 patients who underwent laparoscopic colorectal surgery with TAP block, compared with 762 patients without TAP block. Meta-analysis of these studies showed that TAP block was associated with a significantly reduced postoperative opioid consumption on the first day after surgery [weighted mean difference (WMD) -14.54 (-25.14; -3.94); P = 0.007] and a significantly shorter time to first bowel movement [WMD -0.53 (-0.61; -0.44); P < 0.001] but failed to show any impact on length of hospital stay [WMD -0.32 (-0.83; 0.20); P = 0.23] although no study considered length of stay as its primary outcome. Finally, TAP block was not associated with a significant increase in the postoperative overall complication rate [OR = 0.84 (0.62-1.14); P = 0.27]. Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative opioid consumption and recovery of postoperative digestive function without any significant drawback. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Patterning nonisometric origami in nematic elastomer sheets

NASA Astrophysics Data System (ADS)

Plucinsky, Paul; Kowalski, Benjamin A.; White, Timothy J.; Bhattacharya, Kaushik

Nematic elastomers dramatically change their shape in response to diverse stimuli including light and heat. In this paper, we provide a systematic framework for the design of complex three dimensional shapes through the actuation of heterogeneously patterned nematic elastomer sheets. These sheets are composed of \\textit{nonisometric origami} building blocks which, when appropriately linked together, can actuate into a diverse array of three dimensional faceted shapes. We demonstrate both theoretically and experimentally that: 1) the nonisometric origami building blocks actuate in the predicted manner, 2) the integration of multiple building blocks leads to complex multi-stable, yet predictable, shapes, 3) we can bias the actuation experimentally to obtain a desired complex shape amongst the multi-stable shapes. We then show that this experimentally realized functionality enables a rich possible design landscape for actuation using nematic elastomers. We highlight this landscape through theoretical examples, which utilize large arrays of these building blocks to realize a desired three dimensional origami shape. In combination, these results amount to an engineering design principle, which we hope will provide a template for the application of nematic elastomers to emerging technologies.

Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications.

PubMed

Lee, Yeji; Phat, Chanvorleak; Hong, Soon-Cheol

2017-09-01

Many cyclic peptides and analogues derived from marine sources are known to possess biological properties, including anticancer, antitumor, antibacterial, antifungal, antiparasitic, anti-inflammation, anti-proliferative, anti-hypertensive, cytotoxic, and antibiotic properties. These compounds demonstrate different activities and modes of action according to their structure such as cyclic oligopeptide, cyclic lipopeptide, cyclic glycopeptide and cyclic depsipeptide. The recent advances in application of the above-mentioned cyclic peptides were reported in dolastatins, soblidotin, didemnin B, aplidine, salinosporamide A, kahalalide F and bryostatin 1 and they are currently in clinical trials. These cyclic peptides are possible novel drugs discovered and developed from marine origin. Literature data concerning the potential properties of marine cyclic peptides were reviewed here, and the structural diversity and biological activities of marine cyclic peptides are discussed in relation to the molecular mechanisms of these marine cyclic peptides. Copyright © 2017 Elsevier Inc. All rights reserved.

Geomechanical rock properties of a basaltic volcano

NASA Astrophysics Data System (ADS)

Schaefer, Lauren; Kendrick, Jackie; Lavallée, Yan; Oommen, Thomas; Chigna, Gustavo

2015-06-01

In volcanic regions, reliable estimates of mechanical properties for specific volcanic events such as cyclic inflation-deflation cycles by magmatic intrusions, thermal stressing, and high temperatures are crucial for building accurate models of volcanic phenomena. This study focuses on the challenge of characterizing volcanic materials for the numerical analyses of such events. To do this, we evaluated the physical (porosity, permeability) and mechanical (strength) properties of basaltic rocks at Pacaya Volcano (Guatemala) through a variety of laboratory experiments, including: room temperature, high temperature (935 °C), and cyclically-loaded uniaxial compressive strength tests on as-collected and thermally-treated rock samples. Knowledge of the material response to such varied stressing conditions is necessary to analyze potential hazards at Pacaya, whose persistent activity has led to 13 evacuations of towns near the volcano since 1987. The rocks show a non-linear relationship between permeability and porosity, which relates to the importance of the crack network connecting the vesicles in these rocks. Here we show that strength not only decreases with porosity and permeability, but also with prolonged stressing (i.e., at lower strain rates) and upon cooling. Complimentary tests in which cyclic episodes of thermal or load stressing showed no systematic weakening of the material on the scale of our experiments. Most importantly, we show the extremely heterogeneous nature of volcanic edifices that arise from differences in porosity and permeability of the local lithologies, the limited lateral extent of lava flows, and the scars of previous collapse events. Input of these process-specific rock behaviors into slope stability and deformation models can change the resultant hazard analysis. We anticipate that an increased parameterization of rock properties will improve mitigation power.

Exposure of embryos to cyclically cold incubation temperatures durably affects energy metabolism and antioxidant pathways in broiler chickens.

PubMed

Loyau, T; Collin, A; Yenisey, C; Crochet, S; Siegel, P B; Akşit, M; Yalçin, S

2014-08-01

Cyclically cold incubation temperatures have been suggested as a means to improve resistance of broiler chickens to ascites; however, the underlying mechanisms are not known. Nine hundred eggs obtained from 48 wk Ross broiler breeders were randomly assigned to 2 incubation treatments: control I eggs were incubated at 37.6°C throughout, whereas for cold I eggs the incubation temperature was reduced by 1°C for 6 h daily from 10 to 18 d of incubation. Thereafter, chickens were reared at standard temperatures or under cold exposure that was associated or not with a postnatal cold acclimation at d 5 posthatch. At hatch, hepatic catalase activity and malondialdehyde content were measured. Serum thyroid hormone and triglyceride concentrations, and muscle expression of several genes involved in the regulation of energy metabolism and oxidative stress were also measured at hatch and 5 and 25 d posthatch. Cold incubation induced modifications in antioxidant pathways with higher catalase activity, but lower expression of avian uncoupling protein 3 at hatch. However, long-term enhancement in the expression of avian uncoupling protein 3 was observed, probably caused by an increase in the expression of the transcription factor peroxisome proliferator activated receptor-γ coactivator-1α. These effects were not systematically associated with an increase in serum triiodothyronine concentrations that were observed only in chickens exposed to both cold incubation and later acclimation at 5 d with cold rearing. Our results suggest that these conditions of cyclically cold incubation resulted in the long-term in changes in antioxidant pathways and energy metabolism, which could enhance the health of chickens reared under cold conditions. © Poultry Science Association Inc.

Dynamic characteristics and simplified numerical methods of an all-vertical-piled wharf in offshore deep water

NASA Astrophysics Data System (ADS)

Zhang, Hua-qing; Sun, Xi-ping; Wang, Yuan-zhan; Yin, Ji-long; Wang, Chao-yang

2015-10-01

There has been a growing trend in the development of offshore deep-water ports in China. For such deep sea projects, all-vertical-piled wharves are suitable structures and generally located in open waters, greatly affected by wave action. Currently, no systematic studies or simplified numerical methods are available for deriving the dynamic characteristics and dynamic responses of all-vertical-piled wharves under wave cyclic loads. In this article, we compare the dynamic characteristics of an all-vertical-piled wharf with those of a traditional inshore high-piled wharf through numerical analysis; our research reveals that the vibration period of an all-vertical-piled wharf under cyclic loading is longer than that of an inshore high-piled wharf and is much closer to the period of the loading wave. Therefore, dynamic calculation and analysis should be conducted when designing and calculating the characteristics of an all-vertical-piled wharf. We establish a dynamic finite element model to examine the dynamic response of an all-vertical-piled wharf under wave cyclic loads and compare the results with those under wave equivalent static load; the comparison indicates that dynamic amplification of the structure is evident when the wave dynamic load effect is taken into account. Furthermore, a simplified dynamic numerical method for calculating the dynamic response of an all-vertical-piled wharf is established based on the P-Y curve. Compared with finite element analysis, the simplified method is more convenient to use and applicable to large structural deformation while considering the soil non-linearity. We confirmed that the simplified method has acceptable accuracy and can be used in engineering applications.

Is Soleus Muscle-Tendon-Unit Behavior Related to Ground-Force Application During the Sprint Start?

PubMed

Schrödter, Erik; Brüggemann, Gert-Peter; Willwacher, Steffen

2017-04-01

To describe the stretch-shortening behavior of ankle plantar-flexing muscle-tendon units (MTUs) during the push-off in a sprint start. Fifty-four male (100-m personal best: 9.58-12.07 s) and 34 female (100-m personal best: 11.05-14.00 s) sprinters were analyzed using an instrumented starting block and 2-dimensional high-speed video imaging. Analysis was performed separately for front and rear legs, while accounting for block obliquities and performance levels. The results showed clear signs of a dorsiflexion in the upper ankle joint (front block 15.8° ± 7.4°, 95% CI 13.2-18.2°; rear block 8.0° ± 5.7°, 95% CI 6.4-9.7°) preceding plantar flexion. When observed in their natural block settings, the athletes' block obliquity did not significantly affect push-off characteristics. It seems that the stretch-shortening-cycle-like motion of the soleus MTU has an enhancing influence on push-off force generation. This study provides the first systematic observation of ankle-joint stretch-shortening behavior for sprinters of a wide range of performance levels. The findings highlight the importance of reactive-type training for the improvement of starting performance. Nonetheless, future studies need to resolve the independent contributions of tendinous and muscle-fascicle structures to overall MTU performance.

Computationally efficient algorithm for high sampling-frequency operation of active noise control

NASA Astrophysics Data System (ADS)

Rout, Nirmal Kumar; Das, Debi Prasad; Panda, Ganapati

2015-05-01

In high sampling-frequency operation of active noise control (ANC) system the length of the secondary path estimate and the ANC filter are very long. This increases the computational complexity of the conventional filtered-x least mean square (FXLMS) algorithm. To reduce the computational complexity of long order ANC system using FXLMS algorithm, frequency domain block ANC algorithms have been proposed in past. These full block frequency domain ANC algorithms are associated with some disadvantages such as large block delay, quantization error due to computation of large size transforms and implementation difficulties in existing low-end DSP hardware. To overcome these shortcomings, the partitioned block ANC algorithm is newly proposed where the long length filters in ANC are divided into a number of equal partitions and suitably assembled to perform the FXLMS algorithm in the frequency domain. The complexity of this proposed frequency domain partitioned block FXLMS (FPBFXLMS) algorithm is quite reduced compared to the conventional FXLMS algorithm. It is further reduced by merging one fast Fourier transform (FFT)-inverse fast Fourier transform (IFFT) combination to derive the reduced structure FPBFXLMS (RFPBFXLMS) algorithm. Computational complexity analysis for different orders of filter and partition size are presented. Systematic computer simulations are carried out for both the proposed partitioned block ANC algorithms to show its accuracy compared to the time domain FXLMS algorithm.

Alternating block polyurethanes based on PCL and PEG as potential nerve regeneration materials.

PubMed

Li, Guangyao; Li, Dandan; Niu, Yuqing; He, Tao; Chen, Kevin C; Xu, Kaitian

2014-03-01

Polyurethanes with regular and controlled block arrangement, i.e., alternating block polyurethanes (abbreviated as PUCL-alt-PEG) based on poly(ε-caprolactone) (PCL-diol) and poly(ethylene glycol) (PEG) was prepared via selectively coupling reaction between PCL-diol and diisocyanate end-capped PEG. Chemical structure, molecular weight, distribution, and thermal properties were systematically characterized by FTIR, (1)H NMR, GPC, DSC, and TGA. Hydrophilicity was studied by static contact angle of H2O and CH2I2. Film surface was observed by scanning electron microscope (SEM) and atomic force microscopy, and mechanical properties were assessed by universal test machine. Results show that alternating block polyurethanes give higher crystal degree, higher mechanical properties, and more hydrophilic and rougher (deep ravine) surface than their random counterpart, due to regular and controlled structure. Platelet adhesion illustrated that PUCL-alt-PEG has better hemocompatibility and the hemacompatibility was affected significantly by PEG content. Excellent hemocompatibility was obtained with high PEG content. CCK-8 assay and SEM observation revealed much better cell compatibility of fibroblast L929 and rat glial cells on the alternating block polyurethanes than that on random counterpart. Alternating block polyurethane PUC20-a-E4 with optimized composition, mechanical, surface properties, hemacompatibility, and highest cell growth and proliferation was achieved for potential use in nerve regeneration. Copyright © 2013 Wiley Periodicals, Inc.

GPS radio collar 3D performance as influenced by forest structure and topography

Treesearch

R. Scott Gamo; Mark A. Rumble; Fred Lindzey; Matt Stefanich

2000-01-01

Global Positioning System (GPS) telemetry enables biologists to obtain accurate and systematic locations of animals. Vegetation can block signals from satellites to GPS radio collars. Therefore, a vegetation dependent bias to telemetry data may occur which if quantified, could be accounted for. We evaluated the performance of GPS collars in 6 structural stage...

