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Sample records for replacement mechanism directs

  1. A Helix Replacement Mechanism Directs Metavinculin Functions

    SciTech Connect

    Rangarajan, Erumbi S.; Lee, Jun Hyuck; Yogesha, S.D.; Izard, Tina

    2010-10-11

    Cells require distinct adhesion complexes to form contacts with their neighbors or the extracellular matrix, and vinculin links these complexes to the actin cytoskeleton. Metavinculin, an isoform of vinculin that harbors a unique 68-residue insert in its tail domain, has distinct actin bundling and oligomerization properties and plays essential roles in muscle development and homeostasis. Moreover, patients with sporadic or familial mutations in the metavinculin-specific insert invariably develop fatal cardiomyopathies. Here we report the high resolution crystal structure of the metavinculin tail domain, as well as the crystal structures of full-length human native metavinculin (1,134 residues) and of the full-length cardiomyopathy-associated {Delta}Leu954 metavinculin deletion mutant. These structures reveal that an {alpha}-helix (H1{prime}) and extended coil of the metavinculin insert replace {alpha}-helix H1 and its preceding extended coil found in the N-terminal region of the vinculin tail domain to form a new five-helix bundle tail domain. Further, biochemical analyses demonstrate that this helix replacement directs the distinct actin bundling and oligomerization properties of metavinculin. Finally, the cardiomyopathy associated {Delta}Leu954 and Arg975Trp metavinculin mutants reside on the replaced extended coil and the H1{prime} {alpha}-helix, respectively. Thus, a helix replacement mechanism directs metavinculin's unique functions.

  2. Mechanical versus biological aortic valve replacement strategies.

    PubMed

    Reineke, D; Gisler, F; Englberger, L; Carrel, T

    2016-01-01

    Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology. PMID:26678683

  3. Efficient gene replacement and direct hyphal transformation in Sclerotinia sclerotiorum.

    PubMed

    Levy, M; Erental, A; Yarden, O

    2008-09-01

    Homologous recombination is required for gene-targeted procedures such as gene disruption and gene replacement. Ku80 is part of the non-homologous end-joining DNA repair mechanism in many organisms. We identified and disrupted the Ku80 homologue in Sclerotinia sclerotiorum and generated heterokaryon mutants enriched with Ku80-deficient nuclei (ssku80). Sclerotial formation and pathogenicity of ssku80 mutants were normal on tomato fruits. The frequencies of homologous recombination in these strains were much higher than those of the wild type when transformed with a cna1 (encoding calcineurin) replacement construct. We coupled the increase in homologous recombination with a direct BIM-LAB-mediated transformation procedure, which utilizes compressed air to assist the transforming DNA in penetrating fungal hyphae of S. sclerotiorum. We found this method to be efficient and reproducible, and it did not alter the fitness of the mutants. We also demonstrated the first case of direct transformation of sclerotia. Nourseothricin was introduced as a selectable marker in S. sclerotiorum. The tools and procedures described will improve our ability to study gene function in S. sclerotiorum and are most likely to be adaptable for use in other plant pathogens. PMID:19019000

  4. New directions in mechanics

    SciTech Connect

    Kassner, Michael E.; Nemat-Nasser, Sia; Suo, Zhigang; Bao, Gang; Barbour, J. Charles; Brinson, L. Catherine; Espinosa, Horacio; Gao, Huajian; Granick, Steve; Gumbsch, Peter; Kim, Kyung -Suk; Knauss, Wolfgang; Kubin, Ladislas; Larson, Ben C.; Mahadevan, L.; Majumdar, Arun; Torquato, Salvatore; van Swol, Frank

    2004-09-15

    The Division of Materials Sciences and Engineering of the US Department of Energy (DOE) sponsored a workshop to identify cutting-edge research needs and opportunities, enabled by the application of theoretical and applied mechanics. The workshop also included input from biochemical, surface science, and computational disciplines, on approaching scientific issues at the nanoscale, and the linkage of atomistic-scale with nano-, meso-, and continuum-scale mechanics. This paper is a summary of the outcome of the workshop, consisting of three main sections, each put together by a team of workshop participants. Section 1 addresses research opportunities that can be realized by the application of mechanics fundamentals to the general area of self-assembly, directed self-assembly, and fluidics. Section 2 examines the role of mechanics in biological, bioinspired, and biohybrid material systems, closely relating to and complementing the material covered in Section 1. In this manner, it was made clear that mechanics plays a fundamental role in understanding the biological functions at all scales, in seeking to utilize biology and biological techniques to develop new materials and devices, and in the general area of bionanotechnology. While direct observational investigations are an essential ingredient of new discoveries and will continue to open new exciting research doors, it is the basic need for controlled experimentation and fundamentally- based modeling and computational simulations that will be truly empowered by a systematic use of the fundamentals of mechanics. Section 3 brings into focus new challenging issues in inelastic deformation and fracturing of materials that have emerged as a result of the development of nanodevices, biopolymers, and hybrid bio–abio systems. As a result, each section begins with some introductory overview comments, and then provides illustrative examples that were presented at the workshop and which are believed to highlight the enabling

  5. New directions in mechanics

    DOE PAGESBeta

    Kassner, Michael E.; Nemat-Nasser, Sia; Suo, Zhigang; Bao, Gang; Barbour, J. Charles; Brinson, L. Catherine; Espinosa, Horacio; Gao, Huajian; Granick, Steve; Gumbsch, Peter; et al

    2004-09-15

    The Division of Materials Sciences and Engineering of the US Department of Energy (DOE) sponsored a workshop to identify cutting-edge research needs and opportunities, enabled by the application of theoretical and applied mechanics. The workshop also included input from biochemical, surface science, and computational disciplines, on approaching scientific issues at the nanoscale, and the linkage of atomistic-scale with nano-, meso-, and continuum-scale mechanics. This paper is a summary of the outcome of the workshop, consisting of three main sections, each put together by a team of workshop participants. Section 1 addresses research opportunities that can be realized by the applicationmore » of mechanics fundamentals to the general area of self-assembly, directed self-assembly, and fluidics. Section 2 examines the role of mechanics in biological, bioinspired, and biohybrid material systems, closely relating to and complementing the material covered in Section 1. In this manner, it was made clear that mechanics plays a fundamental role in understanding the biological functions at all scales, in seeking to utilize biology and biological techniques to develop new materials and devices, and in the general area of bionanotechnology. While direct observational investigations are an essential ingredient of new discoveries and will continue to open new exciting research doors, it is the basic need for controlled experimentation and fundamentally- based modeling and computational simulations that will be truly empowered by a systematic use of the fundamentals of mechanics. Section 3 brings into focus new challenging issues in inelastic deformation and fracturing of materials that have emerged as a result of the development of nanodevices, biopolymers, and hybrid bio–abio systems. As a result, each section begins with some introductory overview comments, and then provides illustrative examples that were presented at the workshop and which are believed to highlight the

  6. Vaccine-induced pathogen strain replacement: what are the mechanisms?

    PubMed

    Martcheva, Maia; Bolker, Benjamin M; Holt, Robert D

    2008-01-01

    Host immune systems impose natural selection on pathogen populations, which respond by evolving different antigenic signatures. Like many evolutionary processes, pathogen evolution reflects an interaction between different levels of selection; pathogens can win in between-strain competition by taking over individual hosts (within-host level) or by infecting more hosts (population level). Vaccination, which intensifies and modifies selection by protecting hosts against one or more pathogen strains, can drive the emergence of new dominant pathogen strains-a phenomenon called vaccine-induced pathogen strain replacement. Here, we review reports of increased incidence of subdominant variants after vaccination campaigns and extend the current model for pathogen strain replacement, which assumes that pathogen strain replacement occurs only through the differential effectiveness of vaccines against different pathogen strains. Based on a recent theoretical study, we suggest a broader range of possible mechanisms, some of which allow pathogen strain replacement even when vaccines are perfect-that is, they protect all vaccinated individuals completely against all pathogen strains. We draw an analogy with ecological and evolutionary explanations for competitive dominance and coexistence that allow for tradeoffs between different competitive and life-history traits. PMID:17459810

  7. Directional cultural change by modification and replacement of memes.

    PubMed

    Cardoso, Gonçalo C; Atwell, Jonathan W

    2011-01-01

    Evolutionary approaches to culture remain contentious. A source of contention is that cultural mutation may be substantial and, if it drives cultural change, then current evolutionary models are not adequate. But we lack studies quantifying the contribution of mutations to directional cultural change. We estimated the contribution of one type of cultural mutations--modification of memes--to directional cultural change using an amenable study system: learned birdsongs in a species that recently entered an urban habitat. Many songbirds have higher minimum song frequency in cities, to alleviate masking by low-frequency noise. We estimated that the input of meme modifications in an urban songbird population explains about half the extent of the population divergence in song frequency. This contribution of cultural mutations is large, but insufficient to explain the entire population divergence. The remaining divergence is due to selection of memes or creation of new memes. We conclude that the input of cultural mutations can be quantitatively important, unlike in genetic evolution, and that it operates together with other mechanisms of cultural evolution. For this and other traits, in which the input of cultural mutations might be important, quantitative studies of cultural mutation are necessary to calibrate realistic models of cultural evolution.

  8. Directional cultural change by modification and replacement of memes.

    PubMed

    Cardoso, Gonçalo C; Atwell, Jonathan W

    2011-01-01

    Evolutionary approaches to culture remain contentious. A source of contention is that cultural mutation may be substantial and, if it drives cultural change, then current evolutionary models are not adequate. But we lack studies quantifying the contribution of mutations to directional cultural change. We estimated the contribution of one type of cultural mutations--modification of memes--to directional cultural change using an amenable study system: learned birdsongs in a species that recently entered an urban habitat. Many songbirds have higher minimum song frequency in cities, to alleviate masking by low-frequency noise. We estimated that the input of meme modifications in an urban songbird population explains about half the extent of the population divergence in song frequency. This contribution of cultural mutations is large, but insufficient to explain the entire population divergence. The remaining divergence is due to selection of memes or creation of new memes. We conclude that the input of cultural mutations can be quantitatively important, unlike in genetic evolution, and that it operates together with other mechanisms of cultural evolution. For this and other traits, in which the input of cultural mutations might be important, quantitative studies of cultural mutation are necessary to calibrate realistic models of cultural evolution. PMID:20722726

  9. Bi-Directional Evolutionary Topology Optimization Using Element Replaceable Method

    NASA Astrophysics Data System (ADS)

    Zhu, J. H.; Zhang, W. H.; Qiu, K. P.

    2007-06-01

    In the present paper, design problems of maximizing the structural stiffness or natural frequency are considered subject to the material volume constraint. A new element replaceable method (ERPM) is proposed for evolutionary topology optimization of structures. Compared with existing versions of evolutionary structural optimization methods, contributions are twofold. On the one hand, a new automatic element deletion/growth procedure is established. The deletion of a finite element means that a solid element is replaced with an orthotropic cellular microstructure (OCM) element. The growth of an element means that an OCM element is replaced with a solid element of full materials. In fact, both operations are interchangeable depending upon how the value of element sensitivity is with respect to the objective function. The OCM design strategy is beneficial in preventing artificial modes for dynamic problems. Besides, the iteration validity is greatly improved with the introduction of a check position (CP) technique. On the other hand, a new checkerboard control algorithm is proposed to work together with the above procedure. After the identification of local checkerboards and detailed structures over the entire design domain, the algorithm will fill or delete elements depending upon the prescribed threshold of sensitivity values. Numerical results show that the ERPM is efficient and a clear and valuable material pattern can be achieved for both static and dynamic problems.

  10. Reaction mechanism of Escherichia coli cystathionine gamma-synthase: direct evidence for a pyridoxamine derivative of vinylglyoxylate as a key intermediate in pyridoxal phosphate dependent gamma-elimination and gamma-replacement reactions.

    PubMed

    Brzović, P; Holbrook, E L; Greene, R C; Dunn, M F

    1990-01-16

    Cystathionine gamma-synthase catalyzes a pyridoxal phosphate dependent synthesis of cystathionine from O-succinyl-L-homoserine (OSHS) and L-cysteine via a gamma-replacement reaction. In the absence of L-cysteine, OSHS undergoes an enzyme-catalyzed, gamma-elimination reaction to form succinate, alpha-ketobutyrate, and ammonia. Since elimination of the gamma-substituent is necessary for both reactions, it is reasonable to assume that the replacement and elimination reaction pathways diverge from a common intermediate. Previously, this partitioning intermediate has been assigned to a highly conjugated alpha-iminovinylglycine quininoid (Johnston et al., 1979a). The experiments reported herein support an alternative assignment for the partitioning intermediate. We have examined the gamma-replacement and gamma-elimination reactions of cystathionine gamma-synthase via rapid-scanning stopped-flow and single-wavelength stopped-flow UV-visible spectroscopy. The gamma-elimination reaction is characterized by a rapid decrease in the amplitude of the enzyme internal aldimine spectral band at 422 nm with a concomitant appearance of a new species which absorbs in the 300-nm region. A 485-nm species subsequently accumulates in a much slower relaxation. The gamma-replacement reaction shows a red shift of the 422-nm peak to 425 nm which occurs in the experiment dead time (approximately 3 ms). This relaxation is followed by a decrease in absorbance at 425 nm that is tightly coupled to the appearance of a species which absorbs in the 300-nm region. Reaction of the substrate analogues L-alanine and L-allylglycine with cystathionine gamma-synthase results in bleaching of the 422-nm absorbance and the appearance of a 300-nm species. In the absence of L-cysteine, L-allylglycine undergoes facile proton exchange; in the presence of L-cysteine, L-allylglycine undergoes a gamma-replacement reaction to form a new amino acid, gamma-methylcystathionine. No long-wavelength-absorbing species

  11. Climatological effects of replacing mechanic thermometers with electronic thermometers.

    NASA Astrophysics Data System (ADS)

    Delitala, Alessandro M. S.; Fois, Giuliano

    2010-05-01

    In the last decade of 20th century, most of the traditional temperature recording systems of meteorological networks worldwide were replaced by electronic stations. Both sensors and data processing systems were changed. Before the above instrumental change, mechanical thermographers had bimetallic sensors inside and liquid-in-glass thermometers usually contained lead or other liquids. Nowadays, electronic thermometers are based upon resistors or thermocouples. In order to register those data, mechanical thermographers would make continuous analogical recording upon paper strips while liquid-in-glass thermometers were read every day. Modern stations, on the other hand, digitally process measures from their thermometers by means of data-loggers. The impact of such a major instrumental change received little attentions by meteorological services, except for a few scientific analysis, although it is likely to have been quite significant upon long time series of observation, as it has been pointed out even by the World Meteorological Organization. The authors of the present talk analysed about ten years of measures registered between 1996 and 2007 by a couple of stations: one mechanical thermographer and one electronic thermometer, operated in parallel in the same field in Sardinia. The two stations were operated by two different institutions: the "Department of Agronomy and Agrarian Vegetal Genetics of the University of Sassari" and the Italian research institute "CRA-CMA"; they both received a fair maintenance and their site was well cured by the hosting institution. A systematic difference of +0.9°C in minimum temperatures was detected, almost independent of seasons. A very low mean bias (+0.1°C) was highlighted in maximum temperatures, instead; however the authors detected a seasonal effect, ranging from +1.1°C in January to -0.8°C in June. The very high number of records renders such results very robust from a statistical point of view. The authors then made

  12. The mechanical and tribological properties of UHMWPE loaded ALN after mechanical activation for joint replacements.

    PubMed

    Gong, Kemeng; Qu, Shuxin; Liu, Yumei; Wang, Jing; Zhang, Yongchao; Jiang, Chongxi; Shen, Ru

    2016-08-01

    Ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN) has tremendous potential as an orthopeadic biomaterial for joint replacements. However, poor mechanical and tribological properties of UHMWPE-ALN are still obstacle for further application. The purpose of this study was to investigate the effect and mechanism of mechanical activation on mechanical and tribological properties of 1wt% ALN-loaded UHMWPE (UHMWPE-ALN-ma). In this study, tensile test, small punch test and reciprocating sliding wear test were applied to characterize the mechanical and tribological properties of UHMWPE-ALN-ma. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) were employed to characterize UHMWPE-ALN-ma. Tensile test and small punch test showed that Young׳s modulus, tensile strength and work-to-failure (WTF) of UHMWPE-ALN-ma increased significantly compared to those of UHMWPE-ALN. The friction coefficients and wear factors of UHMWPE-ALN-ma both decreased significantly compared to those of UHMWPE-ALN. Mechanical activation obviously reduced type 1 (void) and type 2 (the disconnected and dislocated machining marks) fusion defects of UHMWPE-ALN-ma, which were revealed by SEM images of freeze fracture surfaces after etching and lateral surfaces of specimens after extension to fracture, respectively. It was attributed to peeled-off layers and chain scission of molecular chains of UHMWPE particles after mechanical activation, which were revealed by SEM images and FTIR spectra of UHMWPE-ALN-ma and UHMWPE-ALN, respectively. Moreover, EDS spectra revealed the more homogeneous distribution of ALN in UHMWPE-ALN-ma compared to that of UHMWPE-ALN. The present results showed that mechanical activation was a potential strategy to improve mechanical and tribological properties of UHMWPE-ALN-ma as an orthopeadic biomaterial for joint replacements. PMID:27104932

  13. The mechanical and tribological properties of UHMWPE loaded ALN after mechanical activation for joint replacements.

    PubMed

    Gong, Kemeng; Qu, Shuxin; Liu, Yumei; Wang, Jing; Zhang, Yongchao; Jiang, Chongxi; Shen, Ru

    2016-08-01

    Ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN) has tremendous potential as an orthopeadic biomaterial for joint replacements. However, poor mechanical and tribological properties of UHMWPE-ALN are still obstacle for further application. The purpose of this study was to investigate the effect and mechanism of mechanical activation on mechanical and tribological properties of 1wt% ALN-loaded UHMWPE (UHMWPE-ALN-ma). In this study, tensile test, small punch test and reciprocating sliding wear test were applied to characterize the mechanical and tribological properties of UHMWPE-ALN-ma. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) were employed to characterize UHMWPE-ALN-ma. Tensile test and small punch test showed that Young׳s modulus, tensile strength and work-to-failure (WTF) of UHMWPE-ALN-ma increased significantly compared to those of UHMWPE-ALN. The friction coefficients and wear factors of UHMWPE-ALN-ma both decreased significantly compared to those of UHMWPE-ALN. Mechanical activation obviously reduced type 1 (void) and type 2 (the disconnected and dislocated machining marks) fusion defects of UHMWPE-ALN-ma, which were revealed by SEM images of freeze fracture surfaces after etching and lateral surfaces of specimens after extension to fracture, respectively. It was attributed to peeled-off layers and chain scission of molecular chains of UHMWPE particles after mechanical activation, which were revealed by SEM images and FTIR spectra of UHMWPE-ALN-ma and UHMWPE-ALN, respectively. Moreover, EDS spectra revealed the more homogeneous distribution of ALN in UHMWPE-ALN-ma compared to that of UHMWPE-ALN. The present results showed that mechanical activation was a potential strategy to improve mechanical and tribological properties of UHMWPE-ALN-ma as an orthopeadic biomaterial for joint replacements.

  14. Factors affecting the placement or replacement of direct restorations in a dental school

    PubMed Central

    Silvani, Samara; Trivelato, Roberta Ferreira; Nogueira, Ruchele Dias; Gonçalves, Luciano de Souza; Geraldo-Martins, Vinícius Rangel

    2014-01-01

    Context: The knowledge of the reasons for the placement of direct restorations makes possible to trace an epidemiological profile of a specific population and to direct the teaching of dentistry to techniques that are commonly used today and will be continued performed in the future. Purpose: The aim of this study was to verify the reasons for placement and replacement of direct restorations in patients treated in the Dental Clinic of the Uberaba University – Brazil. Materials and Methods: This study evaluated 306 restorative procedures carried out on 60 patients. During the treatment planning, a form that contained information about the patient's gender, tooth number, the classification of restorations, the reasons for placement and replacement of amalgam and tooth-colored restorations, the material that had to be removed and the new material used to fill the cavities was filled for each patient. Statistical analysis was carried out using Chi-square test (α = 0.05). Results: The data showed that most of the patients were female (66.7%). Of all the restorations placed, 60.45% were 1st-time placements, while 39.55% were replacements. For 1st-time restorations, the main reason for placement was primary caries (76.76%), followed by non-carious cervical lesions (15.14%). The amalgam restorations were replaced more frequently (67.77%). The primary reason for replacements was the presence of secondary caries (for both previous amalgam (42.68%) and composite (66.67%) restorations (P < 0.05). The resin composite was the most indicated material for the new restorations (98.04%) (P < 0.05). Conclusions: The main reason for placement of direct restorations was primary caries, while secondary caries was the main reason for replacements. In almost all cases, the material used to fill the cavities was the resin composite. PMID:24808696

  15. Fluid Mechanics of Heart Valves and Their Replacements

    NASA Astrophysics Data System (ADS)

    Sotiropoulos, Fotis; Le, Trung Bao; Gilmanov, Anvar

    2016-01-01

    As the pulsatile cardiac blood flow drives the heart valve leaflets to open and close, the flow in the vicinity of the valve resembles a pulsed jet through a nonaxisymmetric orifice with a dynamically changing area. As a result, three-dimensional vortex rings with intricate topology emerge that interact with the complex cardiac anatomy and give rise to shear layers, regions of recirculation, and flow instabilities that could ultimately lead to transition to turbulence. Such complex flow patterns, which are inherently valve- and patient-specific, lead to mechanical forces at scales that can cause blood cell damage and thrombosis, increasing the likelihood of stroke, and can trigger the pathogenesis of various life-threatening valvular heart diseases. We summarize the current understanding of flow phenomena induced by heart valves, discuss their linkage with disease pathways, and emphasize the research advances required to translate in-depth understanding of valvular hemodynamics into effective patient therapies.

  16. Development of Therapeutic Chimeric Uricase by Exon Replacement/Restoration and Site-Directed Mutagenesis

    PubMed Central

    Xie, Guangrong; Yang, Weizhen; Chen, Jing; Li, Miaomiao; Jiang, Nan; Zhao, Baixue; Chen, Si; Wang, Min; Chen, Jianhua

    2016-01-01

    The activity of urate oxidase was lost during hominoid evolution, resulting in high susceptibility to hyperuricemia and gout in humans. In order to develop a more “human-like” uricase for therapeutic use, exon replacement/restoration and site-directed mutagenesis were performed to obtain porcine–human uricase with higher homology to deduced human uricase (dHU) and increased uricolytic activity. In an exon replacement study, substitution of exon 6 in wild porcine uricase (wPU) gene with corresponding exon in dhu totally abolished its activity. Substitutions of exon 5, 3, and 1–2 led to 85%, 60%, and 45% loss of activity, respectively. However, replacement of exon 4 and 7–8 did not significantly change the enzyme activity. When exon 5, 6, and 3 in dhu were replaced by their counterparts in wpu, the resulting chimera H1-2P3H4P5-6H7-8 was active, but only about 28% of wPU. Multiple sequence alignment and homology modeling predicted that mutations of E24D and E83G in H1-2P3H4P5-6H7-8 were favorable for further increase of its activity. After site-directed mutagenesis, H1-2P3H4P5-6H7-8 (E24D & E83G) with increased homology (91.45%) with dHU and higher activity and catalytic efficiency than the FDA-approved porcine–baboon chimera (PBC) was obtained. It showed optimum activity at pH 8.5 and 35 °C and was stable in a pH range of 6.5–11.0 and temperature range of 20–40 °C. PMID:27213357

  17. Development of Therapeutic Chimeric Uricase by Exon Replacement/Restoration and Site-Directed Mutagenesis.

    PubMed

    Xie, Guangrong; Yang, Weizhen; Chen, Jing; Li, Miaomiao; Jiang, Nan; Zhao, Baixue; Chen, Si; Wang, Min; Chen, Jianhua

    2016-01-01

    The activity of urate oxidase was lost during hominoid evolution, resulting in high susceptibility to hyperuricemia and gout in humans. In order to develop a more "human-like" uricase for therapeutic use, exon replacement/restoration and site-directed mutagenesis were performed to obtain porcine-human uricase with higher homology to deduced human uricase (dHU) and increased uricolytic activity. In an exon replacement study, substitution of exon 6 in wild porcine uricase (wPU) gene with corresponding exon in dhu totally abolished its activity. Substitutions of exon 5, 3, and 1-2 led to 85%, 60%, and 45% loss of activity, respectively. However, replacement of exon 4 and 7-8 did not significantly change the enzyme activity. When exon 5, 6, and 3 in dhu were replaced by their counterparts in wpu, the resulting chimera H1-2P₃H₄P5-6H7-8 was active, but only about 28% of wPU. Multiple sequence alignment and homology modeling predicted that mutations of E24D and E83G in H1-2P₃H₄P5-6H7-8 were favorable for further increase of its activity. After site-directed mutagenesis, H1-2P₃H₄P5-6H7-8 (E24D & E83G) with increased homology (91.45%) with dHU and higher activity and catalytic efficiency than the FDA-approved porcine-baboon chimera (PBC) was obtained. It showed optimum activity at pH 8.5 and 35 °C and was stable in a pH range of 6.5-11.0 and temperature range of 20-40 °C. PMID:27213357

  18. Compliant mechanism road bicycle brake: a rigid-body replacement case study

    SciTech Connect

    Olsen, Brian M; Howell, Larry L; Magleby, Spencer P

    2011-01-19

    The design of high-performance bicycle brakes is complicated by the competing design objectives of increased performance and low weight. But this challenge also provides a good case study to demonstrate the design of compliant mechanisms to replace current rigid-link mechanisms. This paper briefly reviews current road brake designs, demonstrates the use of rigid-body replacement synthesis to design a compliant mechanism, and illustrates the combination of compliant mechanism design tools. The resulting concept was generated from the modified dual-pivot brake design and is a partially compliant mechanism where one pin has the dual role of a joint and a mounting pin. The pseudo-rigid-body model, finite element analysis, and optimization algorithms are used to generate design dimensions, and designs are considered for both titanium and E-glass flexures. The resulting design has the potential of reducing the part count and overall weight while maintaining a performance similar to the benchmark.

  19. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis.

    PubMed

    Elahi, Maqsood M; Choi, Charles H; Konda, Subbareddy; Shake, Jay G

    2015-01-01

    This report describes a patient's self-substitution of nattokinase for the vitamin K antagonist warfarin after aortic valve replacement with a mechanical prosthesis. Nattokinase is an enzyme derived from a popular fermented soybean preparation in Japan (natto), which has fibrinolytic properties and is gaining popularity in nontraditional health journals and nonmedical health websites as an over-the-counter thrombolytic. After nearly a year of use of nattokinase without warfarin, the patient developed thrombus on the mechanical valve and underwent successful repeat valve replacement. We believe this is the first documented case of nattokinase being used as a substitute for warfarin after valve replacement, and we strongly discourage its use for this purpose.

  20. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis

    PubMed Central

    Elahi, Maqsood M.; Choi, Charles H.; Konda, Subbareddy

    2015-01-01

    This report describes a patient's self-substitution of nattokinase for the vitamin K antagonist warfarin after aortic valve replacement with a mechanical prosthesis. Nattokinase is an enzyme derived from a popular fermented soybean preparation in Japan (natto), which has fibrinolytic properties and is gaining popularity in nontraditional health journals and nonmedical health websites as an over-the-counter thrombolytic. After nearly a year of use of nattokinase without warfarin, the patient developed thrombus on the mechanical valve and underwent successful repeat valve replacement. We believe this is the first documented case of nattokinase being used as a substitute for warfarin after valve replacement, and we strongly discourage its use for this purpose. PMID:25552810

  1. Unravelling the mechanism of action of enzyme replacement therapy in Fabry disease.

    PubMed

    Ko, Younhee; Lee, CheolHo; Moon, Myeong Hee; Hong, Geu-Ru; Cheon, Chong-Kun; Lee, Jin-Sung

    2016-02-01

    Fabry disease (FD) is a rare X-linked recessive glycosphingolipid-storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Intravenous enzyme replacement therapy (ERT) has been used to supplement deficient enzyme activity in patients with FD. Despite its clinical effect and manifestations, clear criteria for the clinical effectiveness and cost-effectiveness of ERT have not been well established. In this study, we investigated the pharmacodynamic actions and short-term effects of ERT in patients with FD through direct molecular profiling from blood samples of patients before and after ERT. Based on this comparison, we observed that immune/inflammation-related pathways and growth factor-related pathways such as innate/adaptive immune pathway, lymphocyte proliferation and leukocyte proliferation were actively regulated under ERT. We also found that TINAGL1, DAAM2, CDK5R1 and MYO5B known to be related with clinical symptoms of FD showed increased levels after ERT, leading to the amelioration of clinical manifestations. Especially the catabolic process-related genes, including USP15 and ERUN1, showed direct increasing after ERT in vivo in male patients. These results suggest that male patients with FD respond more actively to ERT than do female patients with FD. Pathway analysis revealed that oxidative phosphorylation pathway-related genes are downregulated under ERT. ERT has a role to protect the proteins from oxidative damage and such deactivation of oxidative phosphorylation is one of direct pharmacodynamic actions of ERT. These results extended our understanding of the pathophysiology of ERT. To our knowledge, this is the first study to observe the molecular basis for the mechanism of ERT in vivo through the comprehensive comparison of transcriptome study with next-generation sequencing data. PMID:26490183

  2. Bi-directional planar slide mechanism

    SciTech Connect

    Bieg, Lothar F.

    2003-11-04

    A bi-directional slide mechanism. A pair of master and slave disks engages opposite sides of the platform. Rotational drivers are connected to master disks so the disks rotate eccentrically about their respective axes of rotation. Opposing slave disks are connected to master disks on opposite sides of the platform by a circuitous mechanical linkage, or are electronically synchronized together using stepper motors, to effect coordinated motion. The synchronized eccentric motion of the pairs of master/slave disks compels smooth linear motion of the platform forwards and backwards without backlash. The apparatus can be incorporated in a MEMS device.

  3. Kinematics and Mechanical Properties of Knees following Patellar Replacing and Patellar Retaining Total Knee Arthroplasty

    PubMed Central

    Huang, Rongying; Liu, Yanqiang; Zhu, Jun

    2015-01-01

    Knee injury is a common medical issue. A full understanding of the kinematics and mechanical properties of knees following total knee arthroplasty (TKA) repair utilizing patellar replacement (only the base of the patella is replaced) versus patellar retaining surgical techniques is still lacking. In the current paper, we investigated magnetic resonance (MR) imaging data from knees repaired by these two methods and evaluated total knee models created using imaging reconstruction technology that simulated gait conditions. Results revealed that patellar replacement had little influence on tibiofemoral kinematics, although the tibia-surface equivalent stress increased slightly. By contrast, patellar replacement had a significant influence on the patellofemoral joint; patellar internal rotation, external rotation, and medial-lateral translation were all increased. Moreover, the stress distribution on patellar prostheses was altered, resulting in an increased surface maximal equivalent stress on the corresponding area. Moreover, during the gait cycle, we found that the area with maximal equivalent stress shifted its position. Finally, the patellofemoral joint showed decreased motion stability. From the view of kinematics and mechanics, this paper suggests that patella should be retained during TKA if it is possible. The present study presented approaches and technologies for evaluating kinematics and mechanical properties of total knee joint after TKA under gait loads. PMID:27057134

  4. Experimental study of the mechanism and sequence of calcite-dolomite replacement

    NASA Astrophysics Data System (ADS)

    Moraila-Martinez, Teresita; Putnis, Christine V.; Putnis, Andrew

    2015-04-01

    For many years the formation, mechanism and environmental settings of dolomite formation have been under discussion, mainly because dolomite is commonly found in ancient rocks, whereas it is rarely present in modern sediments. The most favoured hypothesis is the 'dolomitization' of limestone by Mg-bearing aqueous solutions [1,2]. The existence of sharp limestone-dolomite contacts in natural rocks suggests that dolomitization involves a coupled dissolution-precipitation process. For a better understanding of the replacement mechanism of calcite by dolomite we performed hydrothermal experiments using Carrara marble cubes of 1.5 mm size, that reacted with 1M (Ca,Mg)Cl2 solutions with a Mg:Ca ratio of 3, at 200°C for different duration times (10, 20, 40, 50 and 58 days). After reaction, the product phases were characterized using Raman spectroscopy, electron microprobe analysis, and scanning electron microscopy. After reaction, the external morphology of the samples was preserved. Back-scattered images revealed two replacement end products: dolomite and magnesite. Grain boundaries of the samples were maintained. Shorter time duration experiments resulted in the replacement reaction occurring mainly along grain boundaries, whereas in longer duration time experiments more replacement was located in the core of the sample. In this type of reaction, grain boundaries are very important for the replacement to occur, acting as fluid pathways, allowing the infiltration of the solution further from the rock surface, enhancing fluid permeability within the sample and allowing further replacement reactions to occur. 1. Kaczmarek S.E., Sibley D.F. On the evolution of dolomite stoichiometry and cation order during high temperature synthesis experiments: An alternative model for geochemical evolution of natural dolomites. Sedimentary Geology. 240, 30-40 (2011). 2. Etschmann B., Brugger J., Pearce M.A., Ta C., Brautigan D., Jung M., Pring A. Grain boundaries as microreactors during

  5. Contact mechanics of modular metal-on-polyethylene total hip replacement under adverse edge loading conditions

    PubMed Central

    Hua, Xijin; Li, Junyan; Wang, Ling; Jin, Zhongmin; Wilcox, Ruth; Fisher, John

    2014-01-01

    Edge loading can negatively impact the biomechanics and long-term performance of hip replacements. Although edge loading has been widely investigated for hard-on-hard articulations, limited work has been conducted for hard-on-soft combinations. The aim of the present study was to investigate edge loading and its effect on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR). A three-dimensional finite element model was developed based on a modular MoP bearing. Different cup inclination angles and head lateral microseparation were modelled and their effect on the contact mechanics of the modular MoP hip replacement were examined. The results showed that lateral microseparation caused loading of the head on the rim of the cup, which produced substantial increases in the maximum von Mises stress in the polyethylene liner and the maximum contact pressure on both the articulating surface and backside surface of the liner. Plastic deformation of the liner was observed under both standard conditions and microseparation conditions, however, the maximum equivalent plastic strain in the liner under microseparation conditions of 2000 µm was predicted to be approximately six times that under standard conditions. The study has indicated that correct positioning the components to avoid edge loading is likely to be important clinically even for hard-on-soft bearings for THR. PMID:25218504

  6. Contact mechanics of modular metal-on-polyethylene total hip replacement under adverse edge loading conditions.

    PubMed

    Hua, Xijin; Li, Junyan; Wang, Ling; Jin, Zhongmin; Wilcox, Ruth; Fisher, John

    2014-10-17

    Edge loading can negatively impact the biomechanics and long-term performance of hip replacements. Although edge loading has been widely investigated for hard-on-hard articulations, limited work has been conducted for hard-on-soft combinations. The aim of the present study was to investigate edge loading and its effect on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR). A three-dimensional finite element model was developed based on a modular MoP bearing. Different cup inclination angles and head lateral microseparation were modelled and their effect on the contact mechanics of the modular MoP hip replacement were examined. The results showed that lateral microseparation caused loading of the head on the rim of the cup, which produced substantial increases in the maximum von Mises stress in the polyethylene liner and the maximum contact pressure on both the articulating surface and backside surface of the liner. Plastic deformation of the liner was observed under both standard conditions and microseparation conditions, however, the maximum equivalent plastic strain in the liner under microseparation conditions of 2000 µm was predicted to be approximately six times that under standard conditions. The study has indicated that correct positioning the components to avoid edge loading is likely to be important clinically even for hard-on-soft bearings for THR.

  7. Mechanical properties of the fiberglass prepreg system used for the National Transonic Facility replacement blade set

    NASA Technical Reports Server (NTRS)

    Young, Clarence P., Jr.; Wallace, John W.

    1991-01-01

    The results are presented of mechanical and physical properties characterization testing for the fiber glass prepreg system used to fabricate 15 of the replacement set of 25 fan blades for the National Transonic Facility. The fan blades were fabricated to be identical to the original blade set with the exception that the 7576 style E glass cloth used for the replacement set has a different surface finish than the original 7576 cloth. The 7781 E glass cloth and resin system were unchanged. The data are presented for elevated, room, and cryogenic temperatures. The results are compared with data from the original blade set and evaluated against selected structural design criteria. Test experience is described along with recommendations for future testing of these materials if required.

  8. An experimental approach to testing modular evolution: directed replacement of alpha-helices in a bacterial protein.

    PubMed Central

    DuBose, R F; Hartl, D L

    1989-01-01

    We have used oligonucleotide site-directed mutagenesis to ask whether certain structural motifs in proteins are determined mainly by local interactions among amino acids. Multiple consecutive amino acids in three alpha-helices in the alkaline phosphatase (EC 3.1.3.1) of Escherichia coli have been replaced with helical sequences from four other sources. Altogether, 12 distinct helical replacements were created, 9 of which retain enzymatic activity. Most short stretches of helical sequence can be replaced with unrelated helical sequences without eliminating enzyme activity. Replacements of the carboxyl half of an alpha-helix are less harmful than those of the amino half, and the two together are synergistic rather than additive. These results are consistent with the hypothesis that proteins originally evolved by the assembly of small functional folding units. Images PMID:2690081

  9. Longest Event-Free Survival without Anticoagulation in a Mechanical Aortic Valve Replacement

    PubMed Central

    Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald

    2016-01-01

    Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922

  10. Mechanical cloak design by direct lattice transformation.

    PubMed

    Bückmann, Tiemo; Kadic, Muamer; Schittny, Robert; Wegener, Martin

    2015-04-21

    Spatial coordinate transformations have helped simplifying mathematical issues and solving complex boundary-value problems in physics for decades already. More recently, material-parameter transformations have also become an intuitive and powerful engineering tool for designing inhomogeneous and anisotropic material distributions that perform wanted functions, e.g., invisibility cloaking. A necessary mathematical prerequisite for this approach to work is that the underlying equations are form invariant with respect to general coordinate transformations. Unfortunately, this condition is not fulfilled in elastic-solid mechanics for materials that can be described by ordinary elasticity tensors. Here, we introduce a different and simpler approach. We directly transform the lattice points of a 2D discrete lattice composed of a single constituent material, while keeping the properties of the elements connecting the lattice points the same. After showing that the approach works in various areas, we focus on elastic-solid mechanics. As a demanding example, we cloak a void in an effective elastic material with respect to static uniaxial compression. Corresponding numerical calculations and experiments on polymer structures made by 3D printing are presented. The cloaking quality is quantified by comparing the average relative SD of the strain vectors outside of the cloaked void with respect to the homogeneous reference lattice. Theory and experiment agree and exhibit very good cloaking performance. PMID:25848021

  11. Mechanical cloak design by direct lattice transformation

    PubMed Central

    Bückmann, Tiemo; Kadic, Muamer; Schittny, Robert; Wegener, Martin

    2015-01-01

    Spatial coordinate transformations have helped simplifying mathematical issues and solving complex boundary-value problems in physics for decades already. More recently, material-parameter transformations have also become an intuitive and powerful engineering tool for designing inhomogeneous and anisotropic material distributions that perform wanted functions, e.g., invisibility cloaking. A necessary mathematical prerequisite for this approach to work is that the underlying equations are form invariant with respect to general coordinate transformations. Unfortunately, this condition is not fulfilled in elastic–solid mechanics for materials that can be described by ordinary elasticity tensors. Here, we introduce a different and simpler approach. We directly transform the lattice points of a 2D discrete lattice composed of a single constituent material, while keeping the properties of the elements connecting the lattice points the same. After showing that the approach works in various areas, we focus on elastic–solid mechanics. As a demanding example, we cloak a void in an effective elastic material with respect to static uniaxial compression. Corresponding numerical calculations and experiments on polymer structures made by 3D printing are presented. The cloaking quality is quantified by comparing the average relative SD of the strain vectors outside of the cloaked void with respect to the homogeneous reference lattice. Theory and experiment agree and exhibit very good cloaking performance. PMID:25848021

  12. The effects of standing balance in anteroposterior and mediolateral directions on knee strengthening in post-total knee replacement.