Metalworking Lathe; Machine Shop Work--Intermediate: 9555.03.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

The course outline has been prepared as a guide to assist the instructor to plan systematically and to present meaningful lessons to provide the training needed by the machine shop student. This is the third course of instruction in a series of machine shop work courses. The six blocks of instruction contained in this outline are designed to…

Fine Motor Control Is Related to Cognitive Control in Adolescents with Down Syndrome

ERIC Educational Resources Information Center

Chen, Chih-Chia; Ringenbach, Shannon D. R.; Albert, Andrew; Semken, Keith

2014-01-01

The connection between human cognitive development and motor functioning has been systematically examined in many typical and atypical populations; however, only a few studies focus on people with Down syndrome (DS). Twelve adolescents with DS participated and their cognitive control, measured by the Corsi-Block tapping test (e.g., visual working…

Introduction to Machine Tool Technology, Machine Shop Work--Intermediate: 9555.01.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

The course outline has been prepared as a guide to assist the instructor to plan systematically and to present meaningful lessons programmed to meet the necessary training needed by the machine shop student. A beginning course, the four blocks of instruction contained in the outline are designed to enable the student to obtain the manipulative…

Bench Work and Support Operations, Machine Shop Work--Intermediate: 9555.02.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

The course outline has been prepared as a guide to assist the instructor to plan systematically and to present meaningful lessons programmed to meet the necessary training needed by the machine shop student who has completed an introductory course in machine tool technology. The five blocks of instruction contained in this outline are designed to…

Experimental demonstration of wavelength domain rogue-free ONU based on wavelength-pairing for TDM/WDM optical access networks.

PubMed

Lee, Jie Hyun; Park, Heuk; Kang, Sae-Kyoung; Lee, Joon Ki; Chung, Hwan Seok

2015-11-30

In this study, we propose and experimentally demonstrate a wavelength domain rogue-free ONU based on wavelength-pairing of downstream and upstream signals for time/wavelength division-multiplexed optical access networks. The wavelength-pairing tunable filter is aligned to the upstream wavelength channel by aligning it to one of the downstream wavelength channels. Wavelength-pairing is implemented with a compact and cyclic Si-AWG integrated with a Ge-PD. The pairing filter covered four 100 GHz-spaced wavelength channels. The feasibility of the wavelength domain rogue-free operation is investigated by emulating malfunction of the misaligned laser. The wavelength-pairing tunable filter based on the Si-AWG blocks the upstream signal in the non-assigned wavelength channel before data collision with other ONUs.

Design and Synthesis of a Library of Tetracyclic Hydroazulenoisoindoles

PubMed Central

Brummond, Kay M.; Mao, Shuli; Shinde, Sunita N.; Johnston, Paul J.; Day, Billy W.

2009-01-01

Forty-four tetracyclic hydroazulenoisoindoles were synthesized via a tandem cyclopropanation/Cope rearrangement followed by a Diels-Alder sequence from easily available five-membered cyclic cross-conjugated trienones. These trienones were obtained from two different routes depending upon whether R1 and R2 are alkyl or amino acid derived functional groups, via a rhodium(I)-catalyzed cycloisomerization reaction. In order to increase diversity, four maleimides and two 1,2,4-triazoline-3,5-diones were used as dienophiles in the Diels-Alder step. Several Diels-Alder adducts were further reacted under palladium-catalyzed hydrogenation conditions, leading to a diastereoselective reduction of the trisubstituted double bond. This library has demonstrated rapid access to a variety of structurally complex natural product-like compounds via stereochemical diversity and building block diversity approaches. PMID:19366169

Lignin-based Biochar/graphene Oxide Composites as Supercapacitor Electrode Materials

NASA Astrophysics Data System (ADS)

Cai, Z.; Jiang, C.; Xiao, X. F.; Zhang, Y. S.; Liang, L.

2018-05-01

The lignin-based biochar/graphene composites were effectively obtained via an easy and rapid co-precipitation method. The chemical structure, microstructure, electrochemical properties of lignin/graphene oxide composites before and after carbonization were investigated by Fourier transformation infrared spectrum (FTIR), Scanning electron microscope (SEM), x-ray diffraction (XRD) and cyclic voltammetry (CV). FTIR results confirmed that the oxygen-containing groups of lignin, GO and their composites were partly removed after 800 °C carbonization and GO had a positive impact on the formation of graphitic structure for lignin. XRD results showed that lignin could completely block the restacking of GO sheets. The electrochemical test presented that lignin/graphene oxide composites exhibited a typical CV curve and the specific capacitance reached ∼103F/g at a scan rate of 20mv/s.

GREEN CHEMISTRY. Shape-selective zeolite catalysis for bioplastics production.

PubMed

Dusselier, Michiel; Van Wouwe, Pieter; Dewaele, Annelies; Jacobs, Pierre A; Sels, Bert F

2015-07-03

Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-based catalytic process, which converts lactic acid into lactide. The shape-selective properties of zeolites are essential to attain record lactide yields, outperforming those of the current multistep process by avoiding both racemization and side-product formation. The highly productive process is strengthened by facile recovery and practical reactivation of the catalyst, which remains structurally fit during at least six consecutive reactions, and by the ease of solvent and side-product recycling. Copyright © 2015, American Association for the Advancement of Science.

Optimizing the Distribution of Tie Points for the Bundle Adjustment of HRSC Image Mosaics

NASA Astrophysics Data System (ADS)

Bostelmann, J.; Breitkopf, U.; Heipke, C.

2017-07-01

For a systematic mapping of the Martian surface, the Mars Express orbiter is equipped with a multi-line scanner: Since the beginning of 2004 the High Resolution Stereo Camera (HRSC) regularly acquires long image strips. By now more than 4,000 strips covering nearly the whole planet are available. Due to the nine channels, each with different viewing direction, and partly with different optical filters, each strip provides 3D and color information and allows the generation of digital terrain models (DTMs) and orthophotos. To map larger regions, neighboring HRSC strips can be combined to build DTM and orthophoto mosaics. The global mapping scheme Mars Chart 30 is used to define the extent of these mosaics. In order to avoid unreasonably large data volumes, each MC-30 tile is divided into two parts, combining about 90 strips each. To ensure a seamless fit of these strips, several radiometric and geometric corrections are applied in the photogrammetric process. A simultaneous bundle adjustment of all strips as a block is carried out to estimate their precise exterior orientation. Because size, position, resolution and image quality of the strips in these blocks are heterogeneous, also the quality and distribution of the tie points vary. In absence of ground control points, heights of a global terrain model are used as reference information, and for this task a regular distribution of these tie points is preferable. Besides, their total number should be limited because of computational reasons. In this paper, we present an algorithm, which optimizes the distribution of tie points under these constraints. A large number of tie points used as input is reduced without affecting the geometric stability of the block by preserving connections between strips. This stability is achieved by using a regular grid in object space and discarding, for each grid cell, points which are redundant for the block adjustment. The set of tie points, filtered by the algorithm, shows a more homogenous distribution and is considerably smaller. Used for the block adjustment, it yields results of equal quality, with significantly shorter computation time. In this work, we present experiments with MC-30 half-tile blocks, which confirm our idea for reaching a stable and faster bundle adjustment. The described method is used for the systematic processing of HRSC data.

Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review.

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; de Carvalho, Marta Rodrigues

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Published by Elsevier Editora Ltda.

[Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review].

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; Carvalho, Marta Rodrigues de

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Publicado por Elsevier Editora Ltda.

Hyperbaric Versus Isobaric Bupivacaine for Spinal Anesthesia: Systematic Review and Meta-analysis for Adult Patients Undergoing Noncesarean Delivery Surgery.

PubMed

Uppal, Vishal; Retter, Susanne; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

2017-11-01

It is widely believed that the choice between isobaric bupivacaine and hyperbaric bupivacaine formulations alters the block characteristics for the conduct of surgery under spinal anesthesia. The aim of this study was to systematically review the comparative evidence regarding the effectiveness and safety of the 2 formulations when used for spinal anesthesia for adult noncesarean delivery surgery. Key electronic databases were searched for randomized controlled trials, excluding cesarean delivery surgeries under spinal anesthesia, without any language or date restrictions. The primary outcome measure for this review was the failure of spinal anesthesia. Two independent reviewers selected the studies and extracted the data. Results were expressed as relative risk (RR) or mean differences (MDs) with 95% confidence intervals (CIs). Seven hundred fifty-one studies were identified between 1946 and 2016. After screening, there were 16 randomized controlled clinical trials, including 724 participants, that provided data for the meta-analysis. The methodological reporting of most studies was poor, and appropriate judgment of their individual risk of bias elements was not possible. There was no difference between the 2 drugs regarding the need for conversion to general anesthesia (RR, 0.60; 95% CI, 0.08-4.41; P = .62; I = 0%), incidence of hypotension (RR, 1.15; 95% CI, 0.69-1.92; P = .58; I = 0%), nausea/vomiting (RR, 0.29; 95% CI, 0.06-1.32; P = .11; I = 7%), or onset of sensory block (MD = 1.7 minutes; 95% CI, -3.5 to 0.1; P = .07; I = 0%). The onset of motor block (MD = 4.6 minutes; 95% CI, 7.5-1.7; P = .002; I = 78%) was significantly faster with hyperbaric bupivacaine. Conversely, the duration of motor (MD = 45.2 minutes; 95% CI, 66.3-24.2; P < .001; I = 87%) and sensory (MD = 29.4 minutes; 95% CI, 15.5-43.3; P < .001; I = 73%) block was longer with isobaric bupivacaine. Both hyperbaric bupivacaine and isobaric bupivacaine provided effective anesthesia with no difference in the failure rate or adverse effects. The hyperbaric formulation allows for a relatively rapid motor block onset, with shorter duration of motor and sensory block. The isobaric formulation has a slower onset and provides a longer duration of both sensory and motor block. Nevertheless, the small sample size and high heterogeneity involving these outcomes suggest that all the results should be treated with caution.

Visual search of cyclic spatio-temporal events

NASA Astrophysics Data System (ADS)

Gautier, Jacques; Davoine, Paule-Annick; Cunty, Claire

2018-05-01

The analysis of spatio-temporal events, and especially of relationships between their different dimensions (space-time-thematic attributes), can be done with geovisualization interfaces. But few geovisualization tools integrate the cyclic dimension of spatio-temporal event series (natural events or social events). Time Coil and Time Wave diagrams represent both the linear time and the cyclic time. By introducing a cyclic temporal scale, these diagrams may highlight the cyclic characteristics of spatio-temporal events. However, the settable cyclic temporal scales are limited to usual durations like days or months. Because of that, these diagrams cannot be used to visualize cyclic events, which reappear with an unusual period, and don't allow to make a visual search of cyclic events. Also, they don't give the possibility to identify the relationships between the cyclic behavior of the events and their spatial features, and more especially to identify localised cyclic events. The lack of possibilities to represent the cyclic time, outside of the temporal diagram of multi-view geovisualization interfaces, limits the analysis of relationships between the cyclic reappearance of events and their other dimensions. In this paper, we propose a method and a geovisualization tool, based on the extension of Time Coil and Time Wave, to provide a visual search of cyclic events, by allowing to set any possible duration to the diagram's cyclic temporal scale. We also propose a symbology approach to push the representation of the cyclic time into the map, in order to improve the analysis of relationships between space and the cyclic behavior of events.

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

PubMed

Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

2017-06-02

Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

Pt/glassy carbon model catalysts prepared from PS-b-P2VP micellar templates.

PubMed

Gu, Yunlong; St-Pierre, Jean; Ploehn, Harry J

2008-11-04

Poly(styrene)-block-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymer was used as a micellar template to fabricate arrays of Pt nanoparticles on mica and glassy carbon (GC) supports. Polymer micellar deposition yields Pt nanoparticles with tunable particle size and surface number density on both mica and GC. After deposition of precursor-loaded micelles onto GC, oxygen plasma etching removes the polymer shell, followed by thermal treatment with H2 gas to reduce the Pt. Etching conditions were optimized to maximize removal of the polymer while minimizing damage to the GC. Arrays of Pt nanoparticles with controlled size and surface number density can be prepared on mica (for particle size characterization) and GC to make Pt/GC model catalysts. These model catalysts were characterized by tapping mode atomic force microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry to measure activity for oxidation of carbon monoxide or methanol. Cyclic voltammetry results demonstrate the existence of a correlation between Pt particle size and electrocatalytic properties including onset potential, tolerance of carbonaceous adsorbates, and intrinsic activity (based on active Pt area from CO stripping voltammetry). Results obtained with Pt/GC model catalysts duplicate prior results obtained with Pt/porous carbon catalysts therefore validating the synthesis approach and offering a new, tunable platform to study catalyst structure and other effects such as aging on proton exchange membrane fuel cell (PEMFC) reactions.

Fabrication of graphene/polyaniline composite multilayer films by electrostatic layer-by-layer assembly

NASA Astrophysics Data System (ADS)

Cong, Jiaojiao; Chen, Yuze; Luo, Jing; Liu, Xiaoya

2014-10-01

A novel graphene/polyaniline composite multilayer film was fabricated by electrostatic interactions induced layer-by-layer self-assembly technique, using water dispersible and negatively charged chemically converted graphene (CCG) and positively charged polyaniline (PANI) as building blocks. CCG was achieved through partly reduced graphene oxide, which remained carboxyl group on its surface. The remaining carboxyl groups not only retain the dispersibility of CCG, but also allow the growth of the multilayer films via electrostatic interactions between graphene and PANI. The structure and morphology of the obtained CCG/PANI multilayer film are characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Ultraviolet-visible absorption spectrum (UV-vis), scanning electron microscopy (SEM), Raman spectroscopy and X-Ray Diffraction (XRD). The electrochemical properties of the resulting film are studied using cyclic voltammetry (CV), which showed that the resulting CCG/PANI multilayer film kept electroactivity in neutral solution and showed outstanding cyclic stability up to 100 cycles. Furthermore, the composite film exhibited good electrocatalytic ability toward ascorbic acid (AA) with a linear response from 1×10-4 to 1.2×10-3 M with the detect limit of 5×10-6 M. This study provides a facile and effective strategy to fabricate graphene/PANI nanocomposite film with good electrochemical property, which may find potential applications in electronic devices such as electrochemical sensor.

Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

PubMed

Pettorossi, Vito E; Frondaroli, Adele; Grassi, Silvarosa

2011-04-01

The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17β-estradiol (cE(2)). The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

Urinary Podocyte Microparticles Identify Prealbuminuric Diabetic Glomerular Injury

PubMed Central

Burger, Dylan; Thibodeau, Jean-Francois; Holterman, Chet E.; Burns, Kevin D.; Touyz, Rhian M.

2014-01-01

Microparticles (MPs) are small (0.1–1.0 µm) vesicles shed from the surface of cells in response to stress. Whether podocytes produce MPs and whether this production reflects glomerular injury are unclear. We examined MP formation in cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-β. Urinary podocyte MPs were assessed in three mouse models of diabetic nephropathy: streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG increased MP release as assessed by flow cytometry (P<0.01 and P<0.05, respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited increased urinary podocyte MPs compared with age-matched nondiabetic mice. Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs compared with wild-type littermates (P<0.01). In 1 week post-STZ–treated and 6- and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our results indicate that podocytes produce MPs that are released into urine. Podocyte-derived MPs are generated by exposure to mechanical stretch and high glucose in vitro and could represent early markers of glomerular injury in diabetic nephropathy. PMID:24676640

Evaluation of Heterogeneous Metal-Organic Framework Organocatalysts Prepared by Postsynthetic Modification

PubMed Central

Garibay, Sergio J.; Wang, Zhenqiang; Cohen, Seth M.

2010-01-01

A metal-organic framework (MOF) containing 2-amino-1,4-benzenedicarboxylate (NH2-BDC) as a building block is shown to undergo chemical modification with a set of cyclic anhydrides. The modification of the aluminum-based MOF known as MIL-53(Al)-NH2 (MIL = Matérial Institut Lavoisier) by these reagents is demonstrated by using a variety of methods, including NMR and ESI-MS, and the structural integrity of the modified MOFs has been confirmed by TGA, PXRD, and gas sorption analysis. Reaction with these cyclic anhydrides produces MOFs that display carboxylic acid functional groups within their pores. Furthermore, it is shown that maleic acid functionalized MIL-53(Al)-AMMal can act as a Brønsted acid catalyst and facilitate the methanolysis of several small epoxides. Experiments show that MIL-53(Al)-AMMal acts in a heterogeneous manner and is recyclable with consistent activity over at least three catalytic cycles. The findings presented here demonstrate several important features of covalent postsynthetic modification (PSM) on MOFs, including: 1) facile introduction of catalytic functionality using simple organic reagents (e.g. anhydrides); 2) the ability to utilize and recycle organocatalytic MOFs; 3) control of catalytic activity through choice of functional group. The findings clearly illustrate that covalent postsynthetic modification represents a powerful means to access new MOF compounds that serve as organocatalytic materials. PMID:20698561

Simulation-based Discovery of Cyclic Peptide Nanotubes

NASA Astrophysics Data System (ADS)

Ruiz Pestana, Luis A.

Today, there is a growing need for environmentally friendly synthetic membranes with selective transport capabilities to address some of society's most pressing issues, such as carbon dioxide pollution, or access to clean water. While conventional membranes cannot stand up to the challenge, thin nanocomposite membranes, where vertically aligned subnanometer pores (e.g. nanotubes) are embedded in a thin polymeric film, promise to overcome some of the current limitations, namely, achieving a monodisperse distribution of subnanometer size pores, vertical pore alignment across the membrane thickness, and tunability of the pore surface chemistry. Self-assembled cyclic peptide nanotubes (CPNs), are particularly promising as selective nanopores because the pore size can be controlled at the subnanometer level, exhibit high chemical design flexibility, and display remarkable mechanical stability. In addition, when conjugated with polymer chains, the cyclic peptides can co-assemble in block copolymer domains to form nanoporous thin films. CPNs are thus well positioned to tackle persistent challenges in molecular separation applications. However, our poor understanding of the physics underlying their remarkable properties prevents the rational design and implementation of CPNs in technologically relevant membranes. In this dissertation, we use a simulation-based approach, in particular molecular dynamics (MD) simulations, to investigate the critical knowledge gaps hindering the implementation of CPNs. Computational mechanical tests show that, despite the weak nature of the stabilizing hydrogen bonds and the small cross section, CPNs display a Young's modulus of approximately 20 GPa and a maximum strength of around 1 GPa, placing them among the strongest proteinaceous materials known. Simulations of the self-assembly process reveal that CPNs grow by self-similar coarsening, contrary to other low-dimensional peptide systems, such as amyloids, that are believed to grow through nucleation and elongation. We also establish a generic route that does not require complex chemical synthesis pathways or elaborated design rules to direct the self-assembly of binary mixtures of polymer conjugated cyclic peptides towards nanotubes with specific stripped patterns. The study of the molecular transport properties shows that bioinspired single point amino acid mutations can be effectively used to regulate the ion flow rate over an order of magnitude depending on the size and polarity of the functional groups inserted in the nanotube lumen. Our computational framework circumvents synthetic challenges, and lays the foundation for developing artificial nanochannels for separation applications.

Controlling the Pore Size of Mesoporous Carbon Thin Films through Thermal and Solvent Annealing.

PubMed

Zhou, Zhengping; Liu, Guoliang

2017-04-01

Herein an approach to controlling the pore size of mesoporous carbon thin films from metal-free polyacrylonitrile-containing block copolymers is described. A high-molecular-weight poly(acrylonitrile-block-methyl methacrylate) (PAN-b-PMMA) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The authors systematically investigate the self-assembly behavior of PAN-b-PMMA thin films during thermal and solvent annealing, as well as the pore size of mesoporous carbon thin films after pyrolysis. The as-spin-coated PAN-b-PMMA is microphase-separated into uniformly spaced globular nanostructures, and these globular nanostructures evolve into various morphologies after thermal or solvent annealing. Surprisingly, through thermal annealing and subsequent pyrolysis of PAN-b-PMMA into mesoporous carbon thin films, the pore size and center-to-center spacing increase significantly with thermal annealing temperature, different from most block copolymers. In addition, the choice of solvent in solvent annealing strongly influences the block copolymer nanostructure and the pore size of mesoporous carbon thin films. The discoveries herein provide a simple strategy to control the pore size of mesoporous carbon thin films by tuning thermal or solvent annealing conditions, instead of synthesizing a series of block copolymers of various molecular weights and compositions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Study on Properties of Methane Diffusion of Coal Block under Triaxial Compressive Stress

PubMed Central

Zhao, Hong-Bao

2014-01-01

Taking the standard size coal block samples defined by ISRM as research objects, both properties of methane diffusion of coal block under triaxial compressive stress and characteristic influences caused by methane pressure were systematically studied with thermo-fluid-solid coupling with triaxial servocontrolled seepage equipment of methane-containing coal. The result shows the methane diffusion property of coal block under triaxial compressive stress was shown in four-stage as follow, first is sharply reduce stage, second is hyperbolic reduce stage, third is close to a fixed value stage, fourth stage is 0. There is a special point making the reduced rate of characteristic curve of methane diffusion speed become sharply small; the influences of shape of methane diffusion speed characteristic curve caused by methane pressure are not obvious, which only is shown in numerical size of methane diffusion speed. Test time was extended required by appear of the special point makes the reduce rate of methane diffusion speed become sharply small. The fitting four-phase relation of methane diffusion of coal block under triaxial compressive stress was obtained, and the idea is proposed that influences of the fitting four-phase relation caused by methane pressure were only shown in value of fitting parameters. PMID:25531000

Nanostructured Block Copolymer Solutions and Composites: Mechanical and Structural Properties

NASA Astrophysics Data System (ADS)

Walker, Lynn

2015-03-01

Self-assembled block copolymer templates are used to control the nanoscale structure of materials that would not otherwise order in solution. In this work, we have developed a technique to use close-packed cubic and cylindrical mesophases of a thermoreversible block copolymer (PEO-PPO-PEO) to impart spatial order on dispersed nanoparticles. The thermoreversible nature of the template allows for the dispersion of particles synthesized outside the template. This feature extends the applicability of this templating method to many particle-polymer systems, including proteins, and also permits a systematic evaluation of the impact of design parameters on the structure and mechanical properties of the nanocomposites. The criteria for forming co-crystals have been characterized using small-angle scatting and the mechanical properties of these soft crystals determined. Numerous crystal structures have been reported for the block copolymer system and we have taken advantage of several to generate soft co-crystals. The result of this templating is spatially ordered nanoparticle arrays embedded within the block copolymer nanostructure. These soft materials can be shear aligned into crystals with long range order and this shear alignment is discussed. Finally, the dynamics of nanoparticles within the nanostructured material are characterized with fluorescence recovery after photobleaching (FRAP). The applications and general behavior of these nanostructured hydrogels are outlined.

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries.

PubMed

Chen, Zhengju; Zhang, Xu; Ying, Lei; Dou, Dou; Li, Yanhui; Bai, Yun; Liu, Juan; Liu, Limei; Feng, Han; Yu, Xiaoxing; Leung, Susan Wai-Sum; Vanhoutte, Paul M; Gao, Yuansheng

2014-08-01

cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3',5'-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (Po2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5'-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK. Copyright © 2014 the American Physiological Society.

In silico design of novel hERG-neutral sildenafil-like PDE5 inhibitors.

PubMed

Kayık, Gülru; Tüzün, Nurcan Ş; Durdagi, Serdar

2017-10-01

Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Patch clamp experiments showed that the IC 50 values of the human ether-à-go-go-related gene (hERG1) potassium (K) ion channel blocking affinity of PDE5 inhibitors sildenafil, vardenafil, and tadalafil as 33, 12, and 100 μM, respectively. hERG1 channel is responsible for the regulation of the action potential of human ventricular myocyte by contributing the rapid component of delayed rectifier K + current (I Kr ) component of the cardiac action potential. In this work, interaction patterns and binding affinity predictions of selected PDE5 inhibitors against the hERG1 channel are studied. It is attempted to develop PDE5 inhibitor analogs with lower binding affinity to hERG1 ion channel while keeping their pharmacological activity against their principal target PDE5 using in silico methods. Based on detailed analyses of docking poses and predicted interaction energies, novel analogs of PDE5 inhibitors with lower predicted binding affinity to hERG1 channels without loosing their principal target activity were proposed. Moreover, molecular dynamics (MD) simulations and post-processing MD analyses (i.e. Molecular Mechanics/Generalized Born Surface Area calculations) were performed. Detailed analysis of molecular simulations helped us to better understand the PDE5 inhibitor-target binding interactions in the atomic level. Results of this study can be useful for designing of novel and safe PDE5 inhibitors with enhanced activity and other tailored properties.

Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels

PubMed Central

Meighan, Peter C.; Peng, Changhong; Varnum, Michael D.

2015-01-01

Cyclic nucleotide gated (CNG) channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F) or complete achromatopsia (S156F, P309L, and G558C), by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype). The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs) on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C) produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or non-genetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis. PMID:26106334

Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

PubMed

Schuller, Hildegard M; Al-Wadei, Hussein A N; Majidi, Mourad

2008-10-01

Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

Equilibrium 2H/1H fractionation in organic molecules: III. Cyclic ketones and hydrocarbons

NASA Astrophysics Data System (ADS)

Wang, Ying; Sessions, Alex L.; Nielsen, Robert J.; Goddard, William A.