    PubMed

    Lim, Sung-Joon; Cho, Sung-Hyoun; Nam, Gi-San

    2016-01-01

    [Purpose] The purpose of this study was to examine the association between muscle-strengthening exercises applied to the knee extensor muscles and the maintenance of standing balance in both, the anteroposterior and mediolateral directions in patients who had undergone total knee replacement. [Subjects and Methods] Thirty patients who underwent total knee replacement with bilateral artificial joints participated in this study. During the eight-week study period, the load on the knee extensors was gradually increased, and the standing balance ability was measured by differentiating the anteroposterior and mediolateral directions both, before and after the experimental period. [Results] In both, the anteroposterior and the mediolateral directions, there were statistically significant increases after the eight-week experiment, with a 29% increase in standing balance maintenance in the anteroposterior direction and a 22% increase in the mediolateral direction. [Conclusion] In patients who underwent bilateral total knee replacement, strengthening exercises applied to the knee extensor muscles with gradually increasing load positively affected standing balance in both anteroposterior and mediolateral directions. PMID:26957770

  13. Risk of breast cancer among patients with bioprosthetic or mechanical valve replacement: a population-based study in Sweden.

    PubMed

    Ji, Jianguang; Zöller, Bengt; Giaccia, Amato; Haile, Robert; Sundquist, Jan; Sundquist, Kristina

    2015-11-01

    The association between breast cancer and warfarin is inconclusive as most previous studies examined their association using patients with thromboembolism, whereas thromboembolism itself is a risk factor for cancer. We explored this issue using patients received mechanical heart valves replacement as a proxy for warfarin exposure as these patients need a lifelong warfarin treatment, and compared them with patients received bioprosthesis valves replacement (short-term warfarin treatment) in Sweden between 1987 and 2010. Patients who were operated on for valve replacement were identified from the Swedish Hospital Discharge Registry and linked to the Swedish Cancer Registry to examine the hazard ratios of subsequent breast cancer. A total of 12,242 women were operated on for valve replacement (5481 with mechanical valve and 6401 with bioprosthetic valve). For the entire cohort, the HR of breast cancer was 1.49 (95 % CI 1.09-2.02) among patients with mechanical valve replacement compared to those with bioprosthetic valve replacement. After controlling for a number of confounding factors using propensity score weighting, the HR was 1.69 (95 % CI 1.15-2.47). Our study found that patients with mechanical valve replacement have an increased risk of breast cancer compared to those with bioprosthetic valve replacement. If confirmed, this increased risk should be considered when recommending breast cancer screening for women with mechanical valve replacement. Long-term use of warfarin may explain the observed increase. If so, patients who have used warfarin long-term for other reasons should be studied for a possible increased risk of breast cancer.

  14. Effect of enzyme replacement therapy (ERT) added to Home Mechanical Ventilation (HMV) in Adult Pompe disease.

    PubMed

    Sayeed, Nadia; Sharma, Pooja; Abdelhalim, Manahil; Mukherjee, Rahul

    2015-12-01

    Adult Pompe disease/acid maltase deficiency is an autosomal recessive disorder resulting in accumulation of glycogen in skeletal muscles, leading to myopathy frequently involving respiratory muscles. This involvement can cause respiratory insufficiency that may present as acute hypercapnic respiratory failure. Enzyme replacement therapy (ERT) with alpha - glucosidase alfa, the only disease-specific treatment, has been available as treatment option since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients as well as positive association with survival. We present two cases where addition of ERT to Home Mechanical Ventilation (HMV) showed improvements in lung function and gas exchange that may not be entirely attributable to nocturnal HMV and therefore may further indicate the beneficial role of ERT in conjunction with HMV in Adult Pompe disease. PMID:26740886

  15. Defectivity control of aluminum chemical mechanical planarization in replacement metal gate process of MOSFET

    NASA Astrophysics Data System (ADS)

    Jin, Zhang; Yuling, Liu; Chenqi, Yan; Yangang, He; Baohong, Gao

    2016-04-01

    The replacement metal gate (RMG) defectivity performance control is very challenging in high-k metal gate (HKMG) chemical mechanical polishing (CMP). In this study, three major defect types, including fall-on particles, micro-scratch and corrosion have been investigated. The research studied the effects of polishing pad, pressure, rotating speed, flow rate and post-CMP cleaning on the three kinds of defect, which finally eliminated the defects and achieved good surface morphology. This study will provide an important reference value for the future research of aluminum metal gate CMP. Project supported by the Major National Science and Technology Special Projects (No. 2009ZX02308), the Natural Science Foundation for the Youth of Hebei Province (Nos. F2012202094, F2015202267), and the Outstanding Youth Science and Technology Innovation Fund of Hebei University of Technology (No. 2013010).

  16. Mechanical evaluation of bacterial nanocellulose as an implant material for ear cartilage replacement.

    PubMed

    Nimeskern, Luc; Martínez Ávila, Héctor; Sundberg, Johan; Gatenholm, Paul; Müller, Ralph; Stok, Kathryn S

    2013-06-01

    Bacterial nanocellulose (BNC) is a novel non-degradable biocompatible material that promotes chondrocyte adhesion and proliferation. In this work, its potential use in ear cartilage tissue engineering (TE) is investigated. Firstly, the mechanical properties of native ear cartilage are measured in order to set a preliminary benchmark for ear cartilage replacement materials. Secondly, the capacity of BNC to match these requirements is assessed. Finally, a biofabrication process to produce patient-specific BNC auricular implants is demonstrated. BNC samples (n=78) with varying cellulose content (2.5-15%) were compared using stress-relaxation indentation with human ear cartilage (n=17, from 4 males, aged 49-93 years old). Additionally, an auricle from a volunteer was scanned using a 3T MRI with a spoiled gradient-echo sequence. A negative ear mold was produced from the MRI data in order to investigate if an ear-shaped BNC prototype could be produced from this mold. The results show that the instantaneous modulus Ein, equilibrium modulus Eeq, and maximum stress σmax of the BNC samples are correlated to effective cellulose content. Despite significantly different relaxation kinetics, the Ein, Eeq and σmax of BNC at 14% effective cellulose content reached values equivalent to ear cartilage (for Eeq, BNC: 2.4±0.4MPa and ear cartilage: 3.3±1.3MPa). Additionally, this work shows that BNC can be fabricated into patient-specific auricular shapes. In conclusion, BNC has the capability to reach mechanical properties of relevance for ear cartilage replacement, and can be produced in patient-specific ear shapes. PMID:23611922

  17. Augmentation Improves Human Cadaveric Vertebral Body Compression Mechanics For Lumbar Total Disc Replacement

    PubMed Central

    Yoder, Jonathon H.; Auerbach, Joshua D.; Maurer, Philip M.; Erbe, Erik M.; Entrekin, Dean; Balderston, Richard A.; Bertagnoli, Rudolf; Elliott, Dawn M.

    2012-01-01

    Study Design Cadaveric biomechanical study. Objectives Quantify the effects of vertebral body augmentation on biomechanics under axial compression by a total disc replacement (TDR) implant. Summary of Background Data TDR is a surgical alternative to lumbar spinal fusion to treat degenerative disc disease. Osteoporosis in the adjacent vertebrae to the interposed TDR may lead to implant subsidence or vertebral body fracture. Vertebral augmentation is used to treat osteoporotic compression fracture. The study sought to evaluate whether vertebral augmentation improves biomechanics under TDR axial loading. Methods Forty-five L1-L5 lumbar vertebral body segments with intact posterior elements were used. Peripheral quantitative computed tomography scans were performed to determine bone density, block randomizing specimens by bone density into augmentation and control groups. A semi-constrained keeled lumbar disc replacement device was implanted providing 50% endplate coverage. Vertebral augmentation of 17.6 ± 0.9% vertebral volume fill with Cortoss was performed on augmentation group. All segments underwent axial compression at a rate of 0.2 mm/s to 6mm. Results The load-displacement response for all specimens was non-linear. Subfailure mechanical properties with augmentation were significantly different from control; in all cases the augmented group was 2× higher than control. At failure, the maximum load and stiffness with augmentation was not significantly different from control. The maximum apparent stress and modulus with augmentation were 2× and 1.3× greater than control, respectively. The subfailure stress and apparent modulus with augmentation was moderately correlated with bone density while the control subfailure properties were not. The augmented maximum stress was not correlated with bone density, while the control was weakly correlated. The maximum apparent modulus was moderately correlated with bone density for both the augmented and control groups

  18. Mechanical evaluation of bacterial nanocellulose as an implant material for ear cartilage replacement.

    PubMed

    Nimeskern, Luc; Martínez Ávila, Héctor; Sundberg, Johan; Gatenholm, Paul; Müller, Ralph; Stok, Kathryn S

    2013-06-01

    Bacterial nanocellulose (BNC) is a novel non-degradable biocompatible material that promotes chondrocyte adhesion and proliferation. In this work, its potential use in ear cartilage tissue engineering (TE) is investigated. Firstly, the mechanical properties of native ear cartilage are measured in order to set a preliminary benchmark for ear cartilage replacement materials. Secondly, the capacity of BNC to match these requirements is assessed. Finally, a biofabrication process to produce patient-specific BNC auricular implants is demonstrated. BNC samples (n=78) with varying cellulose content (2.5-15%) were compared using stress-relaxation indentation with human ear cartilage (n=17, from 4 males, aged 49-93 years old). Additionally, an auricle from a volunteer was scanned using a 3T MRI with a spoiled gradient-echo sequence. A negative ear mold was produced from the MRI data in order to investigate if an ear-shaped BNC prototype could be produced from this mold. The results show that the instantaneous modulus Ein, equilibrium modulus Eeq, and maximum stress σmax of the BNC samples are correlated to effective cellulose content. Despite significantly different relaxation kinetics, the Ein, Eeq and σmax of BNC at 14% effective cellulose content reached values equivalent to ear cartilage (for Eeq, BNC: 2.4±0.4MPa and ear cartilage: 3.3±1.3MPa). Additionally, this work shows that BNC can be fabricated into patient-specific auricular shapes. In conclusion, BNC has the capability to reach mechanical properties of relevance for ear cartilage replacement, and can be produced in patient-specific ear shapes.

  19. Directions for computational mechanics in automotive crashworthiness

    NASA Technical Reports Server (NTRS)

    Bennett, James A.; Khalil, T. B.

    1993-01-01

    The automotive industry has used computational methods for crashworthiness since the early 1970's. These methods have ranged from simple lumped parameter models to full finite element models. The emergence of the full finite element models in the mid 1980's has significantly altered the research direction. However, there remains a need for both simple, rapid modeling methods and complex detailed methods. Some directions for continuing research are discussed.

  20. Interaction of Materials and Biology in Total Joint Replacement – Successes, Challenges and Future Directions

    PubMed Central

    Sato, T; Yao, Z; Goodman, SB

    2014-01-01

    Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function. PMID:25541591

  1. Strategic directions and mechanisms in technology transfer

    NASA Technical Reports Server (NTRS)

    Mackin, Robert

    1992-01-01

    An outline summarizing the Working Panel discussion related to strategic directions for technology transfer is presented. Specific topics addressed include measuring success, management of technology, innovation and experimentation in the tech transfer process, integration of tech transfer into R&D planning, institutionalization of tech transfer, and policy/legislative resources.

  2. A mechanism of mineral replacement: isotope tracing in the model system KCl-KBr-H 2O

    NASA Astrophysics Data System (ADS)

    Putnis, Christine V.; Mezger, Klaus

    2004-07-01

    The solid solution-aqueous solution system KCl-KBr-H 2O is used as a model system to determine the mechanism of the replacement process of one crystalline phase by another. A single crystal of KBr was allowed to react with a saturated KCl solution enriched in 40K and the resulting new product phases were analyzed for changes in both anion and K isotope composition, using SEM, EDX, microprobe analysis, mass spectrometry and X-ray diffraction. The results show that the new product, K(Cl,Br), contains elements derived from both the original fluid and solid phases, indicating that both anions and K isotopes are exchanged during the replacement reaction. The interface between the advancing reaction front and the original parent crystal is sharp on a micron scale, showing no reaction profile that could indicate a solid state diffusion mechanism. Macroscopically the new phase is turbid due to the development of porosity that is consistent with a net volume deficit replacement reaction and this porosity may act as an indication that a replacement process has taken place. Single crystal X-ray diffraction patterns show the preservation of the crystallographic orientation during the replacement process. The replacement mechanism is interpreted as a result of a coupled process of dissolution and recrystallization occurring at the fluid-crystal interface.

  3. Direct Replacement of Arbitrary Grid-Overlapping by Non-Structured Grid

    NASA Technical Reports Server (NTRS)

    Kao, Kai-Hsiung; Liou, Meng-Sing

    1994-01-01

    A new approach that uses nonstructured mesh to replace the arbitrarily overlapped structured regions of embedded grids is presented. The present methodology uses the Chimera composite overlapping mesh system so that the physical domain of the flowfield is subdivided into regions which can accommodate easily-generated grid for complex configuration. In addition, a Delaunay triangulation technique generates nonstructured triangular mesh which wraps over the interconnecting region of embedded grids. It is designed that the present approach, termed DRAGON grid, has three important advantages: eliminating some difficulties of the Chimera scheme, such as the orphan points and/or bad quality of interpolation stencils; making grid communication in a fully conservative way; and implementation into three dimensions is straightforward. A computer code based on a time accurate, finite volume, high resolution scheme for solving the compressible Navier-Stokes equations has been further developed to include both the Chimera overset grid and the nonstructured mesh schemes. For steady state problems, the local time stepping accelerates convergence based on a Courant - Friedrichs - Leury (CFL) number near the local stability limit. Numerical tests on representative steady and unsteady supersonic inviscid flows with strong shock waves are demonstrated.

  4. Direct monophasic replacement of fatty acid by DMSA on SPION surface

    NASA Astrophysics Data System (ADS)

    Gogoi, M.; Deb, P.; Vasan, G.; Keil, P.; Kostka, A.; Erbe, A.

    2012-10-01

    Tailoring the surface and understanding the surface characteristics is necessary for biomedical applications of superparamagnetic nanoparticles. In this paper, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared by thermal decomposition of iron nitrate in presence of stearic acid as surfactant. Due to the multilayer organization of surfactant molecules over the nanoparticle surface, the surface potential can be tuned by pH changes and hence the nanoparticles can be made dispersible in nonpolar as well as in polar solvents. We have presented a simple, facile procedure for controlled replacement of stearic acid from maghemite surface and subsequent derivatization by biocompatible dimercaptosuccinic acid (DMSA) to obtain ultrastable hydrophilic nanoparticles with unaltered morphology, phase and properties. The surface chemistry of the functionalized SPIONs was analyzed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) revealing the presence of bound and unbound thiol groups and disulfides, leading to its prolonged stability in aqueous medium. The consequence of spatially selective functionalization on the stability and solubility of surface hydrophilic SPION has also been realized.

  5. Outcome of unilateral ankle arthrodesis and total ankle replacement in terms of bilateral gait mechanics.

    PubMed

    Chopra, Swati; Rouhani, Hossein; Assal, Mathieu; Aminian, Kamiar; Crevoisier, Xavier

    2014-03-01

    Previous studies assessed the outcome of ankle arthrodesis (AA) and total ankle replacement (TAR) surgeries; however, the extent of postoperative recovery towards bilateral gait mechanics (BGM) is unknown. We evaluated the outcome of the two surgeries at least 2 years post rehabilitation, focusing on BGM. 36 participants, including 12 AA patients, 12 TAR patients, and 12 controls were included. Gait assessment over 50 m distance was performed utilizing pressure insoles and 3D inertial sensors, following which an intraindividual comparison was performed. Most spatiotemporal and kinematic parameters in the TAR group were indicative of good gait symmetry, while the AA group presented significant differences. Plantar pressure symmetry among the AA group was also significantly distorted. Abnormality in biomechanical behavior of the AA unoperated, contralateral foot was observed. In summary, our results indicate an altered BGM in AA patients, whereas a relatively fully recovered BGM is observed in TAR patients, despite the quantitative differences in several parameters when compared to a healthy population. Our study supports a biomechanical assessment and rehabilitation of both operated and unoperated sides after major surgeries for ankle osteoarthrosis.

  6. Human Adult Dental Pulp Stem Cells Enhance Poststroke Functional Recovery Through Non-Neural Replacement Mechanisms

    PubMed Central

    Leong, Wai Khay; Henshall, Tanya L.; Arthur, Agnes; Kremer, Karlea L.; Lewis, Martin D.; Helps, Stephen C.; Field, John; Hamilton-Bruce, Monica A.; Warming, Scott; Manavis, Jim; Vink, Robert; Gronthos, Stan

    2012-01-01

    Human adult dental pulp stem cells (DPSCs), derived from third molar teeth, are multipotent and have the capacity to differentiate into neurons under inductive conditions both in vitro and following transplantation into the avian embryo. In this study, we demonstrate that the intracerebral transplantation of human DPSCs 24 hours following focal cerebral ischemia in a rodent model resulted in significant improvement in forelimb sensorimotor function at 4 weeks post-treatment. At this time, 2.3 ± 0.7% of engrafted cells had survived in the poststroke brain and demonstrated targeted migration toward the stroke lesion. In the peri-infarct striatum, transplanted DPSCs differentiated into astrocytes in preference to neurons. Our data suggest that the dominant mechanism of action underlying DPSC treatment that resulted in enhanced functional recovery is unlikely to be due to neural replacement. Functional improvement is more likely to be mediated through DPSC-dependent paracrine effects. This study provides preclinical evidence for the future use of human DPSCs in cell therapy to improve outcome in stroke patients. PMID:23197777

  7. Curative effect of mechanical heart valve replacement and anticoagulant therapy after surgery.

    PubMed

    Chuai, J B; Shi, L; Ma, X Y; Wu, D; Kang, K; Jiang, S L

    2016-01-01

    This study was carried out to determine the curative effect of low-intensity anticoagulant therapy by observing the oral administration of warfarin (anticoagulant therapy) on patients who had undergone mechanical heart valve replacement (MHVR) surgery with subsequent anticoagulation complications. Fifty patients who underwent MHVR in the Second Affiliated Hospital of Harbin Medical University and 52 patients in the Cardiovascular Surgery of Daqing Oilfield General Hospital between January 2013 and January 2016 were selected (63 males and 39 females, ages 26-77 years). They took warfarin after treatment and were followed-up by means of outpatient review and telephone after leaving the hospital. The effect of warfarin and the occurrence of anticoagulation complications were analyzed. The operations lasted 230±106 min, extracorporeal circulation for 110±50 min and aorta occlusion for 82±23 min. During post-operation 3 patients developed skin purpura and one patient died. During follow-up we found 3 cases of anemia caused by excessive menstruation, 4 cases of hematuresis, 3 cases of peated epistaxis, 1 case of gastrointestinal bleeding, 1 case of cerebral hemorrhage, 1 case of embolism in the lower limbs and 1 case of cerebral infarction, although they all improved or were totally cured. Therefore, the incidence of complications can be reduced significantly by the correct administration of warfarin as well as timely monitoring of interference factors after MHVR. PMID:27049085

  8. Relative contributions of design, alignment, and loading variability in knee replacement mechanics.

    PubMed

    Fitzpatrick, Clare K; Clary, Chadd W; Laz, Peter J; Rullkoetter, Paul J

    2012-12-01

    Substantial variation in total knee replacement (TKR) outcomes exists within the patient population. Some of this variability is due to differences in the design of the implanted components and variation in surgical alignment, while other variability is due to differences in the applied forces and torques due to anatomic and physiological differences within a patient population. We evaluated the relative contributions of implant design, surgical alignment, and patient-specific loading variability to overall tibiofemoral joint mechanics to provide insight into which measures can be influenced through design and surgical decisions, and which are inherently dependent on variation within the patient population and should be considered in the robustness of the implant design and surgical procedure. Design, surgical, and loading parameters were assessed using probabilistic finite element methods during simulated stance-phase gait and squat activities. Patient-specific loading was found to be the primary contributor to joint loading and kinematics during low flexion, particularly under conditions of high external loads (for instance, the gait cycle with high internal-external torque), while design and surgical factors, particularly femoral posterior radius and posterior slope of the tibial insert became increasingly important in TKR performance in deeper flexion.

  9. Atrial fibrillation: mechanisms, therapeutics, and future directions.

    PubMed

    Pellman, Jason; Sheikh, Farah

    2015-04-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca(2+) current, various K(+) currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

  10. A compliant-mechanism approach to achieving specific quality of motion in a lumbar total disc replacement

    PubMed Central

    Halverson, Peter A.; Bowden, Anton E.; Howell, Larry L.

    2012-01-01

    Background The current generation of total disc replacements achieves excellent short- and medium-term results by focusing on restoring the quantity of motion. Recent studies indicate that additional concerns (helical axes of motion, segmental torque-rotation behavior) may have important implications in the health of adjacent segments as well as the health of the surrounding tissue of the operative level. The objective of this article is to outline the development, validation, and biomechanical performance of a novel, compliant-mechanism total disc replacement that addresses these concerns by including them as essential design criteria. Methods Compliant-mechanism design techniques were used to design a total disc replacement capable of replicating the moment-rotation response and the location and path of the helical axis of motion. A prototype was evaluated with the use of bench-top testing and single-level cadaveric experiments in flexion-extension, lateral bending, and axial torsion. Results Bench-top testing confirmed that the moment-rotation response of the disc replacement matched the intended design behavior. Cadaveric testing confirmed that the moment-rotation and displacement response of the implanted segment mimicked those of the healthy spinal segment. Conclusions Incorporation of segmental quality of motion into the foundational stages of the design process resulted in a total disc replacement design that provides torque-rotation and helical axis–of–motion characteristics to the adjacent segments and the operative-level facets that are similar to those observed in healthy spinal segments. PMID:25694875

  11. Complementary mechanisms create direction selectivity in the fly.

    PubMed

    Haag, Juergen; Arenz, Alexander; Serbe, Etienne; Gabbiani, Fabrizio; Borst, Alexander

    2016-01-01

    How neurons become sensitive to the direction of visual motion represents a classic example of neural computation. Two alternative mechanisms have been discussed in the literature so far: preferred direction enhancement, by which responses are amplified when stimuli move along the preferred direction of the cell, and null direction suppression, where one signal inhibits the response to the subsequent one when stimuli move along the opposite, i.e. null direction. Along the processing chain in the Drosophila optic lobe, directional responses first appear in T4 and T5 cells. Visually stimulating sequences of individual columns in the optic lobe with a telescope while recording from single T4 neurons, we find both mechanisms at work implemented in different sub-regions of the receptive field. This finding explains the high degree of directional selectivity found already in the fly's primary motion-sensing neurons and marks an important step in our understanding of elementary motion detection. PMID:27502554

  12. Extracorporeal membrane oxygenation treatment of a H7N9-caused respiratory failure patient with mechanical valves replacement history

    PubMed Central

    Qian, Linfeng; Zheng, Junnan; Xu, Hongfei; Shi, Liping; Li, Lanjuan

    2016-01-01

    Abstract Background: Patients with respiratory failure caused by H7N9 may benefit from veno-venous, veno-arterial, and veno-veno-arterial extracorporeal membrane oxygenation (ECMO) support. Case summary: A 55-year-old male patient was suffering from H7N9-caused acute respiratory distress syndrome (ARDS). He had a mechanical mitral and aortic valve replacement surgery and was using warfarin for anticoagulation. After prolonged mechanical ventilation, oxygen saturation was not improved. Veno-veno ECMO was then applied. After 16 days of extracorporeal life support, the patient successfully weaned from ECMO, with relatively good pulmonary recovery. Conclusion: This report demonstrates that ECMO support can help treating life-threatening diseases such as H7N9-associated ARDS. Because of his special mitral and aortic valve replacement surgery history and long duration of mechanical ventilation before ECMO, we report it as a separate case, hoping to provide some reference for ECMO treatment. PMID:27749569

  13. Direct evidence for redundant segmental replacement between multiple 18S rRNA genes in a single Prototheca strain.

    PubMed

    Ueno, Ryohei; Huss, Volker A R; Urano, Naoto; Watabe, Shugo

    2007-11-01

    Informational genes such as those encoding rRNAs are related to transcription and translation, and are thus considered to be rarely subject to lateral gene transfer (LGT) between different organisms, compared to operational genes having metabolic functions. However, several lines of evidence have suggested or confirmed the occurrence of LGT of DNA segments encoding evolutionarily variable regions of rRNA genes between different organisms. In the present paper, we show, for the first time to our knowledge, that variable regions of the 18S rRNA gene are segmentally replaced by multiple copies of different sequences in a single strain of the green microalga Prototheca wickerhamii, resulting in at least 17 genotypes, nine of which were actually transcribed. Recombination between different 18S rRNA genes occurred in seven out of eight variable regions (V1-V5 and V7-V9) of eukaryotic small subunit (SSU) rRNAs. While no recombination was observed in V1, one to three different recombination loci were demonstrated for the other regions. Such segmental replacement was also implicated for helix H37, which is defined as V6 of prokaryotic SSU rRNAs. Our observations provide direct evidence for redundant recombination of an informational gene, which encodes a component of mature ribosomes, in a single strain of one organism.

  14. Nucleotide replacement at two sites can be directed by modified single-stranded oligonucleotides in vitro and in vivo.

    PubMed

    Agarwal, Sheba; Gamper, Howard B; Kmiec, Eric B

    2003-01-01

    Studies involving the alteration of DNA sequences by modified single-stranded oligonucleotides in vitro and in vivo have revealed potential applications for functional genomics. Repair of a replacement, deletion, or insertion mutation has already been achieved with molecules having lengths between 25 and 74 bases. But, other vector parameters still remain to be explored. Here, the position of the single base in the vector directing the alteration was examined and the optimal site was found to be at or near the center of the vector. If that position is staggered 3' or 5', the frequencies of gene repair in vitro decreases. The potential of a single vector to direct two nucleotide changes at a specific site in a target sequence was also examined. Both targeted bases are corrected together at the same frequency if the sites are separated by three bases, but conversion linkage decreases precipitously when the distance is expanded to 15 and 27 nucleotides, respectively. These results suggest that single oligonucleotides can be used to direct nucleotide exchange at two independent sites, a reaction characteristic that may be useful for many genomics applications.

  15. Bioprosthetic versus mechanical prostheses for valve replacement in end-stage renal disease patients: systematic review and meta-analysis

    PubMed Central

    Zhao, Dong Fang; Zhou, Jessie J.; Karagaratnam, Aran; Phan, Steven; Yan, Tristan D.

    2016-01-01

    Background Patients with end-stage renal disease (ESRD) indicated for dialysis are increasingly requiring cardiac valve surgery. The choice of bioprosthetic or mechanic valve prosthesis for such patients requires careful risk assessment. A systematic review and meta-analysis was performed to assess current evidence available. Methods A comprehensive search from six electronic databases was performed from their inception to February 2015. Results from patients with ESRD undergoing cardiac surgery for bioprosthetic or mechanical valve replacement were identified. Results Sixteen studies with 8,483 patients with ESRD undergoing cardiac valve replacement surgery were included. No evidence of publication bias was detected. Prior angioplasty by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery was significantly higher in the bioprosthetic group compared to the mechanical group (16.0% vs. 12.0%, P=0.04); all other preoperative baseline patient characteristics were similar. There was no significant difference in 30-day mortality or all-cause mortality between the two comparisons. Compared with the mechanical group, the frequency of bleeding (5.2% vs. 6.4%, P=0.04) and risk of thromboembolism (2.7% vs. 12.8%, P=0.02) were significantly lower in the bioprosthetic group. There were similar rates of reoperation and valve endocarditis. Conclusions The present study demonstrated that patients with ESRD undergoing bioprosthetic or mechanical valve replacement had similar mid-long term survival. The bioprosthetic group had lower rates of bleeding and thromboembolism. Further studies are required to differentiate the impact of valve location. The presented results may be applicable for ESRD patients requiring prosthetic valve replacement. PMID:27162649

  16. Recovery Act: Hydroelectric Facility Improvement Project - Replacement of Current Mechanical Seal System with Rope Packing System

    SciTech Connect

    Stephens, Jessica D.

    2013-05-29

    had an IMD installed. This further study of facilities revealed that the implementation of the project as originally described, while proving the benefits described in the original grant application, would likely intensify sand intake. Increased sand intake would lead to an increase in required shutdowns for maintenance and more rapid depreciation of key equipment which would result in a loss of generation capacity. A better solution to the problem, one that continued to meet the criteria for the original grant and ARRA standards, was developed. A supporting day trip was planned to visit other facilities located on the Arkansas River to determine how they were coping with the same strong amounts of sand, silt, and debris. Upon returning from the trip to other Arkansas River facilities it was extremely clear what direction to go in order to most efficiently address the issue of generator capacity and efficiency. Of the plants visited on the Arkansas River, every one of them was running what is called a rope packing shaft sealing system as opposed to mechanical shaft seals, which the facility was running. Rope packing is a time proven sealing method that has been around for centuries. It has proved to perform very well in dirty water situations just like that of the Arkansas River. In April of 2012 a scope change proposal was submitted to the DOE for approval. In August of 2012 the City received word that the change of scope had been approved. Plans were immediately set in motion to begin the conversion from mechanical seals to a packing box at the facility. Contractors arrived on October 1st, 2012 and the project team began unwatering the unit for disassembly. The seal conversion was completed on February 29th, 2013 with start-up of the unit. Further testing and adjusting was done throughout the first two weeks of March.

  17. Analysis of mixed lubrication mechanism in metal-on-metal hip joint replacements.

    PubMed

    Jin, Z M

    2002-01-01

    A simple mixed lubrication model has been developed to predict the asperity contact and wear for the metal-on-metal bearing couple for total hip joint replacements. It has been shown that the femoral head radius has a large effect on the predicted asperity contact and wear depending on the lubrication regime. An increase in the femoral head radius can lead to an increase in wear under a predominantly boundary lubrication regime, but this trend can be reversed under a mixed lubrication regime towards fluid film lubrication. These observations are consistent with the recent experimental findings from hip simulator studies by Smith and co-workers.

  18. Multiscale Homogenization Theory: An Analysis Tool for Revealing Mechanical Design Principles in Bone and Bone Replacement Materials

    NASA Astrophysics Data System (ADS)

    Hellmich, Christian; Fritsch, Andreas; Dormieux, Luc

    Biomimetics deals with the application of nature-made "design solutions" to the realm of engineering. In the quest to understand mechanical implications of structural hierarchies found in biological materials, multiscale mechanics may hold the key to understand "building plans" inherent to entire material classes, here bone and bone replacement materials. Analyzing a multitude of biophysical hierarchical and biomechanical experiments through homogenization theories for upscaling stiffness and strength properties reveals the following design principles: The elementary component "collagen" induces, right at the nanolevel, the mechanical anisotropy of bone materials, which is amplified by fibrillar collagen-based structures at the 100-nm scale, and by pores in the micrometer-to-millimeter regime. Hydroxyapatite minerals are poorly organized, and provide stiffness and strength in a quasi-brittle manner. Water layers between hydroxyapatite crystals govern the inelastic behavior of the nanocomposite, unless the "collagen reinforcement" breaks. Bone replacement materials should mimic these "microstructural mechanics" features as closely as possible if an imitation of the natural form of bone is desired (Gebeshuber et al., Adv Mater Res 74:265-268, 2009).

  19. Complementary mechanisms create direction selectivity in the fly

    PubMed Central

    Haag, Juergen; Arenz, Alexander; Serbe, Etienne; Gabbiani, Fabrizio; Borst, Alexander

    2016-01-01

    How neurons become sensitive to the direction of visual motion represents a classic example of neural computation. Two alternative mechanisms have been discussed in the literature so far: preferred direction enhancement, by which responses are amplified when stimuli move along the preferred direction of the cell, and null direction suppression, where one signal inhibits the response to the subsequent one when stimuli move along the opposite, i.e. null direction. Along the processing chain in the Drosophila optic lobe, directional responses first appear in T4 and T5 cells. Visually stimulating sequences of individual columns in the optic lobe with a telescope while recording from single T4 neurons, we find both mechanisms at work implemented in different sub-regions of the receptive field. This finding explains the high degree of directional selectivity found already in the fly’s primary motion-sensing neurons and marks an important step in our understanding of elementary motion detection. DOI: http://dx.doi.org/10.7554/eLife.17421.001 PMID:27502554

  20. Star GK Bileaflet Mechanical Valve Prosthesis-Patient Mismatch After Mitral Valve Replacement: A Chinese Multicenter Clinical Study

    PubMed Central

    Cao, Hua; Qiu, Zhihuang; Chen, Liangwan; Chen, Daozhong; Chen, Qiang

    2015-01-01

    Background The aim of this study was to investigate the incidence and immediate and mid-term effects of heart valve prosthesis-patient mismatch (PPM) after mitral valve replacement using the GK bileaflet mechanical valve. Material/Methods A total of 493 cases of mechanical mitral valve replacement were performed in the departments of cardiac surgery in 7 hospitals from January 2000 to January 2008. The patients included 142 men and 351 women ages 21 to 67 (average age, 48.75). The patients were followed for 3 years after surgery. The effective orifice area index (EOAI), ≤1.2 cm2/m2, was detected during the follow-up period and was defined as PPM. The patients were assigned to either the PPM group or the non-PPM group. Finally, the preoperative, perioperative and postoperative indexes of the 2 groups of patients were compared. Results A total of 157 patients had PPM 3 years after surgery. The incidence of PPM was 31.84%. Sixty-three patients in the PPM group received a 25-mm GK bileaflet valve (40.13%), 82 received a 27-mm valve (52.23%), and 12 (7.64%) received a 29-mm valve. There were significant differences in length of intensive care unit stay, duration of ventilator use, length of hospitalization, body surface area, EOAI, mean transmitral pressure gradient, and pulmonary artery pressure between the PPM and non-PPM group (P<0.05). There was a significant difference between preoperative and postoperative pulmonary artery pressures among non-PPM patients (P<0.05); however, there was no statistical difference in preoperative and postoperative pulmonary artery pressures among patients with PPM (P>0.05). Conclusions PPM after mitral valve replacement influences postoperative hemodynamics. Thus, larger-sized GK bileaflet mechanical valves are often used to reduce the risk of PPM. PMID:26313311

  1. Functional assessment of toad parotoid macroglands: a study based on poison replacement after mechanical compression.

    PubMed

    Jared, Simone G S; Jared, Carlos; Egami, Mizue I; Mailho-Fontana, Pedro L; Rodrigues, Miguel T; Antoniazzi, Marta M

    2014-09-01

    Toads have a pair of parotoid macroglands behind the eyes that secrete poison used in passive defence against predators. These macroglands are composed of juxtaposed alveoli, each one bearing a syncytial gland, all connected to the exterior by ducts. When the parotoids are bitten, the poison is expelled on the predator oral mucosa in the form of jets, causing several pharmacological actions. After poison release, the empty secretory syncytia immediately collapse in the interior of their respective alveoli and gradually start refilling. After parotoid manual compression, simulating a predator's bite, we studied, by means of morphological methods, the replacement of the poison inside the alveoli. The results showed that after compression, a considerable number of alveoli remained intact. In the alveoli that were effectively affected the recovery occurs in different levels, from total to punctual and often restrict to some areas of the syncytia. The severely affected alveoli seem not recover their original functional state. The fact that only a part of the parotoid alveoli is compressed during an attack seems to be crucial for toad survival, since the amphibian, after being bitten by a predator, do not lose all its poison stock, remaining protected in case of new attacks. PMID:24911375

  2. Evaluating knee replacement mechanics during ADL with PID-controlled dynamic finite element analysis.

    PubMed

    Fitzpatrick, Clare K; Baldwin, Mark A; Clary, Chadd W; Maletsky, Lorin P; Rullkoetter, Paul J

    2014-01-01

    Validated computational knee simulations are valuable tools for design phase development of knee replacement devices. Recently, a dynamic finite element (FE) model of the Kansas knee simulator was kinematically validated during gait and deep flexion cycles. In order to operate the computational simulator in the same manner as the experiment, a proportional-integral-derivative (PID) controller was interfaced with the FE model to control the quadriceps actuator excursion and produce a target flexion profile regardless of implant geometry or alignment conditions. The controller was also expanded to operate multiple actuators simultaneously in order to produce in vivo loading conditions at the joint during dynamic activities. Subsequently, the fidelity of the computational model was improved through additional muscle representation and inclusion of relative hip-ankle anterior-posterior (A-P) motion. The PID-controlled model was able to successfully recreate in vivo loading conditions (flexion angle, compressive joint load, medial-lateral load distribution or varus-valgus torque, internal-external torque, A-P force) for deep knee bend, chair rise, stance-phase gait and step-down activities.

  3. Mechanical failure of metal-polyethylene sandwich liner in metal-on-metal total hip replacement.

    PubMed

    Oshima, Yasushi; Fetto, Joseph F

    2015-01-01

    Metal-on-metal had been proposed as an optimal articulation in THRs, however, many monoblock prostheses have been recalled in the USA because of significant high rates of early failure. Metal-on-metal prostheses had been implanted in our institution, and this is a case history of a single patient, in whom metal-on-metal THRs with different femoral sizes of heads were implanted. A 57-year-old female patient underwent bilateral total hip replacements with metal-on-metal prostheses using metal-polyethylene "sandwich" liners 9 years ago on the right side and 7 years ago on the left side respectively. The only difference in both sides was the femoral head diameter of 28 mm in right and 34 mm in left. Seven years after the left surgery, the acetabular liner was dissociated, however, metallosis was not detected. Although the larger femoral head was thought to increase hip joint stability, it dictated a reduction in polyethylene thickness in this prosthesis design, and it was 4 mm in the left hip. Recently, metal-on-metal articulations are thought not to be optimal for hip joint bearing surface, however, this clinical failure was due to the polyethylene thickness and quality.