2013-04-01

Quantitative interpretation of stable hydrogen isotope ratios (2H/1H) in organic compounds is greatly aided by knowledge of the relevant equilibrium fractionation factors (ɛeq). Previous efforts have combined experimental measurements and hybrid Density Functional Theory (DFT) calculations to accurately predict equilibrium fractionations in linear (acyclic) organic molecules (Wang et al., 2009a,b), but the calibration produced by that study is not applicable to cyclic compounds. Here we report experimental measurements of equilibrium 2H/1H fractionation in six cyclic ketones, and use those data to evaluate DFT calculations of fractionation in diverse monocyclic and polycyclic compounds commonly found in sedimentary organic matter and petroleum. At 25, 50, and 75 °C, the experimentally measured ɛeq values for secondary and tertiary Hα in isotopic equilibrium with water are in the ranges of -130‰ to -150‰ and +10‰ to -40‰ respectively. Measured data are similar to DFT calculations of ɛeq for axial Hα but not equatorial Hα. In tertiary Cα positions with methyl substituents, this can be understood as a result of the methyl group forcing Hα atoms into a dominantly axial position. For secondary Cα positions containing both axial and equatorial Hα atoms, we propose that axial Hα exchanges with water significantly faster than the equatorial Hα does, due to the hyperconjugation-stabilized transition state. Interconversion of axial and equatorial positions via ring flipping is much faster than isotopic exchange at either position, and as a result the steady-state isotopic composition of both H's is strongly weighted toward that of axial Hα. Based on comparison with measured ɛeq values, a total uncertainty of 10-30‰ remains for theoretical ɛeq values. Using DFT, we systematically estimated the ɛeq values for individual H positions in various cyclic structures. By summing over all individual H positions, the molecular equilibrium fractionation was estimated to be -75‰ to -95‰ for steroids, -90‰ to -105‰ for hopanoids, and -65‰ to -100‰ for typical cycloparaffins between 0 and 100 °C relative to water. These are distinct from the typical biosynthetic fractionations of -150‰ to -300‰, but are similar to equilibrium fractionations for linear hydrocarbons (Wang et al., 2009b). Thus post-burial H exchange will generally remove the ˜50-100‰ biosynthetic fractionations between cyclic isoprenoid and n-alkyl lipid molecules, which can be used to evaluate the extent of H exchange in sedimentary organic matter and oils.

Degradation of lead-zirconate-titanate ceramics under different dc loads

NASA Astrophysics Data System (ADS)

Balke, Nina; Granzow, Torsten; Rödel, Jürgen

2009-05-01

During poling and application in actuators, piezoelectric ceramics like lead-zirconate-titanate are exposed to static or cyclically varying electric fields, often leading to pronounced changes in the electromechanical properties. These fatigue phenomena depend on time, peak electric load, and temperature. Although this process impacts the performance of many actuator materials, its physical understanding remains elusive. This paper proposes a set of key experiments to systematically investigate the changes in the ferroelectric hysteresis, field-dependent relative permittivity, and piezoelectric coefficient after submitting the material to dc loads of varying amplitude and duration. The observed effects are explained based on a model of domain stabilization due to charge accumulation at domain boundaries.

Hot-salt stress-corrosion of titanium alloys as related to turbine operation

NASA Technical Reports Server (NTRS)

Gray, H. R.

1972-01-01

In an effort to simulate typical compressor operating conditions of current turbine engines, special test facilities were designed. Air velocity, air pressure, air dewpoint, salt deposition temperature, salt concentration, and specimen surface condition were systematically controlled and their influence on hot-salt stress-corrosion evaluated. The influence of both continuous and cyclic stress-temperature exposures was determined. The relative susceptibility of a variety of titanium alloys in commonly used heat-treated conditions was determined. The effects of both environmental and material variables were used to interpret the behavior of titanium alloys under hot-salt stress-corrosion conditions found in jet engines and to appraise their future potential under such conditions.

Clinical audit in dentistry: From a concept to an initiation

PubMed Central

Malleshi, Suchetha N; Joshi, Mahasweta; Nair, Soumya K; Ashraf, Irshad

2012-01-01

Clinical audit is a quality improvement process that aims to improve patient care through a systematic review of care against explicit criteria. It is a cyclic and multidisciplinary process which involves a series of steps from planning the audit through measuring the performance to implementing and sustaining the change. Although audit contains some facets of research, it is essential to understand the difference between the two. Auditing can be done right from the record maintaining, diagnosis and treatment and postoperative evaluation and follow-up. The immense potential of clinical audit can be utilized only when open-mindedness and innovativeness are encouraged and evidence-based work culture is cultivated. PMID:23559939

Efficacy of ultrasound and nerve stimulation guidance in peripheral nerve block: A systematic review and meta-analysis.

PubMed

Wang, Zhi-Xue; Zhang, De-Li; Liu, Xin-Wei; Li, Yan; Zhang, Xiao-Xia; Li, Ru-Hong

2017-09-01

Evidence was controversial about whether nerve stimulation (NS) can optimize ultrasound guidance (US)-guided nerve blockade for peripheral nerve block. This review aims to explore the effects of the two combined techniques. We searched EMBASE (from 1974 to March 2015), PubMed (from 1966 to Mar 2015), Medline (from 1966 to Mar 2015), the Cochrane Central Register of Controlled Trials and clinicaltrials.gov. Finally, 15 randomized trials were included into analysis involving 1,019 lower limb and 696 upper limb surgery cases. Meta-analysis indicated that, compared with US alone, USNS combination had favorable effects on overall block success rate (risk ratio [RR] 1.17; confidence interval [CI] 1.05 to 1.30, P = 0.004), sensory block success rate (RR 1.56; CI 1.29 to 1.89, P < 0.00001), and block onset time (mean difference [MD] -3.84; CI -5.59 to -2.08, P < 0.0001). USNS guidance had a longer procedure time in both upper and lower limb nerve block (MD 1.67; CI 1.32 to 2.02, P < 0.00001; MD 1.17; CI 0.95 to 1.39, P < 0.00001) and more patients with anesthesia supplementation (RR 2.5; CI 1.02 to 6.13, P = 0.05). USNS guidance trends to result in a shorter block onset time than US alone as well as higher block success rate, but no statistical difference was demonstrated, as more data are required. © 2017 IUBMB Life, 69(9):720-734, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis.

PubMed

Ciardulli, Andrea; D'Antonio, Francesco; Magro-Malosso, Elena R; Manzoli, Lamberto; Anisman, Paul; Saccone, Gabriele; Berghella, Vincenzo

2018-03-07

To explore the effect of maternal fluorinated steroid therapy on fetuses affected by second-degree immune-mediated congenital atrioventricular block. Studies reporting the outcome of fetuses with second-degree immune-mediated congenital atrioventricular block diagnosed on prenatal ultrasound and treated with fluorinated steroids compared with those not treated were included. The primary outcome was the overall progression of congenital atrioventricular block to either continuous or intermittent third-degree congenital atrioventricular block at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used. Five studies (71 fetuses) were included. The progression rate to congenital atrioventricular block at birth in fetuses treated with steroids was 52% (95% confidence interval 23-79) and in fetuses not receiving steroid therapy 73% (95% confidence interval 39-94). The overall rate of regression to either first-degree, intermittent first-/second-degree or sinus rhythm in fetuses treated with steroids was 25% (95% confidence interval 12-41) compared with 23% (95% confidence interval 8-44) in those not treated. Stable (constant) second-degree congenital atrioventricular block at birth was present in 11% (95% confidence interval 2-27) of cases in the treated group and in none of the newborns in the untreated group, whereas complete regression to sinus rhythm occurred in 21% (95% confidence interval 6-42) of fetuses receiving steroids vs. 9% (95% confidence interval 0-41) of those untreated. There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second-degree immune-mediated congenital atrioventricular block. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Large expansion of oil industry in the Ecuadorian Amazon: biodiversity vulnerability and conservation alternatives.

PubMed

Lessmann, Janeth; Fajardo, Javier; Muñoz, Jesús; Bonaccorso, Elisa

2016-07-01

Ecuador will experience a significant expansion of the oil industry in its Amazonian region, one of the most biodiverse areas of the world. In view of the changes that are about to come, we explore the conflicts between oil extraction interests and biodiversity protection and apply systematic conservation planning to identify priority areas that should be protected in different oil exploitation scenarios. First, we quantified the current extent of oil blocks and protected zones and their overlap with two biodiversity indicators: 25 ecosystems and 745 species (whose distributions were estimated via species distribution models). With the new scheme of oil exploitation, oil blocks cover 68% (68,196 km(2)) of the Ecuadorian Amazon; half of it occupied by new blocks open for bids in the southern Amazon. This region is especially vulnerable to biodiversity losses, because peaks of species diversity, 19 ecosystems, and a third of its protected zones coincide spatially with oil blocks. Under these circumstances, we used Marxan software to identify priority areas for conservation outside oil blocks, but their coverage was insufficient to completely represent biodiversity. Instead, priority areas that include southern oil blocks provide a higher representation of biodiversity indicators. Therefore, preserving the southern Amazon becomes essential to improve the protection of Amazonian biodiversity in Ecuador, and avoiding oil exploitation in these areas (33% of the extent of southern oil blocks) should be considered a conservation alternative. Also, it is highly recommended to improve current oil exploitation technology to reduce environmental impacts in the region, especially within five oil blocks that we identified as most valuable for the conservation of biodiversity. The application of these and other recommendations depends heavily on the Ecuadorian government, which needs to find a better balance between the use of the Amazon resources and biodiversity conservation.

Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells.

PubMed

Liu, F; Weng, S-J; Yang, X-L; Zhong, Y-M

2015-10-01

Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-β-S/GPAnt-2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Gö6976. Neither adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of fluoride dentifrice and casein phosphopeptide-amorphous calcium phosphate cream with and without fluoride in preventing enamel demineralization in a pH cyclic study

PubMed Central

Sinfiteli, Priscila de Pinto; Coutinho, Thereza Christina Lopes; de Oliveira, Patrícia Regina Almeida; Vasques, Wesley Felisberto; Azevedo, Leandra Matos; Pereira, André Maues Brabo; Tostes, Monica Almeida

2017-01-01

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complexes are anticariogenic and capable of remineralizing the early stages of enamel lesions. The use of fluoride prevents dental decay and the association of CPP-ACP with fluoride can increase remineralization. Objective: To evaluate the effect of CPP-ACP and CPP-ACPF creams associated with a fluoride dentifrice to prevent enamel demineralization in a pH cyclic model. Material and Methods: Previously selected by surface microhardness (SH) analysis, human enamel blocks (n = 56) were submitted to daily treatment with dentifrice in a pH-cycling model. The enamel blocks were divided into four groups; G1: Crest™ Cavity Protection - Procter & Gamble (1,100 ppmF of NaF); G2: Crest™ +MI Paste (MP) - Recaldent™ GC Corporation Tokyo, Japan); G3: Crest™ + MI Paste Plus (MPP) - Recaldent™ 900 ppm as NaF, GC Corporation Tokyo, Japan), and G4: control, saliva. Specimens were soaked alternatively in a demineralizing solution and in artificial saliva for 5 d. The fluoride dentifrice, with proportion of 1:3 (w/w), was applied three times for 60 s after the remineralization period. The undiluted MP and MPP creams were applied for 3 m/d. After cycling, SH was re-measured and cross section microhardness measurements were taken. Results: The SH values observed for the groups G3 (257±70), G1 (205±70), and G2 (208±84) differed from the G4 group (98±110) (one-way ANOVA and Tukey's post hoc test). There were no differences between the groups G1xG2, G2xG3, and G1xG3 for demineralization inhibition. The percentage of volume mineral showed that, when applied with fluoride dentifrice, MPP was the most effective in preventing enamel demineralization at 50 µ from the outer enamel surface (Kruskal-Wallis and Mann Whitney p<0.05). Conclusion: Fluoride dentifrice associated with CPP-ACPF inhibited subsurface enamel demineralization. PMID:29211281

Endothelial atheroprotective and anti-inflammatory mechanisms.

PubMed

Berk, B C; Abe, J I; Min, W; Surapisitchat, J; Yan, C

2001-12-01

Atherosclerosis preferentially occurs in areas of turbulent flow and low fluid shear stress, whereas laminar flow and high shear stress are atheroprotective. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF), have been shown to stimulate expression of endothelial cell (EC) genes that may promote atherosclerosis. Recent data suggest that steady laminar flow decreases EC apoptosis and blocks TNF-mediated EC activation. EC apoptosis is likely important in the process termed "plaque erosion" that leads to platelet aggregation. Steady laminar flow inhibits EC apoptosis by preventing cell cycle entry, by increasing antioxidant mechanisms (e.g., superoxide dismutase), and by stimulating nitric oxide-dependent protective pathways that involve enzymes PI3-kinase and Akt. Conversely, our laboratory has identified nitric oxide-independent mechanisms that limit TNF signal transduction. TNF regulates gene expression in EC, in part, by stimulating mitogen-activated protein kinases (MAPK) which phosphorylate transcription factors. We hypothesized that fluid shear stress modulates TNF effects on EC by inhibiting TNF-mediated activation of MAP kinases. To test this hypothesis, we determined the effects of steady laminar flow (shear stress = 12 dynes/cm2) on TNF-stimulated activity of two MAP kinases: extracellular signal regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). Flow alone stimulated ERK1/2 activity, but decreased JNK activity compared to static controls. TNF (10 ng/ml) alone activated both ERK1/2 and JNK maximally at 15 minutes in human umbilical vein EC (HUVEC). Pre-exposing HUVEC for 10 minutes to flow inhibited TNF activation of JNK by 46%, but it had no significant effect on ERK1/2 activation. Incubation of EC with PD98059, a specific mitogen-activated protein kinase kinase inhibitor, blocked the flow-mediated inhibition of TNF activation of JNK. Flow-mediated inhibition of JNK was unaffected by 0.1 mM L-nitroarginine, 100 pM 8-bromo-cyclic GMP, or 100 microM 8-bromo-cyclic AMP. Transfection studies with dominant negative constructs of the protein kinase MEK1 and MEK5 suggested an important role for BMK1 in flow-mediated regulation of TNF signals. In summary, the atheroprotective effects of steady laminar flow on the endothelium involve multiple synergistic mechanisms.

Selective blockade of a slowly inactivating potassium current in striatal neurons by (+/-) 6-chloro-APB hydrobromide (SKF82958).

PubMed

Nisenbaum, E S; Mermelstein, P G; Wilson, C J; Surmeier, D J

1998-07-01

The ion channels of rat striatal neurons are known to be modulated by stimulation of D1 dopamine receptors. The susceptibility of depolarization-activated K+ currents to be modulated by the D1 agonist, 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzaze pine (APB) was investigated using whole-cell voltage-clamp recording techniques from acutely isolated neurons. APB (0.01-100 microM) produced a concentration-dependent reduction in the total K+ current. At intermediate concentrations (ca. 10 microM), APB selectively depressed the slowly inactivating A-current (I(As)). A similar effect was produced by application of the D1 agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1-H-2-benzazepine (SKF38393, 10 microM). APB reduced I(As) rapidly, having onset and recovery time constants of 1.2 sec and 1.6 sec, respectively. Unexpectedly, the effect of APB could not be mimicked by application of Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Sp-cAMPS, 100-200 microM), a membrane-permeable analog of cyclic AMP (cAMP), or by pretreatment with forskolin (25 microM), an activator of adenylyl cyclase. The reduction in I(As) also was not blocked by pretreatment with the D1 receptor antagonist, R(+)-SCH23390 hydrochloride (SCH23390, 10-20 microM). In addition, intracellular dialysis with guanosine-5'-O-(2-thiodiphosphate (GDP-beta-S, 200 microM) did not preclude the APB-induced inhibition of I(As), nor did dialysis with guanosine-5'-O-(3-thiotriphosphate (GTP-gamma-S, 400 microM) prevent reversal of the effect. The effect of APB was produced by a reduction in the maximal conductance of I(As) without changing the voltage-dependence of the current. Collectively, these results argue that APB does not inhibit I(As) through D1 receptors coupled to stimulation of adenylyl cyclase, but rather by allosterically regulating or blocking the channels giving rise to this current.

Structural Analysis of a β-Helical Protein Motif Stabilized by Targeted Replacements with Conformationally Constrained Amino Acids

PubMed Central

Ballano, Gema; Zanuy, David; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

2009-01-01

Here we study conformational stabilization induced in a β-helical nanostructure by position-specific mutations. The nanostructure is constructed through the self-assembly of the β-helical building block excised from E. coli galactoside acetyltransferase (PDB code 1krr, chain A; residues 131-165). The mutations involve substitutions by cyclic, conformationally constrained amino acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence [with Xaa being Gly, Ac3c (1-aminocyclopropane-1-carboxylic acid) and Ac5c (1-aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region in the wild-type (Gly) and mutated (Ac3c and Ac5c) 1krr, has been performed using Molecular Dynamics simulations and X-ray crystallography. Simulations have been performed for the wild-type and mutants of three different systems, namely the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide. Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa-Val sequences have been solved by X-ray diffraction analysis and compared with theoretical predictions. Both the theoretical and crystallographic studies indicate that the Pro-Acnc-Val sequences exhibit a high propensity to adopt turn-like conformations, and this propensity is little affected by the chemical environment. Overall, the results indicate that replacement of Gly149 by Ac3c or Ac5c significantly reduce the conformational flexibility of the target site enhancing the structural specificity of the building block and the nanoconstruct derived from the 1krr β-helical motif. PMID:18811190

Making Sense of Dynamic Systems: How Our Understanding of Stocks and Flows Depends on a Global Perspective

ERIC Educational Resources Information Center

Fischer, Helen; Gonzalez, Cleotilde

2016-01-01

Stocks and flows (SF) are building blocks of dynamic systems: Stocks change through inflows and outflows, such as our bank balance changing with withdrawals and deposits, or atmospheric CO[subscript 2] with absorptions and emissions. However, people make systematic errors when trying to infer the behavior of dynamic systems, termed SF failure,…

A Dynamical View of High School Attendance: An Assessment of Short-term and Long-term Dependencies in Five Urban Schools.

PubMed

Koopmans, Matthijs

2015-01-01

While school attendance is a critical mediator to academic achievement, its time dependent characteristics are rarely investigated. To remedy situation, this paper reports on the analysis of daily attendance rates in five urban high schools over a seven-year period. Traditional time series analyses were conducted to estimate short-range and cyclical dependencies in the data. An Autoregressive Fractional Integrated Moving Average (ARFIMA) approach was used to address long-range correlational patterns, and detect signs of self-organized criticality. The analysis reveals a strong cyclical pattern (weekly) in all five schools, and evidence for self-organized criticality in one of the five. These findings illustrate the insufficiency of traditional statistical summary measures to characterize the distribution of daily attendance, and they suggest that daily attendance is not necessarily the stable and predictable feature of school effectiveness it is conventionally assumed to be. While educational practitioners can probably attest to the many of the irregularities in attendance patterns as well as some of their sources, a systematic description of these temporal aspects needs to be included in our assessment of daily attendance behavior to inform policy decisions, if only to better align formal research in this area with existing local knowledge about those patterns.

Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis

PubMed Central

Ju, Bum Jun; Jang, Yoo Kyung; You, Hae Seun; Kang, Hyun; Park, Ji Yong

2017-01-01

Background Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA) effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB). This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery. Methods We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs) that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software. Results We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004), motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003), and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001) compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001) and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010). In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05) but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies. Conclusions In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and shorten the time to onset of sensory and motor blocks without altering adverse effects. PMID:28953949

Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis.

PubMed

Shin, Hye Won; Ju, Bum Jun; Jang, Yoo Kyung; You, Hae Seun; Kang, Hyun; Park, Ji Yong

2017-01-01

Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA) effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB). This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery. We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs) that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software. We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004), motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003), and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001) compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001) and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010). In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05) but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies. In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and shorten the time to onset of sensory and motor blocks without altering adverse effects.

Cyclic steady state stress-strain behavior of UHMW polyethylene.

PubMed

Krzypow, D J; Rimnac, C M

2000-10-01

To increase the long-term performance of total joint replacements, finite element analyses of ultra high molecular weight polyethylene (UHMWPE) components have been conducted to predict the effect of load on the stress and strain distributions occurring on and within these components. Early models incorporated the monotonic behavior of UHMWPE without considering the unloading and cyclic loading behavior. However, UHMWPE components undergo cyclic loading during use and at least two wear damage modes (pitting and delamination) are thought to be associated with the fatigue fracture properties of UHMWPE. The objective of this study was to examine the fully reversed uniaxial tension/compression cyclic steady state stress-strain behavior of UHMWPE as a first step towards developing a cyclic constitutive relationship for UHMWPE. The hypothesis that cycling results in a permanent change in the stress-strain relationship, that is, that the cyclic steady state represents a new cyclically stabilized state, was examined. It was found that, like other ductile polymers, UHMWPE substantially cyclically softens under fully reversed uniaxial straining. More cyclic softening occurred in tension than in compression. Furthermore, cyclic steady state was attained, but not cyclic stability. It is suggested that it may be more appropriate to base a material constitutive relationship for UHMWPE for finite element analyses of components upon a cyclically modified stress-strain relationship.

Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction.

PubMed

Sanna, M Germana; Vincent, Kevin P; Repetto, Emanuela; Nguyen, Nhan; Brown, Steven J; Abgaryan, Lusine; Riley, Sean W; Leaf, Nora B; Cahalan, Stuart M; Kiosses, William B; Kohno, Yasushi; Brown, Joan Heller; McCulloch, Andrew D; Rosen, Hugh; Gonzalez-Cabrera, Pedro J

2016-01-01

The molecular pharmacology of the G protein-coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations. The agonist effects on complete heart block are absent in S1P3-knockout mice and are reversed in wild-type mice with SPM-354, as characterized and described here. Homologous knockin of S1P3-mCherry is fully functional pharmacologically and is strongly expressed by immunohistochemistry confocal microscopy in Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4)-positive atrioventricular node and His-Purkinje fibers, with relative less expression in the HCN4-positive sinoatrial node. In Langendorff studies, at constant pressure, SPM-354 restored sinus rhythm in S1P-induced complete heart block and fully reversed S1P-mediated bradycardia. S1P3 distribution and function in the mouse ventricular cardiac conduction system suggest a direct mechanism for heart block risk that should be further studied in humans. A richer understanding of receptor and ligand usage in the pacemaker cells of the cardiac system is likely to be useful in understanding ventricular conduction in health, disease, and pharmacology. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Estimating the decline in excess risk of cerebrovascular disease following quitting smoking--a systematic review based on the negative exponential model.

PubMed

Lee, Peter N; Fry, John S; Thornton, Alison J

2014-02-01

We attempted to quantify the decline in stroke risk following quitting using the negative exponential model, with methodology previously employed for IHD. We identified 22 blocks of RRs (from 13 studies) comparing current smokers, former smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases and controls/at risk formed the data for model-fitting. We tried to estimate the half-life (H, time since quit when the excess risk becomes half that for a continuing smoker) for each block. The method failed to converge or produced very variable estimates of H in nine blocks with a current smoker RR <1.40. Rejecting these, and combining blocks by amount smoked in one study where problems arose in model-fitting, the final analyses used 11 blocks. Goodness-of-fit was adequate for each block, the combined estimate of H being 4.78(95%CI 2.17-10.50) years. However, considerable heterogeneity existed, unexplained by any factor studied, with the random-effects estimate 3.08(1.32-7.16). Sensitivity analyses allowing for reverse causation or differing assumed times for the final quitting period gave similar results. The estimates of H are similar for stroke and IHD, and the individual estimates similarly heterogeneous. Fitting the model is harder for stroke, due to its weaker association with smoking. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Aqueous dispersion polymerization: a new paradigm for in situ block copolymer self-assembly in concentrated solution.

PubMed

Sugihara, Shinji; Blanazs, Adam; Armes, Steven P; Ryan, Anthony J; Lewis, Andrew L

2011-10-05

Reversible addition-fragmentation chain transfer polymerization has been utilized to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macromolecular chain transfer agent based on poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has been elucidated for this aqueous dispersion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described in the literature, this strategy enables the facile, efficient, and reproducible preparation of diblock copolymer spheres, worms, or vesicles directly in concentrated aqueous solution. Chain extension of the highly hydrated zwitterionic PMPC block with HPMA in water at 70 °C produces a hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in situ self-assembly to form well-defined diblock copolymer spheres, worms, or vesicles. The final particle morphology obtained at full monomer conversion is dictated by (i) the target degree of polymerization of the PHPMA block and (ii) the total solids concentration at which the HPMA polymerization is conducted. Moreover, if the targeted diblock copolymer composition corresponds to vesicle phase space at full monomer conversion, the in situ particle morphology evolves from spheres to worms to vesicles during the in situ polymerization of HPMA. In the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the direct, reproducible, and highly efficient preparation of either block copolymer vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous solution.

Detecting agitation and aggression in people with dementia using sensors-A systematic review.

PubMed

Khan, Shehroz S; Ye, Bing; Taati, Babak; Mihailidis, Alex

2018-06-01

Agitation and aggression are among the most challenging symptoms of dementia. Agitated persons with dementia can harm themselves, their caregivers, or other patients in a care facility. Automatic detection of agitation would be useful to alert caregivers so that appropriate interventions can be performed. The building blocks in the automatic detection of agitation and aggression are appropriate sensing platforms and generalized predictive models. In this article, we perform a systematic review of studies that use different types of sensors to detect agitation and aggression in persons with dementia. We conclude that actigraphy shows some evidence of correlation with incidences of agitation and aggression; however, multimodal sensing has not been fully evaluated for this purpose. Based on this systematic review, we provide guidelines and recommendations for future research directions in this field. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Nanoscale superstructures assembled by polymerase chain reaction (PCR): programmable construction, structural diversity, and emerging applications.

PubMed

Kuang, Hua; Ma, Wei; Xu, Liguang; Wang, Libing; Xu, Chuanlai

2013-11-19

Polymerase chain reaction (PCR) is an essential tool in biotechnology laboratories and is becoming increasingly important in other areas of research. Extensive data obtained over the last 12 years has shown that the combination of PCR with nanoscale dispersions can resolve issues in the preparation DNA-based materials that include both inorganic and organic nanoscale components. Unlike conventional DNA hybridization and antibody-antigen complexes, PCR provides a new, effective assembly platform that both increases the yield of DNA-based nanomaterials and allows researchers to program and control assembly with predesigned parameters including those assisted and automated by computers. As a result, this method allows researchers to optimize to the combinatorial selection of the DNA strands for their nanoparticle conjugates. We have developed a PCR approach for producing various nanoscale assemblies including organic motifs such as small molecules, macromolecules, and inorganic building blocks, such as nanorods (NRs), metal, semiconductor, and magnetic nanoparticles (NPs). We start with a nanoscale primer and then modify that building block using the automated steps of PCR-based assembly including initialization, denaturation, annealing, extension, final elongation, and final hold. The intermediate steps of denaturation, annealing, and extension are cyclic, and we use computer control so that the assembled superstructures reach their predetermined complexity. The structures assembled using a small number of PCR cycles show a lower polydispersity than similar discrete structures obtained by direct hybridization between the nanoscale building blocks. Using different building blocks, we assembled the following structural motifs by PCR: (1) discrete nanostructures (NP dimers, NP multimers including trimers, pyramids, tetramers or hexamers, etc.), (2) branched NP superstructures and heterochains, (3) NP satellite-like superstructures, (4) Y-shaped nanostructures and DNA networks, (5) protein-DNA co-assembly structures, and (6) DNA block copolymers including trimers and pentamers. These results affirm that this method can produce a variety of chemical structures and in yields that are tunable. Using PCR-based preparation of DNA-bridged nanostructures, we can program the assembly of the nanoscale blocks through the adjustment of the primer intensity on the assembled units, the number of PCR cycles, or both. The resulting structures are highly complex and diverse and have interesting dynamics and collective properties. Potential applications of these materials include chirooptical materials, probe fabrication, and environmental and biomedical sensors.