  4. Effect of ultra-high molecular weight polyethylene thickness on contact mechanics in total knee replacement.

    PubMed

    El-Deen, M; García-Fiñana, M; Jin, Z M

    2006-10-01

    One of the important design parameters in current knee joint replacements is the thickness of the ultra-high molecular weight polyethylene (UHMWPE) tibial insert, yet there is no clear definition of the upper limit of the 'thick' polyethylene insert. Using one design knee implant and subjecting it to the physiological loads encountered throughout the gait cycle, measurements of the lengths of contact imprints generated were compared with the corresponding theoretical predictions for different insert thicknesses under the same applied load. Multiple regression analysis was applied to test whether the dimensions of contact imprints are influenced by UHMWPE thickness. Good agreement was obtained between the theoretical predictions and the experimental measurements of the dimensions of contact imprints when the knee was at 60 degrees flexion. Therefore, it was possible to estimate the contact pressure at the articulating surface using the theoretical model. Contact imprint dimensions increased with increasing applied load. Statistical analysis of the experimental data revealed that, at 0 degree flexion, the overall imprint dimensions increased as the UHMWPE thickness increased from 8 to 20 mm. However, the increment was not significant when the thickness subinterval 10-15 mm was considered. Furthermore, at 60 degrees flexion, thickness was not a significant factor for the overall imprint dimensions. No evidence was found from the data to suggest that an increment in polyethylene thickness over 10 mm would significantly reduce the contact imprint dimensions. These findings suggest that thicker inserts can be avoided, as they require unnecessary bone resection.

  5. Functional assessment of toad parotoid macroglands: a study based on poison replacement after mechanical compression.

    PubMed

    Jared, Simone G S; Jared, Carlos; Egami, Mizue I; Mailho-Fontana, Pedro L; Rodrigues, Miguel T; Antoniazzi, Marta M

    2014-09-01

    Toads have a pair of parotoid macroglands behind the eyes that secrete poison used in passive defence against predators. These macroglands are composed of juxtaposed alveoli, each one bearing a syncytial gland, all connected to the exterior by ducts. When the parotoids are bitten, the poison is expelled on the predator oral mucosa in the form of jets, causing several pharmacological actions. After poison release, the empty secretory syncytia immediately collapse in the interior of their respective alveoli and gradually start refilling. After parotoid manual compression, simulating a predator's bite, we studied, by means of morphological methods, the replacement of the poison inside the alveoli. The results showed that after compression, a considerable number of alveoli remained intact. In the alveoli that were effectively affected the recovery occurs in different levels, from total to punctual and often restrict to some areas of the syncytia. The severely affected alveoli seem not recover their original functional state. The fact that only a part of the parotoid alveoli is compressed during an attack seems to be crucial for toad survival, since the amphibian, after being bitten by a predator, do not lose all its poison stock, remaining protected in case of new attacks.

  6. The effects of a low international normalized ratio on thromboembolic and bleeding complications in patients with mechanical mitral valve replacement

    PubMed Central

    2014-01-01

    Background Mechanical heart valve replacement has an inherent risk of thromboembolic events (TEs). Current guidelines recommend an international normalized ratio (INR) of at least 2.5 after mechanical mitral valve replacement (MVR). This study aimed to evaluate the effects of a low INR (2.0–2.5) on thromboembolic and bleeding complications in patients with mechanical MVR on warfarin therapy. Methods One hundred and thirty-five patients who underwent mechanical MVR were enrolled in this study. The end points of this study were defined as TEs (valve thrombosis, transient ischemic attack, stroke) and bleeding (all minor and major bleeding) complications. Patients were followed up for a mean of 39.6 months and the mean INR of the patients was calculated. After data collection, patients were divided into 3 groups according to their mean INR, as follows: group 1 (n = 34), INR <2.0; group 2 (n = 49), INR 2.0–2.5; and group 3 (n = 52), INR >2.5. Results A total of 22 events (10 [7.4%] thromboembolic and 12 [8.8%] bleeding events) occurred in the follow-up period. The mean INR was an independent risk factor for the development of TEs. Mean INR and neurological dysfunction were independent risk factors for the development of bleeding events. A statistically significant positive correlation was found between the log mean INR and all bleeding events, and a negative correlation was found between the log mean INR and all TEs. The total number of events was significantly lower in group 2 than in groups 1 and 3 (P = 0.036). Conclusions This study showed that a target INRs of 2.0–2.5 are acceptable for preventing TEs and safe in terms of bleeding complications in patients with mechanical MVR. PMID:24885719

  7. Mechanism of directional emission from a peanut-shaped microcavity

    SciTech Connect

    Shu Fangjie; Zou Changling; Sun Fangwen; Xiao Yunfeng

    2011-05-15

    Collimated directional emission is essentially required for an asymmetric resonant cavity. In this paper, we theoretically investigate a type of peanut-shaped microcavity which can support highly directional emission with a beam divergence as small as 2.5 deg. The mechanism of the collimated emission of this type of peanut-shaped microcavity is explained with a short-term ray trajectory. Moreover, the explanations are also confirmed by a numerical wave simulation. This extremely narrow divergence of the emission holds great potential in highly collimated lasing from on-chip microcavities.

  8. A directional nucleation-zipping mechanism for triple helix formation.

    PubMed

    Alberti, Patrizia; Arimondo, Paola B; Mergny, Jean-Louis; Garestier, Thérèse; Hélène, Claude; Sun, Jian-Sheng

    2002-12-15

    A detailed kinetic study of triple helix formation was performed by surface plasmon resonance. Three systems were investigated involving 15mer pyrimidine oligonucleotides as third strands. Rate constants and activation energies were validated by comparison with thermodynamic values calculated from UV-melting analysis. Replacement of a T.A base pair by a C.G pair at either the 5' or the 3' end of the target sequence allowed us to assess mismatch effects and to delineate the mechanism of triple helix formation. Our data show that the association rate constant is governed by the sequence of base triplets on the 5' side of the triplex (referred to as the 5' side of the target oligopurine strand) and provides evidence that the reaction pathway for triple helix formation in the pyrimidine motif proceeds from the 5' end to the 3' end of the triplex according to the nucleation-zipping model. It seems that this is a general feature for all triple helices formation, probably due to the right-handedness of the DNA double helix that provides a stronger base stacking at the 5' than at the 3' duplex-triplex junction. Understanding the mechanism of triple helix formation is not only of fundamental interest, but may also help in designing better triple helix-forming oligonucleotides for gene targeting and control of gene expression.

  9. Mechanism for direct graphite-to-diamond phase transition

    PubMed Central

    Xie, Hongxian; Yin, Fuxing; Yu, Tao; Wang, Jian-Tao; Liang, Chunyong

    2014-01-01

    Using classical molecular dynamics with a more reliable reactive LCBOPII potential, we have performed a detailed study on the direct graphite-to-diamond phase transition. Our results reveal a new so-called “wave-like buckling and slipping” mechanism, which controls the transformation from hexagonal graphite to cubic diamond. Based on this mechanism, we have explained how polycrystalline cubic diamond is converted from hexagonal graphite, and demonstrated that the initial interlayer distance of compressed hexagonal graphite play a key role to determine the grain size of cubic diamond. These results can broaden our understanding of the high pressure graphite-to-diamond phase transition. PMID:25088720

  10. Mechanism for direct graphite-to-diamond phase transition.

    PubMed

    Xie, Hongxian; Yin, Fuxing; Yu, Tao; Wang, Jian-Tao; Liang, Chunyong

    2014-08-04

    Using classical molecular dynamics with a more reliable reactive LCBOPII potential, we have performed a detailed study on the direct graphite-to-diamond phase transition. Our results reveal a new so-called "wave-like buckling and slipping" mechanism, which controls the transformation from hexagonal graphite to cubic diamond. Based on this mechanism, we have explained how polycrystalline cubic diamond is converted from hexagonal graphite, and demonstrated that the initial interlayer distance of compressed hexagonal graphite play a key role to determine the grain size of cubic diamond. These results can broaden our understanding of the high pressure graphite-to-diamond phase transition.

  11. The effect of lubricant constituents on lubrication mechanisms in hip joint replacements.

    PubMed

    Nečas, David; Vrbka, Martin; Urban, Filip; Křupka, Ivan; Hartl, Martin

    2015-03-01

    The aim of the present paper is to provide a novel experimental approach enabling to assess the thickness of lubricant film within hip prostheses in meaning of the contribution of particular proteins. Thin film colorimetric interferometry was combined with fluorescent microscopy finding that a combination of optical methods can help to better understand the interfacial lubrication processes in hip replacements. The contact of metal femoral head against a glass disc was investigated under various operating conditions. As a test lubricant, the saline solution containing the albumin and γ-globulin in a concentration 2:1 was employed. Two different mean speeds were applied, 5.7 and 22mm/s, respectively. The measurements were carried out under pure rolling, partial negative and partial positive sliding conditions showing that kinematic conditions substantially affects the formation of protein film. Under pure rolling conditions, an increasing tendency of lubricant film independently on rolling speed was detected, while the total thickness of lubricant film can be attributed mainly to albumin. When the ball was faster than the disc (negative sliding), a very thin lubricant film was observed for lower speed with no significant effect of particular proteins. The increase in sliding speed led to the increase of film thickness mainly caused due to the presence of γ-globulin. On the contrary, when the disc was faster than the ball (positive sliding), the film formation was very complex and time dependent while both of the studied proteins have shown any qualitative change during the test, however the effect of albumin seems to be much more important. Since a very good agreement of the results was obtained, it can be concluded that the approach consisting of two optical methods can provide the fundamental information about the lubricant film formation in meaning of particular proteins while the simultaneous presence of other constituents in model synovial fluid. PMID

  12. Direct and indirect coupling mechanisms in a chiral plasmonic system

    NASA Astrophysics Data System (ADS)

    Wang, Yongkai; Wen, Xiaojing; Qu, Yu; Fu, Tong; Zhang, Zhongyue

    2016-10-01

    Artificial chiral plasmonic nanostructures (ACPNs) are widely studied and used in biological monitoring, analytical chemistry, and negative-refractive-index media. The mechanism of direct coupling between two twist metal nanorods has been obtained in usual ACPNs. In this work, we proposed a nanosystem of twist nanorods separated by a metal film (TNMF). By analyzing the charge distributions, a new indirect coupling mechanism is found. According to the equivalent LC resonant circuits, gold nanorods on the two sides of the gold film can be regarded as a receiver and an emitter. These components enhanced transmittance and provided direct and indirect coupling mechanisms for the circular dichroism (CD). The direct coupling mode cannot be explained by impedance matching and can be tuned monotonously by monotonously varying geometric dimensions. However, the CD signal of indirect coupling can be explained by impedance matching and can be tuned to its maximum by varying geometric dimensions when the impedances of both sides of the gold film match. These results can help design novel chiral optical structures and promote combined applications between photons and electrons when a gold film is powered on.

  13. Replace Double Replacement

    NASA Astrophysics Data System (ADS)

    Martin, R. Bruce

    1999-01-01

    Reactions described as double replacements in high school texts are poorly described by this designation. The driving force for such reactions is precipitation of a solid derived from ions in solution or the production of water in acid-base reactions.

  14. Directed triadic closure and edge deletion mechanism induce asymmetry in directed edge properties

    NASA Astrophysics Data System (ADS)

    Brot, Hilla; Muchnik, Lev; Louzoun, Yoram

    2015-01-01

    Many directed real world networks, such as the WWW, genetic regulation networks and economic networks exhibit significant differences between the properties of the incoming and outgoing edges, while the differences exhibited by other networks, such as Social Netw. are far more limited. This phenomenon is most evident in the differences between the distributions of incoming and outgoing degrees and direct clustering coefficients. There is currently no generic network generation model that would reproduce and tune these observed dissimilarities. We propose and empirically validate a simple and realistic model that can explain the emergence of the dissimilarities between the incoming and outgoing network degrees and clustering coefficients by combining directed triadic closure, random edge addition and directed edge removal. Surprisingly, we find that the difference between in and out degree distributions is attributed to asymmetries in the edge removal, highlighting the neglected yet crucial importance of edge removal mechanisms to the static and dynamic properties of real world networks. The model is governed by only two parameters: the first tunes the randomness of the edge addition mechanism, while the second controls the difference between the in and out degrees. The combination of these parameters reproduces the observed variety of directed degree distributions and clustering coefficients. Further comparisons of the model's microscopic dynamics against the empirically observed evolution of real world social network confirms that while quite simple, the model properly describes both the edge addition and deletion processes in directed networks.

  15. Axial ligand replacement mechanism in heme transfer from streptococcal heme-binding protein Shp to HtsA of the HtsABC transporter.

    PubMed

    Ran, Yanchao; Malmirchegini, G Reza; Clubb, Robert T; Lei, Benfang

    2013-09-17

    The heme-binding protein Shp of Group A Streptococcus rapidly transfers its heme to HtsA, the lipoprotein component of the HtsABC transporter, in a concerted two-step process with one kinetic phase. Heme axial residue-to-alanine replacement mutant proteins of Shp and HtsA (Shp(M66A), Shp(M153A), HtsA(M79A), and HtsA(H229A)) were used to probe the axial displacement mechanism of this heme transfer reaction. Ferric Shp(M66A) at high pH and Shp(M153A) have a pentacoordinate heme iron complex with a methionine axial ligand. ApoHtsA(M79A) efficiently acquires heme from ferric Shp but alters the reaction mechanism to two kinetic phases from a single phase in the wild-type protein reactions. In contrast, apoHtsA(H229A) cannot assimilate heme from ferric Shp. The conversion of pentacoordinate holoShp(M66A) into pentacoordinate holoHtsA(H229A) involves an intermediate, whereas holoHtsA(H229A) is directly formed from pentacoordinate holoShp(M153A). Conversely, apoHtsA(M79A) reacts with holoShp(M66A) and holoShp(M153A) in mechanisms with one and two kinetic phases, respectively. These results imply that the Met79 and His229 residues of HtsA displace the Met66 and Met153 residues of Shp, respectively. Structural docking analysis supports this mechanism of the specific axial residue displacement. Furthermore, the rates of the cleavage of the axial bond in Shp in the presence of a replacing HtsA axial residue are greater than that in the absence of a replacing HtsA axial residue. These findings reveal a novel heme transfer mechanism of the specific displacement of the Shp axial residues with the HtsA axial residues and the involvement of the HtsA axial residues in the displacement.

  16. How much, and by what mechanisms, does growth hormone replacement improve the quality of life in GH-deficient adults?

    PubMed

    Chrisoulidou, A; Kousta, E; Beshyah, S A; Robinson, S; Johnston, D G

    1998-07-01

    The majority of studies (but not all) have demonstrated that adults with hypopituitarism of both childhood and adult onset have a diminished quality of life (QOL) in comparison with the normal population. Reductions in physical and mental energy, dissatisfaction with body image and poor memory have been reported most consistently. A specific role for growth hormone (GH) deficiency, as opposed to multiple pituitary hormone deficiency, has been observed for the memory deficit, which extends to both short- and long-term memory. Comparisons with normal siblings have confirmed the reduced QOL, although differences have been small. There is less consensus for a reduction in QOL when hypopituitary subjects are compared with patients with other chronic diseases, with studies supporting (in comparison with diabetics) and refuting (in comparison with patients following mastoid surgery) the reduction in QOL. GH replacement in adults has improved QOL, particularly in the domains of energy level and self-esteem, and memory has improved. The social impact of these changes may be considerable, with patients requiring fewer days' sick leave. A major placebo effect is present, however, and neutral results as well as positive have been reported in placebo-controlled trials. Where a positive effect has been observed, it has been more likely to occur in patients with a low QOL at the outset. It is otherwise impossible to predict at the outset those who will benefit from GH replacement. GH treatment has effects on body composition, exercise capacity, muscle strength, total body water and intermediary metabolism which would be expected to improve QOL. Replacement therapy also has side-effects, and it is the variable balance of the positive and negative effects, coupled with the difficulties of measuring QOL, which have led to the disparate results in the literature. There is probably also a true inter-individual variation, although the mechanisms of this are currently unknown.

  17. Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

    PubMed Central

    Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

    2014-01-01

    Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han

  18. The contact mechanics and occurrence of edge loading in modular metal-on-polyethylene total hip replacement during daily activities.

    PubMed

    Hua, Xijin; Li, Junyan; Jin, Zhongmin; Fisher, John

    2016-06-01

    The occurrence of edge loading in hip joint replacement has been associated with many factors such as prosthetic design, component malposition and activities of daily living. The present study aimed to quantify the occurrence of edge loading/contact at the articulating surface and to evaluate the effect of cup angles and edge loading on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR) during different daily activities. A three-dimensional finite element model was developed based on a modular MoP bearing system. Different cup inclination and anteversion angles were modelled and six daily activities were considered. The results showed that edge loading was predicted during normal walking, ascending and descending stairs activities under steep cup inclination conditions (≥55°) while no edge loading was observed during standing up, sitting down and knee bending activities. The duration of edge loading increased with increased cup inclination angles and was affected by the cup anteversion angles. Edge loading caused elevated contact pressure at the articulating surface and substantially increased equivalent plastic strain of the polyethylene liner. The present study suggested that correct positioning the component to avoid edge loading that may occur during daily activities is important for MoP THR in clinical practice.

  19. Recycled reinforced plastics as replacement for coremat and plywood cores in sandwich laminates: A comparison of mechanical properties

    SciTech Connect

    Pettersson, J.; Nilsson, P.

    1996-11-01

    A sprayable formulation, here called a scrap-mix, based on polyester resin, fillers and reground RP-scrap has been compared in mechanical tests to core materials used in marine applications. The tests have been carried out on sandwich laminates with glassfiber-reinforced polyester skins on various cores. The results indicate that significant increase in strength can be achieved for sandwich laminates when plywood is replaced with the scrap-mix. Flexural strength, here measured by three-point bending, is more than doubled when replacing 9 mm plywood-core with equal thickness of a scrap-mix core. When compared to Firet coremat, the increase in strength when using a scrap-mix core is in the region of 5% for a single layer (3 mm) coremat, and 15% when compared to a double layer (6 mm) of coremat. A test for screw-holding strength was carried out on similar samples. Depending on the type of screws the screw-holding strength was from 40% up to 60% higher for the scrap-mix laminates as compared to plywood laminates. After aging samples in distilled water at 40 C, the difference increased up to 100% after one week.

  20. Mechanical Behavior and Microstructure Characteristics of Directionally Solidified TWIP Steel

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Wang, Kun; Man, Jianfeng; Yang, Jianzhong; Han, Fusheng

    2016-07-01

    The mechanical behavior and microstructure characteristics of three high Mn austenitic steels prepared by directional solidification at withdrawal rates of 60, 120, and 240 μm s-1 were investigated and compared with common TWIP steel with equiaxed grains. For each steel, the Hollomon analysis, differential C-J analysis, and modified C-J analysis as an alternative method to describe the work-hardening behavior were studied. The directionally solidified samples (DS samples) exhibited higher mechanical properties along the axis, five stages (A, B, C, D, and E) divided on the plot of stain hardening rate vs true strain, and a more stable and uniform deformation feature with larger strain-hardening coefficients when the true strain is over 0.25, in comparison with the common TWIP steel. The modified C-J analysis was found to be the best one for revealing the strain-hardening behavior characterized by several different stages with a definite work-hardening exponent n. In the case of DS samples, the dendrite spacings increase but the morphology becomes simple when decreasing the withdrawal rate. The larger volume fraction of twins and prevalent activation of twin systems, together with the fragmentations of the original grains in a sample solidified at a withdrawal rate of 120 μm s-1, lead to the best mechanical behavior in a medium-to-large strain range.

  1. Directed Replacement of Mt a by Mt a-1 Effects a Mating Type Switch in Neurospora Crassa

    PubMed Central

    Chang, S.; Staben, C.

    1994-01-01

    To test the functions of a mating type genes, we developed an efficient strategy to select transformants of Neurospora crassa in which resident A mating type DNA was replaced by cloned DNA from the mt a idiomorph. Cloned a idiomorphic DNA could specify all functions, including fertility, of a mating type, but only when it replaced A DNA at the mating type locus. Only the mt a-1 region of the a idiomorph was necessary in order to specify a mating type. Gene replacement events involved the homologous sequences flanking the unique mating type idiomorphic DNA, resulting in apparently isogenic a and A strains. These isogenic strains were fertile when crossed with one another, indicating that no determinants outside the transforming DNA are necessary for fertility as a and that no host sequences of A strains interfere with fertility as a. One a replacement strain bore a duplication of the transforming mt a-1 and hph DNA. The duplication strain had unexpected properties. Although mating type segregated 1:1 in crosses of this strain to A, the duplicated regions were efficiently altered during the sexual process to generate a single copy in the progeny. No progeny were recovered that had undergone RIP (repeat induced point mutation) sufficient to inactivate the mt a-1 gene. We infer that the mt a-1 gene is necessary and sufficient to specify a mating type identity in all vegetative and sexual activities. Mt a-1 may also play an essential role in ascosporogenesis after fertilization. PMID:8001795

  2. The computational structural mechanics testbed architecture. Volume 2: Directives

    NASA Technical Reports Server (NTRS)

    Felippa, Carlos A.

    1989-01-01

    This is the second of a set of five volumes which describe the software architecture for the Computational Structural Mechanics Testbed. Derived from NICE, an integrated software system developed at Lockheed Palo Alto Research Laboratory, the architecture is composed of the command language (CLAMP), the command language interpreter (CLIP), and the data manager (GAL). Volumes 1, 2, and 3 (NASA CR's 178384, 178385, and 178386, respectively) describe CLAMP and CLIP and the CLIP-processor interface. Volumes 4 and 5 (NASA CR's 178387 and 178388, respectively) describe GAL and its low-level I/O. CLAMP, an acronym for Command Language for Applied Mechanics Processors, is designed to control the flow of execution of processors written for NICE. Volume 2 describes the CLIP directives in detail. It is intended for intermediate and advanced users.

  3. DNA Strand Replacement Mechanism in Molecular Beacons Encoded for the Detection of Cancer Biomarkers.

    PubMed

    Stobiecka, Magdalena; Chalupa, Agata

    2016-06-01

    Signaling properties of a fluorescent hairpin oligonucleotide molecular beacon (MB) encoded to recognize protein survivin (Sur) mRNA have been investigated. The process of complementary target binding to SurMB with 20-mer loop sequence is spontaneous, as expected, and characterized by a high affinity constant (K = 2.51 × 10(16) M(-1)). However, the slow kinetics at room temperature makes it highly irreversible. To understand the intricacies of target binding to MB, a detailed kinetic study has been performed to determine the rate constants and activation energy Ea for the reaction at physiological temperature (37 °C). Special attention has been paid to assess the value of Ea in view of reports of negative activation enthalpy for some nucleic acid reactions that would make the target binding even slower at increasing temperatures in a non-Arrhenius process. The target-binding rate constant determined is k = 3.99 × 10(3) M(-1) s(-1) at 37 °C with Ea = 28.7 ± 2.3 kcal/mol (120.2 ± 9.6 kJ/mol) for the temperature range of 23 to 55 °C. The positive high value of Ea is consistent with a kinetically controlled classical Arrhenius process. We hypothesize that the likely contribution to the activation energy barrier comes from the SurMB stem melting (tm = 53.7 ± 0.2 °C), which is a necessary step in the completion of target strand hybridization with the SurMB loop. A low limit of detection (LOD = 2 nM) for target tDNA has been achieved. Small effects of conformational polymorphs of SurMB have been observed on melting curves. Although these polymorphs could potentially cause a negative Ea, their effect on kinetic transients for target binding is negligible. No toehold preceding steps in the mechanism of target binding were identified. PMID:27187043

  4. DNA Strand Replacement Mechanism in Molecular Beacons Encoded for the Detection of Cancer Biomarkers.

    PubMed

    Stobiecka, Magdalena; Chalupa, Agata

    2016-06-01

    Signaling properties of a fluorescent hairpin oligonucleotide molecular beacon (MB) encoded to recognize protein survivin (Sur) mRNA have been investigated. The process of complementary target binding to SurMB with 20-mer loop sequence is spontaneous, as expected, and characterized by a high affinity constant (K = 2.51 × 10(16) M(-1)). However, the slow kinetics at room temperature makes it highly irreversible. To understand the intricacies of target binding to MB, a detailed kinetic study has been performed to determine the rate constants and activation energy Ea for the reaction at physiological temperature (37 °C). Special attention has been paid to assess the value of Ea in view of reports of negative activation enthalpy for some nucleic acid reactions that would make the target binding even slower at increasing temperatures in a non-Arrhenius process. The target-binding rate constant determined is k = 3.99 × 10(3) M(-1) s(-1) at 37 °C with Ea = 28.7 ± 2.3 kcal/mol (120.2 ± 9.6 kJ/mol) for the temperature range of 23 to 55 °C. The positive high value of Ea is consistent with a kinetically controlled classical Arrhenius process. We hypothesize that the likely contribution to the activation energy barrier comes from the SurMB stem melting (tm = 53.7 ± 0.2 °C), which is a necessary step in the completion of target strand hybridization with the SurMB loop. A low limit of detection (LOD = 2 nM) for target tDNA has been achieved. Small effects of conformational polymorphs of SurMB have been observed on melting curves. Although these polymorphs could potentially cause a negative Ea, their effect on kinetic transients for target binding is negligible. No toehold preceding steps in the mechanism of target binding were identified.

  5. Prediction of contact mechanics in metal-on-metal Total Hip Replacement for parametrically comprehensive designs and loads.

    PubMed

    Donaldson, Finn E; Nyman, Edward; Coburn, James C

    2015-07-16

    Manufacturers and investigators of Total Hip Replacement (THR) bearings require tools to predict the contact mechanics resulting from diverse design and loading parameters. This study provides contact mechanics solutions for metal-on-metal (MoM) bearings that encompass the current design space and could aid pre-clinical design optimization and evaluation. Stochastic finite element (FE) simulation was used to calculate the head-on-cup contact mechanics for five thousand combinations of design and loading parameters. FE results were used to train a Random Forest (RF) surrogate model to rapidly predict the contact patch dimensions, contact area, pressures and plastic deformations for arbitrary designs and loading. In addition to widely observed polar and edge contact, FE results included ring-polar, asymmetric-polar, and transitional categories which have previously received limited attention. Combinations of design and load parameters associated with each contact category were identified. Polar contact pressures were predicted in the range of 0-200 MPa with no permanent deformation. Edge loading (with subluxation) was associated with pressures greater than 500 MPa and induced permanent deformation in 83% of cases. Transitional-edge contact (with little subluxation) was associated with intermediate pressures and permanent deformation in most cases, indicating that, even with ideal anatomical alignment, bearings may face extreme wear challenges. Surrogate models were able to accurately predict contact mechanics 18,000 times faster than FE analyses. The developed surrogate models enable rapid prediction of MoM bearing contact mechanics across the most comprehensive range of loading and designs to date, and may be useful to those performing bearing design optimization or evaluation.

  6. The effect of cup outer sizes on the contact mechanics and cement fixation of cemented total hip replacements.

    PubMed

    Hua, Xijin; Li, Junyan; Wang, Ling; Wilcox, Ruth; Fisher, John; Jin, Zhongmin

    2015-10-01

    One important loosening mechanism of the cemented total hip arthroplasty is the mechanical overload at the bone-cement interface and consequent failure of the cement fixation. Clinical studies have revealed that the outer diameter of the acetabular component is a key factor in influencing aseptic loosening of the hip arthroplasty. The aim of the present study was to investigate the influence of the cup outer diameter on the contact mechanics and cement fixation of a cemented total hip replacement (THR) with different wear penetration depths and under different cup inclination angles using finite element (FE) method. A three-dimensional FE model was developed based on a typical Charnley hip prosthesis. Two acetabular cup designs with outer diameters of 40 and 43 mm were modelled and the effect of cup outer diameter, penetration depth and cup inclination angle on the contact mechanics and cement fixation stresses in the cemented THR were studied. The results showed that for all penetration depths and cup inclination angles considered, the contact mechanics in terms of peak von Mises stress in the acetabular cup and peak contact pressure at the bearing surface for the two cup designs were similar (within 5%). However, the peak von Mises stress, the peak maximum principal stress and peak shear stress in the cement mantle at the bone-cement interface for the 43 mm diameter cup design were predicted to be lower compared to those for the 40 mm diameter cup design. The differences were predicted to be 15-19%, 15-22% and 18-20% respectively for different cup penetration depths and inclination angles, which compares to the clinical difference of aseptic loosening incidence of about 20% between the two cup designs.

  7. The effect of cup outer sizes on the contact mechanics and cement fixation of cemented total hip replacements.

    PubMed

    Hua, Xijin; Li, Junyan; Wang, Ling; Wilcox, Ruth; Fisher, John; Jin, Zhongmin

    2015-10-01

    One important loosening mechanism of the cemented total hip arthroplasty is the mechanical overload at the bone-cement interface and consequent failure of the cement fixation. Clinical studies have revealed that the outer diameter of the acetabular component is a key factor in influencing aseptic loosening of the hip arthroplasty. The aim of the present study was to investigate the influence of the cup outer diameter on the contact mechanics and cement fixation of a cemented total hip replacement (THR) with different wear penetration depths and under different cup inclination angles using finite element (FE) method. A three-dimensional FE model was developed based on a typical Charnley hip prosthesis. Two acetabular cup designs with outer diameters of 40 and 43 mm were modelled and the effect of cup outer diameter, penetration depth and cup inclination angle on the contact mechanics and cement fixation stresses in the cemented THR were studied. The results showed that for all penetration depths and cup inclination angles considered, the contact mechanics in terms of peak von Mises stress in the acetabular cup and peak contact pressure at the bearing surface for the two cup designs were similar (within 5%). However, the peak von Mises stress, the peak maximum principal stress and peak shear stress in the cement mantle at the bone-cement interface for the 43 mm diameter cup design were predicted to be lower compared to those for the 40 mm diameter cup design. The differences were predicted to be 15-19%, 15-22% and 18-20% respectively for different cup penetration depths and inclination angles, which compares to the clinical difference of aseptic loosening incidence of about 20% between the two cup designs. PMID:26343226

  8. Directed networks' different link formation mechanisms causing degree distribution distinction

    NASA Astrophysics Data System (ADS)

    Behfar, Stefan Kambiz; Turkina, Ekaterina; Cohendet, Patrick; Burger-Helmchen, Thierry

    2016-11-01

    Within undirected networks, scientists have shown much interest in presenting power-law features. For instance, Barabási and Albert (1999) claimed that a common property of many large networks is that vertex connectivity follows scale-free power-law distribution, and in another study Barabási et al. (2002) showed power law evolution in the social network of scientific collaboration. At the same time, Jiang et al. (2011) discussed deviation from power-law distribution; others indicated that size effect (Bagrow et al., 2008), information filtering mechanism (Mossa et al., 2002), and birth and death process (Shi et al., 2005) could account for this deviation. Within directed networks, many authors have considered that outlinks follow a similar mechanism of creation as inlinks' (Faloutsos et al., 1999; Krapivsky et al., 2001; Tanimoto, 2009) with link creation rate being the linear function of node degree, resulting in a power-law shape for both indegree and outdegree distribution. Some other authors have made an assumption that directed networks, such as scientific collaboration or citation, behave as undirected, resulting in a power-law degree distribution accordingly (Barabási et al., 2002). At the same time, we claim (1) Outlinks feature different degree distributions than inlinks; where different link formation mechanisms cause the distribution distinctions, (2) in/outdegree distribution distinction holds for different levels of system decomposition; therefore this distribution distinction is a property of directed networks. First, we emphasize in/outlink formation mechanisms as causal factors for distinction between indegree and outdegree distributions (where this distinction has already been noticed in Barker et al. (2010) and Baxter et al. (2006)) within a sample network of OSS projects as well as Java software corpus as a network. Second, we analyze whether this distribution distinction holds for different levels of system decomposition: open

  9. Soil fungal community development in a high Arctic glacier foreland follows a directional replacement model, with a mid-successional diversity maximum.

    PubMed

    Dong, Ke; Tripathi, Binu; Moroenyane, Itumeleng; Kim, Woosung; Li, Nan; Chu, Haiyan; Adams, Jonathan

    2016-05-31

    Directional replacement and directional non-replacement models are two alternative paradigms for community development in primary successional environments. The first model emphasizes turnover in species between early and late successional niches. The second emphasizes accumulation of additional diversity over time. To test whether the development of soil fungal communities in the foreland of an Arctic glacier conforms to either of these models, we collected samples from the Midtre Lovénbreen Glacier, Svalbard, along a soil successional series spanning >80 years. Soil DNA was extracted, and fungal ITS1 region was amplified and sequenced on an Illumina Miseq. There was a progressive change in community composition in the soil fungal community, with greatest fungal OTU richness in the Mid Stage (50-80 years). A nestedness analysis showed that the Early Stage (20-50 years) and the Late Stage (>80 years) fungal communities were nested within the Mid Stage communities. These results imply that fungal community development in this glacier succession follows a directional replacement model. Soil development processes may initially be important in facilitating arrival of additional fungal species, to give a mid-successional diversity maximum that contains both early- and late-successional fungi. Competition may then decrease the overall diversity due to the loss of early successional species.

  10. Soil fungal community development in a high Arctic glacier foreland follows a directional replacement model, with a mid-successional diversity maximum

    PubMed Central

    Dong, Ke; Tripathi, Binu; Moroenyane, Itumeleng; Kim, Woosung; Li, Nan; Chu, Haiyan; Adams, Jonathan

    2016-01-01

    Directional replacement and directional non-replacement models are two alternative paradigms for community development in primary successional environments. The first model emphasizes turnover in species between early and late successional niches. The second emphasizes accumulation of additional diversity over time. To test whether the development of soil fungal communities in the foreland of an Arctic glacier conforms to either of these models, we collected samples from the Midtre Lovénbreen Glacier, Svalbard, along a soil successional series spanning >80 years. Soil DNA was extracted, and fungal ITS1 region was amplified and sequenced on an Illumina Miseq. There was a progressive change in community composition in the soil fungal community, with greatest fungal OTU richness in the Mid Stage (50–80 years). A nestedness analysis showed that the Early Stage (20–50 years) and the Late Stage (>80 years) fungal communities were nested within the Mid Stage communities. These results imply that fungal community development in this glacier succession follows a directional replacement model. Soil development processes may initially be important in facilitating arrival of additional fungal species, to give a mid-successional diversity maximum that contains both early- and late-successional fungi. Competition may then decrease the overall diversity due to the loss of early successional species. PMID:27240660

  11. Wear of the Charité® lumbar intervertebral disc replacement investigated using an electro-mechanical spine simulator

    PubMed Central

    Moghadas, Parshia; Shepherd, Duncan ET; Hukins, David WL

    2015-01-01

    The Charité® lumbar intervertebral disc replacement was subjected to wear testing in an electro-mechanical spine simulator. Sinusoidally varying compression (0.6–2 kN, frequency 2 Hz), rotation (±2°, frequency 1 Hz), flexion–extension (6° to −3°, frequency 1 Hz) and lateral bending (±2°, frequency 1 Hz) were applied out of phase to specimens immersed in diluted calf serum at 37 °C. The mass of the ultra-high-molecular weight polyethylene component of the device was measured at intervals of 0.5, 1, 2, 3, 4 and 5 million cycles; its volume was also measured by micro-computed tomography. Total mass and volume losses were 60.3 ± 4.6 mg (mean ± standard deviation) and 64.6 ± 6.0 mm3. Corresponding wear rates were 12.0 ± 1.4 mg per million cycles and 12.8 ± 1.2 mm3 per million cycles; the rate of loss of volume corresponds to a mass loss of 11.9 ± 1.1 mg per million cycles, that is, the two sets of measurements of wear agree closely. Wear rates also agree closely with measurements made in another laboratory using the same protocol but using a conventional mechanical spine simulator. PMID:25834002

  12. Fluid mechanics of directional solidification at reduced gravity

    NASA Technical Reports Server (NTRS)

    Chen, C. F.

    1992-01-01

    The primary objective of the proposed research is to provide additional groundbased support for the flight experiment 'Casting and Solidification Technology' (CAST). This experiment is to be performed in the International Microgravity Laboratory-1 (IML-1) scheduled to be flown on a space shuttle mission scheduled for 1992. In particular, we will provide data on the convective motion and freckle formation during directional solidification of NH4Cl from its aqueous solution at simulated parameter ranges equivalent to reducing the gravity from the sea-level value down to 0.1 g or lower. The secondary objectives of the proposed research are to examine the stability phenomena associated with the onset of freckles and the mechanisms for their subsequent growth and decline (to eventual demise of some) by state-of-the-art imaging techniques and to formulate mathematical models for the prediction of the observed phenomena.

  13. Mechanically flexible organic electroluminescent device with directional light emission

    DOEpatents

    Duggal, Anil Raj; Shiang, Joseph John; Schaepkens, Marc

    2005-05-10

    A mechanically flexible and environmentally stable organic electroluminescent ("EL") device with directional light emission comprises an organic EL member disposed on a flexible substrate, a surface of which is coated with a multilayer barrier coating which includes at least one sublayer of a substantially transparent organic polymer and at least one sublayer of a substantially transparent inorganic material. The device includes a reflective metal layer disposed on the organic EL member opposite to the substrate. The reflective metal layer provides an increased external quantum efficiency of the device. The reflective metal layer and the multilayer barrier coating form a seal around the organic EL member to reduce the degradation of the device due to environmental elements.

  14. Direct simulation Monte Carlo method with a focal mechanism algorithm

    NASA Astrophysics Data System (ADS)

    Rachman, Asep Nur; Chung, Tae Woong; Yoshimoto, Kazuo; Yun, Sukyoung

    2015-01-01

    To simulate the observation of the radiation pattern of an earthquake, the direct simulation Monte Carlo (DSMC) method is modified by implanting a focal mechanism algorithm. We compare the results of the modified DSMC method (DSMC-2) with those of the original DSMC method (DSMC-1). DSMC-2 shows more or similarly reliable results compared to those of DSMC-1, for events with 12 or more recorded stations, by weighting twice for hypocentral distance of less than 80 km. Not only the number of stations, but also other factors such as rough topography, magnitude of event, and the analysis method influence the reliability of DSMC-2. The most reliable result by DSMC-2 is obtained by the best azimuthal coverage by the largest number of stations. The DSMC-2 method requires shorter time steps and a larger number of particles than those of DSMC-1 to capture a sufficient number of arrived particles in the small-sized receiver.