Sequencing Cyclic Peptides by Multistage Mass Spectrometry

PubMed Central

Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.

2012-01-01

Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357

Cyclic nucleotide binding proteins in the Arabidopsis thaliana and Oryza sativa genomes

PubMed Central

Bridges, Dave; Fraser, Marie E; Moorhead, Greg BG

2005-01-01

Background Cyclic nucleotides are ubiquitous intracellular messengers. Until recently, the roles of cyclic nucleotides in plant cells have proven difficult to uncover. With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed genomes of the higher plants Arabidopsis thaliana (mustard weed) and Oryza sativa (rice) for the effectors of these signalling molecules. Results Our analysis found that several ion channels and a class of thioesterases constitute the possible cyclic nucleotide binding proteins in plants. Contrary to some reports, we found no biochemical or bioinformatic evidence for a plant cyclic nucleotide regulated protein kinase, suggesting that cyclic nucleotide functions in plants have evolved differently than in mammals. Conclusion This paper provides a molecular framework for the discussion of cyclic nucleotide function in plants, and resolves a longstanding debate about the presence of a cyclic nucleotide dependent kinase in plants. PMID:15644130

Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors.

PubMed

Ge, Zhishen; Chen, Qixian; Osada, Kensuke; Liu, Xueying; Tockary, Theofilus A; Uchida, Satoshi; Dirisala, Anjaneyulu; Ishii, Takehiko; Nomoto, Takahiro; Toh, Kazuko; Matsumoto, Yu; Oba, Makoto; Kano, Mitsunobu R; Itaka, Keiji; Kataoka, Kazunori

2014-03-01

Adequate retention in systemic circulation is the preliminary requirement for systemic gene delivery to afford high bioavailability into the targeted site. Polyplex micelle formulated through self-assembly of oppositely-charged poly(ethylene glycol) (PEG)-polycation block copolymer and plasmid DNA has gained tempting perspective upon its advantageous core-shell architecture, where outer hydrophilic PEG shell offers superior stealth behaviors. Aiming to promote these potential characters toward systemic applications, we strategically introduced hydrophobic cholesteryl moiety at the ω-terminus of block copolymer, anticipating to promote not only the stability of polyplex structure but also the tethered PEG crowdedness. Moreover, Mw of PEG in the PEGylated polyplex micelle was elongated up to 20 kDa for expecting further enhancement in PEG crowdedness. Furthermore, cyclic RGD peptide as ligand molecule to integrin receptors was installed at the distal end of PEG in order for facilitating targeted delivery to the tumor site as well as promoting cellular uptake and intracellular trafficking behaviors. Thus constructed cRGD conjugated polyplex micelle with the elevated PEG shielding was challenged to a modeled intractable pancreatic cancer in mice, achieving potent tumor growth suppression by efficient gene expression of antiangiogenic protein (sFlt-1) at the tumor site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of the thrombin receptor in restenosis and atherosclerosis.

PubMed

Baykal, D; Schmedtje, J F; Runge, M S

1995-02-23

Thrombus generation is central to thrombosis at vascular lesion sites, including post-PCTA acute reocclusion and chronic restenosis. Thrombin stimulates platelet activation, monocyte and neutrophil chemotaxis, and endothelial production of prothrombotic factors. The varied physiologic effects of thrombin are due to the widespread presence of thrombin receptors in many cell types. The receptor is uniquely activated: thrombin binds to the receptor at the thrombin anion-binding exosite, the receptor ligand ("tethered ligand") apparently being a sequence of 6 amino acids (SFLLRN). Thus, peptides corresponding to the sequence of the tethered ligand can stimulate almost all functions of native thrombin itself. Several intracellular signaling pathways have been identified as important in the restenosis process: the G protein-related pathway, cyclic adenosine monophosphate (cAMP) mediator pathway, and tyrosine kinase activation pathway. In situ hybridization has demonstrated an increase in thrombin receptor mRNA throughout the period of neointimal and vascular lesion development. The mechanism of this increase is unknown, but may be mediated by multiple inflammatory modulators. Several strategies have been tested in animal models for inhibiting thrombin: (1) Hirudin not only prevents thrombin from cleaving fibrinogen, but also prevents thrombin receptor activation. (2) Thrombin receptor antagonist peptides block platelet aggregation effects of thrombin. (3) Mono- and polyclonal antibodies inhibit thrombin receptor activation. (4) Antisense oligonucleotides block thrombin receptor expression.

Variable thickness double-refracting plate

DOEpatents

Hadeishi, Tetsuo

1976-01-01

This invention provides an A.C., cyclic, current-controlled, phase retardation plate that uses a magnetic clamp to produce stress birefringence. It was developed for an Isotope-Zeeman Atomic Absorption Spectrometer that uses polarization modulation to effect automatic background correction in atomic absorption trace-element measurements. To this end, the phase retardation plate of the invention is a variable thickness, photoelastic, double-refracting plate that is alternately stressed and released by the magnetic clamp selectively to modulate specific components selected from the group consisting of circularly and plane polarized Zeeman components that are produced in a dc magnetic field so that they correspond respectively to Zeeman reference and transmission-probe absorption components. The polarization modulation changes the phase of these polarized Zeeman components, designated as .sigma. reference and .pi. absorption components, so that every half cycle the components change from a transmission mode to a mode in which the .pi. component is blocked and the .sigma. components are transmitted. Thus, the Zeeman absorption component, which corresponds in amplitude to the amount of the trace element to be measured in a sample, is alternately transmitted and blocked by a linear polarizer, while the circularly polarized reference components are continuously transmitted thereby. The result is a sinusoidally varying output light amplitude whose average corresponds to the amount of the trace element present in the sample.

Controlling the Morphology of Side Chain Liquid Crystalline Block Copolymer Thin Films through Variations in Liquid Crystalline Content

PubMed Central

Verploegen, Eric; Zhang, Tejia; Jung, Yeon Sik; Ross, Caroline; Hammond, Paula T.

2009-01-01

In this paper we describe methods for manipulating the morphology of side-chain liquid crystalline block copolymers through variations in the liquid crystalline content. By systematically controlling the covalent attachment of side chain liquid crystals to a block copolymer (BCP) backbone, the morphology of both the liquid crystalline (LC) mesophase and the phase segregated BCP microstructures can be precisely manipulated. Increases in LC functionalization lead to stronger preferences for the anchoring of the LC mesophase relative to the substrate and the inter-material dividing surface (IMDS). By manipulating the strength of these interactions the arrangement and ordering of the ultrathin film block copolymer nanostructures can be controlled, yielding a range of morphologies that includes perpendicular and parallel cylinders, as well as both perpendicular and parallel lamellae. Additionally, we demonstrate the utilization of selective etching to create a nanoporous liquid crystalline polymer thin film. The unique control over the orientation and order of the self-assembled morphologies with respect to the substrate will allow for the custom design of thin films for specific nano-patterning applications without manipulation of the surface chemistry or the application of external fields. PMID:18763835

Reliabilities of mental rotation tasks: limits to the assessment of individual differences.

PubMed

Hirschfeld, Gerrit; Thielsch, Meinald T; Zernikow, Boris

2013-01-01

Mental rotation tasks with objects and body parts as targets are widely used in cognitive neuropsychology. Even though these tasks are well established to study between-groups differences, the reliability on an individual level is largely unknown. We present a systematic study on the internal consistency and test-retest reliability of individual differences in mental rotation tasks comparing different target types and orders of presentations. In total n = 99 participants (n = 63 for the retest) completed the mental rotation tasks with hands, feet, faces, and cars as targets. Different target types were presented in either randomly mixed blocks or blocks of homogeneous targets. Across all target types, the consistency (split-half reliability) and stability (test-retest reliabilities) were good or acceptable both for intercepts and slopes. At the level of individual targets, only intercepts showed acceptable reliabilities. Blocked presentations resulted in significantly faster and numerically more consistent and stable responses. Mental rotation tasks-especially in blocked variants-can be used to reliably assess individual differences in global processing speed. However, the assessment of the theoretically important slope parameter for individual targets requires further adaptations to mental rotation tests.

Proteins detection by polymer optical fibers sensitised with overlayers of block and random copolymers

NASA Astrophysics Data System (ADS)

El Sachat, Alexandros; Meristoudi, Anastasia; Markos, Christos; Pispas, Stergios; Riziotis, Christos

2014-03-01

A low cost and low complexity optical detection method of proteins is presented by employing a detection scheme based on electrostatic interactions, and implemented by sensitization of a polymer optical fibers' (POF) surface by thin overlayers of properly designed sensitive copolymer materials with predesigned charges. This method enables the fast detection of proteins having opposite charge to the overlayer, and also the effective discrimination of differently charged proteins like lysozyme (LYS) and bovine serum albumin (BSA). As sensitive materials the block and the random copolymers of the same monomers were employed, namely the block copolymer poly(styrene-b-2vinylpyridine) (PS-b- P2VP) and the corresponding random copolymer poly(styrene-r-2vinylpyridine) (PS-r-P2VP), of similar composition and molecular weights. Results show systematically different response between the block and the random copolymers, although of the same order of magnitude, drawing thus important conclusions on their applications' techno-economic aspects given that they have significantly different associated manufacturing method and costs. The use of the POF platform, in combination with those adaptable copolymer sensing materials could lead to efficient low cost bio-detection schemes.

Controlling the morphology of side chain liquid crystalline block copolymer thin films through variations in liquid crystalline content.

PubMed

Verploegen, Eric; Zhang, Tejia; Jung, Yeon Sik; Ross, Caroline; Hammond, Paula T

2008-10-01

In this paper, we describe methods for manipulating the morphology of side-chain liquid crystalline block copolymers through variations in the liquid crystalline content. By systematically controlling the covalent attachment of side chain liquid crystals to a block copolymer (BCP) backbone, the morphology of both the liquid crystalline (LC) mesophase and the phase-segregated BCP microstructures can be precisely manipulated. Increases in LC functionalization lead to stronger preferences for the anchoring of the LC mesophase relative to the substrate and the intermaterial dividing surface. By manipulating the strength of these interactions, the arrangement and ordering of the ultrathin film block copolymer nanostructures can be controlled, yielding a range of morphologies that includes perpendicular and parallel cylinders, as well as both perpendicular and parallel lamellae. Additionally, we demonstrate the utilization of selective etching to create a nanoporous liquid crystalline polymer thin film. The unique control over the orientation and order of the self-assembled morphologies with respect to the substrate will allow for the custom design of thin films for specific nanopatterning applications without manipulation of the surface chemistry or the application of external fields.

Desensitization of atriopeptin stimulated accumulation and extrusion of cyclic GMP from a kidney epithelial cell line (MDCK).

PubMed

Woods, M; Houslay, M D

1991-02-01

Atriopeptin caused dose- (EC50 ca. 2 x 10(-8) M) and time-dependent increases in the intracellular concentration of cyclic GMP in the MDCK kidney epithelial cell line; an effect potentiated by the phosphodiesterase inhibitor, IBMX. The atriopeptin-catalysed increase in cyclic GMP was transient and reached a maximum some 10-20 min after challenge of cells with atriopeptin. The basis for the transience of this increase was shown to be due to the desensitization of guanylate cyclase coupled with extrusion of cyclic GMP from the cells and the degradation of cyclic GMP by phosphodiesterase activity. Atriopeptin-catalysed extrusion of cyclic GMP was time- and dose-(EC50 ca. 1.5 x 10(-8) M) dependent and was inhibited by probenecid but not by high external cyclic GMP concentrations. The extrusion process underwent apparent desensitization as did guanylate cyclase with similar half lives (T1/2 of ca. 20 min). Desensitization was dose-dependent upon atriopeptin and did not appear to be mediated by elevated cyclic GMP concentrations as pre-incubation with 8-bromo cyclic GMP did not cause desensitization and the half-times for desensitization were similar whether or not IBMX was present. The majority of the cyclic nucleotide phosphodiesterase activity was found in the cytosol fraction of the cells and could be separated into two cyclic AMP specific forms and two cyclic GMP preferring forms.

On the engineering design for systematic integration of agent-orientation in industrial automation.