  15. Mechanisms of Heart Block after Transcatheter Aortic Valve Replacement – Cardiac Anatomy, Clinical Predictors and Mechanical Factors that Contribute to Permanent Pacemaker Implantation

    PubMed Central

    Young Lee, Mark; Chilakamarri Yeshwant, Srinath; Chava, Sreedivya; Lawrence Lustgarten, Daniel

    2015-01-01

    Transcatheter aortic valve replacement (TAVR) has emerged as a valuable, minimally invasive treatment option in patients with symptomatic severe aortic stenosis at prohibitive or increased risk for conventional surgical replacement. Consequently, patients undergoing TAVR are prone to peri-procedural complications including cardiac conduction disturbances, which is the focus of this review. Atrioventricular conduction disturbances and arrhythmias before, during or after TAVR remain a matter of concern for this high-risk group of patients, as they have important consequences on hospital duration, short- and long-term medical management and finally on decisions of device-based treatment strategies (pacemaker or defibrillator implantation). We discuss the mechanisms of atrioventricular disturbances and characterise predisposing factors. Using validated clinical predictors, we discuss strategies to minimise the likelihood of creating permanent high-grade heart block, and identify factors to expedite the decision to implant a permanent pacemaker when the latter is unavoidable. We also discuss optimal pacing strategies to mitigate the possibility of pacing-induced cardiomyopathy. PMID:26835105

  16. Mechanical compaction directly modulates the dynamics of bile canaliculi formation.

    PubMed

    Wang, Yan; Toh, Yi-Chin; Li, Qiushi; Nugraha, Bramasta; Zheng, Baixue; Lu, Thong Beng; Gao, Yi; Ng, Mary Mah Lee; Yu, Hanry

    2013-02-01

    Homeostatic pressure-driven compaction is a ubiquitous mechanical force in multicellular organisms and is proposed to be important in the maintenance of multicellular tissue integrity and function. Previous cell-free biochemical models have demonstrated that there are cross-talks between compaction forces and tissue structural functions, such as cell-cell adhesion. However, its involvement in physiological tissue function has yet to be directly demonstrated. Here, we use the bile canaliculus (BC) as a physiological example of a multicellular functional structure in the liver, and employ a novel 3D microfluidic hepatocyte culture system to provide an unprecedented opportunity to experimentally modulate the compaction states of primary hepatocyte aggregates in a 3D physiological-mimicking environment. Mechanical compaction alters the physical attributes of the hepatocyte aggregates, including cell shape, cell packing density and cell-cell contact area, but does not impair the hepatocytes' remodeling and functional capabilities. Characterization of structural and functional polarity shows that BC formation in compact hepatocyte aggregates is accelerated to as early as 12 hours post-seeding; whereas non-compact control requires 48 hours for functional BC formation. Further dynamic immunofluorescence imaging and gene expression profiling reveal that compaction accelerated BC formation is accompanied by changes in actin cytoskeleton remodeling dynamics and transcriptional levels of hepatic nuclear factor 4α and Annexin A2. Our report not only provides a novel strategy of modeling BC formation for in vitro hepatology research, but also shows a first instance that homeostatic pressure-driven compaction force is directly coupled to the higher-order multicellular functions. PMID:23233209

  17. Postoperative ileus: mechanisms and future directions for research.

    PubMed

    Vather, Ryash; O'Grady, Greg; Bissett, Ian P; Dinning, Phil G

    2014-05-01

    Postoperative ileus (POI) is an abnormal pattern of gastrointestinal motility characterized by nausea, vomiting, abdominal distension and/or delayed passage of flatus or stool, which may occur following surgery. Postoperative ileus slows recovery, increases the risk of developing postoperative complications and confers a significant financial load on healthcare institutions. The aim of the present review is to provide a succinct overview of the clinical features and pathophysiological mechanisms of POI, with final comment on selected directions for future research.Terminology used when describing POI is inconsistent, with little differentiation made between the obligatory period of gut dysfunction seen after surgery ('normal POI') and the more clinically and pathologically significant entity of a 'prolonged POI'. Both normal and prolonged POI represent a fundamentally similar pathophysiological phenomenon. The aetiology of POI is postulated to be multifactorial, with principal mediators being inflammatory cell activation, autonomic dysfunction (both primarily and as part of the surgical stress response), agonism at gut opioid receptors, modulation of gastrointestinal hormone activity and electrolyte derangements. A final common pathway for these effectors is impaired contractility and motility and gut wall oedema. There are many potential directions for future research. In particular, there remains scope to accurately characterize the gastrointestinal dysfunction that underscores an ileus, development of an accurate risk stratification tool will facilitate early implementation of preventive measures and clinical appraisal of novel therapeutic strategies that target individual pathways in the pathogenesis of ileus warrant further investigation. PMID:24754527

  18. Direct micro-mechanical measurements on C. elegans

    NASA Astrophysics Data System (ADS)

    Backholm, Matilda; Ryu, William S.; Dalnoki-Veress, Kari

    2013-03-01

    The millimeter-sized nematode Caenorhabditis elegans provides an excellent biophysical system for both static and dynamic biomechanical studies. The undulatory motion exhibited by this model organism as it crawls or swims through a medium is ubiquitous in nature at scales from microns to meters. A successful description of this form of locomotion requires knowledge of the material properties of the crawler, as well as its force output as it moves. Here we present an experimental technique with which the material properties and dynamics of C. elegans can be directly probed. By using the deflection of a flexible micropipette, the bending stiffness of C. elegans has been measured at all stages of its life cycle, as well as along the body of the adult worm. The mechanical properties of the worm are modelled as a viscoelastic material which provides new insights into its material properties. The forces exerted by the worm during undulatory motion are also discussed. Direct experimental characterization of this model organism provides guidance for theoretical treatments of undulatory locomotion in general.

  19. Morphogenetic mechanisms of coelom formation in the direct-developing sea urchin Heliocidaris erythrogramma.

    PubMed

    Smith, Margaret S; Collins, Steve; Raff, Rudolf A

    2009-01-01

    Indirect development via a feeding pluteus larva represents the ancestral mode of sea urchin development. However, some sea urchin species exhibit a derived form of development, called direct development, in which features of the feeding larva are replaced by accelerated development of the adult. A major difference between these two developmental modes is the timing of the formation of the left coelom and initiation of adult development. These processes occur much earlier in developmental and absolute time in direct developers and may be underlain by changes in morphogenetic processes. In this study, we explore whether differences in the cellular mechanisms responsible for the development of the left coelom and adult structures are associated with the change in the timing of their formation in the direct-developing sea urchin Heliocidaris erythrogramma. We present evidence that left coelom formation in H. erythrogramma, which differs in major aspects of coelom formation in indirect developers, is not a result of cell division. Further, we demonstrate that subsequent development of adult structures requires cell division.

  20. Direct measures of mechanical energy for knife mill size reduction

    SciTech Connect

    Bitra, V.S.P.; Womac, A.R.; Igathinathane, C.; Miu, P.I; Yang, Y.T.; Smith, D.R.; Chevanan, Nehru; Sokhansanj, Shahabaddine

    2009-08-01

    Lengthy straw/stalk of biomass may not be directly fed into grinders such as hammer mills and disc refiners. Hence, biomass needs to be preprocessed using coarse grinders like a knife mill to allow for efficient feeding in refiner mills without bridging and choking. Size reduction mechanical energy was directly measured for switchgrass (Panicum virgatum L.), wheat straw (Triticum aestivum L.), and corn stover (Zea mays L.) in an instrumented knife mill. Direct power inputs were determined for different knife mill screen openings from 12.7 to 50.8 mm, rotor speeds between 250 and 500 rpm, and mass feed rates from 1 to 11 kg/min. Overall accuracy of power measurement was calculated to be 0.003 kW. Total specific energy (kWh/Mg) was defined as size reduction energy to operate mill with biomass. Effective specific energy was defined as the energy that can be assumed to reach the biomass. The difference is parasitic or no-load energy of mill. Total specific energy for switchgrass, wheat straw, and corn stover chopping increased with knife mill speed, whereas, effective specific energy decreased marginally for switchgrass and increased for wheat straw and corn stover. Total and effective specific energy decreased with an increase in screen size for all the crops studied. Total specific energy decreased with increase in mass feed rate, but effective specific energy increased for switchgrass and wheat straw, and decreased for corn stover at increased feed rate. For knife mill screen size of 25.4 mm and optimum speed of 250 rpm, optimum feed rates were 7.6, 5.8, and 4.5 kg/min for switchgrass, wheat straw, and corn stover, respectively, and the corresponding total specific energies were 7.57, 10.53, and 8.87 kWh/Mg and effective specific energies were 1.27, 1.50, and 0.24 kWh/Mg for switchgrass, wheat straw, and corn stover, respectively. Energy utilization ratios were calculated as 16.8%, 14.3%, and 2.8% for switchgrass, wheat straw, and corn stover, respectively. These

  1. Hip Replacement

    MedlinePlus

    ... replacement is an operation in which a damaged hip joint is removed and replaced with an artificial joint. ... are many medical conditions that can damage the hip joint. (Watch the video to learn about what goes ...

  2. Hip Replacement

    MedlinePlus

    ... surgeon removes damaged cartilage and bone from your hip joint and replaces them with new, man-made parts. A hip replacement can Relieve pain Help your hip joint work better Improve walking and other movements The ...

  3. Ankle replacement

    MedlinePlus

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... You may not be able to have a total ankle replacement if you have had ankle joint infections ...

  4. Knee Replacement

    MedlinePlus

    Knee replacement is surgery for people with severe knee damage. Knee replacement can relieve pain and allow you to ... Your doctor may recommend it if you have knee pain and medicine and other treatments are not ...

  5. Hardwiring microbes via direct interspecies electron transfer: mechanisms and applications.

    PubMed

    Cheng, Qiwen; Call, Douglas F

    2016-08-10

    Multicellular microbial communities are important catalysts in engineered systems designed to treat wastewater, remediate contaminated sediments, and produce energy from biomass. Understanding the interspecies interactions within them is therefore essential to design effective processes. The flow of electrons within these communities is especially important in the determination of reaction possibilities (thermodynamics) and rates (kinetics). Conventional models of electron transfer incorporate the diffusion of metabolites generated by one organism and consumed by a second, frequently referred to as mediated interspecies electron transfer (MIET). Evidence has emerged in the last decade that another method, called direct interspecies electron transfer (DIET), may occur between organisms or in conjunction with electrically conductive materials. Recent research has suggested that DIET can be stimulated in engineered systems to improve desired treatment goals and energy recovery in systems such as anaerobic digesters and microbial electrochemical technologies. In this review, we summarize the latest understanding of DIET mechanisms, the associated microorganisms, and the underlying thermodynamics. We also critically examine approaches to stimulate DIET in engineered systems and assess their effectiveness. We find that in most cases attempts to promote DIET in mixed culture systems do not yield the improvements expected based on defined culture studies. Uncertainties of other processes that may be co-occurring in real systems, such as contaminant sorption and biofilm promotion, need to be further investigated. We conclude by identifying areas of future research related to DIET and its application in biological treatment processes. PMID:27349520

  6. Minireview: beta-cell replacement therapy for diabetes in the 21st century: manipulation of cell fate by directed differentiation.

    PubMed

    Yechoor, Vijay; Chan, Lawrence

    2010-08-01

    Pancreatic beta-cell failure underlies type 1 diabetes; it also contributes in an essential way to type 2 diabetes. beta-Cell replacement is an important component of any cure for diabetes. The current options of islet and pancreas transplantation are not satisfactory as definitive forms of therapy. Here, we review strategies for induced de novo pancreatic beta-cell formation, which depend on the targeted differentiation of cells into pancreatic beta-cells. With this objective in mind, one can manipulate the fate of three different types of cells: 1) from terminally differentiated cells, e.g. exocrine pancreatic cells, into beta-cells; 2) from multipotent adult stem cells, e.g. hepatic oval cells, into pancreatic islets; and 3) from pluripotent stem cells, e.g. embryonic stem cells and induced pluripotent stem cells, into beta-cells. We will examine the pros and cons of each strategy as well as the hurdles that must be overcome before these approaches to generate new beta-cells will be ready for clinical application. PMID:20219891

  7. Minireview: beta-cell replacement therapy for diabetes in the 21st century: manipulation of cell fate by directed differentiation.

    PubMed

    Yechoor, Vijay; Chan, Lawrence

    2010-08-01

    Pancreatic beta-cell failure underlies type 1 diabetes; it also contributes in an essential way to type 2 diabetes. beta-Cell replacement is an important component of any cure for diabetes. The current options of islet and pancreas transplantation are not satisfactory as definitive forms of therapy. Here, we review strategies for induced de novo pancreatic beta-cell formation, which depend on the targeted differentiation of cells into pancreatic beta-cells. With this objective in mind, one can manipulate the fate of three different types of cells: 1) from terminally differentiated cells, e.g. exocrine pancreatic cells, into beta-cells; 2) from multipotent adult stem cells, e.g. hepatic oval cells, into pancreatic islets; and 3) from pluripotent stem cells, e.g. embryonic stem cells and induced pluripotent stem cells, into beta-cells. We will examine the pros and cons of each strategy as well as the hurdles that must be overcome before these approaches to generate new beta-cells will be ready for clinical application.

  8. Using a magnetite/thermoplastic composite in 3D printing of direct replacements for commercially available flow sensors

    NASA Astrophysics Data System (ADS)

    Leigh, S. J.; Purssell, C. P.; Billson, D. R.; Hutchins, D. A.

    2014-09-01

    Flow sensing is an essential technique required for a wide range of application environments ranging from liquid dispensing to utility monitoring. A number of different methodologies and deployment strategies have been devised to cover the diverse range of potential application areas. The ability to easily create new bespoke sensors for new applications is therefore of natural interest. Fused deposition modelling is a 3D printing technology based upon the fabrication of 3D structures in a layer-by-layer fashion using extruded strands of molten thermoplastic. The technology was developed in the late 1980s but has only recently come to more wide-scale attention outside of specialist applications and rapid prototyping due to the advent of low-cost 3D printing platforms such as the RepRap. Due to the relatively low-cost of the printers and feedstock materials, these printers are ideal candidates for wide-scale installation as localized manufacturing platforms to quickly produce replacement parts when components fail. One of the current limitations with the technology is the availability of functional printing materials to facilitate production of complex functional 3D objects and devices beyond mere concept prototypes. This paper presents the formulation of a simple magnetite nanoparticle-loaded thermoplastic composite and its incorporation into a 3D printed flow-sensor in order to mimic the function of a commercially available flow-sensing device. Using the multi-material printing capability of the 3D printer allows a much smaller amount of functional material to be used in comparison to the commercial flow sensor by only placing the material where it is specifically required. Analysis of the printed sensor also revealed a much more linear response to increasing flow rate of water showing that 3D printed devices have the potential to at least perform as well as a conventionally produced sensor.

  9. New mechanism to reduce the size of the monopivot magnetic suspension blood pump: direct drive mechanism.

    PubMed

    Yamane, T; Nishida, M; Kijima, T; Maekawa, J

    1997-07-01

    Size reduction of the monopivot magnetic suspension blood pump has been achieved by reducing the size of the magnetic suspension and employing a direct drive mechanism in place of a brushless DC motor and a magnetic coupling. The flow has also been improved using a closed hollow impeller to remove flow obstruction at the inlet and using radial straight vanes to reduce the impeller speed by 30%. Hemolysis testing was conducted for the new models. Results showed that model DD1 presented only a slightly higher level of hemolysis than a regular extracorporeal centrifugal pump. PMID:9212927

  10. Replacing surrogate measures by direct quantification of ultraviolet radiation exposure in registry-based analyses of seasonality of melanoma diagnoses.

    PubMed

    Keller, Andrea K; Uter, Wolfgang; Pfahlberg, Annette B; Radespiel-Tröger, Martin; Mayer, Ingo; Gefeller, Olaf

    2015-12-01

    Seasonal variation in melanoma diagnoses has been observed in numerous studies that used calendar time indicators. Depending on the latitude (and altitude) of the study region, the magnitude of seasonal and year-to-year variation of ultraviolet radiation (UVR) is neglected in these studies. An alternative approach comprises the direct incorporation of UVR measurements into such analyses. The aim of this investigation is a comparative evaluation of these approaches. The population-based Bavarian cancer registry recorded 11 901 incident melanoma cases between 2003 and 2008 that were used for the analysis. UVR intensity data for the same period were available from the solar radiation station at Munich-Neuherberg. Negative binomial regression modelling yielded adjusted relative risks (RR) controlled for year of diagnosis and age in 16 subgroups defined by sex, Breslow thickness and localization. Overall, the analyses showed slightly differing yet consistent results for exposure effects in subgroups. Melanoma evolving on the extremities showed the most pronounced association with increasing level of the UV index among men [e.g. RR=1.086, 95% confidence interval (CI) 1.054-1.119, and RR=1.102, 95% CI 1.046-1.161, for thin and thick melanoma on the upper limbs, respectively] and women (e.g. RR=1.088, 95% CI 1.058-1.119, and RR=1.056, 95% CI 1.010-1.103, for thin and thick melanoma on the lower limbs, respectively). Our analysis provides a benchmark for international comparisons and synthesis of epidemiologic evidence of seasonal variability in melanoma diagnoses. Future studies should use direct UVR measures to enable pooling of risk estimates and resolve remaining inconsistencies potentially resulting from latitudinal differences in exposure between international studies.

  11. Microstructure and Mechanical Properties of AA1235 Aluminum Foil Stocks Produced Directly from Electrolytic Aluminum Melt

    NASA Astrophysics Data System (ADS)

    Xiong, Hanqing; Yu, Kun; Wen, Li; Yao, Sujuan; Dai, Yilong; Wang, Zhifeng

    2016-02-01

    A new process is developed to obtain high-quality AA1235 aluminum foil stocks and to replace the traditional manufacture process. During the new manufacture process, AA1235 aluminum sheets are twin-roll casted directly through electrolytic aluminum melt (EAM), and subsequently the sheets are processed into aluminum foil stocks by cold rolling and annealing. Microstructure and mechanical properties of the AA1235 aluminum sheets produced through such new process are investigated in each state by optimal microscope, scanning electron microscopy, X-ray diffraction, orientation imaging microscopy, transmission electron microscopy, etc. The results show that compared with the traditional AA1235 aluminum foil stocks produced through re-melted aluminum melt (RAM), the amount of impurities is decreased in the EAM aluminum foil stocks. The EAM aluminum foil stock obtains less β-FeSiAl5 phases, but more α-Fe2SiAl8 phases. The elongation of EAM aluminum foil stocks is improved significantly owing to more cubic orientation. Especially, the elongation value of the EAM aluminum foil stocks is approximately 25 pct higher than that of the RAM aluminum foil stocks. As a result, the EAM aluminum foil stocks are at an advantage in increasing the processing performance for the aluminum foils during subsequent processes.

  12. New directions: Atmospheric chemical mechanisms for the future

    NASA Astrophysics Data System (ADS)

    Kaduwela, Ajith; Luecken, Deborah; Carter, William; Derwent, Richard

    2015-12-01

    The atmospheric chemical reaction scheme, commonly referred to as the chemical mechanism, is the portion of an air quality model that represents the atmospheric chemistry of the pollutants. It is at the heart of every air quality model used in research and policy applications to predict and analyse the complex air pollutants: ozone, air toxics and PM2.5. The chemical mechanism should incorporate available information on chemical kinetics and reaction pathways and be the conduit through which the fundamental science of atmospheric chemistry is applied to solve real-world problems. The efficiency and effectiveness of policies developed to reduce exposure to harmful pollutants depend on how well the mechanisms reflect the actual chemistry. If the mechanism has reaction pathways that are incorrectly characterised or completely missing, the resulting predictions may underestimate emission reduction requirements needed to meet public health and ecosystem protection targets, or may overstate the emission reductions needed and cause unnecessary implementation costs. It is therefore essential that mechanisms utilise the best, most up-to-date atmospheric chemistry information available so that policy development is based on air quality model predictions that are robust, transparent and free from scientific challenge. We are concerned that this may not continue to be the case.

  13. An experimental study of the mechanism of the replacement of magnetite by pyrite up to 300 °C

    NASA Astrophysics Data System (ADS)

    Qian, Gujie; Brugger, Joël; Skinner, William M.; Chen, Guorong; Pring, Allan

    2010-10-01

    We present the results of an experimental study into the sulfidation of magnetite to form pyrite/marcasite under hydrothermal conditions (90-300 °C, vapor saturated pressures), a process associated with gold deposition in a number of ore deposits. The formation of pyrite/marcasite was studied as a function of reaction time, temperature, pH, sulfide concentration, solid-weight-to-fluid-volume ratio, and geometric surface area of magnetite in polytetrafluoroethylene-lined autoclaves (PTFE) and a titanium and stainless steel flow-through cell. Marcasite was formed only at pH 21°C <4 and was the dominant Fe disulfide at pH 21°C 1.11, while pyrite predominated at pH 21°C >2 and formed even under basic conditions (up to pH 21°C 12-13). Marcasite formation was favored at higher temperatures. Fine-grained pyrrhotite formed in the initial stage of the reaction together with pyrite in some experiments with large surface area of magnetite (grain size <125 μm). This pyrrhotite eventually gave way to pyrite. The transformation rate of magnetite to Fe disulfide increased with decreasing pH (at 120 °C; pH 120°C 0.96-4.42), and that rate of the transformation increased from 120 to 190 °C. Scanning electron microscope (SEM) imaging revealed that micro-pores (0.1-5 μm scale) existed at the reaction front between the parent magnetite and the product pyrite, and that the pyrite and/or marcasite were euhedral at pH 21°C <4 and anhedral at higher pH. The newly formed pyrite was micro-porous (0.1-5 μm); this micro-porosity facilitates fluid transport to the reaction interface between magnetite and pyrite, thus promoting the replacement reaction. The pyrite precipitated onto the parent magnetite was polycrystalline and did not preserve the crystallographic orientation of the magnetite. The pyrite precipitation was also observed on the PTFE liner, which is consistent with pyrite crystallizing from solution. The mechanism of the reaction is that of a dissolution

  14. New directions: Atmospheric chemical mechanisms for the future

    EPA Science Inventory

    The chemical reaction scheme or mechanism used to represent atmospheric chemical reactions is at the heart of each air quality model used in research and policy applications to predict and analyse the complex air pollutants: ozone, air toxics and PM2.5. This is necessarily only a...

  15. Direct selection for a catalytic mechanism from combinatorial antibody libraries.

    PubMed Central

    Janda, K D; Lo, C H; Li, T; Barbas, C F; Wirsching, P; Lerner, R A

    1994-01-01

    Semisynthetic combinatorial antibody library methodology in the phage-display format was used to select for a cysteine residue in complementarity-determining regions. Libraries were panned with an alpha-phenethyl pyridyl disulfide that undergoes disulfide interchange. Out of 10 randomly picked clones, two contained an unpaired cysteine, one of which was studied. The antibody catalyzed the hydrolysis of the corresponding thioester where the electrophilic carbonyl occupies the three-dimensional space that was defined by the reactive sulfur atom during selection. The reaction operates by covalent catalysis. Although the steady-state rate enhancement relative to the activated thiol ester substrate is modest, hydrolysis of the acylated cysteine intermediate is remarkably efficient with a catalytic advantage of about four orders of magnitude. The results suggest that iterative mechanism-based selection procedures can recapitulate the enzymatic mechanisms refined through evolution. Images PMID:8146149

  16. Mechanisms of early life programming: current knowledge and future directions.

    PubMed

    Tarry-Adkins, Jane L; Ozanne, Susan E

    2011-12-01

    It has been >20 y since epidemiologic studies showed a relation between patterns of early growth and subsequent risk of diseases, such as type 2 diabetes, cardiovascular disease, and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, and animal models have provided strong evidence that the early environment, including early nutrition, plays an important role in mediating these relations. The concept of early life programming is therefore widely accepted. However, the mechanisms by which a phenomenon that occurs in early life can have long-term effects on the function of a cell and therefore on the metabolism of an organism many years later are only starting to emerge. These mechanisms include 1) permanent structural changes in an organ resulting from suboptimal concentrations of an important factor during a critical period of development, eg, the permanent reduction in β cell mass in the endocrine pancreas; 2) persistent alterations in epigenetic modifications (eg, DNA methylation and histone modifications) that lead to changes in gene expression (eg, several transcription factors are susceptible to programmed changes in gene expression through such mechanisms); and 3) permanent effects on the regulation of cellular aging (eg, increases in oxidative stress that lead to macromolecular damage, including that to DNA and specifically to telomeres, can contribute to such effects). Further understanding of such processes will enable the development of preventive and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease. PMID:21543536

  17. Mechanisms of early life programming: current knowledge and future directions.

    PubMed

    Tarry-Adkins, Jane L; Ozanne, Susan E

    2011-12-01

    It has been >20 y since epidemiologic studies showed a relation between patterns of early growth and subsequent risk of diseases, such as type 2 diabetes, cardiovascular disease, and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, and animal models have provided strong evidence that the early environment, including early nutrition, plays an important role in mediating these relations. The concept of early life programming is therefore widely accepted. However, the mechanisms by which a phenomenon that occurs in early life can have long-term effects on the function of a cell and therefore on the metabolism of an organism many years later are only starting to emerge. These mechanisms include 1) permanent structural changes in an organ resulting from suboptimal concentrations of an important factor during a critical period of development, eg, the permanent reduction in β cell mass in the endocrine pancreas; 2) persistent alterations in epigenetic modifications (eg, DNA methylation and histone modifications) that lead to changes in gene expression (eg, several transcription factors are susceptible to programmed changes in gene expression through such mechanisms); and 3) permanent effects on the regulation of cellular aging (eg, increases in oxidative stress that lead to macromolecular damage, including that to DNA and specifically to telomeres, can contribute to such effects). Further understanding of such processes will enable the development of preventive and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease.

  18. Crystal Growth and Fluid Mechanics Problems in Directional Solidification

    NASA Technical Reports Server (NTRS)

    Tanveer, Saleh A.; Baker, Gregory R.; Foster, Michael R.

    2001-01-01

    Our work in directional solidification has been in the following areas: (1) Dynamics of dendrites including rigorous mathematical analysis of the resulting equations; (2) Examination of the near-structurally unstable features of the mathematically related Hele-Shaw dynamics; (3) Numerical studies of steady temperature distribution in a vertical Bridgman device; (4) Numerical study of transient effects in a vertical Bridgman device; (5) Asymptotic treatment of quasi-steady operation of a vertical Bridgman furnace for large Rayleigh numbers and small Biot number in 3D; and (6) Understanding of Mullins-Sererka transition in a Bridgman device with fluid dynamics is accounted for.

  19. Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis.

    PubMed

    Nucifora, Gaetano; Muser, Daniele; Gianfagna, Pasquale; Morocutti, Giorgio; Proclemer, Alessandro

    2015-12-01

    Aim of the present study was to investigate the relations between myocardial mechanics and the extent of hypertrophy and fibrosis in hypertrophic cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects without structural heart disease were included. Cardiac magnetic resonance with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index and presence/extent of LGE, expression of replacement fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was measured from Look-Locker sequence. Feature-tracking analysis was applied to LV basal, mid and apical short-axis images to assess systolic and diastolic global LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr were significantly higher among HCM patients as compared to control subjects (p = 0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to peak systolic CSr was significantly lower among HCM patients (p = 0.002). At multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p = 0.011) were significantly and independently related to peak systolic CS; LV mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p = 0.006) were significantly and independently related to the ratio of peak CSr during early filling to peak systolic CSr. LV systolic mechanics are enhanced and LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement fibrosis influence the LV systolic mechanics while extent of replacement fibrosis and interstitial fibrosis influence the LV diastolic mechanics.

  20. Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities

    PubMed Central

    2009-01-01

    Abstract Redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. This review will present an update on drug discovery, target identification, and mechanisms of action of experimental redox chemotherapeutics with a focus on pro- and antioxidant redox modulators now in advanced phases of preclinal and clinical development. Recent research indicates that numerous oncogenes and tumor suppressor genes exert their functions in part through redox mechanisms amenable to pharmacological intervention by redox chemotherapeutics. The pleiotropic action of many redox chemotherapeutics that involves simultaneous modulation of multiple redox sensitive targets can overcome cancer cell drug resistance originating from redundancy of oncogenic signaling and rapid mutation. Moreover, some redox chemotherapeutics may function according to the concept of synthetic lethality (i.e., drug cytotoxicity is confined to cancer cells that display loss of function mutations in tumor suppressor genes or upregulation of oncogene expression). The impressive number of ongoing clinical trials that examine therapeutic performance of novel redox drugs in cancer patients demonstrates that redox chemotherapy has made the crucial transition from bench to bedside. Antioxid. Redox Signal. 11, 3013–3069. PMID:19496700

  1. Eye Nutrition in Context: Mechanisms, Implementation, and Future Directions

    PubMed Central

    Demmig-Adams, Barbara; Adams, Robert B.

    2013-01-01

    Carotenoid-based visual cues and roles of carotenoids in human vision are reviewed, with an emphasis on protection by zeaxanthin and lutein against vision loss, and dietary sources of zeaxanthin and lutein are summarized. In addition, attention is given to synergistic interactions of zeaxanthin and lutein with other dietary factors affecting human vision (such as antioxidant vitamins, phenolics, and poly-unsaturated fatty acids) and the emerging mechanisms of these interactions. Emphasis is given to lipid oxidation products serving as messengers with functions in gene regulation. Lastly, the photo-physics of light collection and photoprotection in photosynthesis and vision are compared and their common principles identified as possible targets of future research. PMID:23857222

  2. TNFα blockade in human diseases: Mechanisms and future directions

    PubMed Central

    Wong, Maida; Ziring, David; Korin, Yael; Desai, Sheetal; Kim, Sungjin; Lin, Jan; Gjertson, David; Braun, Jonathan; Reed, Elaine; Singh, Ram Raj

    2008-01-01

    Tumor necrosis factor-alpha (TNFα) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFα antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFα antibodies are effective in other IMIDs. Early efforts at understanding how TNFα antagonists act in IMIDs centered on their ability to neutralize soluble TNFα or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFα blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFα antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFα antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFα antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations. PMID:17916444

  3. Crystal growth and fluid mechanics problems in directional solidification

    NASA Technical Reports Server (NTRS)

    Tanveer, Saleh; Baker, Gregory R.; Foster, Michael R.

    1994-01-01

    Broadly speaking, our efforts have been concentrated in two aspects of directional solidification: (A) a more complete theoretical understanding of convection effects in a Bridgman apparatus; and (B) a clear understanding of scalings of various features of dendritic crystal growth in the sensitive limit of small capillary effects. For studies that fall within class A, the principal objectives are as follows: (A1) Derive analytical formulas for segregation, interfacial shape and fluid velocities in mathematically amenable asymptotic limits. (A2) Numerically verify and extend asymptotic results to other ranges of parameter space with a view to a broader physical understanding of the general trends. With respect to studies that fall within class B, the principal objectives include answering the following questions about dendritic crystal growth: (B1) Are there unsteady dendrite solutions in 2-D to the completely nonlinear time evolving equations in the small surface tension limit with only a locally steady tip region with well defined tip radius and velocity? Is anisotropy in surface tension necessary for the existence of such solutions as it is for a true steady state needle crystal? How does the size of such a local region depend on capillary effects, anisotropy and undercooling? (B2) How do the different control parameters affect the nonlinear amplification of tip noise and dendritic side branch coarsening?

  4. Crystal growth and fluid mechanics problems in directional solidification

    NASA Astrophysics Data System (ADS)

    Tanveer, Saleh; Baker, Gregory R.; Foster, Michael R.

    1994-08-01

    Broadly speaking, our efforts have been concentrated in two aspects of directional solidification: (A) a more complete theoretical understanding of convection effects in a Bridgman apparatus; and (B) a clear understanding of scalings of various features of dendritic crystal growth in the sensitive limit of small capillary effects. For studies that fall within class A, the principal objectives are as follows: (A1) Derive analytical formulas for segregation, interfacial shape and fluid velocities in mathematically amenable asymptotic limits. (A2) Numerically verify and extend asymptotic results to other ranges of parameter space with a view to a broader physical understanding of the general trends. With respect to studies that fall within class B, the principal objectives include answering the following questions about dendritic crystal growth: (B1) Are there unsteady dendrite solutions in 2-D to the completely nonlinear time evolving equations in the small surface tension limit with only a locally steady tip region with well defined tip radius and velocity? Is anisotropy in surface tension necessary for the existence of such solutions as it is for a true steady state needle crystal? How does the size of such a local region depend on capillary effects, anisotropy and undercooling? (B2) How do the different control parameters affect the nonlinear amplification of tip noise and dendritic side branch coarsening?

  5. Integrated molecular mechanism directing nucleosome reorganization by human FACT

    PubMed Central

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-01-01

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT–histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3–H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid–H2A steric collision on the H2A-docking surface of the H3–H4 tetramer within the nucleosome induces H2A–H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  6. Replacing Chemicals in Recycle Mills with Mechanical Alternatives. Quarterly progress report covering period October 1, 1999 to December 31, 1999

    SciTech Connect

    Sujit Banerjee

    2000-01-13

    The objective of this project is to explore potential applications of underwater pulsed power technology to the paper industry. These included fiber refining, disinfection, stickies dispersion, and stickies control. In pulsed power a spark is discharged underwater. Present commercial applications of the technology include the detonation of land mines, zebra mussel control, and water disinfection. In preliminary work the authors have found that stickies are rapidly dispersed under the influence of pulsed power. The purpose of this project is to explore other applications of the technology in the recycle paper industry, especially in applications where the technology can replace potentially expensive chemical use. The authors have found that sparking improves the screenability of stickies in the presence of pulp. Sparking is also able to detackify pitch coated on metal surfaces. This is potentially a major finding since it extends the range of the application from recycle to virgin mills. They need to determine if the effect also occurs for pitch particles suspended in whitewater. Some stickies such as Robond, a PSA used in the paint industry, are relatively unaffected by spark treatment. They find that this polymer is oxidized to a lower extent. A sparker unit has been purchased and installed at IPST. A licensing agreement with Sparktec Environmental, Stoney Creek, Canada, the manufacturer of the device, has been negotiated. It was found that sparking improves the screenability of stickies in the presence of pulp. Sparking is also able to detackify pitch coated on metal surfaces.

  7. Effect of microseparation on contact mechanics in metal-on-metal hip replacements-A finite element analysis.

    PubMed

    Liu, Feng; Williams, Sophie; Fisher, John

    2015-08-01

    Some early failures of metal-on-metal (MoM) hip replacements associated with elevated wear have caused concerns for the use of this bearing combination. Simulator studies have shown that microseparation and its associated rim contact and edge loading may produce the most severe wear in MoM bearings. It is generally recognized that this high wear can be attributed to the high contact stress of the head on the rim of the cup. In this study, an improved finite element contact model that incorporates an elastic-perfectly plastic material property for cobalt-chrome alloy of the metal bearing was developed in an attempt to provide an accurate prediction of the stress and strain for the rim contact. The effects of the microseparation displacement (0.1-2 mm), cup inclination angle (25-65°) and cup rim radius (0.5-4 mm) on the contact stress/strain were investigated. The results show that a translational displacement >0.1 mm under a load >0.5 kN can produce a highly concentrated contact stress at the surface of the cup rim which can lead to plastic deformation. This study also suggests that the magnitude of translational displacement was the major factor that determined the severity of the contact conditions and level of stress and strain under microseparation conditions. Future studies will address the effect of surgical translational and rotational malposition and component design on the magnitude of microseparation, contact stress and strain and severity of wear.

  8. Effect of progressive wear on the contact mechanics of hip replacements--does the realistic surface profile matter?

    PubMed

    Wang, Ling; Yang, Wenjian; Peng, Xifeng; Li, Dichen; Dong, Shuangpeng; Zhang, Shu; Zhu, Jinyu; Jin, Zhongmin

    2015-04-13

    The contact mechanics of artificial metal-on-polyethylene hip joints are believed to affect the lubrication, wear and friction of the articulating surfaces and may lead to the joint loosening. Finite element analysis has been widely used for contact mechanics studies and good agreements have been achieved with current experimental data; however, most studies were carried out with idealist spherical geometries of the hip prostheses rather than the realistic worn surfaces, either for simplification reason or lacking of worn surface profile. In this study, the worn surfaces of the samples from various stages of hip simulator testing (0 to 5 million cycles) were reconstructed as solid models and were applied in the contact mechanics study. The simulator testing results suggested that the center of the head has various departure value from that of the cup and the value of the departure varies with progressively increased wear. This finding was adopted into the finite element study for better evaluation accuracy. Results indicated that the realistic model provided different evaluation from that of the ideal spherical model. Moreover, with the progressively increased wear, large increase of the contact pressure (from 12 to 31 MPa) was predicted on the articulating surface, and the predicted maximum von Mises stress was increased from 7.47 to 13.26 MPa, indicating the marked effect of the worn surface profiles on the contact mechanics of the joint. This study seeks to emphasize the importance of realistic worn surface profile of the acetabular cup especially following large wear volume.

  9. Role of boric acid in nickel nanotube electrodeposition: a surface-directed growth mechanism.

    PubMed

    Graham, Lauren M; Cho, Seungil; Kim, Sung Kyoung; Noked, Malachi; Lee, Sang Bok

    2014-01-18

    Nickel nanotubes have been synthesized by the popular and versatile method of template-assisted electrodeposition, and a surface-directed growth mechanism based on the adsorption of the nickel-borate complex has been proposed.

  10. Impact of lipid-induced degradation on the mechanical properties of ultra-high molecular weight polyethylene for joint replacements.

    PubMed

    Sakoda, Hideyuki; Niimi, Shingo

    2016-01-01

    Gamma or electron beam irradiation of ultra-high molecular weight polyethylene (UHMWPE) used in artificial joints for sterilization and/or crosslinking purposes generates free radicals in the material, which causes long-term oxidative degradation of UHMWPE. Recently, another mechanism for the degradation of UHMWPE by the absorption of lipids during in vivo clinical use was proposed. However, knowledge on lipid-induced degradation is quite limited, compared with that on radical-induced degradation. In this study, lipid-induced degradation was simulated using squalene absorption and subsequent accelerated aging, and its impact on the mechanical properties of UHMWPE was evaluated. The simulated lipid-induced degradation caused an increased elastic modulus and decreased elongation with maximum degradation at the surfaces. These results imply that degradation of UHMWPE may occur during in vivo long-term use, even if free radicals are completely eliminated. Therefore, further investigation is required to clarify the impact of lipid-induced degradation on clinical outcomes, such as the wear and fatigue characteristics of UHMWPE components. PMID:26340645

  11. Impact of lipid-induced degradation on the mechanical properties of ultra-high molecular weight polyethylene for joint replacements.

    PubMed

    Sakoda, Hideyuki; Niimi, Shingo

    2016-01-01

    Gamma or electron beam irradiation of ultra-high molecular weight polyethylene (UHMWPE) used in artificial joints for sterilization and/or crosslinking purposes generates free radicals in the material, which causes long-term oxidative degradation of UHMWPE. Recently, another mechanism for the degradation of UHMWPE by the absorption of lipids during in vivo clinical use was proposed. However, knowledge on lipid-induced degradation is quite limited, compared with that on radical-induced degradation. In this study, lipid-induced degradation was simulated using squalene absorption and subsequent accelerated aging, and its impact on the mechanical properties of UHMWPE was evaluated. The simulated lipid-induced degradation caused an increased elastic modulus and decreased elongation with maximum degradation at the surfaces. These results imply that degradation of UHMWPE may occur during in vivo long-term use, even if free radicals are completely eliminated. Therefore, further investigation is required to clarify the impact of lipid-induced degradation on clinical outcomes, such as the wear and fatigue characteristics of UHMWPE components.

  12. A haplotype of CYP2C9 associated with warfarin sensitivity in mechanical heart valve replacement patients

    PubMed Central

    Lee, Su-Jun; Jang, Yin Jin; Cha, Eun-Young; Kim, Ho-Sook; Lee, Sang Seop; Shin, Jae-Gook

    2010-01-01

    AIMS The objectives of this study were to determine the distribution of CYP2C9 variants in Koreans and investigate their association with warfarin dose requirements in patients who received MHVRs. METHODS All nine exons, intron–exon junction, and promoter region of CYP2C9 were amplified and directly sequenced in 50 healthy normal Koreans. Additional direct DNA sequencing of the CYP2C9 gene was conducted in 36 of the 267 MHVR patients who required low maintenance warfarin doses without carrying CYP2C9*3 and VKORC1 1173T mutations. The effects of CYP2C9 genetics on warfarin maintenance dose were assessed in 267 MHVR patients. RESULTS Thirty-nine single nucleotide polymorphisms (SNPs) including seven previously unidentified SNPs were identified in 50 Koreans by direct DNA sequencing. One of the CYP2C9 haplotypes exhibited an association with warfarin low dose requirement. The adjusted odds ratio for the haplotype between the low dose group and the normal subjects was 2.5 (95% confidence interval 1.05, 6.16). This haplotype consisting of -1565C>T, -1188T>C, IVS3+197G>A, IVS3-334C>T, IVS3-65G>C, IVS4-115A>G, and IVS5-73A>G was found in 15% of 36 MHVR patients who required low warfarin doses, while 4% of 50 normal healthy subjects exhibited this haplotype. One of the SNPs comprising this haplotype, -1565C>T, apparently changed a protein binding pattern as observed in electrophoretic mobility shift assay. CONCLUSION The haplotype including -1565C>T, -1188T>C, IVS3+197G>A, IVS3-334C>T, IVS3-65G>C, IVS4-115A>G, and IVS5-73A>G seems to be associated with low warfarin dose requirement and this haplotype could be considered in the development of a warfarin dose prediction model for Asian populations. PMID:20653674

  13. Target- and Effect-Directed Actions towards Temporal Goals: Similar Mechanisms?

    ERIC Educational Resources Information Center

    Walter, Andrea M.; Rieger, Martina

    2012-01-01

    The goal of an action can consist of generating a change in the environment (to produce an effect) or changing one's own situation in the environment (to move to a physical target). To investigate whether the mechanisms of effect-directed and target-directed action control are similar, participants performed continuous reversal movements. They…

  14. Experimental Data in Support of a Direct Displacement Mechanism for Type I/II L-Asparaginases.

    PubMed

    Schalk, Amanda M; Antansijevic, Aleksandar; Caffrey, Michael; Lavie, Arnon

    2016-03-01

    Bacterial L-asparaginases play an important role in the treatment of certain types of blood cancers. We are exploring the guinea pig L-asparaginase (gpASNase1) as a potential replacement of the immunogenic bacterial enzymes. The exact mechanism used by L-asparaginases to catalyze the hydrolysis of asparagine into aspartic acid and ammonia has been recently put into question. Earlier experimental data suggested that the reaction proceeds via a covalent intermediate using a ping-pong mechanism, whereas recent computational work advocates the direct displacement of the amine by an activated water. To shed light on this controversy, we generated gpASNase1 mutants of conserved active site residues (T19A, T116A, T19A/T116A, K188M, and Y308F) suspected to play a role in hydrolysis. Using x-ray crystallography, we determined the crystal structures of the T19A, T116A, and K188M mutants soaked in asparagine. We also characterized their steady-state kinetic properties and analyzed the conversion of asparagine to aspartate using NMR. Our structures reveal bound asparagine in the active site that has unambiguously not formed a covalent intermediate. Kinetic and NMR assays detect significant residual activity for all of the mutants. Furthermore, no burst of ammonia production was observed that would indicate covalent intermediate formation and the presence of a ping-pong mechanism. Hence, despite using a variety of techniques, we were unable to obtain experimental evidence that would support the formation of a covalent intermediate. Consequently, our observations support a direct displacement rather than a ping-pong mechanism for l-asparaginases.

  15. Design and development of a solar array drive. [a direct drive solar array pointing mechanism

    NASA Technical Reports Server (NTRS)

    Rees, T.; Standing, J. M.

    1977-01-01

    The design and development of a dry lubricated direct drive solar array pointing mechanism is discussed for use on the Orbital Test Satellite (OTS), MAROTS, European Communication Satellite (ECS), and others. Results of life testing the original prototype and the OTS mechanism are presented together with an appraisal of expected future development.

  16. An Experimental Investigation of Mechanical Properties in Clay Brick Masonry by Partial Replacement of Fine Aggregate with Clay Brick Waste

    NASA Astrophysics Data System (ADS)

    Kumavat, Hemraj Ramdas

    2016-09-01

    The compressive stress-strain behavior and mechanical properties of clay brick masonry and its constituents clay bricks and mortar, have been studied by several laboratory tests. Using linear regression analysis, a analytical model has been proposed for obtaining the stress-strain curves for masonry that can be used in the analysis and design procedures. The model requires only the compressive strengths of bricks and mortar as input data, which can be easily obtained experimentally. Development of analytical model from the obtained experimental results of Young's modulus and compressive strength. Simple relationships have been identified for obtaining the modulus of elasticity of bricks, mortar, and masonry from their corresponding compressive strengths. It was observed that the proposed analytical model clearly demonstrates a reasonably good prediction of the stress-strain curves when compared with the experimental curves.

  17. Porous vitalium-base nano-composite for bone replacement: Fabrication, mechanical, and in vitro biological properties.

    PubMed

    Dehaghani, Majid Taghian; Ahmadian, Mehdi

    2016-04-01

    Porous nano-composites were successfully prepared on addition of 58S bioactive glass to Co-base alloy with porosities of 37.2-58.8% by the combination of milling, space-holder and powder metallurgy techniques. The results of X-ray diffraction analysis showed that induced strain during milling of the Co-base alloy powder and also isothermal heat treatment during sintering process led to HCP↔FCC phase transformation which affected mechanical properties of the samples during compression test. Field emission scanning electron microscopy images showed that despite the remaining 58S powder in nanometer size in the composite, there were micro-particles due to sintering at high temperature which led to two different apatite morphologies after immersion in simulated body fluid. Calculated elastic modulus and 0.2% proof strength from stress-strain curves of compression tests were in the range of 2.2-8.3GPa and 34-198MPa, respectively. In particular, the mechanical properties of sample with 37.2% were found to be similar to those of human cortical bone. Apatite formation which was identified by scanning electron microscopy (SEM), pH meter and Fourier-transform infrared spectroscopy (FTIR) analysis showed that it could successfully convert bioinert Co-base alloy to bioactive type by adding 58S bioglass nano-particles. SEM images of cell cultured on the porous nano-composite with 37.2% porosity showed that cells properly grew on the surface and inside the micro and macro-pores. PMID:26874088

  18. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

    PubMed Central

    Safari, Tahereh; Nematbakhsh, Mehdi; Evans, Roger G.; Denton, Kate M.

    2015-01-01

    Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7 ± 1.9% in estradiol-treated rats but only by 27.3 ± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. PMID:26681937

  19. Direct mechanical stimulation of tip links in hair cells through DNA tethers

    PubMed Central

    Basu, Aakash; Lagier, Samuel; Vologodskaia, Maria; Fabella, Brian A; Hudspeth, AJ

    2016-01-01

    Mechanoelectrical transduction by hair cells commences with hair-bundle deflection, which is postulated to tense filamentous tip links connected to transduction channels. Because direct mechanical stimulation of tip links has not been experimentally possible, this hypothesis has not been tested. We have engineered DNA tethers that link superparamagnetic beads to tip links and exert mechanical forces on the links when exposed to a magnetic-field gradient. By pulling directly on tip links of the bullfrog's sacculus we have evoked transduction currents from hair cells, confirming the hypothesis that tension in the tip links opens transduction channels. This demonstration of direct mechanical access to tip links additionally lays a foundation for experiments probing the mechanics of individual channels. DOI: http://dx.doi.org/10.7554/eLife.16041.001 PMID:27331611

  20. The behavior of the micro-mechanical cement-bone interface affects the cement failure in total hip replacement

    PubMed Central

    Waanders, Daan; Janssen, Dennis; Mann, Kenneth A.; Verdonschot, Nico

    2010-01-01

    In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle was investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro FEA-models. Case II, III and IV were analyzed using data from a stiff and a compliant micro-FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement-bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seem to be necessary. PMID:21036358

  1. Effect of Partial Replacement of Si with Al on the Microstructures and Mechanical Properties of 1000 MPa TRIP Steels

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Ding, Hua; Zhang, Jun; Di, Huafang

    2014-11-01

    Two newly synthesized C-Mn-Si-Mo-Nb transformation-induced plasticity (TRIP) steels with and without Al addition were designed in order to achieve significant improvements in the mechanical properties. The effect of substitution of Si by Al on tensile properties and the microstructure of cold-rolled C-Mn-Si TRIP steel was investigated under different heat treatments. It was shown that a complex ultrafine microstructure composed of different phases was formed and two types of morphology for ferrite were detected (equiaxial and polygonal). The distribution of alloying elements was observed by using electron probe microanalysis. It was clear that C was concentrated in the retained austenite (RA) and small M/A (austenite/martensite) islands. The Al addition facilitated the formation of polygonal ferrite and increased the stability of the RA. The strain-hardening behavior was studied in detail. All the investigated specimens showed a very high strain-hardening exponent (instantaneous n) but their strain dependence was different. For the C-Mn-Si-Mo-Nb TRIP steel, the maximum n value was achieved when the strain was only about 0.04, while the n value of the Al substituted TRIP steel increased gradually until strains in the range of 0.07-0.10 were reached and the maximum value was achieved. As a result, the elongations of the steel with Al addition increased considerably without obvious deterioration of strength. It was the first time to find microtwinned martensite located between ferrite and bainitic ferrite after tensile deformation in the low alloy TRIP steel with Al.

  2. Biological and mechanical properties of an experimental glass-ionomer cement modified by partial replacement of CaO with MgO or ZnO.

    PubMed

    Kim, Dong-Ae; Abo-Mosallam, Hany; Lee, Hye-Young; Lee, Jung-Hwan; Kim, Hae-Won; Lee, Hae-Hyoung

    2015-01-01

    Some weaknesses of conventional glass ionomer cement (GIC) as dental materials, for instance the lack of bioactive potential and poor mechanical properties, remain unsolved.Objective The purpose of this study was to investigate the effects of the partial replacement of CaO with MgO or ZnO on the mechanical and biological properties of the experimental glass ionomer cements.Material and Methods Calcium fluoro-alumino-silicate glass was prepared for an experimental glass ionomer cement by melt quenching technique. The glass composition was modified by partial replacement (10 mol%) of CaO with MgO or ZnO. Net setting time, compressive and flexural properties, and in vitrorat dental pulp stem cells (rDPSCs) viability were examined for the prepared GICs and compared to a commercial GIC.Results The experimental GICs set more slowly than the commercial product, but their extended setting times are still within the maximum limit (8 min) specified in ISO 9917-1. Compressive strength of the experimental GIC was not increased by the partial substitution of CaO with either MgO or ZnO, but was comparable to the commercial control. For flexural properties, although there was no significance between the base and the modified glass, all prepared GICs marked a statistically higher flexural strength (p<0.05) and comparable modulus to control. The modified cements showed increased cell viability for rDPSCs.Conclusions The experimental GICs modified with MgO or ZnO can be considered bioactive dental materials. PMID:26398508

  3. Biological and mechanical properties of an experimental glass-ionomer cement modified by partial replacement of CaO with MgO or ZnO.

    PubMed

    Kim, Dong-Ae; Abo-Mosallam, Hany; Lee, Hye-Young; Lee, Jung-Hwan; Kim, Hae-Won; Lee, Hae-Hyoung

    2015-01-01

    Some weaknesses of conventional glass ionomer cement (GIC) as dental materials, for instance the lack of bioactive potential and poor mechanical properties, remain unsolved.Objective The purpose of this study was to investigate the effects of the partial replacement of CaO with MgO or ZnO on the mechanical and biological properties of the experimental glass ionomer cements.Material and Methods Calcium fluoro-alumino-silicate glass was prepared for an experimental glass ionomer cement by melt quenching technique. The glass composition was modified by partial replacement (10 mol%) of CaO with MgO or ZnO. Net setting time, compressive and flexural properties, and in vitrorat dental pulp stem cells (rDPSCs) viability were examined for the prepared GICs and compared to a commercial GIC.Results The experimental GICs set more slowly than the commercial product, but their extended setting times are still within the maximum limit (8 min) specified in ISO 9917-1. Compressive strength of the experimental GIC was not increased by the partial substitution of CaO with either MgO or ZnO, but was comparable to the commercial control. For flexural properties, although there was no significance between the base and the modified glass, all prepared GICs marked a statistically higher flexural strength (p<0.05) and comparable modulus to control. The modified cements showed increased cell viability for rDPSCs.Conclusions The experimental GICs modified with MgO or ZnO can be considered bioactive dental materials.

  4. Target- and effect-directed actions towards temporal goals: similar mechanisms?

    PubMed

    Walter, Andrea M; Rieger, Martina

    2012-08-01

    The goal of an action can consist of generating a change in the environment (to produce an effect) or changing one's own situation in the environment (to move to a physical target). To investigate whether the mechanisms of effect-directed and target-directed action control are similar, participants performed continuous reversal movements. They either synchronized movement reversals with regularly presented tones (temporal targets) or produced tones at reversals isochronously (temporal effects). In both goal conditions an irrelevant goal characteristic was integrated into the goal representation (loudness, Experiment 1). When targets and effects were presented within the same reversal movement, similarities were enhanced (Experiment 2). When the task posed spatial demands in addition to temporal demands, target- and effect-directed movement kinematics changed equally with tempo (Experiment 3). Correlations between target-directed and effect-directed movements in temporal variability indicated similar timing mechanisms (Experiments 1 and 2). Only gradual differences between target- and effect-directed movements were observed. We conclude that the same mechanisms of action control, including the anticipation of upcoming events, underlie effect-directed and target-directed movements. Ideomotor theories of action control should incorporate action targets as goals similar to action effects. PMID:22686693

  5. The effect of cup inclination and wear on the contact mechanics and cement fixation for ultra high molecular weight polyethylene total hip replacements.

    PubMed

    Hua, Xijin; Wroblewski, B Michael; Jin, Zhongmin; Wang, Ling

    2012-04-01

    The present study aimed to investigate individual and combined influences of the cup inclination and wear on the contact mechanics and fixation of a Charnley hip replacement using finite element method. The effects of cup inclination and penetration on the contact mechanics of articulating bearings as well as the stress within the cement and at the bone-cement interface were examined. The maximum contact pressure and the von Mises stress on the cup were reduced by ~30% and ~20% respectively when even a small penetration occurred. However, no large differences were found between different cup penetration depths with regards to either the contact pressure or the von Mises stress. The von Mises stress at the bone-cement interface was predicted almost unaltered with an increased cup inclination angle to 55° for a cup penetration to 4mm. These predictions suggest that the contact mechanics and the cement stress are insensitive to the cup inclination and wear under these normal conditions investigated, therefore explaining the robustness of the Charnley hip implant. An increase in the cup inclination angle to 65°, coupled with a maximum penetration of 4mm, resulted in a large increase in the maximum von Mises stress at the bone-cement interface.

  6. A comparison in mechanical properties of cermets of calcium silicate with Ti-55Ni and Ti-6Al-4V alloys for hard tissues replacement.

    PubMed

    Ataollahi Oshkour, Azim; Pramanik, Sumit; Shirazi, Seyed Farid Seyed; Mehrali, Mehdi; Yau, Yat-Huang; Abu Osman, Noor Azuan

    2014-01-01

    This study investigated the impact of calcium silicate (CS) content on composition, compressive mechanical properties, and hardness of CS cermets with Ti-55Ni and Ti-6Al-4V alloys sintered at 1200°C. The powder metallurgy route was exploited to prepare the cermets. New phases of materials of Ni16Ti6Si7, CaTiO3, and Ni31Si12 appeared in cermet of Ti-55Ni with CS and in cermet of Ti-6Al-4V with CS, the new phases Ti5Si3, Ti2O, and CaTiO3, which were emerged during sintering at different CS content (wt%). The minimum shrinkage and density were observed in both groups of cermets for the 50 and 100 wt% CS content, respectively. The cermets with 40 wt% of CS had minimum compressive Young's modulus. The minimum of compressive strength and strain percentage at maximum load were revealed in cermets with 50 and 40 wt% of CS with Ti-55Ni and Ti-6Al-4V cermets, respectively. The cermets with 80 and 90 wt% of CS showed more plasticity than the pure CS. It concluded that the composition and mechanical properties of sintered cermets of Ti-55Ni and Ti-6Al-4V with CS significantly depend on the CS content in raw cermet materials. Thus, the different mechanical properties of the cermets can be used as potential materials for different hard tissues replacements. PMID:25538954

  7. Direct Associations or Internal Transformations? Exploring the Mechanisms Underlying Sequential Learning Behavior

    PubMed Central

    Gureckis, Todd M.; Love, Bradley C.

    2009-01-01

    We evaluate two broad classes of cognitive mechanisms that might support the learning of sequential patterns. According to the first, learning is based on the gradual accumulation of direct associations between events based on simple conditioning principles. The other view describes learning as the process of inducing the transformational structure that defines the material. Each of these learning mechanisms predict differences in the rate of acquisition for differently organized sequences. Across a set of empirical studies, we compare the predictions of each class of model with the behavior of human subjects. We find that learning mechanisms based on transformations of an internal state, such as recurrent network architectures (e.g., Elman, 1990), have difficulty accounting for the pattern of human results relative to a simpler (but more limited) learning mechanism based on learning direct associations. Our results suggest new constraints on the cognitive mechanisms supporting sequential learning behavior. PMID:20396653

  8. [Estrogen replacement].

    PubMed

    Søgaard, A J; Berntsen, G K; Magnus, J H; Tollan, A

    1998-02-10

    Recent research on long-term postmenopausal hormone replacement therapy (HRT) indicates a positive effect on both total mortality and morbidity. This has raised the question of widespread preventive long-term use of HRT. Possible side-effects and ideological issues related to preventive HRT have led to debate and uncertainty among health professionals, in the media, and in the population at large. In order to evaluate the level of knowledge about and attitudes towards HRT, a randomly selected group of 737 Norwegian women aged 16-79 was interviewed by the Central Bureau of Statistics. One in three women had received information about HRT in the last two years, mainly through weekly magazines and physicians. The proportion who answered the questions on knowledge correctly varied from 36% to 47%. Those who had been given information by a physician possessed accurate knowledge, had more positive attitudes towards HRT and were more willing to use HRT than women who had reviewed information through other channels. Women with a higher level of education were better informed and more knowledgeable than others, but were nevertheless more reluctant to use HRT than those who were less educated. The limited number of women who actually receive information on HRT, the low level of knowledge and the ambivalent attitudes toward HRT are a major challenge to the public health service.

  9. Nicotine replacement therapy

    MedlinePlus

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11: ...

  10. Skeletal mechanism generation for surrogate fuels using directed relation graph with error propagation and sensitivity analysis

    SciTech Connect

    Niemeyer, Kyle E.; Sung, Chih-Jen; Raju, Mandhapati P.

    2010-09-15

    A novel implementation for the skeletal reduction of large detailed reaction mechanisms using the directed relation graph with error propagation and sensitivity analysis (DRGEPSA) is developed and presented with examples for three hydrocarbon components, n-heptane, iso-octane, and n-decane, relevant to surrogate fuel development. DRGEPSA integrates two previously developed methods, directed relation graph-aided sensitivity analysis (DRGASA) and directed relation graph with error propagation (DRGEP), by first applying DRGEP to efficiently remove many unimportant species prior to sensitivity analysis to further remove unimportant species, producing an optimally small skeletal mechanism for a given error limit. It is illustrated that the combination of the DRGEP and DRGASA methods allows the DRGEPSA approach to overcome the weaknesses of each, specifically that DRGEP cannot identify all unimportant species and that DRGASA shields unimportant species from removal. Skeletal mechanisms for n-heptane and iso-octane generated using the DRGEP, DRGASA, and DRGEPSA methods are presented and compared to illustrate the improvement of DRGEPSA. From a detailed reaction mechanism for n-alkanes covering n-octane to n-hexadecane with 2115 species and 8157 reactions, two skeletal mechanisms for n-decane generated using DRGEPSA, one covering a comprehensive range of temperature, pressure, and equivalence ratio conditions for autoignition and the other limited to high temperatures, are presented and validated. The comprehensive skeletal mechanism consists of 202 species and 846 reactions and the high-temperature skeletal mechanism consists of 51 species and 256 reactions. Both mechanisms are further demonstrated to well reproduce the results of the detailed mechanism in perfectly-stirred reactor and laminar flame simulations over a wide range of conditions. The comprehensive and high-temperature n-decane skeletal mechanisms are included as supplementary material with this article

  11. Direct imaging of mechanical and chemical gradients across the thickness of graded organosilicone microwave PECVD coatings.

    PubMed

    Hall, Colin J; Murphy, Peter J; Griesser, Hans J

    2014-01-22

    The characterization of variations in the chemical composition and ensuing mechanical properties across the thickness of coatings with continuously varying compositions through their thickness (graded coatings) presents considerable challenges for current analytical techniques in materials science. We report here the direct imaging of nanomechanical and chemical gradients across cross-sections of an organosilicone coating fabricated via microwave plasma enhanced chemical vapor deposition (PECVD). Cross-sectional nanoindentation was used to determine the mechanical properties of uniform and graded organosilicone coatings. Both hardness and modulus across the coatings were directly measured. Additionally, "modulus mapping" on cross-sections was used to map the complex modulus. For the graded coating, it was found that variations in the complex modulus was predominantly due to varying storage modulus. It was observed that at the interface with the substrate there was a low storage modulus, which linearly increased to a relatively high storage modulus at the surface. It is proposed that the increase in stiffness, from the substrate interface to the outer surface, is due to the increasing content of a cross-linked O-Si-O network. This mechanical gradient has been linked to a change in the Si:O ratio via direct compositional mapping using ToF-SIMS. Direct mapping of the mechanical and compositional gradients across these protective coatings provides insight into the changes in properties with depth and supports optimization of the critical mechanical performance of PECVD graded coatings.

  12. Prickle isoforms control the direction of tissue polarity by microtubule independent and dependent mechanisms.

    PubMed

    Sharp, Katherine A; Axelrod, Jeffrey D

    2016-01-01

    Planar cell polarity signaling directs the polarization of cells within the plane of many epithelia. While these tissues exhibit asymmetric localization of a set of core module proteins, in Drosophila, more than one mechanism links the direction of core module polarization to the tissue axes. One signaling system establishes a polarity bias in the parallel, apical microtubules upon which vesicles containing core proteins traffic. Swapping expression of the differentially expressed Prickle isoforms, Prickle and Spiny-legs, reverses the direction of core module polarization. Studies in the proximal wing and the anterior abdomen indicated that this results from their differential control of microtubule polarity. Prickle and Spiny-legs also control the direction of polarization in the distal wing (D-wing) and the posterior abdomen (P-abd). We report here that this occurs without affecting microtubule polarity in these tissues. The direction of polarity in the D-wing is therefore likely determined by a novel mechanism independent of microtubule polarity. In the P-abd, Prickle and Spiny-legs interpret at least two directional cues through a microtubule-polarity-independent mechanism.

  13. Prickle isoforms control the direction of tissue polarity by microtubule independent and dependent mechanisms

    PubMed Central

    Sharp, Katherine A.; Axelrod, Jeffrey D.

    2016-01-01

    ABSTRACT Planar cell polarity signaling directs the polarization of cells within the plane of many epithelia. While these tissues exhibit asymmetric localization of a set of core module proteins, in Drosophila, more than one mechanism links the direction of core module polarization to the tissue axes. One signaling system establishes a polarity bias in the parallel, apical microtubules upon which vesicles containing core proteins traffic. Swapping expression of the differentially expressed Prickle isoforms, Prickle and Spiny-legs, reverses the direction of core module polarization. Studies in the proximal wing and the anterior abdomen indicated that this results from their differential control of microtubule polarity. Prickle and Spiny-legs also control the direction of polarization in the distal wing (D-wing) and the posterior abdomen (P-abd). We report here that this occurs without affecting microtubule polarity in these tissues. The direction of polarity in the D-wing is therefore likely determined by a novel mechanism independent of microtubule polarity. In the P-abd, Prickle and Spiny-legs interpret at least two directional cues through a microtubule-polarity-independent mechanism. PMID:26863941

  14. Dissecting the Catalytic Mechanism of Betaine-Homocysteine S-Methyltransferase Using Intrinsic Tryptophan Fluorescence and Site-Directed Mutagenesis

    SciTech Connect

    Castro, C.; Gratson, A.A.; Evans, J.C.; Jiracek, J.; Collinsova, M.; Ludwig, M.L.; Garrow, T.A.

    2010-03-05

    Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met). Previous studies in other laboratories have indicated that catalysis proceeds through the formation of a ternary complex, with a transition state mimicked by the inhibitor S-({delta}-carboxybutyl)-l-homocysteine (CBHcy). Using changes in intrinsic tryptophan fluorescence to determine the affinity of human BHMT for substrates, products, or CBHcy, we now demonstrate that the enzyme-substrate complex reaches its transition state through an ordered bi-bi mechanism in which Hcy is the first substrate to bind and Met is the last product released. Hcy, Met, and CBHcy bind to the enzyme to form binary complexes with K{sub d} values of 7.9, 6.9, and 0.28 {micro}M, respectively. Binary complexes with Bet and DMG cannot be detected with fluorescence as a probe, but Bet and DMG bind tightly to BHMT-Hcy to form ternary complexes with K{sub d} values of 1.1 and 0.73 {micro}M, respectively. Mutation of each of the seven tryptophan residues in human BHMT provides evidence that the enzyme undergoes two distinct conformational changes that are reflected in the fluorescence of the enzyme. The first is induced when Hcy binds, and the second, when Bet binds. As predicted by the crystal structure of BHMT, the amino acids Trp44 and Tyr160 are involved in binding Bet, and Glu159 in binding Hcy. Replacing these residues by site-directed mutagenesis significantly reduces the catalytic efficiency (V{sub max}/K{sub m}) of the enzyme. Replacing Tyr77 with Phe abolishes enzyme activity.

  15. Brain mechanisms associated with internally directed attention and self-generated thought.

    PubMed

    Benedek, Mathias; Jauk, Emanuel; Beaty, Roger E; Fink, Andreas; Koschutnig, Karl; Neubauer, Aljoscha C

    2016-01-01

    Internal cognition like imagination and prospection require sustained internally directed attention and involve self-generated thought. This fMRI study aimed to disentangle the brain mechanisms associated with attention-specific and task-specific processes during internally directed cognition. The direction of attention was manipulated by either keeping a relevant stimulus visible throughout the task, or by masking it, so that the task had to be performed "in the mind's eye". The level of self-directed thought was additionally varied between a convergent and a divergent thinking task. Internally directed attention was associated with increased activation in the right anterior inferior parietal lobe (aIPL), bilateral lingual gyrus and the cuneus, as well as with extended deactivations of superior parietal and occipital regions representing parts of the dorsal attention network. The right aIPL further showed increased connectivity with occipital regions suggesting an active top-down mechanism for shielding ongoing internal processes from potentially distracting sensory stimulation in terms of perceptual decoupling. Activation of the default network was not related to internally directed attention per se, but rather to a higher level of self-generated thought. The findings hence shed further light on the roles of inferior and superior parietal cortex for internally directed cognition. PMID:26960259

  16. Brain mechanisms associated with internally directed attention and self-generated thought

    PubMed Central

    Benedek, Mathias; Jauk, Emanuel; Beaty, Roger E.; Fink, Andreas; Koschutnig, Karl; Neubauer, Aljoscha C.

    2016-01-01

    Internal cognition like imagination and prospection require sustained internally directed attention and involve self-generated thought. This fMRI study aimed to disentangle the brain mechanisms associated with attention-specific and task-specific processes during internally directed cognition. The direction of attention was manipulated by either keeping a relevant stimulus visible throughout the task, or by masking it, so that the task had to be performed “in the mind’s eye”. The level of self-directed thought was additionally varied between a convergent and a divergent thinking task. Internally directed attention was associated with increased activation in the right anterior inferior parietal lobe (aIPL), bilateral lingual gyrus and the cuneus, as well as with extended deactivations of superior parietal and occipital regions representing parts of the dorsal attention network. The right aIPL further showed increased connectivity with occipital regions suggesting an active top-down mechanism for shielding ongoing internal processes from potentially distracting sensory stimulation in terms of perceptual decoupling. Activation of the default network was not related to internally directed attention per se, but rather to a higher level of self-generated thought. The findings hence shed further light on the roles of inferior and superior parietal cortex for internally directed cognition. PMID:26960259

  17. A Comparison in Mechanical Properties of Cermets of Calcium Silicate with Ti-55Ni and Ti-6Al-4V Alloys for Hard Tissues Replacement

    PubMed Central

    Pramanik, Sumit; Shirazi, Seyed Farid Seyed; Mehrali, Mehdi; Yau, Yat-Huang; Abu Osman, Noor Azuan

    2014-01-01

    This study investigated the impact of calcium silicate (CS) content on composition, compressive mechanical properties, and hardness of CS cermets with Ti-55Ni and Ti-6Al-4V alloys sintered at 1200°C. The powder metallurgy route was exploited to prepare the cermets. New phases of materials of Ni16Ti6Si7, CaTiO3, and Ni31Si12 appeared in cermet of Ti-55Ni with CS and in cermet of Ti-6Al-4V with CS, the new phases Ti5Si3, Ti2O, and CaTiO3, which were emerged during sintering at different CS content (wt%). The minimum shrinkage and density were observed in both groups of cermets for the 50 and 100 wt% CS content, respectively. The cermets with 40 wt% of CS had minimum compressive Young's modulus. The minimum of compressive strength and strain percentage at maximum load were revealed in cermets with 50 and 40 wt% of CS with Ti-55Ni and Ti-6Al-4V cermets, respectively. The cermets with 80 and 90 wt% of CS showed more plasticity than the pure CS. It concluded that the composition and mechanical properties of sintered cermets of Ti-55Ni and Ti-6Al-4V with CS significantly depend on the CS content in raw cermet materials. Thus, the different mechanical properties of the cermets can be used as potential materials for different hard tissues replacements. PMID:25538954

  18. Directional and temporal variation of the mechanical properties of robocast scaffold during resorption.

    PubMed

    Waygood, J; Murch, G E; Fiedler, T

    2015-09-01

    This paper addresses the mechanical behavior of robocast PCL-Bioglass(®) scaffolds. These structures can be used as 3rd generation implants in tissue engineering to support the regrowth of damaged tissue, in particular bone. After successful tissue regeneration the scaffolds slowly dissolve leaving no foreign material permanently inside the body. However, to avoid mechanical separation from surrounding tissue they must exhibit similar mechanical properties. The present study introduces a detailed numerical study focusing on the determination of effective mechanical material properties, their anisotropy, and mechanical degradation due to scaffold resorption. In order to accurately capture the complex scaffold geometry, micro-computed tomography scans of actual samples are conducted. The resulting three-dimensional data are directly converted into finite element calculation models. Numerical compressive tests of these unmodified models are repeated for three perpendicular directions to investigate mechanical anisotropy, after which the effect of scaffold degradation due to exposure to body fluid is simulated. To this end, two different resorption models, namely surface erosion and bulk degradation, are applied to the micro-computed tomography data. The modified geometry data are then converted into calculation models and numerical compression tests then allow the prediction of the mechanical properties of partially resorbed scaffolds.

  19. Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

    PubMed Central

    Verrier, Cécile; Lassalas, Pierrik; Théveau, Laure; Quéguiner, Guy; Trécourt, François; Marsais, Francis

    2011-01-01

    Summary Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki–Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented. PMID:22238536

  20. Mechanism of sulfide mineralization through successive metasomatic replacement stages of zoned host dolomite in Cracow-Silesian Zn-Pb deposits (Mississippi Valley type), Pomorzany Mine, Poland

    NASA Astrophysics Data System (ADS)

    Osman, A.; Piestrzyński, A.

    1989-01-01

    Replacement of dolomite rhombs is zone selective in Cracow-Silesian Zn-Pb deposits. The discussed replacement of dolomite by sphalerite occurs as spotted sphalerite ore constituting about one-fourth of the economic sulfide mineralization of the Pomorzany Mine. Replacement is controlled by two factors, i.e., microporosity and chemical composition. The epigenetic host dolomite rhombs are zoned into three main zones, i.e., the outer rhombohedral rim which is hard and Fe rich with remarkable Zn content, the inner zone which is porous and Zn rich but usually low in Fe content, and the core of the dolomite rhombs which is Fe free but may contain some Zn. Zones rich in Zn were the first to be replaced by sphalerite; the same holds true for zones with higher microporosity showing a high degree of crystallographic disorder of cations. The other zones seem to be intact. There are four successive replacement stages, i.e., partial, moderate, intense, and advanced. During replacement the intact parts become more Zn-rich, consequently being replaced completely in the later stages, the greater the zinc content in the host dolomite is, the more reactive it is to replacement by sphalerite. The liberated iron from replaced Fe-rich zones is fixed as finely crystalline pyrite.

  1. Study on the Mechanical Properties of Three-Dimensional Directly Binding Hydroxyapatite Powder.

    PubMed

    Wang, Yanen; Li, Xinpei; Wei, Qinghua; Yang, Mingming; Wei, Shengmin

    2015-05-01

    In the three-dimensional directly fabricating hydroxyapatite composite artificial bone scaffold process, the liquid bio-binder is sprayed on the surface of bioceramics powder layer. The spraying volume and the powder size directly influence the mechanical properties of the bone scaffold and the future biodegradation performance. When the size of powder is stable, the amount of binder spraying will directly affect the mechanical strength of bone scaffold. In order to figure out the solidification mechanism of α-n-butyl cyanoacrylate (NBCA) bio-binder on the hydroxyapatite (HA) powder layer, the molecular dynamics simulation method is applied to investigate the binding energy shifts between NBCA on HA crystallographic planes. The mechanical properties can be deduced from this methodology; furthermore, the Knoop identification experiments are used to investigate the effective elastic modules of pure HA system and HA/NBCA composite model. Both the simulation and the experiments results elucidate that HA (110) has the highest binding energy with NBCA as the high planar atom density and the mechanical properties of HA/NBCA mixed system are stronger than the pure HA system on three-dimensional crystallographic; in this sense, the bone scaffolds with different strengths could be fabricated by controlling various NBCA binders liquid doses on the surface of HA powder layers during the 3D printing process.

  2. The main problems in the mechanical engineering sector and some possible directions of their solution

    NASA Astrophysics Data System (ADS)

    Strizhakova, E.

    2016-04-01

    The article shows the problems of the sector of mechanical engineering in the industrial system in Russia. The author's method of estimating the relative level of risk and the method of determining the de-industrialization degree of the sector based on the aggregated level of adaptability are given. According to them we have analysed the key indicators, such as basic, developed and advanced technologies, and investments in an old or new technology of industrial sectors. The main directions of the impact of industrial policy allowing a change in the current situation in mechanical engineering are given. The results can be applied in practice in formation of directions and actual control actions to improve the overall efficiency of mechanical engineering industry.

  3. Mechanism for the Direct Synthesis of H2O2 on Pd Clusters: Heterolytic Reaction Pathways at the Liquid-Solid Interface.

    PubMed

    Wilson, Neil M; Flaherty, David W

    2016-01-20

    Direct synthesis (H2 + O2 → H2O2) is a promising reaction for producing H2O2, which can replace chlorinated oxidants in industrial processes. The mechanism of this reaction and the reasons for the importance of seemingly unrelated factors (e.g., Pd cluster size and solvent pH) remain unclear despite significant research. We propose a mechanism for H2O2 formation on Pd clusters consistent with steady-state H2O2 and H2O formation rates measured as functions of reactant pressures and temperature and the interpretations of proton concentration effects. H2O2 forms by sequential proton-electron transfer to O2 and OOH surface intermediates, whereas H2O forms by O-O bond rupture within OOH surface species. Direct synthesis, therefore, does not proceed by the Langmuir-Hinshelwood mechanism often invoked. Rather, H2O2 forms by heterolytic reaction pathways resembling the two-electron oxygen reduction reaction (ORR); however, the chemical potential of H2 replaces an external electrical potential as the thermodynamic driving force. Activation enthalpies (ΔH(⧧)) for H2O formation increase by 14 kJ mol(-1) when Pd cluster diameters increase from 0.7 to 7 nm because changes in the electronic structure of Pd surface atoms decrease their propensity to cleave O-O bonds. ΔH(⧧) values for H2O2 remain nearly constant because barriers for proton-electron transfer depend weakly on the coordinative saturation of Pd surface atoms. Collectively, these results provide a self-consistent mechanism, which clarifies many studies in which H2O2 rates and selectivities were shown to depend on the concentration of acid/halide additives and Pd cluster size. These findings will guide the rational design of selective catalysts for direct synthesis.

  4. Mechanism for the Direct Synthesis of H2O2 on Pd Clusters: Heterolytic Reaction Pathways at the Liquid-Solid Interface.