PubMed

Yu, Liyong; Schüller, Andreas; Epple, Ulrich

2014-09-01

In today's automation industry, agent-oriented development of system functionalities appears to have a great potential for increasing autonomy and flexibility of complex operations, while lowering the workload of users. In this paper, we present a reference model for the harmonious and systematical integration of agent-orientation in industrial automation. Considering compatibility with existing automation systems and best practice, this model combines advantages of function block technology, service orientation and native description methods from the automation standard IEC 61131-3. This approach can be applied as a guideline for the engineering design of future agent-oriented automation systems. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Syntheses, structures and luminescent properties of zero-/two-dimensional Cd(II) and Eu(III) complexes

NASA Astrophysics Data System (ADS)

Fan, Rui-Qing; Wang, Li-Yuan; Wang, Ping; Chen, Hong; Sun, Cun-fa; Yang, Yu-Lin; Su, Qing

2012-12-01

Three metal-organic complexes Cd(HBIDC)(phen)2·4H2O (1), [Cd(BIC)(phen)]n (2) and {[Eu(HBIDC)(H2BIDC)(H2O)]·H2O}n (3) (H3BIDC=benzimidazole-5,6-dicarboxylic acid, H2BIC=benzimidazole-6-carboxylic acid, phen=1,10-phenanthroline) have been synthesized under hydro(solvo)thermal conditions and structurally characterized by elemental analysis, IR spectrum, and single-crystal X-ray diffraction. With similar reaction conditions, reactions of the same ligand with different metal cations selected from different blocks (d-block and f-block) result in different coordination modes of carboxylate groups and final frameworks of complexes 1 and 3. The decarboxylation was observed in complex 2 and resulted in the formation of BIC2- ligand. Complexes 1-3 have intense fluorescent emissions at room temperature in dimethylsulfoxide (DMSO) solution and in the solid-state, which indicate they are potential fluorescence materials. The quantum yields and fluorescence lifetimes of these three complexes were systematically studied.

The Origin of Hierarchical Structure Formation in Highly Grafted Symmetric Supramolecular Double-Comb Diblock Copolymers.

PubMed

Hofman, Anton H; Reza, Mehedi; Ruokolainen, Janne; Ten Brinke, Gerrit; Loos, Katja

2017-09-01

Involving supramolecular chemistry in self-assembling block copolymer systems enables design of complex macromolecular architectures that, in turn, could lead to complex phase behavior. It is an elegant route, as complicated and sensitive synthesis techniques can be avoided. Highly grafted double-comb diblock copolymers based on symmetric double hydrogen bond accepting poly(4-vinylpyridine)-block-poly(N-acryloylpiperidine) diblock copolymers and donating 3-nonadecylphenol amphiphiles are realized and studied systematically by changing the molecular weight of the copolymer. Double perpendicular lamellae-in-lamellae are formed in all complexes, independent of the copolymer molecular weight. Temperature-resolved measurements demonstrate that the supramolecular nature and ability to crystallize are responsible for the formation of such multiblock-like structures. Because of these driving forces and severe plasticization of the complexes in the liquid crystalline state, this supramolecular approach can be useful for steering self-assembly of both low- and high-molecular-weight block copolymer systems. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elfin: An algorithm for the computational design of custom three-dimensional structures from modular repeat protein building blocks.

PubMed

Yeh, Chun-Ting; Brunette, T J; Baker, David; McIntosh-Smith, Simon; Parmeggiani, Fabio

2018-02-01

Computational protein design methods have enabled the design of novel protein structures, but they are often still limited to small proteins and symmetric systems. To expand the size of designable proteins while controlling the overall structure, we developed Elfin, a genetic algorithm for the design of novel proteins with custom shapes using structural building blocks derived from experimentally verified repeat proteins. By combining building blocks with compatible interfaces, it is possible to rapidly build non-symmetric large structures (>1000 amino acids) that match three-dimensional geometric descriptions provided by the user. A run time of about 20min on a laptop computer for a 3000 amino acid structure makes Elfin accessible to users with limited computational resources. Protein structures with controlled geometry will allow the systematic study of the effect of spatial arrangement of enzymes and signaling molecules, and provide new scaffolds for functional nanomaterials. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic sparse matrix error control for linear scaling electronic structure calculations.

PubMed

Rubensson, Emanuel H; Sałek, Paweł

2005-11-30

Efficient truncation criteria used in multiatom blocked sparse matrix operations for ab initio calculations are proposed. As system size increases, so does the need to stay on top of errors and still achieve high performance. A variant of a blocked sparse matrix algebra to achieve strict error control with good performance is proposed. The presented idea is that the condition to drop a certain submatrix should depend not only on the magnitude of that particular submatrix, but also on which other submatrices that are dropped. The decision to remove a certain submatrix is based on the contribution the removal would cause to the error in the chosen norm. We study the effect of an accumulated truncation error in iterative algorithms like trace correcting density matrix purification. One way to reduce the initial exponential growth of this error is presented. The presented error control for a sparse blocked matrix toolbox allows for achieving optimal performance by performing only necessary operations needed to maintain the requested level of accuracy. Copyright 2005 Wiley Periodicals, Inc.

Adaptive neural control of MIMO nonlinear systems with a block-triangular pure-feedback control structure.

PubMed

Chen, Zhenfeng; Ge, Shuzhi Sam; Zhang, Yun; Li, Yanan

2014-11-01

This paper presents adaptive neural tracking control for a class of uncertain multiinput-multioutput (MIMO) nonlinear systems in block-triangular form. All subsystems within these MIMO nonlinear systems are of completely nonaffine pure-feedback form and allowed to have different orders. To deal with the nonaffine appearance of the control variables, the mean value theorem is employed to transform the systems into a block-triangular strict-feedback form with control coefficients being couplings among various inputs and outputs. A systematic procedure is proposed for the design of a new singularity-free adaptive neural tracking control strategy. Such a design procedure can remove the couplings among subsystems and hence avoids the possible circular control construction problem. As a consequence, all the signals in the closed-loop system are guaranteed to be semiglobally uniformly ultimately bounded. Moreover, the outputs of the systems are ensured to converge to a small neighborhood of the desired trajectories. Simulation studies verify the theoretical findings revealed in this paper.

Stress in mangrove forests: early detection and preemptive rehabilitation are essential for future successful worldwide mangrove forest management

USGS Publications Warehouse

Lewis, Roy R; Milbrandt, Eric C; Brown, Benjamin; Krauss, Ken W.; Rovai, Andre S.; Beever, James W.; Flynn, Laura L

2016-01-01

Mangrove forest rehabilitation should begin much sooner than at the point of catastrophic loss. We describe the need for “mangrove forest heart attack prevention”, and how that might be accomplished in a general sense by embedding plot and remote sensing monitoring within coastal management plans. The major cause of mangrove stress at many sites globally is often linked to reduced tidal flows and exchanges. Blocked water flows can reduce flushing not only from the seaward side, but also result in higher salinity and reduced sediments when flows are blocked landward. Long-term degradation of function leads to acute mortality prompted by acute events, but created by a systematic propensity for long-term neglect of mangroves. Often, mangroves are lost within a few years; however, vulnerability is re-set decades earlier when seemingly innocuous hydrological modifications are made (e.g., road construction, blocked tidal channels), but which remain undetected without reasonable large-scale monitoring.

The Mechanism of Action of Zingerone in the Pacemaker Potentials of Interstitial Cells of Cajal Isolated from Murine Small Intestine.

PubMed

Kim, Jung Nam; Kim, Hyun Jung; Kim, Iksung; Kim, Yun Tai; Kim, Byung Joo

2018-01-01

Zingerone, a major component found in ginger root, is clinically effective for the treatment of various diseases. Interstitial cells of Cajal (ICCs) are the pacemaker cells responsible for slow waves in the gastrointestinal (GI) tract. We investigated the effects of zingerone on the pacemaker potentials of ICCs to assess its mechanisms of action and its potential as a treatment for GI tract motility disorder. We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs. Under the current clamping mode, zingerone inhibited pacemaker potentials of ICCs concentration-dependently. These effects were blocked not by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, but by glibenclamide, a specific ATP-sensitive K+ channel blocker. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor), LY294002 (a phosphoinositide 3-kinase inhibitor), and calphostin C (a protein kinase C (PKC) inhibitor) did not block the effects of zingerone on the pacemaker potentials relative to treatment with zingerone alone. However, zingerone-induced pacemaker potential inhibition was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor), KT5823 (a protein kinase G (PKG) inhibitor), and L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor). In addition, zingerone stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. Finally, pretreatment with PD98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and SP600125 (c-Jun N-terminal kinases (JNK)-specific inhibitor) blocked the zingerone-induced pacemaker potential inhibition. These results suggest that zingerone concentration-dependently inhibits pacemaker potentials of ICCs via NO/cGMP-dependent ATP-sensitive K+ channels through MAPK-dependent pathways. Taken together, this study shows that zingerone may have the potential for development as a GI regulation agent. © 2018 The Author(s). Published by S. Karger AG, Basel.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.

PubMed

Burton, Peter; Adams, David R; Abraham, Achamma; Allcock, Robert W; Jiang, Zhong; McCahill, Angela; Gilmour, Jane; McAbney, John; Kaupisch, Alexandra; Kane, Nicole M; Baillie, George S; Baker, Andrew H; Milligan, Graeme; Houslay, Miles D; Mountford, Joanne C

2010-12-15

hESCs (human embryonic stem cells) have enormous potential for use in pharmaceutical development and therapeutics; however, to realize this potential, there is a requirement for simple and reproducible cell culture methods that provide adequate numbers of cells of suitable quality. We have discovered a novel way of blocking the spontaneous differentiation of hESCs in the absence of exogenous cytokines by supplementing feeder-free conditions with EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine], an established inhibitor of ADA (adenosine deaminase) and cyclic nucleotide PDE2 (phosphodiesterase 2). hESCs maintained in feeder-free conditions with EHNA for more than ten passages showed no reduction in hESC-associated markers including NANOG, POU5F1 (POU domain class 5 transcription factor 1, also known as Oct-4) and SSEA4 (stage-specific embryonic antigen 4) compared with cells maintained in feeder-free conditions containing bFGF (basic fibroblast growth factor). Spontaneous differentiation was reversibly suppressed by the addition of EHNA, but, upon removing EHNA, hESC populations underwent efficient spontaneous, multi-lineage and directed differentiation. EHNA also acts as a strong blocker of directed neuronal differentiation. Chemically distinct inhibitors of ADA and PDE2 lacked the capacity of EHNA to suppress hESC differentiation, suggesting that the effect is not driven by inhibition of either ADA or PDE2. Preliminary structure-activity relationship analysis found the differentiation-blocking properties of EHNA to reside in a pharmacophore comprising a close adenine mimetic with an extended hydrophobic substituent in the 8- or 9-position. We conclude that EHNA and simple 9-alkyladenines can block directed neuronal and spontaneous differentiation in the absence of exogenous cytokine addition, and may provide a useful replacement for bFGF in large-scale or cGMP-compliant processes.

Microleakage of composite crowns luted on CAD/CAM-milled human molars: a new method for standardized in vitro tests.

PubMed

Schlenz, Maximiliane Amelie; Schmidt, Alexander; Rehmann, Peter; Niem, Thomas; Wöstmann, Bernd

2018-04-24

To investigate debonding of full crowns made of CAD/CAM composites, CAD/CAM technology was applied to manufacture standardized test abutments to increase the reproducibility of human teeth used in in vitro studies. A virtual test abutment and the corresponding virtual crown were designed and two STL data sets were generated. Sixty-four human third molars and CAD/CAM blocks were milled using a CNC machine. Crowns of four different composite blocks (Lava Ultimate (LU), Brilliant Crios (BC), Cerasmart (CS), Experimental (EX)) were adhesively bonded with their corresponding luting system (LU: Scotchbond Universal/RelyX Ultimate; BC: One Coat 7 Universal/DuoCem; CS: G-PremioBond/G-Cem LinkForce; EX: Experimental-Bond/Experimental-Luting-Cement). Half of the specimens were chemical-cured (CC) and the others were light-cured (LC). Afterwards, specimens were artificially aged in a chewing simulator (WL-tec, 1 million cycles, 50-500 N, 2 Hz, 37 °C). Finally, a dye penetration test was used to detect debonding. For inspection, the specimens were sliced, and penetration depth was measured with a digital microscope. Data were analyzed with the Mann-Whitney U test. No cases of total debonding were observed after cyclic loading. However, the LC specimens showed a significantly lower amount of leakage than the CC ones (p < 0.05). Furthermore, the CC specimens exhibited broad scattering. Only the LC-EX blocks showed no debonding. The CC-CS blocks showed the highest leakage and scattering of all tested specimens. Natural human teeth can be manufactured by CAD/CAM technology in highly standardized test abutments for in vitro testing. For CAD/CAM composites, light curing should be performed. The success of a restoration depends on the long-term sealing ability of the luting materials, which avoids debonding along with microleakage. For CAD/CAM composites, separate light curing of the adhesive and luting composite is highly recommended.

Potential capabilities for compression of information of certain data processing systems

NASA Technical Reports Server (NTRS)

Khodarev, Y. K.; Yevdokimov, V. P.; Pokras, V. M.