    PubMed

    Wilson, Neil M; Flaherty, David W

    2016-01-20

    Direct synthesis (H2 + O2 → H2O2) is a promising reaction for producing H2O2, which can replace chlorinated oxidants in industrial processes. The mechanism of this reaction and the reasons for the importance of seemingly unrelated factors (e.g., Pd cluster size and solvent pH) remain unclear despite significant research. We propose a mechanism for H2O2 formation on Pd clusters consistent with steady-state H2O2 and H2O formation rates measured as functions of reactant pressures and temperature and the interpretations of proton concentration effects. H2O2 forms by sequential proton-electron transfer to O2 and OOH surface intermediates, whereas H2O forms by O-O bond rupture within OOH surface species. Direct synthesis, therefore, does not proceed by the Langmuir-Hinshelwood mechanism often invoked. Rather, H2O2 forms by heterolytic reaction pathways resembling the two-electron oxygen reduction reaction (ORR); however, the chemical potential of H2 replaces an external electrical potential as the thermodynamic driving force. Activation enthalpies (ΔH(⧧)) for H2O formation increase by 14 kJ mol(-1) when Pd cluster diameters increase from 0.7 to 7 nm because changes in the electronic structure of Pd surface atoms decrease their propensity to cleave O-O bonds. ΔH(⧧) values for H2O2 remain nearly constant because barriers for proton-electron transfer depend weakly on the coordinative saturation of Pd surface atoms. Collectively, these results provide a self-consistent mechanism, which clarifies many studies in which H2O2 rates and selectivities were shown to depend on the concentration of acid/halide additives and Pd cluster size. These findings will guide the rational design of selective catalysts for direct synthesis. PMID:26597848

  5. Mechanical Determinants of Faster Change of Direction and Agility Performance in Female Basketball Athletes.

    PubMed

    Spiteri, Tania; Newton, Robert U; Binetti, Molly; Hart, Nicolas H; Sheppard, Jeremy M; Nimphius, Sophia

    2015-08-01

    Change of direction (COD) and agility require the integration of multiple components to produce a faster performance. However, the mechanisms contributing to a faster performance without the confounding factor of athlete expertise or gender is currently unknown. Therefore, the purpose of this study was to assess body composition, strength, and kinetic profile required for a faster COD and agility performance across multiple directional changes. Six faster and 6 slower (n = 12) elite female basketball athletes completed a maximal dynamic back squat; eccentric and concentric only back squat; isometric midthigh pull; whole-body scan to determine lean, fat, and total mass; 505 COD test; T-test; and a multidirectional agility test over in-ground force plates to obtain relevant kinetic measures. Group (faster and slower) by test (2 × 3) multivariate analyses of variance with follow-up analyses of variance were conducted to examine differences between faster and slower groups and each COD and agility test (p ≤ 0.05). Faster athletes during the 505 COD test produced significantly greater vertical force (p = 0.002) and eccentric and isometric strength capacity (p = 0.001). Faster agility and T-test athletes demonstrated significantly shorter contact times (p = 0.001), greater propulsive impulse (p = 0.02), isometric strength, and relative lean mass compared with slower athletes. Differences between faster athletes across each test seem to be attributed to the mechanical demands of the directional change, increasing force and impulse application as the degree of directional change increased. These findings indicate that different mechanical properties are required to produce a faster COD and agility performances, and the importance of a greater strength capacity to enable greater mechanical adjustment through force production and body control, during different directional changes.

  6. [Distinct roles of the direct and indirect pathways in the basal ganglia circuit mechanism].

    PubMed

    Morita, Makiko; Hikida, Takatoshi

    2015-11-01

    The basal ganglia are key neural substrates that control not only motor balance but also emotion, motivation, cognition, learning, and decision-making. Dysfunction of the basal ganglia leads to neurodegenerative diseases (e.g. Parkinson's disease and Huntington's disease) and psychiatric disorders (e.g. drug addiction, schizophrenia, and depression). In the basal ganglia circuit, there are two important pathways: the direct and indirect striatal pathways. Recently, new molecular techniques that activate or inactive selectively the direct or indirect pathway neurons have revealed the function of each pathway. Here we review the distinct roles of the direct and indirect striatal pathways in brain function and drug addiction. We have developed a reversible neurotransmission blocking technique, in which transmission of each pathway is selectively blocked by specific expression of transmission-blocking tetanus toxin, and revealed that the activation of D1 receptors in the direct pathway is critical for reward learning/cocaine addiction, and that the inactivation of D2 receptors is critical for aversive learning/learning flexibility. We propose a new circuit mechanism by which the dopaminergic input from the ventral tegmental area can switch the direct and indirect pathways in the nucleus accumbens. These basal ganglia circuit mechanisms will give us insights into the pathophysiology of mental diseases. PMID:26785520

  7. Reaction Mechanism of Siderite Lump in Coal-Based Direct Reduction

    NASA Astrophysics Data System (ADS)

    Zhu, Deqing; Luo, Yanhong; Pan, Jian; Zhou, Xianlin

    2016-02-01

    Siderite is one of the significant iron ore resources in China and yet is difficult to upgrade by traditional beneficiation processes. A process of coal-based direct reduction-magnetic separation was successfully developed for the beneficiation of siderite. However, few studies have thoroughly investigated the mechanism of the direct reduction of siderite. In order to reveal the reaction mechanism of coal-based direct reduction of siderite lump, thermodynamics of direct reduction was investigated with coal as the reductant. The thermodynamics results indicate that coal-based direct reduction process of siderite lump at 1,050°C follows the steps as FeCO3→ Fe3O4→ FeO → Fe, which is verified by chemical titration analysis, X-ray diffraction and scanning electron microscope. The microstructure of siderite sample varies with different reduction stages and some 45% porosity induced by thermal decomposition of siderite is conductive to subsequent reduction. The conversion of FeO to Fe is the main reduction rate-controlling step. The reduced product with the metallic iron size over 30 μm can be effectively beneficiated by wet magnetic separation after grinding. The obvious layered structure of reduced product is due to different heat transfer resistance, CO and CO2 concentration.

  8. Seizures induced by direct electrical cortical stimulation--Mechanisms and clinical considerations.

    PubMed

    Kovac, Stjepana; Kahane, Philippe; Diehl, Beate

    2016-01-01

    Direct electrical cortical stimulation (CS) is widely used to map eloquent cortex. It can be applied extraoperatively in patients undergoing intracranial EEG recordings using chronically implanted electrodes (subdural, depth or a combination), or it can be used intraoperatively. Seizures can be induced by CS but there is controversy regarding the utility of CS induced seizures in defining the epileptogenic zone and hence practice varies considerably between centres. Some centres use seizures induced by direct CS routinely to aid in defining the epileptogenic zone. In contrast, others do not rely on such information and explicitly avoid stimulating seizures during cortical mapping. Intra- and extraoperative techniques have been used to stimulate seizures with varying results, which may in part reflect these methodological differences. We here aim to review current views, definitions and studies on seizures induced by direct electrical CS. In addition we discuss mechanisms and methodological considerations of this procedure. PMID:25613034

  9. Dissociative Electron Attachment to Phosphoric Acid Esters: The Direct Mechanism for Single Strand Breaks in DNA

    SciTech Connect

    Koenig, Constanze; Kopyra, Janina; Bald, Ilko; Illenberger, Eugen

    2006-07-07

    We use dibutyl phosphate to simulate the behavior of the phosphate group in DNA towards the attack of low energy electrons. We find that the compound undergoes effective dissociative electron attachment within a low energy resonant feature at 1 eV and a further resonance peaking at 8 eV. The dissociative electron attachment (DEA) reactions are associated with the direct cleavage of the C-O and the P-O bond but also the excision of the PO{sup -}, PO{sub 3}{sup -}, H{sub 2}PO{sub 3}{sup -} units. For the phosphate group coupled in the DNA network these reactions represent single strand breaks. We hence propose that the most direct mechanism of single strand breaks occurring in DNA at subexcitation energies (<4 eV) is due to DEA directly to the phosphate group.

  10. Directional variations of mechanical parameters in rat skin depending on maturation and age.

    PubMed

    Vogel, H G

    1981-06-01

    Mechanical properties of rat back skin at low loads and at failure were studied in 2 directions, e.g., perpendicular and longitudinal to body axis beginning with early maturation (from 1 week onwards) until senescence (at 24 mo). Anisotropic behavior, known for human skin, has also been found in rats. Surprisingly, the changes due to maturation and aging were not the same for one area of skin regardless of the direction. Ultimate extension was more influenced by the aging process in samples perpendicular to the body axis than in those parallel to body axis. Elongation at zero load, that means load not measurable under the described conditions, was higher in the longitudinal samples than in the perpendicular ones in young and very old animals, whereas this difference was absent in mature animals. In contrast, ultimate load, tensile strength and modulus of elasticity were higher in perpendicular samples than in samples longitudinal to the body axis for young and very old, but not for mature animals. Elongation at low loads or low stresses shows a different pattern than at medium loads or medium stresses when both directions are compared. Apparently, elements contributing to the mechanical properties in the various directions are differently influenced by the maturation and aging processes. Moreover, the elements contributing to the changes at low loads react differently to the aging process from those responsible for the effects at medium and high loads.

  11. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces.

    PubMed

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-01-01

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field. PMID:24149467

  12. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces

    NASA Astrophysics Data System (ADS)

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-10-01

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.

  13. Nucleation mechanism for the direct graphite-to-diamond phase transition.

    PubMed

    Khaliullin, Rustam Z; Eshet, Hagai; Kühne, Thomas D; Behler, Jörg; Parrinello, Michele

    2011-07-24

    Graphite and diamond have comparable free energies, yet forming diamond from graphite in the absence of a catalyst requires pressures that are significantly higher than those at equilibrium coexistence. At lower temperatures, the formation of the metastable hexagonal polymorph of diamond is favoured instead of the more stable cubic diamond. These phenomena cannot be explained by the concerted mechanism suggested in previous theoretical studies. Using an ab initio quality neural-network potential, we carried out a large-scale study of the graphite-to-diamond transition assuming that it occurs through nucleation. The nucleation mechanism accounts for the observed phenomenology and reveals its microscopic origins. We demonstrate that the large lattice distortions that accompany the formation of diamond nuclei inhibit the phase transition at low pressure, and direct it towards the hexagonal diamond phase at higher pressure. The proposed nucleation mechanism should improve our understanding of structural transformations in a wide range of carbon-based materials.

  14. Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle

    NASA Astrophysics Data System (ADS)

    Lee, Kian-Yong; Esmaeili, Behrooz; Zealley, Ben; Mishima, Masanori

    2015-06-01

    During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, which determine spindle positioning and drive chromosome segregation through spindle elongation. The central spindle should be flexible enough for efficient chromosome segregation while maintaining its structural integrity for reliable cytokinesis. How the cell balances these potentially conflicting requirements is poorly understood. Here, we demonstrate that the central spindle in C. elegans embryos has a resilient mechanism for recovery from perturbations by excess tension derived from cortical pulling forces. This mechanism involves the direct interaction of two different types of conserved microtubule bundlers that are crucial for central spindle formation, PRC1 and centralspindlin.

  15. Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle

    PubMed Central

    Lee, Kian-Yong; Esmaeili, Behrooz; Zealley, Ben; Mishima, Masanori

    2015-01-01

    During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, which determine spindle positioning and drive chromosome segregation through spindle elongation. The central spindle should be flexible enough for efficient chromosome segregation while maintaining its structural integrity for reliable cytokinesis. How the cell balances these potentially conflicting requirements is poorly understood. Here, we demonstrate that the central spindle in C. elegans embryos has a resilient mechanism for recovery from perturbations by excess tension derived from cortical pulling forces. This mechanism involves the direct interaction of two different types of conserved microtubule bundlers that are crucial for central spindle formation, PRC1 and centralspindlin. PMID:26088160

  16. Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle.

    PubMed

    Lee, Kian-Yong; Esmaeili, Behrooz; Zealley, Ben; Mishima, Masanori

    2015-01-01

    During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, which determine spindle positioning and drive chromosome segregation through spindle elongation. The central spindle should be flexible enough for efficient chromosome segregation while maintaining its structural integrity for reliable cytokinesis. How the cell balances these potentially conflicting requirements is poorly understood. Here, we demonstrate that the central spindle in C. elegans embryos has a resilient mechanism for recovery from perturbations by excess tension derived from cortical pulling forces. This mechanism involves the direct interaction of two different types of conserved microtubule bundlers that are crucial for central spindle formation, PRC1 and centralspindlin. PMID:26088160

  17. Nucleation mechanism for the direct graphite-to-diamond phase transition.

    PubMed

    Khaliullin, Rustam Z; Eshet, Hagai; Kühne, Thomas D; Behler, Jörg; Parrinello, Michele

    2011-09-01

    Graphite and diamond have comparable free energies, yet forming diamond from graphite in the absence of a catalyst requires pressures that are significantly higher than those at equilibrium coexistence. At lower temperatures, the formation of the metastable hexagonal polymorph of diamond is favoured instead of the more stable cubic diamond. These phenomena cannot be explained by the concerted mechanism suggested in previous theoretical studies. Using an ab initio quality neural-network potential, we carried out a large-scale study of the graphite-to-diamond transition assuming that it occurs through nucleation. The nucleation mechanism accounts for the observed phenomenology and reveals its microscopic origins. We demonstrate that the large lattice distortions that accompany the formation of diamond nuclei inhibit the phase transition at low pressure, and direct it towards the hexagonal diamond phase at higher pressure. The proposed nucleation mechanism should improve our understanding of structural transformations in a wide range of carbon-based materials. PMID:21785417

  18. A Korean Multi-Center Survey about Warfarin Management before Gastroenterological Endoscopy in Patients with a History of Mechanical Valve Replacement Surgery

    PubMed Central

    Son, Kuk Hui; Choi, Chang-Hyu; Lee, Jae-Ik; Kim, Kun Woo; Kim, Ji Sung; Lee, So Young; Park, Kook Yang; Park, Chul Hyun

    2016-01-01

    Background Guidelines for esophagogastroduodenoscopy (EGD) in the West allow the continued use of warfarin under therapeutic international normalized ratio (INR) level. In Korea, no guidelines have been issued regarding warfarin treatment before EGD. The authors surveyed Korean cardiac surgeons about how Korean cardiac surgeons handle warfarin therapy before EGD using a questionnaire. Participants were requested to make decisions regarding the continuation of warfarin therapy in two hypothetical cases. Methods The questionnaire was administered to cardiac surgeons and consisted of eight questions, including two case scenarios. Results Thirty-six cardiac surgeons at 28 hospitals participated in the survey, and 52.7% of the participants chose to stop warfarin before EGD in aortic valve replacement patients without risk factors for thromboembolism. When the patient’s INR level was 2, 31% of the participants indicated that they would choose to continue warfarin therapy. For EGD with biopsy, 72.2% of the participants chose warfarin withdrawal, and 25% of the participants chose heparin replacement. In mitral valve replacement patients, 47.2% of the participants chose to discontinue warfarin, and 22.2% of the participants chose heparin replacement. For EGD with biopsy in patients with a mitral valve replacement, 58.3% of the participants chose to stop warfarin, and 41.7% of the participants chose heparin replacement. Conclusion This study demonstrated that attitudes regarding warfarin treatment for EGD are very different among Korean surgeons. Guidelines specific to the Korean population are required. PMID:27733991

  19. Renal Replacement Therapy

    PubMed Central

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology. PMID:26918174

  20. Renal Replacement Therapy.

    PubMed

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  1. Hip joint replacement

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002975.htm Hip joint replacement To use the sharing features on this page, please enable JavaScript. Hip joint replacement is surgery to replace all or part ...

  2. Use of an Edwards Sapien S3 valve to replace a dysfunctional mechanical mitral valve in an 11-year old boy: another small step for surgical and interventional collaboration.

    PubMed

    Murphy, Michael; Austin, Conal; Bapat, Vinayak; Morgan, Gareth J

    2016-09-01

    An 11-year old boy, with complex left ventricular morphology in the setting of repaired double outlet right ventricle developed progressive mitral regurgitation leading to a repair which failed, necessitating replacement of the valve with a 21 mm St. Jude mechanical prosthesis. He represented 3 weeks later in extremis with signs of severe mitral stenosis. The valve was replaced via a hybrid technique with a 26 mm Edwards Sapien 3 valve mounted on a MEMO 3D annuloplasty ring. One year later, the valve is functioning well with no regurgitation or evidence of an inflow gradient.

  3. Use of an Edwards Sapien S3 valve to replace a dysfunctional mechanical mitral valve in an 11-year old boy: another small step for surgical and interventional collaboration.

    PubMed

    Murphy, Michael; Austin, Conal; Bapat, Vinayak; Morgan, Gareth J

    2016-09-01

    An 11-year old boy, with complex left ventricular morphology in the setting of repaired double outlet right ventricle developed progressive mitral regurgitation leading to a repair which failed, necessitating replacement of the valve with a 21 mm St. Jude mechanical prosthesis. He represented 3 weeks later in extremis with signs of severe mitral stenosis. The valve was replaced via a hybrid technique with a 26 mm Edwards Sapien 3 valve mounted on a MEMO 3D annuloplasty ring. One year later, the valve is functioning well with no regurgitation or evidence of an inflow gradient. PMID:26994169

  4. Large-scale low temperature fabrication of SnO2 hollow/nanoporous nanostructures: the template-engaged replacement reaction mechanism and high-rate lithium storage

    NASA Astrophysics Data System (ADS)

    Ding, Yuan-Li; Wen, Yuren; van Aken, Peter A.; Maier, Joachim; Yu, Yan

    2014-09-01

    The morphology-controlled synthesis of SnO2 hollow/nanoporous nanostructures (nanotubes, urchin-like morphologies and nanospheres) was achieved via a template-engaged replacement reaction at a mild temperature (lower than 80 °C). The formation mechanism of hollow interior and nanoporous walls for the obtained SnO2 nanostructures (SnO2 nanotubes were used as an example) was investigated based on TEM and HRTEM observations during different reaction stages. It is found that bridge voids firstly form at the MnO2/SnO2 interface, followed by the inward development of voids before the MnO2 core is completely consumed. Two types of short-circuited galvanic cells, MnO2/Mn2+|SnO2/Sn2+ and concentration cell-SnO2/Sn2+ (interior)|SnO2/Sn2+ (exterior), are probably responsible for the formation of SnO2 nanotubes and outward growth of SnO2 along MnO2. Moreover, the calculation result of the outer diameter of SnO2 nanotubes is in good agreement with the observation results by SEM and TEM. When evaluated as anodes for lithium ion batteries (LIBs), the three SnO2 nanostructures exhibit superior rate capability and cycling performance. Especially, SnO2 nanotubes present the best rate capability: specific capacities of above 800 mA h g-1 at 200 mA g-1 and about 500 mA h g-1 at 4000 mA g-1 were achieved, respectively. Importantly, the 1D morphology of SnO2 nanotubes can be well preserved after prolonged cycling at a relatively high current density, indicating good structural stability of the resulting nanotubes during the Li+ insertion/extraction process. These results indicate that the obtained SnO2 hollow/nanoporous nanostructures would be promising anode materials for next-generation LIBs.The morphology-controlled synthesis of SnO2 hollow/nanoporous nanostructures (nanotubes, urchin-like morphologies and nanospheres) was achieved via a template-engaged replacement reaction at a mild temperature (lower than 80 °C). The formation mechanism of hollow interior and nanoporous walls

  5. Direct activation and anti-repression functions of GAL4-VP16 use distinct molecular mechanisms.

    PubMed Central

    Lyons, J G; Chambon, P

    1995-01-01

    In order to determine whether the molecular mechanisms used for direct activation by GAL4-VP16 are the same as those used for anti-repression, we have employed monoclonal antibodies specific for the VP16 activation domain. In the absence of added repressors, GAL4-VP16 was able to stimulate transcription from a template containing GAL4-binding sites, and the antibodies raised against the VP16 activation domain failed to inhibit this direct activation. GAL4-VP16 also was able to prevent histone H1-mediated repression by a mechanism that was strongly dependent on the presence of specific GAL4-binding elements in the promoter. However, in contrast to the assays conducted in the absence of repressors, the antibodies were strong inhibitors of GAL4-VP16-activated transcription in the presence of histone H1. Thus the binding of the antibodies distinguished between the direct activation and anti-repression functions of GAL4-VP16, indicating that these functions operate through distinct molecular mechanisms. The anti-repression-specific mechanism that is inhibitable by the antibodies acted at an early stage of preinitiation complex formation. Deletions of individual subdomains of the VP16 activation domain demonstrated that there was not a discrete subdomain responsible for the anti-repression function of GAL4-VP16. Thus, the inhibitory effect of the antibodies appeared to be due to the location of the epitope within the activator protein rather than to some inherent biochemical property of that region of the protein that is required specifically for anti-repression. The inhibitory effect of the antibodies also ruled out the possibility that steric exclusion of repressor proteins from the promoter was the sole means of anti-repression by the transcriptional activator. Images Figure 1 Figure 2 PMID:8554536

  6. Diesel exhaust particles induce aberrant alveolar epithelial directed cell movement by disruption of polarity mechanisms.

    PubMed

    LaGier, Adriana J; Manzo, Nicholas D; Dye, Janice A

    2013-01-01

    Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following injury requires efficient and directed alveolar epithelial cell migration, this study's goal was to understand the mechanisms underlying alveolar epithelial cells response to DEP, particularly when exposure is accompanied with comorbid lung injury. Separate mechanistic steps of directed migration were investigated in confluent murine LA-4 cells exposed to noncytotoxic concentrations (0-100 μg/cm(2)) of either automobile-emitted diesel exhaust particles (DEP(A)) or carbon black (CB) particles. A scratch wound model ascertained how DEP(A) exposure affected directional cell migration and BCECF ratio fluorimetry-monitored intracellular pH (pHi). Cells were immunostained with giantin to assess cell polarity, and with paxillin to assess focal cell adhesions. Cells were immunoblotted for ezrin/radixin/moesin (ERM) to assess cytoskeletal anchoring. Data demonstrate herein that exposure of LA-4 cells to DEP(A) (but not CB) resulted in delayed directional cell migration, impaired de-adhesion of the trailing edge cell processes, disrupted regulation of pHi, and altered Golgi polarity of leading edge cells, along with modified focal adhesions and reduced ERM levels, indicative of decreased cytoskeletal anchoring. The ability of DEP(A) to disrupt directed cell migration at multiple levels suggests that signaling pathways such as ERM/Rho are critical for transduction of ion transport signals into cytoskeletal arrangement responses. These results provide insights into the mechanisms by which chronic exposure to traffic-based emissions may result in decrements in lung capacity. PMID:23294296

  7. Mechanical interactions between ice crystals and red blood cells during directional solidification.

    PubMed

    Ishiguro, H; Rubinsky, B

    1994-10-01

    Experiments in which red blood cells were frozen on a directional solidification stage under a microscope show that there is a mechanical interaction between ice crystals and cells in which cells are pushed and deformed by the ice crystals. The mechanical interaction occurs during freezing of cells in physiological saline and is significantly inhibited by the addition of 20% v/v glycerol to the solution. The addition of osmotically insignificant quantities of antifreeze proteins from the winter flounder or ocean pout to the physiological saline with 20% v/v glycerol generates strong mechanical interactions between the ice and the cells. The cells were destroyed during freezing in physiological saline, survived freezing in physiological saline with glycerol, and were completely destroyed by the addition of antifreeze proteins to the solution with glycerol. The difference in cell survival through freezing and thawing appears to be related, in part, to the habit of ice crystal growing in the suspension of red blood cells and the nature of mechanical interaction between the ice crystal and the cells. This suggests that mechanical damage may be a factor during cryopreservation of cells.

  8. Direct simulation of proton-coupled electron transfer reaction dynamics and mechanisms

    NASA Astrophysics Data System (ADS)

    Kretchmer, Joshua S.; Miller, Thomas F., III

    2014-03-01

    Proton-coupled electron transfer (PCET) reactions, in which both an electron and an associated proton undergo reactive transfer, play an important role in many chemical and biological systems. Due to the complexity of this class of reactions, a variety of different mechanisms fall under the umbrella of PCET. However, the physical driving forces that determine the preferred mechanism in a given system still remain poorly understood. Towards this end, we extend ring polymer molecular dynamics (RPMD), a path-integral quantum dynamics method, to enable the direct simulation and characterization of PCET reaction dynamics in both fully atomistic and system-bath models of organometallic catalysts. In addition to providing validation for the simulation method via extensive comparison with existing PCET rate theories, we analyze the RPMD trajectories to investigate the competition between the concerted and sequential reaction mechanisms for PCET, elucidating the large role of the solvent in controlling the preferred mechanism. We further employ RPMD to determine the kinetics and mechanistic features of concerted PCET reactions across different regimes of electronic and vibrational coupling, providing evidence for a new and distinct PCET reaction mechanism.

  9. A Direct Mechanism of Ultrafast Intramolecular Singlet Fission in Pentacene Dimers.

    PubMed

    Fuemmeler, Eric G; Sanders, Samuel N; Pun, Andrew B; Kumarasamy, Elango; Zeng, Tao; Miyata, Kiyoshi; Steigerwald, Michael L; Zhu, X-Y; Sfeir, Matthew Y; Campos, Luis M; Ananth, Nandini

    2016-05-25

    Interest in materials that undergo singlet fission (SF) has been catalyzed by the potential to exceed the Shockley-Queisser limit of solar power conversion efficiency. In conventional materials, the mechanism of SF is an intermolecular process (xSF), which is mediated by charge transfer (CT) states and depends sensitively on crystal packing or molecular collisions. In contrast, recently reported covalently coupled pentacenes yield ∼2 triplets per photon absorbed in individual molecules: the hallmark of intramolecular singlet fission (iSF). However, the mechanism of iSF is unclear. Here, using multireference electronic structure calculations and transient absorption spectroscopy, we establish that iSF can occur via a direct coupling mechanism that is independent of CT states. We show that a near-degeneracy in electronic state energies induced by vibronic coupling to intramolecular modes of the covalent dimer allows for strong mixing between the correlated triplet pair state and the local excitonic state, despite weak direct coupling. PMID:27280166

  10. A Direct Mechanism of Ultrafast Intramolecular Singlet Fission in Pentacene Dimers

    PubMed Central

    2016-01-01

    Interest in materials that undergo singlet fission (SF) has been catalyzed by the potential to exceed the Shockley–Queisser limit of solar power conversion efficiency. In conventional materials, the mechanism of SF is an intermolecular process (xSF), which is mediated by charge transfer (CT) states and depends sensitively on crystal packing or molecular collisions. In contrast, recently reported covalently coupled pentacenes yield ∼2 triplets per photon absorbed in individual molecules: the hallmark of intramolecular singlet fission (iSF). However, the mechanism of iSF is unclear. Here, using multireference electronic structure calculations and transient absorption spectroscopy, we establish that iSF can occur via a direct coupling mechanism that is independent of CT states. We show that a near-degeneracy in electronic state energies induced by vibronic coupling to intramolecular modes of the covalent dimer allows for strong mixing between the correlated triplet pair state and the local excitonic state, despite weak direct coupling. PMID:27280166

  11. Density functional theory study of direct and indirect photodegradation mechanisms of sulfameter.

    PubMed

    Shah, Shaheen; Hao, Ce

    2016-10-01

    Sulfonamide antibiotics (SAs) have been observed to undergo direct and indirect photodegradation in natural water environments. In this study, the density functional theory (DFT) method was employed for the study of direct and indirect photodegradation mechanisms of sulfameter (SME) with excited triplet states of dissolved organic matter ((3)DOM(*)) and metal ions. SME was adopted as a representative of SAs, and SO2 extrusion product was obtained with different energy paths in the triplet-sensitized photodegradation of the neutral (SME(0)) and the anionic (SME(-)) form of SME. The selected divalent metal ions (Ca(2+), Mg(2+), and Zn(2+)) promoted the triplet-sensitized photodegradation of SME(0) but showed an inhibitory effect in triplet-sensitized photodegradation of SME(-). The triplet-sensitized indirect photodegradation mechanism of SME was investigated with the three DOM analogues, i.e., 2-acetonaphthone (2-AN), fluorenone (FN), and thioxanthone (TN). Results indicated that the selected DOM analogues are highly responsible for the photodegradation via attacking on amine moiety of SME. According to the natural bond orbital (NBO) analysis, the triplet-sensitized photodegradation mechanism of SME(0) with 2-AN, FN, and TN was H-transfer, and the SME(-) was proton plus electron transfer with these DOM analogues. PMID:27424205

  12. Patterning mechanisms in the evolution of derived developmental life histories: the role of Wnt signaling in axis formation of the direct-developing sea urchin Heliocidaris erythrogramma.

    PubMed

    Kauffman, Jeffrey S; Raff, Rudolf A

    2003-12-01

    A number of echinoderm species have replaced indirect development with highly modified direct-developmental modes, and provide models for the study of the evolution of early embryonic development. These divergent early ontogenies may differ significantly in life history, oogenesis, cleavage pattern, cell lineage, and timing of cell fate specification compared with those of indirect-developing species. No direct-developing echinoderm species has been studied at the level of molecular specification of embryonic axes. Here we report the first functional analysis of Wnt pathway components in Heliocidaris erythrogramma, a direct-developing sea urchin. We show by misexpression and dominant negative knockout construct expression that Wnt8 and TCF are functionally conserved in the generation of the primary (animal/vegetal) axis in two independently evolved direct-developing sea urchins. Thus, Wnt pathway signaling is an overall deeply conserved mechanism for axis formation that transcends radical changes to early developmental ontogenies. However, the timing of expression and linkages between Wnt8, TCF, and components of the PMC-specification pathway have changed. These changes correlate with the transition from an indirect- to a direct-developing larval life history.

  13. Celotex (Registered) Replacement Study

    SciTech Connect

    Couture, S; Hafner, R

    2002-10-01

    advantageous replacement material due to the potential need for additional poisons to avoid criticality concerns for unlimited arrays, potential variability in its performance due to expected variations in natural materials, potential availability concerns for long term use, and increased container weight and cost. For these reasons, an all-foam replacement design was selected for direct comparison to Celotex using the AL-R8 SI test requirements. The materials were compared in drop tests, thermal equilibrium tests, fire tests, and vibration tests. In addition, analyses of the materials were compared for chemical compatibility and structural, thermal, shielding, and criticality performance. The study found the General Plastics FR-3700 Last-A-Foam{reg_sign} family of polyurethane foams to be a good alternative to Celotex and a superior choice for applications where there are material compatibility concerns and fire resistance, thermal and structural performance requirements. The design shown in Figure 5.1.a is an example where a combination of GP FR-3700 series Last-A-Foam materials were used to design a package meeting such requirements. Test and analysis have shown that this design met or exceeded the performance requirements of the AL-R8 SI using Celotex. Based on the tests and analysis conducted to date, the FR-3700 family of foams should be a good candidate to replace Celotex in AL-R8 SI containers. The current estimated cost of the material ({approx}$300/container) could be further reduced by working with the vendor to set up the manufacturing and molding process.

  14. A model of prefrontal cortical mechanisms for goal-directed behavior.

    PubMed

    Hasselmo, Michael E

    2005-07-01

    Many behavioral tasks require goal-directed actions to obtain delayed reward. The prefrontal cortex appears to mediate many aspects of goal-directed decision making. This article presents a model of prefrontal cortex function emphasizing the influence of goal-related activity on the choice of the next motor output. The model can be interpreted in terms of key elements of Reinforcement Learning Theory. Different neocortical minicolumns represent distinct sensory input states and distinct motor output actions. The dynamics of each minicolumn include separate phases of encoding and retrieval. During encoding, strengthening of excitatory connections forms forward and reverse associations between each state, the following action, and a subsequent state, which may include reward. During retrieval, activity spreads from reward states throughout the network. The interaction of this spreading activity with a specific input state directs selection of the next appropriate action. Simulations demonstrate how these mechanisms can guide performance in a range of goal-directed tasks, and provide a functional framework for some of the neuronal responses previously observed in the medial prefrontal cortex during performance of spatial memory tasks in rats.

  15. A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells.

    PubMed

    Hausselt, Susanne E; Euler, Thomas; Detwiler, Peter B; Denk, Winfried

    2007-07-01

    Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca(2+) signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca(2+)] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage-activated Ca(2+) channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination.

  16. Diffusion Bonding of Silicon Carbide for a Micro-Electro-Mechanical Systems Lean Direct Injector

    NASA Technical Reports Server (NTRS)

    Halbig, Michael C.; Singh, Mrityunjay; Shpargel, Tarah P.; Kiser, James D.

    2006-01-01

    Robust approaches for joining silicon carbide (SiC) to silicon carbide sub-elements have been developed for a micro-electro-mechanical systems lean direct injector (MEMS LDI) application. The objective is to join SiC sub-elements to form a leak-free injector that has complex internal passages for the flow and mixing of fuel and air. Previous bonding technology relied upon silicate glass interlayers that were not uniform or leak free. In a newly developed joining approach, titanium foils and physically vapor deposited titanium coatings were used to form diffusion bonds between SiC materials during hot pressing. Microscopy results show the formation of well adhered diffusion bonds. Initial tests show that the bond strength is much higher than required for the component system. Benefits of the joining technology are fabrication of leak free joints with high temperature and mechanical capability.

  17. Architectural and mechanical cues direct mesenchymal stem cell interactions with crosslinked gelatin scaffolds.

    PubMed

    McAndrews, Kathleen M; Kim, Min Jeong; Lam, Tuyet Y; McGrail, Daniel J; Dawson, Michelle R

    2014-12-01

    Naturally derived biomaterials have emerged as modulators of cell function and tissue substitutes. Here, we developed crosslinked glutaraldehyde (GTA) scaffolds for the expansion and differentiation of mesenchymal stem cells (MSCs). The mechanical and architectural properties of the scaffolds were altered by varying the concentration of gelatin and GTA. Higher GTA concentrations were associated with an increase in more confined pores and osteogenic differentiation. In addition, myogenic potential varied with crosslinking degree, although bulk mechanical properties were unaltered. Correlation analysis revealed that ALP activity of differentiated MSCs on higher gelatin concentration scaffolds was dependent on traditional effectors, including environment elasticity and spread area. In contrast, the differentiation capacity of cells cultured on lower gelatin concentration scaffolds did not correlate with these factors, instead it was dependent on the hydrated pore structure. These results suggest that scaffold composition can determine what factors direct differentiation and may have critical implications for biomaterial design.

  18. Direct observation of markovian behavior of the mechanical unfolding of individual proteins.

    PubMed

    Cao, Yi; Kuske, Rachel; Li, Hongbin

    2008-07-01

    Single-molecule force-clamp spectroscopy is a valuable tool to analyze unfolding kinetics of proteins. Previous force-clamp spectroscopy experiments have demonstrated that the mechanical unfolding of ubiquitin deviates from the generally assumed Markovian behavior and involves the features of glassy dynamics. Here we use single molecule force-clamp spectroscopy to study the unfolding kinetics of a computationally designed fast-folding mutant of the small protein GB1, which shares a similar beta-grasp fold as ubiquitin. By treating the mechanical unfolding of polyproteins as the superposition of multiple identical Poisson processes, we developed a simple stochastic analysis approach to analyze the dwell time distribution of individual unfolding events in polyprotein unfolding trajectories. Our results unambiguously demonstrate that the mechanical unfolding of NuG2 fulfills all criteria of a memoryless Markovian process. This result, in contrast with the complex mechanical unfolding behaviors observed for ubiquitin, serves as a direct experimental demonstration of the Markovian behavior for the mechanical unfolding of a protein and reveals the complexity of the unfolding dynamics among structurally similar proteins. Furthermore, we extended our method into a robust and efficient pseudo-dwell-time analysis method, which allows one to make full use of all the unfolding events obtained in force-clamp experiments without categorizing the unfolding events. This method enabled us to measure the key parameters characterizing the mechanical unfolding energy landscape of NuG2 with improved precision. We anticipate that the methods demonstrated here will find broad applications in single-molecule force-clamp spectroscopy studies for a wide range of proteins.

  19. Mechanism behind self-sustained oscillations in direct current glow discharges and dusty plasmas

    SciTech Connect

    Cho, Sung Nae

    2013-04-15

    An alternative explanation to the mechanism behind self-sustained oscillations of ions in direct current (DC) glow discharges is provided. Such description is distinguished from the one provided by the fluid models, where oscillations are attributed to the positive feedback mechanism associated with photoionization of particles and photoemission of electrons from the cathode. Here, oscillations arise as consequence of interaction between an ion and the surface charges induced by it at the bounding electrodes. Such mechanism provides an elegant explanation to why self-sustained oscillations occur only in the negative resistance region of the voltage-current characteristic curve in the DC glow discharges. Furthermore, this alternative description provides an elegant explanation to the formation of plasma fireballs in the laboratory plasma. It has been found that oscillation frequencies increase with ion's surface charge density, but at the rate which is significantly slower than it does with the electric field. The presented mechanism also describes self-sustained oscillations of ions in dusty plasmas, which demonstrates that self-sustained oscillations in dusty plasmas and DC glow discharges involve common physical processes.

  20. Direct and quinone-mediated palladium reduction by Geobacter sulfurreducens: mechanisms and modeling.

    PubMed

    Pat-Espadas, Aurora M; Razo-Flores, Elías; Rangel-Mendez, J Rene; Cervantes, Francisco J

    2014-01-01

    Palladium(II) reduction to Pd(0) nanoparticles by Geobacter sulfurreducens was explored under conditions of neutral pH, 30 °C and concentrations of 25, 50, and 100 mg of Pd(II)/L aiming to investigate the effect of solid species of palladium on their microbial reduction. The influence of anthraquinone-2,6-disulfonate was reported to enhance the palladium reaction rate in an average of 1.7-fold and its addition is determining to achieve the reduction of solid species of palladium. Based on the obtained results two mechanisms are proposed: (1) direct, which is fully described considering interactions of amide, sulfur, and phosphoryl groups associated to proteins from bacteria on palladium reduction reaction, and (2) quinone-mediated, which implies multiheme c-type cytochromes participation. Speciation analysis and kinetic results were considered and integrated into a model to fit the experimental data that explain both mechanisms. This work provides elements for a better understanding of direct and quinone-mediated palladium reduction by G. sulfurreducens, which could facilitate metal recovery with concomitant formation of valuable palladium nanoparticles in industrial processes.

  1. Direct micro-mechanical measurements of the material properties and motility of C. elegans

    NASA Astrophysics Data System (ADS)

    Backholm, Matilda; Ryu, William S.; Dalnoki-Veress, Kari

    2012-11-01

    The model organism C. elegans, a millimeter-sized nematode, provides an excellent biophysical system for both static and dynamic mechanical studies. The undulatory motion exhibited by the worm as it swims or crawls through a medium is ubiquitous in nature at scales from microns to meters, and has been the focus of intense research. However, for a successful description of this form of locomotion, a better knowledge of the material properties as well as the worm's output forces is needed. Here we present a new experimental assay, with which the material properties and dynamics of C. elegans can be directly probed. In this technique, we use the deflection of a very flexible micropipette to measure the flexural rigidity of C. elegans at all stages of its life cycle, as well as along the body of the adult worm. By modelling the worm as a viscoelastic material, we have achieved new insights into its mechanical properties. Furthermore, the forces involved during the undulatory motion of C. elegans have been studied. It is the hope that the direct experimental characterization of this model organism will provide guidance for theoretical treatments of undulatory locomotion in general.

  2. Bacillus subtilis TRAP binds to its RNA target by a 5' to 3' directional mechanism.

    PubMed

    Barbolina, Maria V; Li, Xiufeng; Gollnick, Paul

    2005-01-28

    TRAP is an 11 subunit RNA-binding protein that regulates expression of the Bacillus subtilis trpEDCFBA operon by transcription attenuation and translation control mechanisms. Tryptophan-activated TRAP acts by binding to a site in the 5'-untranslated leader region of trp mRNA consisting of 11 (G/U)AG repeats. We used mung bean nuclease footprinting to analyze the interaction of TRAP with several artificial binding sites composed of 11 GAG repeats in nucleic acids that lack secondary structure. Affinities for individual repeats within a binding site did not vary significantly. In contrast, the association rate constants were highest for repeats at the 5' end and lowest for those at the 3' end of all binding sites tested. These results indicate that TRAP binds to its RNA targets by first associating with one or more repeat at the 5' end of its binding site followed by wrapping the remainder of binding site around the protein in a 5' to 3' direction. This directional binding is novel among RNA-binding proteins. We suggest that this mechanism of binding is important for TRAP-mediated transcription attenuation control of the trp operon. PMID:15588817

  3. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  4. Molecular dynamics simulation and site-directed mutagenesis of alcohol acyltransferase: a proposed mechanism of catalysis.

    PubMed

    Morales-Quintana, Luis; Nuñez-Tobar, María Ximena; Moya-León, María Alejandra; Herrera, Raúl

    2013-10-28

    Aroma in Vasconcellea pubescens fruit is determined by esters, which are the products of catalysis by alcohol acyltransferase (VpAAT1). VpAAT1 protein structure displayed the conserved HxxxD motif facing the solvent channel in the center of the structure. To gain insight into the role of these catalytic residues, kinetic and site-directed mutagenesis studies were carried out in VpAAT1 protein. Based on dead-end inhibition studies, the kinetic could be described in terms of a ternary complex mechanism with the H166 residue as the catalytic base. Kinetic results showed the lowest Km value for hexanoyl-CoA. Additionally, the most favorable predicted substrate orientation was observed for hexanoyl-CoA, showing a coincidence between kinetic studies and molecular docking analysis. Substitutions H166A, D170A, D170N, and D170E were evaluated in silico. The solvent channel in all mutant structures was lost, showing large differences with the native structure. Molecular docking and molecular dynamics simulations were able to describe unfavored energies for the interaction of the mutant proteins with different alcohols and acyl-CoAs. Additionally, in vitro site-directed mutagenesis of H166 and D170 in VpAAT1 induced a loss of activity, confirming the functional role of both residues for the activity, H166 being directly involved in catalysis.

  5. Probing the chemical mechanism of saccharopine reductase from Saccharomyces cerevisiae using site-directed mutagenesis.

    PubMed

    Vashishtha, Ashwani K; West, Ann H; Cook, Paul F

    2015-10-15

    Saccharopine reductase catalyzes the reductive amination of l-α-aminoadipate-δ-semialdehyde with l-glutamate to give saccharopine. Two mechanisms have been proposed for the reductase, one that makes use of enzyme side chains as acid-base catalytic groups, and a second, in which the reaction is catalyzed by enzyme-bound reactants. Site-directed mutagenesis was used to change acid-base candidates in the active site of the reductase to eliminate their ionizable side chain. Thus, the D126A, C154S and Y99F and several double mutant enzymes were prepared. Kinetic parameters in the direction of glutamate formation exhibited modest decreases, inconsistent with the loss of an acid-base catalyst. The pH-rate profiles obtained with all mutant enzymes decrease at low and high pH, suggesting acid and base catalytic groups are still present in all enzymes. Solvent kinetic deuterium isotope effects are all larger than those observed for wild type enzyme, and approximately equal to one another, suggesting the slow step is the same as that of wild type enzyme, a conformational change to open the site and release products (in the direction of saccharopine formation). Overall, the acid-base chemistry is likely catalyzed by bound reactants, with the exception of deprotonation of the α-amine of glutamate, which likely requires an enzyme residue. PMID:26342457

  6. Probing the chemical mechanism of saccharopine reductase from Saccharomyces cerevisiae using site-directed mutagenesis.

    PubMed

    Vashishtha, Ashwani K; West, Ann H; Cook, Paul F

    2015-10-15

    Saccharopine reductase catalyzes the reductive amination of l-α-aminoadipate-δ-semialdehyde with l-glutamate to give saccharopine. Two mechanisms have been proposed for the reductase, one that makes use of enzyme side chains as acid-base catalytic groups, and a second, in which the reaction is catalyzed by enzyme-bound reactants. Site-directed mutagenesis was used to change acid-base candidates in the active site of the reductase to eliminate their ionizable side chain. Thus, the D126A, C154S and Y99F and several double mutant enzymes were prepared. Kinetic parameters in the direction of glutamate formation exhibited modest decreases, inconsistent with the loss of an acid-base catalyst. The pH-rate profiles obtained with all mutant enzymes decrease at low and high pH, suggesting acid and base catalytic groups are still present in all enzymes. Solvent kinetic deuterium isotope effects are all larger than those observed for wild type enzyme, and approximately equal to one another, suggesting the slow step is the same as that of wild type enzyme, a conformational change to open the site and release products (in the direction of saccharopine formation). Overall, the acid-base chemistry is likely catalyzed by bound reactants, with the exception of deprotonation of the α-amine of glutamate, which likely requires an enzyme residue.

  7. Assessing the mechanism of DNA damage induced by lead through direct and indirect interactions.

    PubMed

    Zhang, Hao; Wei, Kai; Zhang, Mengyu; Liu, Rutao; Chen, Yadong

    2014-07-01

    Lead still possesses great threats to human health owing to its widespread distribution in the environment caused by human activities, although various actions have been taken to cut down the use and distribution of lead. In this work, mechanisms of DNA damage caused by lead through indirect and direct interactions were investigated. Results from comet assay showed lead at 1-10 μM induced DNA strand breaks in mice liver cells according to olive tail moment analysis. Signals of DNA-protein crosslinks (DPC) were not significantly detected until exposed at 100 μM Pb(2+). Further more, direct interactions between Pb(2+) and DNA were explored to determine the binding mode between them using spectra analysis, isothermal titration calorimetry studies and molecular docking investigations, which indicated that Pb(2+) could bind to DNA with four binding sites to form Pb(2)(+)-DNA complex by minor groove binding effects and electrostatic forces, resulting in damage to the structure of DNA double helix. Combined studies of lead genotoxicity in indirect (comet assay and DPC assay) and direct (binding mode investigations) interactions can be applied to study the potential damages to DNA induced by heavy metal pollutants.

  8. Recent progress in stem cell differentiation directed by material and mechanical cues.

    PubMed

    Lin, Xunxun; Shi, Yuan; Cao, Yilin; Liu, Wei

    2016-02-02

    Stem cells play essential roles in tissue regeneration in vivo via specific lineage differentiation induced by environmental factors. In the past, biochemical signals were the focus of induced stem cell differentiation. As reported by Engler et al (2006 Cell 126 677-89), biophysical signal mediated stem cell differentiation could also serve as an important inducer. With the advancement of material science, it becomes a possible strategy to generate active biophysical signals for directing stem cell fate through specially designed material microstructures. In the past five years, significant progress has been made in this field, and these designed biophysical signals include material elasticity/rigidity, micropatterned structure, extracellular matrix (ECM) coated materials, material transmitted extracellular mechanical force etc. A large number of investigations involved material directed differentiation of mesenchymal stem cells, neural stem/progenitor cells, adipose derived stem cells, hematopoietic stem/progenitor cells, embryonic stem cells and other cells. Hydrogel based materials were commonly used to create varied mechanical properties via modifying the ratio of different components, crosslinking levels, matrix concentration and conjugation with other components. Among them, polyacrylamide (PAM) and polydimethylsiloxane (PDMS) hydrogels remained the major types of material. Specially designed micropatterning was not only able to create a unique topographical surface to control cell shape, alignment, cell-cell and cell-matrix contact for basic stem cell biology study, but also could be integrated with 3D bioprinting to generate micropattered 3D structure and thus to induce stem cell based tissue regeneration. ECM coating on a specific topographical structure was capable of inducing even more specific and potent stem cell differentiation along with soluble factors and mechanical force. The article overviews the progress of the past five years in this particular

  9. Interleukin-19 induces angiogenesis in the absence of hypoxia by direct and indirect immune mechanisms.

    PubMed

    Kako, Farah; Gabunia, Khatuna; Ray, Mitali; Kelemen, Sheri E; England, Ross N; Kako, Bashar; Scalia, Rosario G; Autieri, Michael V

    2016-06-01

    Neovascularization and inflammation are independent biological processes but are linked in response to injury. The role of inflammation-dampening cytokines in the regulation of angiogenesis remains to be clarified. The purpose of this work was to test the hypothesis that IL-19 can induce angiogenesis in the absence of tissue hypoxia and to identify potential mechanisms. Using the aortic ring model of angiogenesis, we found significantly reduced sprouting capacity in aortic rings from IL-19(-/-) compared with wild-type mice. Using an in vivo assay, we found that IL-19(-/-) mice respond to vascular endothelial growth factor (VEGF) significantly less than wild-type mice and demonstrate decreased capillary formation in Matrigel plugs. IL-19 signals through the IL-20 receptor complex, and IL-19 induces IL-20 receptor subunit expression in aortic rings and cultured human vascular smooth muscle cells, but not endothelial cells, in a peroxisome proliferator-activated receptor-γ-dependent mechanism. IL-19 activates STAT3, and IL-19 angiogenic activity in aortic rings is STAT3-dependent. Using a quantitative RT-PCR screening assay, we determined that IL-19 has direct proangiogenic effects on aortic rings by inducing angiogenic gene expression. M2 macrophages participate in angiogenesis, and IL-19 has indirect angiogenic effects, as IL-19-stimulated bone marrow-derived macrophages secrete proangiogenic factors that induce greater sprouting of aortic rings than unstimulated controls. Using a quantitative RT-PCR screen, we determined that IL-19 induces expression of angiogenic cytokines in bone marrow-derived macrophages. Together, these data suggest that IL-19 can promote angiogenesis in the absence of hypoxia by at least two distinct mechanisms: 1) direct effects on vascular cells and 2) indirect effects by stimulation of macrophages. PMID:27053520

  10. Catalyst Transport in Corn Stover Internodes: Elucidating Transport Mechanisms Using Direct Blue-I

    SciTech Connect

    Viamajala, S.; Selig, M. J.; Vinzant, T. B.; Tucker, M. P.; Himmel, M. E.; McMillan, J. D.; Decker, S. R.

    2006-04-01

    The transport of catalysts (chemicals and enzymes) within plant biomass is believed to be a major bottleneck during thermochemical pretreatment and enzymatic conversion of lignocellulose. Subjecting biomass to size reduction and mechanical homogenization can reduce catalyst transport limitations; however, such processing adds complexity and cost to the over-all process. Using high-resolution light microscopy, we have monitored the transport of an aqueous solution of Direct Blue-I (DB-I) dye through intact corn internodes under a variety of impregnation conditions. DB-I is a hydrophilic anionic dye with affinity for cellulose. This model system has enabled us to visualize likely barriers and mechanisms of catalyst transport in corn stems. Microscopic images were compared with calculated degrees of saturation (i.e., volume fraction of internode void space occupied by dye solution) to correlate impregnation strategies with dye distribution and transport mechanisms. Results show the waxy rind exterior and air trapped within individual cells to be the major barriers to dye transport, whereas the vascular bundles, apoplastic continuum (i.e., the intercellular void space at cell junctions), and fissures formed during the drying process provided the most utilized pathways for transport. Although representing only 20-30% of the internode volume, complete saturation of the apoplast and vascular bundles by fluid allowed dye contact with a majority of the cells in the internode interior.

  11. Evidence and implications of direct charge excitation as the dominant mechanism in plasmon-mediated photocatalysis

    PubMed Central

    Boerigter, Calvin; Campana, Robert; Morabito, Matthew; Linic, Suljo

    2016-01-01

    Plasmonic metal nanoparticles enhance chemical reactions on their surface when illuminated with light of particular frequencies. It has been shown that these processes are driven by excitation of localized surface plasmon resonance (LSPR). The interaction of LSPR with adsorbate orbitals can lead to the injection of energized charge carriers into the adsorbate, which can result in chemical transformations. The mechanism of the charge injection process (and role of LSPR) is not well understood. Here we shed light on the specifics of this mechanism by coupling optical characterization methods, mainly wavelength-dependent Stokes and anti-Stokes SERS, with kinetic analysis of photocatalytic reactions in an Ag nanocube–methylene blue plasmonic system. We propose that localized LSPR-induced electric fields result in a direct charge transfer within the molecule–adsorbate system. These observations provide a foundation for the development of plasmonic catalysts that can selectively activate targeted chemical bonds, since the mechanism allows for tuning plasmonic nanomaterials in such a way that illumination can selectively enhance desired chemical pathways. PMID:26817619

  12. Direct assessment of living cell mechanical responses during deformation inside microchannel restrictions.

    PubMed

    Walter, Nadine; Micoulet, Alexandre; Seufferlein, Thomas; Spatz, Joachim P

    2011-09-01

    The deformation of suspended cells inside microchannel restrictions mimics passive cell transportation in the blood circulation system of the body. The cells traverse or get stuck in narrow vessels, as, e.g., during the metastasis of tumor cells. In this work, the mechanical responses of suspended pancreatic cancer cells as they move through and deform inside microchannel restrictions are assessed with a cantilever-based polydimethylsiloxane (PDMS) force sensor. Incorporated into a flow cell chip, the PDMS cantilever is integrated into the boundary wall of a narrow microrestriction. Upon being forced to enter the restriction by an applied flow, the cell exerts pressure on the cantilever, which then bends. By assuming a uniformly loaded cantilever, the total force and pressure on the cantilever can be calculated using elastic beam theory. This technique has the advantage of presenting an absolute and direct measure, which is independent of the applied flow and frictional processes at the channel-cell interface; in contrast to, e.g., measuring cell mechanics indirectly via cell sliding velocities. Furthermore, a high number of cells can be examined in a short time compared to other single cell mechanical testing devices. PMID:21974682

  13. Evidence and implications of direct charge excitation as the dominant mechanism in plasmon-mediated photocatalysis

    DOE PAGESBeta

    Boerigter, Calvin; Campana, Robert; Morabito, Matthew; Linic, Suljo

    2016-01-28

    Plasmonic metal nanoparticles enhance chemical reactions on their surface when illuminated with light of particular frequencies. It has been shown that these processes are driven by excitation of localized surface plasmon resonance (LSPR). The interaction of LSPR with adsorbate orbitals can lead to the injection of energized charge carriers into the adsorbate, which can result in chemical transformations. The mechanism of the charge injection process (and role of LSPR) is not well understood. Here we shed light on the specifics of this mechanism by coupling optical characterization methods, mainly wavelength-dependent Stokes and anti-Stokes SERS, with kinetic analysis of photocatalytic reactionsmore » in an Ag nanocube–methylene blue plasmonic system. We propose that localized LSPR-induced electric fields result in a direct charge transfer within the molecule–adsorbate system. Lastly, these observations provide a foundation for the development of plasmonic catalysts that can selectively activate targeted chemical bonds, since the mechanism allows for tuning plasmonic nanomaterials in such a way that illumination can selectively enhance desired chemical pathways.« less

  14. Neural Mechanisms Underlying Perilesional Transcranial Direct Current Stimulation in Aphasia: A Feasibility Study

    PubMed Central

    Ulm, Lena; McMahon, Katie; Copland, David; de Zubicaray, Greig I.; Meinzer, Marcus

    2015-01-01

    Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia. PMID:26500522

  15. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    PubMed

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

  16. Direct Role for Smooth Muscle Cell Mineralocorticoid Receptors in Vascular Remodeling: Novel Mechanisms and Clinical Implications

    PubMed Central

    Koenig, Jenny B.; Jaffe, Iris Z.

    2014-01-01

    The mineralocorticoid receptor (MR) is a key regulator of blood pressure. MR-antagonist drugs are used to treat hypertension and heart failure, resulting in decreased mortality by mechanisms that are not completely understood. In addition to the kidney, MR is also expressed in the smooth muscle cells (SMCs) of the vasculature, where it is activated by the hormone aldosterone and affects the expression of genes involved in vascular function at the cellular and systemic levels. Following vascular injury due to mechanical or physiological stresses, vessels undergo remodeling resulting in SMC hypertrophy, migration, and proliferation, as well as vessel fibrosis. Exuberant vascular remodeling is associated with poor outcomes in cardiovascular patients. This review compiles recent findings on the specific role of SMC-MR in the vascular remodeling process. The development and characterization of a SMC-specific MR-knockout mouse has demonstrated a direct role for SMC-MR in vascular remodeling. Additionally, several novel mechanisms contributing to SMC-MR-mediated vascular remodeling have been identified and are reviewed here, including Rho-kinase signaling, placental growth factor signaling through vascular endothelial growth factor type 1 receptor, and galectin signaling. PMID:24633842

  17. The effects of replacing dicalcium phosphate with Busumbu rock phosphate on performance and the mechanical properties of bone in growing chicks.

    PubMed

    Odongo, N E; Plaizier, J; van Straaten, P; McBride, B

    2002-07-01

    Three hundred, day-old broiler chicks, with an average initial weight of 41.8 +/- 1.79 g, were used in a 15-day study (10 birds per battery cage) to characterize their performance and fluorine status when dicalcium phosphate (DCP) was replaced by Busumbu rock phosphate (BRP) as the source of phosphorus in the chicks' ration. The treatments comprised a standard ration with BRP replacing 0, 25%, 50%, 75% or 100% of DCP. Replacing DCP with BRP significantly reduced the final weight of the chicks (p < 0.01), feed intake (p < 0.01), weight gains (p < 0.01) and dry matter digestibility (p < 0.05) but increased (p < 0.05) the feed-to-gain ratio. True phosphorus absorption and the percentage of phosphorus in the tibia were not affected by increasing amounts of BRP in the diet. Increasing levels of BRP in the diet linearly reduced (p < 0.01) the percentage bone ash, calcium, Ca:P ratio, ultimate breaking force, bending moment, stress, and modulus of elasticity. Leg stiffness, lameness, reduced feed intake, and a decline in general health were recorded in 10-40% of the chicks on 75% and 100% BRP, respectively. These results suggest that excessive ingestion of fluorine from the BRP caused the reduction in the chicks' performance.

  18. Direct testing of the biasing effect of manipulations of endolymphatic pressure on cochlear mechanical function

    NASA Astrophysics Data System (ADS)

    LePage, Eric; Avan, Paul

    2015-12-01

    The history of cochlear mechanical investigations has been carried out in two largely separate sets of endeavours; those interested in auditory processing in animal models and those interested in the origin of adverse vestibular symptoms in humans. In respect of the first, mechanical vibratory data is considered pathological and not representative of pristine behaviour if it departs from the reigning model of sharp tuning and high hearing sensitivity. Conversely, when the description of the pathological behaviour is the focus, fluid movements responsible for hearing loss and vestibular symptoms dominate. Yet both extensive sets of data possess a common factor now being reconsidered for its potential to shed light on the mechanisms in general. The common factor is a mechanical bias — the departure of cochlear epithelial membranes from their usual resting position. In both cases the bias modulates hearing sensitivity and distorts tuning characteristics. Indeed several early sets of guinea pig mechanical data were dismissed as "pathological" when in hindsight, the primary effect influencing the data was not loss of outer hair cell function per se, but a mechanical bias unknowingly introduced in process of making the measurement. Such biases in the displacement of the basilar membrane from its position are common, and may be caused by low-frequency sounds (topically including infrasound) or by variations in fluid volume in the chambers particularly applying the case of endolymphatic hydrops. Most biases are quantified in terms of visualisation of fluid volume change, electric potential changes and otoacoustic emissions. Notably many previous studies have also searched for raised pressures with negative results. Yet these repeated findings are contrary to the widespread notion that, at least when homeostasis is lost, it is a rise in endolymphatic pressure which is responsible for membrane rupture and Meniere's attacks. This current investigation in Mongolian gerbils

  19. Direct observation of TALE protein dynamics reveals a two-state search mechanism.

    PubMed

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

    2015-06-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process-a search state and a recognition state-facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state.

  20. Directionally tunable and mechanically deformable ferroelectric crystals from rotating polar globular ionic molecules

    NASA Astrophysics Data System (ADS)

    Harada, Jun; Shimojo, Takafumi; Oyamaguchi, Hideaki; Hasegawa, Hiroyuki; Takahashi, Yukihiro; Satomi, Koichiro; Suzuki, Yasutaka; Kawamata, Jun; Inabe, Tamotsu

    2016-10-01

    Ferroelectrics are used in a wide range of applications, including memory elements, capacitors and sensors. Recently, molecular ferroelectric crystals have attracted interest as viable alternatives to conventional ceramic ferroelectrics because of their solution processability and lack of toxicity. Here we show that a class of molecular compounds—known as plastic crystals—can exhibit ferroelectricity if the constituents are judiciously chosen from polar ionic molecules. The intrinsic features of plastic crystals, for example, the rotational motion of molecules and phase transitions with lattice-symmetry changes, provide the crystals with unique ferroelectric properties relative to those of conventional molecular crystals. This allows a flexible alteration of the polarization axis direction in a grown crystal by applying an electric field. Owing to the tunable nature of the crystal orientation, together with mechanical deformability, this type of molecular crystal represents an attractive functional material that could find use in a diverse range of applications.

  1. Active sites and mechanisms for direct oxidation of benzene to phenol over carbon catalysts.

    PubMed

    Wen, Guodong; Wu, Shuchang; Li, Bo; Dai, Chunli; Su, Dang Sheng

    2015-03-23

    The direct oxidation of benzene to phenol with H2 O2 as the oxidizer, which is regarded as an environmentally friendly process, can be efficiently catalyzed by carbon catalysts. However, the detailed roles of carbon catalysts, especially what is the active site, are still a topic of debate controversy. Herein, we present a fundamental consideration of possible mechanisms for this oxidation reaction by using small molecular model catalysts, Raman spectra, static secondary ion mass spectroscopy (SIMS), DFT calculations, quasi in situ ATR-IR and UV spectra. Our study indicates that the defects, being favorable for the formation of active oxygen species, are the active sites for this oxidation reaction. Furthermore, one type of active defect, namely the armchair configuration defect was successfully identified.

  2. MECHANICAL PROPERTIES OF THIN GDP SHELLS USED AS CRYOGENIC DIRECT DRIVE TARGETS AT OMEGA

    SciTech Connect

    NIKROO,A; CZECHOWICZ,D; CHEN,K.C; DICKEN,M; MORRIS,C; ANDREWS,R; GREENWOOD,A.L; CASTILLO,E

    2003-06-01

    OAK-B135 Thin glow discharge polymer (GDP) shells are currently used as the targets for cryogenic direct drive laser fusion experiments. These shells need to be filled with nearly 1000 atm of D{sub 2} and cooled to cryogenic temperatures without failing due to buckling and bursting pressures they experience in this process. Therefore, the mechanical and permeation properties of these shells are of utmost importance in successful and rapid filling with D{sub 2}. In this paper, they present an overview of buckle and burst pressures of several different types of GDP shells. These include those made using traditional GDP deposition parameters (standard GDP) using a high deposition pressure and using modified parameters (strong GDP) of low deposition pressure that leads to more robust shells.

  3. Direct observation of TALE protein dynamics reveals a two-state search mechanism

    PubMed Central

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

    2015-01-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process—a search state and a recognition state—facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state. PMID:26027871

  4. Direct observation of TALE protein dynamics reveals a two-state search mechanism

    NASA Astrophysics Data System (ADS)

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

    2015-06-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process--a search state and a recognition state--facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state.

  5. Graphene-Catalyzed Direct Friedel-Crafts Alkylation Reactions: Mechanism, Selectivity, and Synthetic Utility.

    PubMed

    Hu, Feng; Patel, Mehulkumar; Luo, Feixiang; Flach, Carol; Mendelsohn, Richard; Garfunkel, Eric; He, Huixin; Szostak, Michal

    2015-11-18

    Transition-metal-catalyzed alkylation reactions of arenes have become a central transformation in organic synthesis. Herein, we report the first general strategy for alkylation of arenes with styrenes and alcohols catalyzed by carbon-based materials, exploiting the unique property of graphenes to produce valuable diarylalkane products in high yields and excellent regioselectivity. The protocol is characterized by a wide substrate scope and excellent functional group tolerance. Notably, this process constitutes the first general application of graphenes to promote direct C-C bond formation utilizing polar functional groups anchored on the GO surface, thus opening the door for an array of functional group alkylations using benign and readily available graphene materials. Mechanistic studies suggest that the reaction proceeds via a tandem catalysis mechanism in which both of the coupling partners are activated by interaction with the GO surface. PMID:26496423

  6. Directionally tunable and mechanically deformable ferroelectric crystals from rotating polar globular ionic molecules.

    PubMed

    Harada, Jun; Shimojo, Takafumi; Oyamaguchi, Hideaki; Hasegawa, Hiroyuki; Takahashi, Yukihiro; Satomi, Koichiro; Suzuki, Yasutaka; Kawamata, Jun; Inabe, Tamotsu

    2016-10-01

    Ferroelectrics are used in a wide range of applications, including memory elements, capacitors and sensors. Recently, molecular ferroelectric crystals have attracted interest as viable alternatives to conventional ceramic ferroelectrics because of their solution processability and lack of toxicity. Here we show that a class of molecular compounds-known as plastic crystals-can exhibit ferroelectricity if the constituents are judiciously chosen from polar ionic molecules. The intrinsic features of plastic crystals, for example, the rotational motion of molecules and phase transitions with lattice-symmetry changes, provide the crystals with unique ferroelectric properties relative to those of conventional molecular crystals. This allows a flexible alteration of the polarization axis direction in a grown crystal by applying an electric field. Owing to the tunable nature of the crystal orientation, together with mechanical deformability, this type of molecular crystal represents an attractive functional material that could find use in a diverse range of applications. PMID:27657871

  7. Direct activation of the apoptosis machinery as a mechanism to target cancer cells.

    PubMed

    Nguyen, Jack T; Wells, James A

    2003-06-24

    Apoptosis plays a pivotal role in the cytotoxic activity of most chemotherapeutic drugs, and defects in this pathway provide a basis for drug resistance in many cancers. Thus the ability to restore apoptosis by using small molecules could have important therapeutic implications. Using a cell-free assay to simultaneously target multiple components of the apoptosis pathway, we identified a class of compounds that activate caspases in a cytochrome c-dependent manner and induce apoptosis in whole cells. By reconstituting the apoptosis pathway with purified proteins, we determined that these compounds promote the protein-protein association of Apaf-1 into the functional apoptosome. These compounds exert cytostatic and cytotoxic effects on a variety of cancer cell lines while having little or no activity against the normal cell lines tested. These findings suggest that direct activation of the basic apoptosis machinery may be a viable mechanism to selectively target cancer.

  8. Inhibition of the Mitochondrial Permeability Transition for Cytoprotection: Direct versus Indirect Mechanisms

    PubMed Central

    Martel, Cécile; Huynh, Le Ha; Garnier, Anne; Ventura-Clapier, Renée; Brenner, Catherine

    2012-01-01

    Mitochondria are fascinating organelles, which fulfill multiple cellular functions, as diverse as energy production, fatty acid β oxidation, reactive oxygen species (ROS) production and detoxification, and cell death regulation. The coordination of these functions relies on autonomous mitochondrial processes as well as on sustained cross-talk with other organelles and/or the cytosol. Therefore, this implies a tight regulation of mitochondrial functions to ensure cell homeostasis. In many diseases (e.g., cancer, cardiopathies, nonalcoholic fatty liver diseases, and neurodegenerative diseases), mitochondria can receive harmful signals, dysfunction and then, participate to pathogenesis. They can undergo either a decrease of their bioenergetic function or a process called mitochondrial permeability transition (MPT) that can coordinate cell death execution. Many studies present evidence that protection of mitochondria limits disease progression and severity. Here, we will review recent strategies to preserve mitochondrial functions via direct or indirect mechanisms of MPT inhibition. Thus, several mitochondrial proteins may be considered for cytoprotective-targeted therapies. PMID:22675634

  9. Metallurgical and Mechanical Evaluation of 4340 Steel Produced by Direct Metal Laser Sintering

    NASA Astrophysics Data System (ADS)

    Jelis, Elias; Clemente, Matthew; Kerwien, Stacey; Ravindra, Nuggehalli M.; Hespos, Michael R.

    2015-03-01

    Direct metal laser sintering (DMLS) was used to produce high-strength low-alloy 4340 steel specimens. Mechanical and metallurgical analyses were performed on the specimens to determine the samples with the highest strengths and the least porosity. The optimal process parameters were thus defined based on the corresponding experimental conditions. Additionally, the effects of fabricating specimens with both virgin and recycled powders were studied. Scanning electron microscopy and electron-dispersive spectroscopy were performed on both types of powders to determine the starting morphology and composition. The initial tensile results are promising, suggesting that DMLS can produce specimens equal in strength to wrought materials. However, there is evidence of cracking on several of the heat-treated tensile specimens that is unexplained. Several theories point to disturbances in the build chamber environment that went undetected while the specimens were being fabricated.

  10. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    PubMed

    You, Jae Sung; Frey, John W; Hornberger, Troy A

    2012-01-01

    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k) T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis. PMID:23077579

  11. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    PubMed

    You, Jae Sung; Frey, John W; Hornberger, Troy A

    2012-01-01

    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k) T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  12. Testing of Replacement Bag Material

    SciTech Connect

    Laurinat, J.E.

    1998-11-03

    Recently, the FB-Line bagout material was changed to simplify the processing of sand, slag, and crucible.The results of the strength tests and the outgassing measurements and calculations demonstrate that the proposed replacement nylon bag materials (HRMP and orange anti-static material) are acceptable substitutes for LDPE and the original nylon with respect to mechanical properties.

  13. Aerocoat 7 Replacement Coatings

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Kennedy Space Center has used Aerocoat 7 (AR-7) to protect stainless-steel flex hoses at Launch Complex (LC-39) and hydraulic lines of the Mobile Launcher Platform (MLP) because it provides excellent corrosion protection in low-temperature applications. The Sovereign Company produced AR-7 exclusively for NASA but discontinued production because the coating released high levels of volatile organic compounds (VOCs) and had a significant environmental impact. The purpose of this project was to select and evaluate potential replacement coatings for AR-7 that would be more environmentally sound. The physical and mechanical properties of commercially available coatings were investigated through the Internet. The ideal coating would be fluid enough to penetrate the outer mesh of a stainless-steel flex hose and coat the inner hose, and flexible enough to withstand the movement of the hose, as well as the expansion and contraction of its metal caused by changes in temperature.

  14. Mechanics of Student-Directed Multi-University Internet Video-Conferencing Course

    NASA Astrophysics Data System (ADS)

    Durant, A. J.; Mann, C. P.; Rose, W. I.; Stix, J.

    2007-12-01

    Connecting graduate students with experts in a given discipline is vital to their success but has often been challenging because of logistics, costs, and scheduling. Advances in Internet video-conferencing now allow multiple parties to meet simultaneously in a virtual classroom environment. Here we describe the mechanics of a recent student-directed graduate-level course that enabled students to directly engage in scientific discussion with experts. Conducted under the auspices of the Earth Hazards (EHaz) Consortium, the spring 2007 Volcano Instability course connected nine previously disparate groups over North America in a combined learning and cultural experience. Each week course participants (including the guest speaker, students and university professors) reviewed current journal articles and a speaker presentation, and used Marratech Internet video- conferencing software to meet online and discuss the material with an expert on the subject. Internet video-conferencing provides an inexpensive and innovative approach to teaching across international boundaries. The EHaz 2007 Volcano Instability course connected 14 experts with 64 students and professors. Many universities can participate through this approach, allowing an advanced graduate class that normally contains 4 - 8 students on one campus to become a class of 50 or more dispersed over many campuses. As evidenced by overwhelmingly positive course evaluations, the approach was stimulating and conducive to learning, and has great potential for application over many other disciplines. This dynamic interaction between students and experts will ultimately raise the standard of instruction and motivate students to self-guide their learning experience to levels of greater understanding.

  15. Direct TEM observations of growth mechanisms of two-dimensional MoS2 flakes

    NASA Astrophysics Data System (ADS)

    Fei, Linfeng; Lei, Shuijin; Zhang, Wei-Bing; Lu, Wei; Lin, Ziyuan; Lam, Chi Hang; Chai, Yang; Wang, Yu

    2016-07-01

    A microscopic understanding of the growth mechanism of two-dimensional materials is of particular importance for controllable synthesis of functional nanostructures. Because of the lack of direct and insightful observations, how to control the orientation and the size of two-dimensional material grains is still under debate. Here we discern distinct formation stages for MoS2 flakes from the thermolysis of ammonium thiomolybdates using in situ transmission electron microscopy. In the initial stage (400 °C), vertically aligned MoS2 structures grow in a layer-by-layer mode. With the increasing temperature of up to 780 °C, the orientation of MoS2 structures becomes horizontal. When the growth temperature reaches 850 °C, the crystalline size of MoS2 increases by merging adjacent flakes. Our study shows direct observations of MoS2 growth as the temperature evolves, and sheds light on the controllable orientation and grain size of two-dimensional materials.

  16. Mechanical motion conversion from reciprocating translation to one-directional rotation for effective energy harvesting

    NASA Astrophysics Data System (ADS)

    Ahmed, Kabir; Lee, Soobum

    2016-04-01

    This paper proposes a new efficient motion conversion system which can be used in an energy harvesting system that converts wasted kinematic energy into electrical energy. In the proposed system, a reciprocating translational motion will be converted into one-directional rotational motion that spins a generator. The system will be devised with a two overlapping chambers (chamber 1 and 2) which move relatively through the sliding joint, and a pair of flexible strings (belt, steel wire, or chain) run around the rotor of the generator. Each end of the string fixed to chamber 1 is designed not to interfere with chamber 2 where the generator is mounted. When the two chambers move relatively, either top or bottom string is tensioned to spin the rotor while the other string is being rewound. One-directional clutch with a coil spring is engaged in a rewinding system - as found in a rowing machine, for example - so each string actuates the rotor only when it is in tension. This device can be applied to any mechanism where reciprocating translational motion exists, such as linear suspension system in a vehicle, a bicycle, and an energy generating marine buoy. The experimental study result will be reported as well as its battery-charging capacity will be demonstrated.

  17. Field emission driven direct current argon discharges and electrical breakdown mechanism across micron scale gaps

    NASA Astrophysics Data System (ADS)

    Matejčik, Štefan; Radjenović, Branislav; Klas, Matej; Radmilović-Radjenović, Marija

    2015-11-01

    In this paper results of the experimental and theoretical studies of the field emission driven direct current argon microdischarges for the gaps between 1 μm and 100 μm are presented and discussed. The breakdown voltage curves and Volt-Ampere characteristics proved to be a fertile basis providing better understanding of the breakdown phenomena in microgaps. Based on the measured breakdown voltage curves, the effective yields have been estimated confirming that the secondary electron emission due to high electric field generated in microgaps depends primarily on the electric field leading directly to the violation of the Paschen's law. Experimental data are supported by the theoretical predictions that suggest departure from the scaling law and a flattening of the Paschen curves at higher pressures confirming that Townsend phenomenology breaks down when field emission becomes the key mechanism leading to the breakdown. Field emission of electrons from the cathode, the space charge effects in the breakdown and distinction between the Fowler-Nordheim field emission and the space charge limited current density are also analyzed. Images and Volt-Ampere characteristics recorded at the electrode gap size of 20 μm indicate the existence of a discharge region similar to arc at the pressure of around 200 Torr has been observed. Contribution to the Topical Issue "Recent Breakthroughs in Microplasma Science and Technology", edited by Kurt Becker, Jose Lopez, David Staack, Klaus-Dieter Weltmann and Wei Dong Zhu.

  18. Direct TEM observations of growth mechanisms of two-dimensional MoS2 flakes

    PubMed Central

    Fei, Linfeng; Lei, Shuijin; Zhang, Wei-Bing; Lu, Wei; Lin, Ziyuan; Lam, Chi Hang; Chai, Yang; Wang, Yu

    2016-01-01

    A microscopic understanding of the growth mechanism of two-dimensional materials is of particular importance for controllable synthesis of functional nanostructures. Because of the lack of direct and insightful observations, how to control the orientation and the size of two-dimensional material grains is still under debate. Here we discern distinct formation stages for MoS2 flakes from the thermolysis of ammonium thiomolybdates using in situ transmission electron microscopy. In the initial stage (400 °C), vertically aligned MoS2 structures grow in a layer-by-layer mode. With the increasing temperature of up to 780 °C, the orientation of MoS2 structures becomes horizontal. When the growth temperature reaches 850 °C, the crystalline size of MoS2 increases by merging adjacent flakes. Our study shows direct observations of MoS2 growth as the temperature evolves, and sheds light on the controllable orientation and grain size of two-dimensional materials. PMID:27412892

  19. Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics

    PubMed Central

    Riley, Blake T.; Ilyichova, Olga; Costa, Mauricio G. S.; Porebski, Benjamin T.; de Veer, Simon J.; Swedberg, Joakim E.; Kass, Itamar; Harris, Jonathan M.; Hoke, David E.; Buckle, Ashley M.

    2016-01-01

    The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel. These structures offer a structural rationalization for the potency and selectivity of these inhibitors, and together with MD simulation and computational analysis, reveal a dynamic pathway between the metal binding exosite and the active site, providing key details of a previously proposed allosteric mode of inhibition. Collectively, this work provides insight into both direct and indirect mechanisms of inhibition for KLK4 that have broad implications for the enzymology of the serine protease superfamily, and may potentially be exploited for the design of therapeutic inhibitors. PMID:27767076

  20. The mechanisms of action of flavonoids in the brain: Direct versus indirect effects.

    PubMed

    Rendeiro, Catarina; Rhodes, Justin S; Spencer, Jeremy P E

    2015-10-01

    The projected increase in the incidence of dementia in the population highlights the urgent need for a more comprehensive understanding of how different aspects of lifestyle, in particular exercise and diet, may affect neural function and consequent cognitive performance throughout the life course. In this regard, flavonoids, found in a variety of fruits, vegetables and derived beverages, have been identified as a group of promising bioactive compounds capable of influencing different aspects of brain function, including cerebrovascular blood flow and synaptic plasticity, both resulting in improvements in learning and memory in mammalian species. However, the precise mechanisms by which flavonoids exert these actions are yet to be fully established, although accumulating data indicate an ability to interact with neuronal receptors and kinase signaling pathways which are key to neuronal activation and communication and synaptic strengthening. Alternatively or concurrently, there is also compelling evidence derived from human clinical studies suggesting that flavonoids can positively affect peripheral and cerebrovascular blood flow, which may be an indirect effective mechanism by which dietary flavonoids can impact on brain health and cognition. The current review examines the beneficial effects of flavonoids on both human and animal brain function and attempts to address and link direct and indirect actions of flavonoids and their derivatives within the central nervous system (CNS).

  1. Comparative study of mechanical properties of direct core build-up materials

    PubMed Central

    Kumar, Girish; Shivrayan, Amit

    2015-01-01

    Background and Objectives: The strength greatly influences the selection of core material because core must withstand forces due to mastication and para-function for many years. This study was conducted to evaluate certain mechanical properties of commonly used materials for direct core build-up, including visible light cured composite, polyacid modified composite, resin modified glass ionomer, high copper amalgam, and silver cermet cement. Materials and Methods: All the materials were manipulated according to the manufacturer's recommendations and standard test specimens were prepared. A universal testing machine at different cross-head speed was used to determine all the four mechanical properties. Mean compressive strength, diametral tensile strength, flexural strength, and elastic modulus with standard deviations were calculated. Multiple comparisons of the materials were also done. Results: Considerable differences in compressive strength, diametral tensile strength, and flexural strength were observed. Visible light cured composite showed relatively high compressive strength, diametral tensile strength, and flexural strength compared with the other tested materials. Amalgam showed the highest value for elastic modulus. Silver cermet showed less value for all the properties except for elastic modulus. Conclusions: Strength is one of the most important criteria for selection of a core material. Stronger materials better resist deformation and fracture provide more equitable stress distribution, greater stability, and greater probability of clinical success. PMID:25684905

  2. Direct measurements of HOx radicals in the marine boundary layer: testing the current tropospheric chemistry mechanism.