1974-01-01

This article undertakes to study a generalized block diagram of a data collection and processing system of a spacecraft in which a number of sensors or outputs of scientific instruments are cyclically interrogated by a commutator, methods of writing the supplementary information in a frame on the example of a certain hypothetical telemetry system, and the influence of statistics of number of active channels in a frame on frame compression factor. The separation of the data compression factor of the collection and processing system of spacecraft into two parts used in this work allows determination of the compression factor of an active frame depending not only on the statistics of activity of channels in the telemetry frame, but also on the method of introduction of the additional address and time information to each frame.

One-Pot Automated Synthesis of Quasi Triblock Copolymers for Self-Healing Physically Crosslinked Hydrogels.

PubMed

Voorhaar, Lenny; De Meyer, Bernhard; Du Prez, Filip; Hoogenboom, Richard

2016-10-01

The preparation of physically crosslinked hydrogels from quasi ABA-triblock copolymers with a water-soluble middle block and hydrophobic end groups is reported. The hydrophilic monomer N-acryloylmorpholine is copolymerized with hydrophobic isobornyl acrylate via a one-pot sequential monomer addition through reversible addition fragmentation chain-transfer (RAFT) polymerization in an automated parallel synthesizer, allowing systematic variation of polymer chain length and hydrophobic-hydrophilic ratio. Hydrophobic interactions between the outer blocks cause them to phase-separate into larger hydrophobic domains in water, forming physical crosslinks between the polymers. The resulting hydrogels are studied using rheology and their self-healing ability after large strain damage is shown. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A generalized method for alignment of block copolymer films: solvent vapor annealing with soft shear.

PubMed

Qiang, Zhe; Zhang, Yuanzhong; Groff, Jesse A; Cavicchi, Kevin A; Vogt, Bryan D

2014-08-28

One of the key issues associated with the utilization of block copolymer (BCP) thin films in nanoscience and nanotechnology is control of their alignment and orientation over macroscopic dimensions. We have recently reported a method, solvent vapor annealing with soft shear (SVA-SS), for fabricating unidirectional alignment of cylindrical nanostructures. This method is a simple extension of the common SVA process by adhering a flat, crosslinked poly(dimethylsiloxane) (PDMS) pad to the BCP thin film. The impact of processing parameters, including annealing time, solvent removal rate and the physical properties of the PDMS pad, on the quality of alignment quantified by the Herman's orientational factor (S) is systematically examined for a model system of polystyrene-block-polyisoprene-block-polystyrene (SIS). As annealing time increases, the SIS morphology transitions from isotropic rods to highly aligned cylinders. Decreasing the rate of solvent removal, which impacts the shear rate imposed by the contraction of the PDMS, improves the orientation factor of the cylindrical domains; this suggests the nanostructure alignment is primarily induced by contraction of PDMS during solvent removal. Moreover, the physical properties of the PDMS controlled by the crosslink density impact the orientation factor by tuning its swelling extent during SVA-SS and elastic modulus. Decreasing the PDMS crosslink density increases S; this effect appears to be primarily driven by the changes in the solubility of the SVA-SS solvent in the PDMS. With this understanding of the critical processing parameters, SVA-SS has been successfully applied to align a wide variety of BCPs including polystyrene-block-polybutadiene-block-polystyrene (SBS), polystyrene-block-poly(N,N-dimethyl-n-octadecylammonium p-styrenesulfonate) (PS-b-PSS-DMODA), polystyrene-block-polydimethylsiloxane (PS-b-PDMS) and polystyrene-block-poly(2-vinlypyridine) (PS-b-P2VP). These results suggest that SVA-SS is a generalizable method for the alignment of BCP thin films.

Resilient self-assembling hydrogels from block copolypeptide amphiphiles

NASA Astrophysics Data System (ADS)

Nowak, Andrew Paul

The ability to produce well defined synthetic polypeptides has been greatly improved by the discovery of transition metal species that mediate the controlled polymerization of N-carboxyanhydrides (NCAs). These metal species create a living polymerization system by producing control over chain length, low polydispersities, and the ability to form complex block architectures. We have applied this system to the synthesis of block copolypeptide amphiphiles. Initial block copolymers synthesized were composed of hydrophilic, cationic poly(L-Lysine) combined with hydrophobic, alpha-helical poly(L-Leucine). These Lysine- block-Leucine copolypeptides were found to form stiff, clear hydrogels at low concentration (˜1 wt%) in low ionic strength water. Based on this unexpected result we used the flexibility of our transition metal polymerization chemistry to better understand the nature and mechanisms of gel formation in these materials. Systematic changes to the original Lysine-block-Leucine copolypeptides were made by altering overall chain size, relative block length, polyelectrolyte charge, and hydrophobic secondary structure. Rheological characterization revealed that the strength of these hydrogels was primarily dependent on degree of polymerization, relative block length, and a well ordered secondary structure in the hydrophobic segment. The Lysine-block-Leucine hydrogels were formed by direct addition of water to dry polypeptide material which swelled to homogeneously fill the entire volume of liquid with no special processing. CryoTEM showed a percolating cellular network at ˜100nm that appears to be comprised of both membranes and fibers. Larger length scales studied with Laser Scanning Confocal Microscopy revealed a spontaneously formed microporous network with large (˜10mum) water rich voids. These hydrogels also displayed interesting mechanical properties including rapid recovery of solid like behavior after being sheared to a liquid and mechanical stability with increased temperature (˜90°C). The behavior of the Lysine- block-Leucine system with salt was also thoroughly investigated. With proper tuning of the relative block composition it was found that hydrogels could be optimized to possess good solubility and mechanical strength in many useful ionic solutions (˜100--200mM) such as pH buffers and cell culture media.

Genetics Home Reference: cyclic neutropenia

MedlinePlus

... Facebook Twitter Home Health Conditions Cyclic neutropenia Cyclic neutropenia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cyclic neutropenia is a disorder that causes frequent infections and ...

Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

PubMed Central

Chao, Julie; Weathersbee, Carolyn J.

1974-01-01

Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

Product Definition Data Interface (PDDI) Product Specification

DTIC Science & Technology

1991-07-01

syntax of the language gives a precise specification of the data without interpretation of it. M - Constituent Read Block. CSECT - Control Section, the...to conform to the PDDI Access Software’s internal data representation so that it may be further processed. JCL - Job Control Language - IBM language...software development and life cycle * phases. OUALITY CONTROL - The planned and systematic application of all actions (management/technical) necessary to

Maturation Constrains the Effect of Exposure in Linking Language and Thought: Evidence from Healthy Preterm Infants

ERIC Educational Resources Information Center

Perszyk, Danielle R.; Ferguson, Brock; Waxman, Sandra R.

2018-01-01

The power of human language rests upon its intricate links to human cognition. By 3 months of age, listening to language supports infants' ability to form object categories, a building block of cognition. Moreover, infants display a systematic shift between 3 and 4 months--a shift from familiarity to novelty preferences--in their expression of…

Adequacy of different experimental designs for eucalyptus spacing trials in Portuguese environmental conditions

Treesearch

Paula Soares; Margarida Tome

2000-01-01

In Portugal, several eucalyptus spacing trials cover a relatively broad range of experimental designs: trials with a non-randomized block design with plots of different size and number of trees per plot; trials based on a non-systematic design in which spacings were randomized resulting in a factorial arrangement with plots of different size and shape and equal number...

Proteomic analysis of formalin-fixed paraffin-embedded renal tissue samples by label-free MS: assessment of overall technical variability and the impact of block age.

PubMed

Craven, Rachel A; Cairns, David A; Zougman, Alexandre; Harnden, Patricia; Selby, Peter J; Banks, Rosamonde E

2013-04-01

Protein profiling of formalin-fixed paraffin-embedded (FFPE) tissues has enormous potential for the discovery and validation of disease biomarkers. The aim of this study was to systematically characterize the effect of length of time of storage of such tissue blocks in pathology archives on the quality of data produced using label-free MS. Normal kidney and clear cell renal cell carcinoma tissues routinely collected up to 10 years prior to analysis were profiled using LC-MS/MS and the data analyzed using MaxQuant. Protein identities and quantification data were analyzed to examine differences between tissue blocks of different ages and assess the impact of technical and biological variability. An average of over 2000 proteins was seen in each sample with good reproducibility in terms of proteins identified and quantification for normal kidney tissue, with no significant effect of block age. Greater biological variability was apparent in the renal cell carcinoma tissue, possibly reflecting disease heterogeneity, but again there was good correlation between technical replicates and no significant effect of block age. These results indicate that archival storage time does not have a detrimental effect on protein profiling of FFPE tissues, supporting the use of such tissues in biomarker discovery studies. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-function study on a de novo synthetic hydrophobic ion channel.

PubMed Central

Qi, Z; Sokabe, M; Donowaki, K; Ishida, H

1999-01-01

Ion conduction properties of a de novo synthesized channel, formed from cyclic octa-peptides consisting of four alternate L-alanine (Ala) and N'-acylated 3-aminobenzoic acid (Aba) moieties, were studied in bilayer membranes. The single-channel conductance was 9 pS in symmetrical 500 mM KCl. The channel favored permeation of cations over anions with a permeability ratio (PCl-/PK+) of 0.15. The selectivity sequence among monovalent cations based on permeability ratio (PX+/PK+) fell into an order: NH4+(1.4) > Cs+(1. 1) >/= K+(1.0) > Na+(0.4) >> Li+(0). The conductance-activity relationship of the channel in K+ solutions followed simple Michaelis-Menten kinetics with a half-maximal saturating activity of 8 mM and a maximal conductance of 9 pS. The permeability ratio PNa+/PK+ remained constant ( approximately 0.40) under biionic concentrations from 10 to 500 mM. These results suggests that the channel is a one-ion channel. The pore diameter probed by a set of organic cations was approximately 6 A. The single-channel current was blocked by Ca2+ in a dose-dependent manner that followed a single-site titration curve with a voltage-dependent dissociation constant of 0.6 mM at 100 mV. The electric distance of the binding site for Ca2+ was 0.07 from both entrances of the channel, indicating the presence of two symmetrical binding sites in each vicinity of the channel entrance. Correlations between conduction properties and structural aspects of the channel are discussed in terms of a three-barrier and two-binding-site (3B2S) model of Eyring rate theory. All available structural information supported an idea that the channel was formed from a tail-to-tail associated dimer of the molecule, the pore of which was lined with hydrophobic acyl chains. This is the first report to have made a systematic analysis of ion permeation through a hydrophobic pore. PMID:9929469

Cyanobacterial biofuels: new insights and strain design strategies revealed by computational modeling.

PubMed

Erdrich, Philipp; Knoop, Henning; Steuer, Ralf; Klamt, Steffen

2014-09-19

Cyanobacteria are increasingly recognized as promising cell factories for the production of renewable biofuels and chemical feedstocks from sunlight, CO2, and water. However, most biotechnological applications of these organisms are still characterized by low yields. Increasing the production performance of cyanobacteria remains therefore a crucial step. In this work we use a stoichiometric network model of Synechocystis sp. PCC 6803 in combination with CASOP and minimal cut set analysis to systematically identify and characterize suitable strain design strategies for biofuel synthesis, specifically for ethanol and isobutanol. As a key result, improving upon other works, we demonstrate that higher-order knockout strategies exist in the model that lead to coupling of growth with high-yield biofuel synthesis under phototrophic conditions. Enumerating all potential knockout strategies (cut sets) reveals a unifying principle behind the identified strain designs, namely to reduce the ratio of ATP to NADPH produced by the photosynthetic electron transport chain. Accordingly, suitable knockout strategies seek to block cyclic and other alternate electron flows, such that ATP and NADPH are exclusively synthesized via the linear electron flow whose ATP/NADPH ratio is below that required for biomass synthesis. The products of interest are then utilized by the cell as sinks for reduction equivalents in excess. Importantly, the calculated intervention strategies do not rely on the assumption of optimal growth and they ensure that maintenance metabolism in the absence of light remains feasible. Our analyses furthermore suggest that a moderately increased ATP turnover, realized, for example, by ATP futile cycles or other ATP wasting mechanisms, represents a promising target to achieve increased biofuel yields. Our study reveals key principles of rational metabolic engineering strategies in cyanobacteria towards biofuel production. The results clearly show that achieving obligatory coupling of growth and product synthesis in photosynthetic bacteria requires fundamentally different intervention strategies compared to heterotrophic organisms.

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

PubMed

St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B

2015-05-01

Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.

Influence of needle position on lumbar segmental nerve root block selectivity.

PubMed

Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

Techniques for grid manipulation and adaptation. [computational fluid dynamics

NASA Technical Reports Server (NTRS)

Choo, Yung K.; Eisemann, Peter R.; Lee, Ki D.

1992-01-01

Two approaches have been taken to provide systematic grid manipulation for improved grid quality. One is the control point form (CPF) of algebraic grid generation. It provides explicit control of the physical grid shape and grid spacing through the movement of the control points. It works well in the interactive computer graphics environment and hence can be a good candidate for integration with other emerging technologies. The other approach is grid adaptation using a numerical mapping between the physical space and a parametric space. Grid adaptation is achieved by modifying the mapping functions through the effects of grid control sources. The adaptation process can be repeated in a cyclic manner if satisfactory results are not achieved after a single application.