    PubMed

    Kanaya, Yugo; Akimoto, Hajime

    2002-01-01

    OH and HO(2) radicals, atmospheric detergents, and the reservoir thereof, play central roles in tropospheric chemistry. In spite of their importance, we had no choice but to trust their concentrations predicted by modeling studies based on known chemical processes. However, recent direct measurements of these radicals have enabled us to test and revise our knowledge of the processes by comparing the predicted and observed values of the radical concentrations. We developed a laser-induced fluorescence (LIF) instrument and successfully observed OH and HO(2) at three remote islands of Japan (Oki Island, Okinawa Island, and Rishiri Island). At Okinawa Island, the observed daytime level of HO(2) agreed closely with the model estimates, suggesting that the photochemistry at Okinawa is well described by the current chemistry mechanism. At Rishiri Island, in contrast, the observed daytime level of HO(2) was consistently much lower than the calculated values. We proposed that iodine chemistry, usually not incorporated into the mechanism, is at least partly responsible for the discrepancy in the results. At night, HO(2) was detected at levels greater than 1 pptv at all three islands, suggesting the presence of processes in the dark that produce radicals. We showed that ozone reactions with unsaturated hydrocarbons, including monoterpenes, could significantly contribute to radical production.

  3. Relation between gravitational and arm-movement direction in the mechanism of perception in bimanual steering.

    PubMed

    Sakajiri, Taiji; Tanaka, Yoshihiro; Sano, Akihito

    2013-11-01

    This paper presents the effects of the opposing directions of gravity relative to right- and left-arm movement in bimanual steering. We developed a simulated steering system that permits independent left- and right-hand steering and torque presentations on a single axis, and independent measurements of the steering force exerted by each hand. In a steering force measurement experiment, left and right system units were mechanically combined to function as a single steering unit. Measurements of the force exerted by the participants with their left and right hands revealed that in human bimanual steering, the arm moving with gravity exerts a larger steering force than the one moving against gravity. In a steering force discrimination experiment, the system was mechanically configured to provide independence in both the function of the left and right steering units and the presentation of different left- and right-side steering torques. Each participant was then asked whether the steering force was felt to be larger on the left or the right during bimanual steering. The results of this experiment showed no difference between the left and the right arm in the discrimination threshold, but did reveal a perceptual bias in which the forces exerted in arm movements with gravity were perceived as being smaller than the forces exerted against gravity. Furthermore, there was no significant difference between the measured force and the force that would be predicted from the obtained perceptual bias.

  4. Direct measurements of HOx radicals in the marine boundary layer: testing the current tropospheric chemistry mechanism.

    PubMed

    Kanaya, Yugo; Akimoto, Hajime

    2002-01-01

    OH and HO(2) radicals, atmospheric detergents, and the reservoir thereof, play central roles in tropospheric chemistry. In spite of their importance, we had no choice but to trust their concentrations predicted by modeling studies based on known chemical processes. However, recent direct measurements of these radicals have enabled us to test and revise our knowledge of the processes by comparing the predicted and observed values of the radical concentrations. We developed a laser-induced fluorescence (LIF) instrument and successfully observed OH and HO(2) at three remote islands of Japan (Oki Island, Okinawa Island, and Rishiri Island). At Okinawa Island, the observed daytime level of HO(2) agreed closely with the model estimates, suggesting that the photochemistry at Okinawa is well described by the current chemistry mechanism. At Rishiri Island, in contrast, the observed daytime level of HO(2) was consistently much lower than the calculated values. We proposed that iodine chemistry, usually not incorporated into the mechanism, is at least partly responsible for the discrepancy in the results. At night, HO(2) was detected at levels greater than 1 pptv at all three islands, suggesting the presence of processes in the dark that produce radicals. We showed that ozone reactions with unsaturated hydrocarbons, including monoterpenes, could significantly contribute to radical production. PMID:12112871

  5. Effects of direct current on dog liver: Possible mechanisms for tumor electrochemical treatment

    SciTech Connect

    Li, K.H.; Gu, Y.N.; Xu, B.I.; Fan, D.J.; Ni, B.F.; Xin, Y.L.

    1997-03-01

    Mechanisms of tumor electrochemical treatment (ECT) were studied using normal dog liver. Five physical and chemical methods were used. Two platinum electrodes were inserted into an anesthetized dog`s liver at 3 cm separation. A voltage of 8.5 V direct current (DC) at an average current of 30 mA was applied for 69 min; total charge was 124 coulombs. Concentrations of selected ions near the anode and cathode were measured. The concentrations of Na{sup +} and K{sup +} ions were higher around the cathode, whereas the concentration of Cl{sup {minus}} ions was higher around the anode. Water contents and pH were determined near the anode and the cathode at the midpoint between the two electrodes and in an untreated area away from the electrodes. Hydration occurred around the cathode, and dehydration occurred around the anode. The pH values were 2.1 near the anode and 12.9 near the cathode. Spectrophotometric scans of the liver sample extract were obtained, and the released gases were identified by gas chromatography as chlorine at the anode and hydrogen at the cathode. These results indicate that a series of electrochemical reactions take place during ECT. The cell metabolism and its environment are severely disturbed. Both normal and tumor cells are rapidly and completely destroyed in this altered environment. The authors believe that the above reactions are the ECT mechanisms for treating tumors.

  6. DIRECT-ACTING, DNA-DAMAGING AS (III)-METHYLATED SPECIES: IMPLICATIONS FOR A CARCINOGENIC MECHANISM OF ACTION OF ARSENICALS

    EPA Science Inventory

    Direct-acting, DNA-damaging As (III)-methylated species: implications for a carcinogenic . mechanism of action of arsenicals

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a carcinogen without reacting directly with DNA; neither iAs nor the As(...

  7. Biology of tooth replacement in amniotes

    PubMed Central

    Whitlock, John A; Richman, Joy M

    2013-01-01

    Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1–2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development. PMID:23788284

  8. Non-mechanical scanning laser Doppler velocimetry with sensitivity to direction of transverse velocity component using optical serrodyne frequency shifting

    NASA Astrophysics Data System (ADS)

    Maru, Koichi; Watanabe, Kento

    2014-05-01

    This paper proposes a non-mechanical axial scanning laser Doppler velocimeter (LDV) with sensitivity to the direction of the transverse velocity component using optical serrodyne frequency shifting. Serrodyne modulation via the electro-optic effect of a LiNbO3 (LN) phase shifter is employed to discriminate the direction of the transverse velocity component. The measurement position is scanned without any moving mechanism in the probe by changing the wavelength of the light input to the probe. The experimental results using a sensor probe setup indicate that both the scan of the measurement position and the introduction of directional sensitivity are successfully demonstrated.

  9. Contingency in the Direction and Mechanics of Soil Organic Matter Responses to Increased Rainfall

    SciTech Connect

    Berhe, Asmeret A.; Suttle, K. Blake; Burton, Sarah D.; Banfield, Jillian F.

    2012-09-03

    Shifts in regional precipitation patterns will be a major component of global climate change. Rainfall will show greater and more variable changes in response to rising earth surface temperatures than most other climatic variables, and will be a major driver of ecosystem change. We studied the consequences of predicted changes in California’s rainy season for storage and stabilization mechanisms of soil organic matter (SOM). In a controlled and replicated experiment, we amended rainfall over large plots of natural grassland in accordance with alternative scenarios of future climate change. Results show that increases in annual rainfall have important consequences for soil C storage, but that the strength and even direction of these effects depend entirely on seasonal timing. Rainfall increases during the winter rainy season led to pronounced C loss from soil while rainfall increases after the typical rainy season increased soil C stocks. Analysis of mineral-OM associations reveals a powerful mechanism underlying this difference: increased winter rainfall vastly diminished the role of Fe and Al oxides in SOM stabilization. Dithionite extractable crystalline Fe oxides explained more than 35 percent of the variability in C storage in ambient control and spring-addition treatments, compared to less than 0.01 percent in the winter-addition treatment. Likewise, poorly crystalline Fe and Al oxides explained more than 25 and 40 percent of the variability in C storage, respectively, in the control and spring-addition treatments compared to less than 5 percent in the -winter-addition treatment. Increases in annual precipitation identical in amount but at three-month offsets produced opposite effects on soil C storage. These results highlight the complexity inherent in biospheric feedbacks to the climate system, and the way that careful experimentation can penetrate that complexity to improve predictions of ecosystem and climatic change.

  10. Biased Brownian motion mechanism for processivity and directionality of single-headed myosin-VI.

    PubMed

    Iwaki, Mitsuhiro; Iwane, Atsuko Hikikoshi; Ikebe, Mitsuo; Yanagida, Toshio

    2008-01-01

    Conventional form to function as a vesicle transporter is not a 'single molecule' but a coordinated 'two molecules'. The coordinated two molecules make it complicated to reveal its mechanism. To overcome the difficulty, we adopted a single-headed myosin-VI as a model protein. Myosin-VI is an intracellular vesicle and organelle transporter that moves along actin filaments in a direction opposite to most other known myosin classes. The myosin-VI was expected to form a dimer to move processively along actin filaments with a hand-over-hand mechanism like other myosin organelle transporters. However, wild-type myosin-VI was demonstrated to be monomer and single-headed, casting doubt on its processivity. Using single molecule techniques, we show that green fluorescent protein (GFP)-fused single-headed myosin-VI does not move processively. However, when coupled to a 200 nm polystyrene bead (comparable to an intracellular vesicle in size) at a ratio of one head per bead, single-headed myosin-VI moves processively with large (40 nm) steps. Furthermore, we found that a single-headed myosin-VI-bead complex moved more processively in a high-viscous solution (40-fold higher than water) similar to cellular environment. Because diffusion of the bead is 60-fold slower than myosin-VI heads alone in water, we propose a model in which the bead acts as a diffusional anchor for the myosin-VI, enhancing the head's rebinding following detachment and supporting processive movement of the bead-monomer complex. This investigation will help us understand how molecular motors utilize Brownian motion in cells.

  11. Spatial Direct Numerical Simulation of Boundary-Layer Transition Mechanisms: Validation of PSE Theory

    NASA Technical Reports Server (NTRS)

    Joslin, R. D.; Streett, C. L.; Chang, C.-L.

    1991-01-01

    A study of instabilities in incompressible boundary-layer flow on a flat plate is conducted by spatial direct numerical simulation (DNS) of the Navier-Stokes equations. Here, the DNS results are used to critically evaluate the results obtained using parabolized stability equations (PSE) theory and to study mechanisms associated with breakdown from laminar to turbulent flow. Three test cases are considered: two-dimensional Tollmien-Schlichting wave propagation, subharmonic instability breakdown, and oblique-wave break-down. The instability modes predicted by PSE theory are in good quantitative agreement with the DNS results, except a small discrepancy is evident in the mean-flow distortion component of the 2-D test problem. This discrepancy is attributed to far-field boundary- condition differences. Both DNS and PSE theory results show several modal discrepancies when compared with the experiments of subharmonic breakdown. Computations that allow for a small adverse pressure gradient in the basic flow and a variation of the disturbance frequency result in better agreement with the experiments.

  12. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism.

    PubMed

    Kim, Hun Sik; Kwon, Hyung-Joon; Kim, Gye Eun; Cho, Mi-Hyang; Yoon, Seung-Yong; Davies, Alexander J; Oh, Seog Bae; Lee, Heuiran; Cho, Young Keol; Joo, Chul Hyun; Kwon, Seog Woon; Kim, Sun Chang; Kim, Yoo Kyum

    2014-07-01

    The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance. PMID:24743513

  13. Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing.

    PubMed

    McCracken, Joselle M; Badea, Adina; Kandel, Mikhail E; Gladman, A Sydney; Wetzel, David J; Popescu, Gabriel; Lewis, Jennifer A; Nuzzo, Ralph G

    2016-05-01

    3D hydrogel scaffolds are widely used in cellular microcultures and tissue engineering. Using direct ink writing, microperiodic poly(2-hydroxyethyl-methacrylate) (pHEMA) scaffolds are created that are then printed, cured, and modified by absorbing 30 kDa protein poly-l-lysine (PLL) to render them biocompliant in model NIH/3T3 fibroblast and MC3T3-E1 preosteoblast cell cultures. Spatial light interference microscopy (SLIM) live cell imaging studies are carried out to quantify cellular motilities for each cell type, substrate, and surface treatment of interest. 3D scaffold mechanics is investigated using atomic force microscopy (AFM), while their absorption kinetics are determined by confocal fluorescence microscopy (CFM) for a series of hydrated hydrogel films prepared from prepolymers with different homopolymer-to-monomer (Mr ) ratios. The observations reveal that the inks with higher Mr values yield relatively more open-mesh gels due to a lower degree of entanglement. The biocompatibility of printed hydrogel scaffolds can be controlled by both PLL content and hydrogel mesh properties.

  14. Mathematical modeling and mechanical and histopathological testing of porous prosthetic pylon for direct skeletal attachment

    PubMed Central

    Pitkin, Mark; Raykhtsaum, Grigory; Pilling, John; Shukeylo, Yuri; Moxson, Vladimir; Duz, Volodimir; Lewandowski, John; Connolly, Raymond; Kistenberg, Robert S.; Dalton, John F.; Prilutsky, Boris; Jacobson, Stewart

    2010-01-01

    This article presents recent results in the development of the skin and bone integrated pylon (SBIP) intended for direct skeletal attachment of limb prostheses. In our previous studies of the porous SBIP-1 and SBIP-2 prototypes, the bond site between the porous pylons and residuum bone and skin did not show the inflammation characteristically observed when solid pylons are used. At the same time, porosity diminished the strength of the pylon. To find a reasonable balance between the biological conductivity and the strength of the porous pylon, we developed a mathematical model of the composite permeable structure. A novel manufacturing process was implemented, and the new SBIP-3 prototype was tested mechanically. The minimal strength requirements established earlier for the SBIP were exceeded threefold. The first histopathological analysis of skin, bone, and the implanted SBIP-2 pylons was conducted on two rats and one cat. The histopathological analysis provided new evidence of inflammation-free, deep ingrowth of skin and bone cells throughout the SBIP structure. PMID:19675985

  15. [Mechanism of groundwater As(V) removal with ferric flocculation and direct filtration].

    PubMed

    Kang, Ying; Duan, Jin-Ming; Jing, Chuan-Yong

    2015-02-01

    The As removal process and mechanism from groundwater using ferric flocculation-direct filtration system was investigated using batch, field pilot tests, extended X-ray absorption fine structure ( EXAFS) spectroscopy, and charge-distribution multisite complexation (CD-MUSIC) model. The results showed that arsenate [As(V)] was the dominant As species in the groundwater with a concentration of 40 μg x L(-1). The treatment system could supply 64 984 L As-safe drinking water (< 10 μg L(-1)) using Fe 1.5 mg x L(-1). Toxicity characteristic leaching procedure (TCLP) demonstrated that the leachate As was 3.4 μg x L(-1), much lower than the EPA regulatory concentration (5 mg x L(-1)). EXAFS and CD-MUSIC model indicated that As(V) was adsorbed onto ferric hydroxide via bidentate binuclear complexes in the pH range of 3 to 9.5, while formation of precipitate with Ca or Mg dominated the As removal at pH > 9.5.

  16. Goal-directed mechanisms that constrain retrieval predict subsequent memory for new "foil" information.

    PubMed

    Vogelsang, David A; Bonnici, Heidi M; Bergström, Zara M; Ranganath, Charan; Simons, Jon S

    2016-08-01

    To remember a previous event, it is often helpful to use goal-directed control processes to constrain what comes to mind during retrieval. Behavioral studies have demonstrated that incidental learning of new "foil" words in a recognition test is superior if the participant is trying to remember studied items that were semantically encoded compared to items that were non-semantically encoded. Here, we applied subsequent memory analysis to fMRI data to understand the neural mechanisms underlying the "foil effect". Participants encoded information during deep semantic and shallow non-semantic tasks and were tested in a subsequent blocked memory task to examine how orienting retrieval towards different types of information influences the incidental encoding of new words presented as foils during the memory test phase. To assess memory for foils, participants performed a further surprise old/new recognition test involving foil words that were encountered during the previous memory test blocks as well as completely new words. Subsequent memory effects, distinguishing successful versus unsuccessful incidental encoding of foils, were observed in regions that included the left inferior frontal gyrus and posterior parietal cortex. The left inferior frontal gyrus exhibited disproportionately larger subsequent memory effects for semantic than non-semantic foils, and significant overlap in activity during semantic, but not non-semantic, initial encoding and foil encoding. The results suggest that orienting retrieval towards different types of foils involves re-implementing the neurocognitive processes that were involved during initial encoding.

  17. Goal-directed mechanisms that constrain retrieval predict subsequent memory for new "foil" information.

    PubMed

    Vogelsang, David A; Bonnici, Heidi M; Bergström, Zara M; Ranganath, Charan; Simons, Jon S

    2016-08-01

    To remember a previous event, it is often helpful to use goal-directed control processes to constrain what comes to mind during retrieval. Behavioral studies have demonstrated that incidental learning of new "foil" words in a recognition test is superior if the participant is trying to remember studied items that were semantically encoded compared to items that were non-semantically encoded. Here, we applied subsequent memory analysis to fMRI data to understand the neural mechanisms underlying the "foil effect". Participants encoded information during deep semantic and shallow non-semantic tasks and were tested in a subsequent blocked memory task to examine how orienting retrieval towards different types of information influences the incidental encoding of new words presented as foils during the memory test phase. To assess memory for foils, participants performed a further surprise old/new recognition test involving foil words that were encountered during the previous memory test blocks as well as completely new words. Subsequent memory effects, distinguishing successful versus unsuccessful incidental encoding of foils, were observed in regions that included the left inferior frontal gyrus and posterior parietal cortex. The left inferior frontal gyrus exhibited disproportionately larger subsequent memory effects for semantic than non-semantic foils, and significant overlap in activity during semantic, but not non-semantic, initial encoding and foil encoding. The results suggest that orienting retrieval towards different types of foils involves re-implementing the neurocognitive processes that were involved during initial encoding. PMID:27431039

  18. Expanding the Enzyme Universe: Accessing Non-Natural Reactions by Mechanism-Guided Directed Evolution

    PubMed Central

    Renata, Hans; Wang, Z. Jane

    2015-01-01

    High selectivities and exquisite control over reaction outcomes entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature’s known repertoire. We will use this review to outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progressions have been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been discovered and exploited for chemical synthesis, emphasizing reactions that do not have natural counterparts. The new functions have mechanistic parallels to the native reaction mechanisms that often manifest as catalytic promiscuity and the ability to convert from one function to the other with minimal mutation. We present examples of how non-natural activities have been improved by directed evolution, mimicking the process used by nature to create new catalysts. Examples of new enzyme functions include epoxide opening reactions with non-natural nucleophiles catalyzed by a laboratory-evolved halohydrin dehalogenase, cyclopropanation and other carbene transfer reactions catalyzed by cytochrome P450 variants, and non-natural modes of cyclization by a modified terpene synthase. Lastly, we describe discoveries of non-native catalytic functions that may provide future opportunities for expanding the enzyme universe. PMID:25649694

  19. Having a direct look: Analysis of DNA damage and repair mechanisms by next generation sequencing

    PubMed Central

    Meier, Bettina; Gartner, Anton

    2014-01-01

    Genetic information is under constant attack from endogenous and exogenous sources, and the use of model organisms has provided important frameworks to understand how genome stability is maintained and how various DNA lesions are repaired. The advance of high throughput next generation sequencing (NGS) provides new inroads for investigating mechanisms needed for genome maintenance. These emerging studies, which aim to link genetic toxicology and mechanistic analyses of DNA repair processes in vivo, rely on defining mutational signatures caused by faulty replication, endogenous DNA damaging metabolites, or exogenously applied genotoxins; the analysis of their nature, their frequency and distribution. In contrast to classical studies, where DNA repair deficiency is assessed by reduced cellular survival, the localization of DNA repair factors and their interdependence as well as limited analysis of single locus reporter assays, NGS based approaches reveal the direct, quantal imprint of mutagenesis genome-wide, at the DNA sequence level. As we will show, such investigations require the analysis of DNA derived from single genotoxin treated cells, or DNA from cell populations regularly passaged through single cell bottlenecks when naturally occurring mutation accumulation is investigated. We will argue that the life cycle of the nematode Caenorhabditis elegans, its genetic malleability combined with whole genome sequencing provides an exciting model system to conduct such analysis. PMID:25131498

  20. Damage and failure mechanisms of a 3-directional carbon/carbon composite under uniaxial tensile and shear loads

    SciTech Connect

    Siron, O.; Lamon, J.

    1998-11-20

    The mechanical behavior of a three-directional carbon/carbon (C/C) composite under tensile and shear loads is investigated in relation with the failure mechanisms and, the fiber architecture. This three-directional C/C composite was produced by Chemical Vapor Infiltration of a needled fiber preform of multiple layers of satin woven tows. The C/C composite exhibited several interesting features including an essentially non-linear stress-strain behavior and permanent deformations. Three families of matrix cracks were identified under tensile and shear loads, including microcracks in the tows, intertow delamination and cracks across the longitudinal tows. It was found that the delamination cracks affect preponderantly the stress-strain behavior and the mechanical properties. Similar features in the mechanical behavior and the failure mechanisms were highlighted under tension and under shear loading.

  1. Insect biotechnology: controllable replacement of disease vectors.

    PubMed

    Wimmer, Ernst A

    2013-05-20

    To fight human vector-borne diseases, first releases of sterile transgenic mosquitoes have been performed. Someday, disease-refractory mosquitoes will replace wild types to stop transmission. For such population replacements, gene drive mechanisms must be established that allow local confinement and reversibility.

  2. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  3. Ion replacement electrorefining

    SciTech Connect

    Willit, J.L.; Tomczuk, Z.; Miller, W.E.; Laidler, J.J.

    1994-04-01

    We are developing a two-step electrochemical process for purifying and separating metals called ion replacement electrorefining. In each step, metal cations formed by oxidation at an electrode replace other metal cations that are reduced at another elecmae. Using this approach, we have separated or purified uranium, dysprosium, and lanthanum on a laboratory scale. This paper explains the ion replacement concept and presents results of these demonstration experiments.

  4. The effects of peroxide content on the wear behavior, microstructure and mechanical properties of peroxide crosslinked ultra-high molecular weight polyethylene used in total hip replacement.

    PubMed

    Gul, Rizwan M

    2008-06-01

    The wear of the ultra-high molecular weight polyethylene (UHMWPE) acetabular components and wear debris induced osteolysis are the major causes of failure in total hip replacements. Crosslinking has been shown to improve the wear resistance of UHMWPE by producing a network structure, resisting the plastic deformation of the surface layer. In this study organic peroxides were used to crosslink two different types of UHMWPE resins, using hot isostatic pressing as the processing method. The effects of peroxide content on the different properties were investigated, along with the effect of the crosslink density on the wear behavior. An increase in peroxide content decreases the melting point and the degree of crystallinity, which results in a decrease in the yield strength. The ultimate tensile strength remains essentially unchanged. The molecular weight between crosslinks decreases with an increase in the peroxide content and reaches a saturation limit at around 0.3-0.5 weight percent peroxide, its value at the saturation limit is a function of the virgin resin used for processing. The wear rate decreases linearly with the increase in crosslink density. PMID:18219557

  5. Exploring a reaction mechanism for acetato ligand replacement in paddlewheel tetrakisacetatodirhodium (II,II) complex by ammonia: computational density functional theory study.

    PubMed

    Futera, Zdenĕk; Koval, TomáS; Leszczynski, Jerzy; Gu, Jiande; Mitoraj, Mariusz; Srebro, Monika; Burda, Jaroslav V

    2011-02-10

    This study focuses on the first step of interaction between DNA and the paddle-wheel dirhodium complex. The ammonia molecule was used to model the oligonucleotide sequence. The reaction was considered in neutral and acidic conditions, in gas phase, and in solvent, using the COSMO model. Molecular structures of the complexes were optimized in both models at the B3PW91/6-31G(d) level. The B3LYP functional and aug-cc-pvdz basis set were employed for single-point energy determination and electron distribution analyses. It was shown that in neutral solution the replacement of axial aqua ligand is mildly exoergic. The reaction is characterized by a relatively low activation barrier (10-12 kcal/mol), and, according to Eyring transition state theory, it proceeds very quickly. The breaking of the Rh-O(ac) bond in neutral solution is mildly endoergic (less than 1 kcal/mol) with an activation barrier of about 21 kcal/mol. However, this process can occur much more spontaneously (ΔG of -14 kcal/mol) when the dirhodium complex is protonated at the acetyl oxygen in remote position.

  6. A channelopathy mechanism revealed by direct calmodulin activation of TrpV4

    PubMed Central

    Loukin, Stephen H.; Teng, Jinfeng; Kung, Ching

    2015-01-01

    Ca2+-calmodulin (CaM) regulates varieties of ion channels, including Transient Receptor Potential vanilloid subtype 4 (TrpV4). It has previously been proposed that internal Ca2+ increases TrpV4 activity through Ca2+-CaM binding to a C-terminal Ca2+-CaM binding domain (CBD). We confirmed this model by directly presenting Ca2+-CaM protein to membrane patches excised from TrpV4-expressing oocytes. Over 50 TRPV4 mutations are now known to cause heritable skeletal dysplasia (SD) and other diseases in human. We have previously examined 14 SD alleles and found them to all have gain-of-function effects, with the gain of constitutive open probability paralleling disease severity. Among the 14 SD alleles examined, E797K and P799L are located immediate upstream of the CBD. They not only have increase basal activity, but, unlike the wild-type or other SD-mutant channels examined, they were greatly reduced in their response to Ca2+-CaM. Deleting a 10-residue upstream peptide (Δ795–804) that covers the two SD mutant sites resulted in strong constitutive activity and the complete lack of Ca2+-CaM response. We propose that the region immediately upstream of CBD is an autoinhibitory domain that maintains the closed state through electrostatic interactions, and adjacent detachable Ca2+-CaM binding to CBD sterically interferes with this autoinhibition. This work further supports the notion that TrpV4 mutations cause SD by constitutive leakage. However, the closed conformation is likely destabilized by various mutations by different mechanisms, including the permanent removal of an autoinhibition documented here. PMID:26170305

  7. LIGHT signals directly to intestinal epithelia to cause barrier dysfunction via cytoskeletal and endocytic mechanisms

    PubMed Central

    Schwarz, Brad T.; Wang, Fengjun; Shen, Le; Clayburgh, Daniel R.; Su, Liping; Wang, Yingmin; Fu, Yang-Xin; Turner, Jerrold R.

    2009-01-01

    BACKGROUND & AIMS LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpes virus entry on T cells) is a TNF core family member that regulates T cell activation and causes experimental inflammatory bowel disease. Additional data suggest that LIGHT may be involved in the pathogenesis of human inflammatory bowel disease. The aim of this study was to determine if LIGHT was capable of signaling directly to intestinal epithelia and to define the mechanisms and consequences of such signaling. METHODS The effects of LIGHT and interferon-γ (IFN-γ) on barrier function, cytoskeletal regulation, and tight junction structure were assessed in mice and intestinal epithelial monolayers. RESULTS LIGHT induced barrier loss in cultured epithelia via myosin II regulatory light chain (MLC) phosphorylation; both barrier loss and MLC phosphorylation were reversed by MLC kinase (MLCK) inhibition. IFN-γ pretreatment, which induced lymphotoxin β receptor (LTβR) expression, was required for these effects and neither barrier dysfunction nor intestinal epithelial MLC phosphorylation occurred in LTβR-knockout mice. In cultured monolayers, endocytosis of the tight junction protein occludin correlated with barrier loss. Internalized occludin co-localized with caveolin-1. LIGHT-induced occludin endocytosis and barrier loss were both prevented by inhibition of caveolar endocytosis. CONCLUSIONS T cell-derived LIGHT activates intestinal epithelial LTβR to disrupt barrier function. This requires MLCK activation and caveolar endocytosis. These data suggest a novel role for LIGHT in disease pathogenesis and suggest that inhibition of MLCK-dependent caveolar endocytosis may represent an approach to restoring barrier function in inflammatory bowel disease. PMID:17570213

  8. [Mitral valve replacement after previous coronary artery bypass grafting with functioning left internal thoracic artery graft: effectiveness of the method using a direct vision retrosternal approach; report of a case].

    PubMed

    Sakata, Junichi; Saito, Tatsuya; Fujii, Akira; Tsukamoto, Masaru; Date, Osamu; Yokoyama, Hideo; Abe, Tomio; Nakase, Atsunobu; Ohori, Katsumi

    2014-08-01

    Performing a redo-sternotomy when a mammary artery graft is patent can be rather difficult. We previously reported a redo-sternotomy technique involving direct visualization with a retrosternal dissection (DR) method using a Kent's retractor. The DR method in detail is as follows: 1) A midline skin incision is extended to the abdomen about 5 cm. 2) The bilateral costal arches are divided from the rectal muscle. 3). A pair of retractors is placed under the costal arch. 4) A stainless steel wire is applied to the previous sternal wire at the center of the sternum. 5) The retractor and sternal wire are lifted up using the Kent's retractor to widen the retrosternal space. 6) The sternum and sub-sternal tissue are carefully divided using an electronic scalpel or metal retractor with an entirely sternal length. 7) Routine sternotomy is performed using a Stryker. Herein, we report a patient who had undergone cardiac surgery, coronary artery bypass grafting (CABG), using a left internal mammary artery and mitral annuloplasty 2 years previously, and then developed mitral regurgitation caused by infectious endocarditis. He successfully underwent redo-sternotomy and mitral valve replacement using the DR method. In a patient with a patent internal mammary artery, the DR method greatly reduces the risk of graft injury.

  9. Dental ontogeny and replacement in Pliosauridae.

    PubMed

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  10. Dental ontogeny and replacement in Pliosauridae.

    PubMed

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context.

  11. Dental ontogeny and replacement in Pliosauridae

    PubMed Central

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-01-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or ‘movement paths’, of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context. PMID:26715998

  12. Radiation Source Replacement Workshop

    SciTech Connect

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

  13. Linear time reduction of large kinetic mechanisms with directed relation graph: n-Heptane and iso-octane

    SciTech Connect

    Lu, Tianfeng; Law, Chung K.

    2006-01-01

    The algorithm of directed relation graph recently developed for skeletal mechanism reduction was extended to overall linear time operation, thereby greatly facilitating the computational effort in mechanism reduction, particularly for those involving large mechanisms. Together with a two-stage reduction strategy and using the kinetic responses of autoignition and perfectly stirred reactor (PSR) with extensive parametric variations as the criteria in eliminating unimportant species, a detailed 561-species n-heptane mechanism and a detailed 857-species iso-octane mechanism were successfully reduced to skeletal mechanisms consisting of 188 and 233 species, respectively. These skeletal mechanisms were demonstrated to mimic well the performance of the detailed mechanisms, not only for the autoignition and PSR systems based on which the reduced mechanisms were developed but also for the independent system of jet-stirred reactor. It was further observed that the accuracy of calculated species concentrations was equivalently bounded by the user-specified error threshold value and that the reduction time for a single reaction state is only about 50 ms for the large iso-octane mechanism.

  14. The mechanical actions of muscles predict the direction of muscle activation during postural perturbations in the cat hindlimb.

    PubMed

    Honeycutt, Claire F; Nichols, T Richard

    2014-03-01

    Humans and cats respond to balance challenges, delivered via horizontal support surface perturbations, with directionally selective muscle recruitment and constrained ground reaction forces. It has been suggested that this postural strategy arises from an interaction of limb biomechanics and proprioceptive networks in the spinal cord. A critical experimental validation of this hypothesis is to test the prediction that the principal directions of muscular activation oppose the directions responding muscles exert their forces on the environment. Therefore, our objective was to quantify the endpoint forces of a diverse set of cat hindlimb muscles and compare them with the directionally sensitive muscle activation patterns generated in the intact and decerebrate cat. We hypothesized that muscles are activated based on their mechanical advantage. Our primary expectation was that the principal direction of muscle activation during postural perturbations will be directed oppositely (180°) from the muscle endpoint ground reaction force. We found that muscle activation during postural perturbations was indeed directed oppositely to the endpoint reaction forces of that muscle. These observations indicate that muscle recruitment during balance challenges is driven, at least in part, by limb architecture. This suggests that sensory sources that provide feedback about the mechanical environment of the limb are likely important to appropriate and effective responses during balance challenges. Finally, we extended the analysis to three dimensions and different stance widths, laying the groundwork for a more comprehensive study of postural regulation than was possible with measurements confined to the horizontal plane and a single stance configuration.

  15. Energy implications of mechanical and mechanical–biological treatment compared to direct waste-to-energy

    SciTech Connect

    Cimpan, Ciprian Wenzel, Henrik

    2013-07-15

    Highlights: • Compared systems achieve primary energy savings between 34 and 140 MJ{sub primary}/100 MJ{sub input} {sub waste.} • Savings magnitude is foremost determined by chosen primary energy and materials production. • Energy consumption and process losses can be upset by increased technology efficiency. • Material recovery accounts for significant shares of primary energy savings. • Direct waste-to-energy is highly efficient if cogeneration (CHP) is possible. - Abstract: Primary energy savings potential is used to compare five residual municipal solid waste treatment systems, including configurations with mechanical (MT) and mechanical–biological (MBT) pre-treatment, which produce waste-derived fuels (RDF and SRF), biogas and/or recover additional materials for recycling, alongside a system based on conventional mass burn waste-to-energy and ash treatment. To examine the magnitude of potential savings we consider two energy efficiency levels (state-of-the-art and best available technology), the inclusion/exclusion of heat recovery (CHP vs. PP) and three different background end-use energy production systems (coal condensing electricity and natural gas heat, Nordic electricity mix and natural gas heat, and coal CHP energy quality allocation). The systems achieved net primary energy savings in a range between 34 and 140 MJ{sub primary}/100 MJ{sub input} {sub waste}, in the different scenario settings. The energy footprint of transportation needs, pre-treatment and reprocessing of recyclable materials was 3–9.5%, 1–18% and 1–8% respectively, relative to total energy savings. Mass combustion WtE achieved the highest savings in scenarios with CHP production, nonetheless, MBT-based systems had similarly high performance if SRF streams were co-combusted with coal. When RDF and SRF was only used in dedicated WtE plants, MBT-based systems totalled lower savings due to inherent system losses and additional energy costs. In scenarios without heat

  16. The use of a novel injectable hydrogel nucleus pulposus replacement in restoring the mechanical properties of cyclically fatigued porcine intervertebral discs.

    PubMed

    Balkovec, Christian; Vernengo, Jennifer; McGill, Stuart M

    2013-06-01

    Repeated flexion and extension of an intervertebral disc has been shown to affect the angular stiffness of spinal motion segments and is a barometer of the mechanical integrity of the disc. A degenerated disc that loses height causes higher levels of stress on the annulus and facet joints which may increase its level of degeneration; restoring disc height may therefore help to slow this degenerative cascade. Previous research has indicated that nucleus implants have the potential to improve the mechanical characteristics of a disc and an implant that is custom-fit to the intervertebral disc yields the best results with respect to decreasing annular degeneration. Two groups of porcine spinal motion segments were exposed to repeated flexion and extension. One group was then injected with a novel hydrogel while the other group was used as a control. Both groups were then exposed to another round of cyclic flexion and extension to examine the effect that the hydrogel had on restoring the original mechanics to the motion segments. Angular stiffness was restored to the group which received the hydrogel injection in addition to a significant improvement in specimen height. No significant changes were seen in the group which did not receive an injection. It would appear that use of the novel injectable hydrogel is able to restore angular stiffness to cyclically fatigued spinal motion segments. It is also important to note that continued repetition of the event causing specimen fatigue after performing hydrogel injection will result in an eventual return to the same fatigued state.

  17. Tensor Arithmetic, Geometric and Mathematic Principles of Fluid Mechanics in Implementation of Direct Computational Experiments

    NASA Astrophysics Data System (ADS)

    Bogdanov, Alexander; Khramushin, Vasily

    2016-02-01

    The architecture of a digital computing system determines the technical foundation of a unified mathematical language for exact arithmetic-logical description of phenomena and laws of continuum mechanics for applications in fluid mechanics and theoretical physics. The deep parallelization of the computing processes results in functional programming at a new technological level, providing traceability of the computing processes with automatic application of multiscale hybrid circuits and adaptive mathematical models for the true reproduction of the fundamental laws of physics and continuum mechanics.

  18. [Organ replacement therapy - renal replacement therapy in intensive care medicine].

    PubMed

    Kraus, Daniel; Wanner, Christoph

    2016-09-01

    Critically ill patients who are treated in an intensive care unit are at increased risk of developing acute renal failure. Every episode of renal failure decreases life expectancy. However, acute renal failure is no longer an immediate cause of death because renal function can be substituted medically and mechanically, by the use of renal replacement therapy. Hemodialysis and hemofiltration are the 2 fundamental modalities of renal replacement therapy and may be performed intermittently or continuously. The decision for one particular therapy has to be made for each patient individually. Peritoneal dialysis is an alternative treatment for acute renal failure, but is not available for immediate use in most centers. Contrast media and rhabdomyolysis are 2 common causes of toxic renal failure in the intensive care unit. However, they cannot be prevented by hemodialysis. PMID:27631449

  19. Mechanical property anisotropy in superalloy El-929 directionally solidified by an exothermic technique

    NASA Technical Reports Server (NTRS)

    Pradhan, D. C.; Sharma, K. K.; Tewari, S. N.

    1986-01-01

    Directional solidification (DS) of the nickel-based superalloy El-929 was carried out by employing the exothermic technique for preparing several 150 mm long x 55 mm diameter rods. Specimens machined from blanks cut at 0, 45, 75 and 90 deg to the chill surface were tensile and stress-rupture tested at different temperatures. The air-melted DS alloy, when loaded parallel to the growth direction, shows considerable improvement in stress-rupture life and tensile ductility as compared with the vacuum induction melted, forged and heat-treated alloy. However, these property advantages rapidly degrade with the increasing deviation of the load axis from the growth direction.

  20. Interplay of directional navigation mechanisms as a function of near-goal distance: experiments with the house mouse.

    PubMed

    Alyan, S H; Jander, R

    1997-12-01

    Mice (Mus musculus) that shuttle between their nest and an outside goal use different navigation mechanisms, depending on their distance from the nest. This was studied by rotating directional cues and the mice relative to one another. Close to home (20-50 cm) mice choose path integration and orientation by beacon, while farther away from the nest distal landmark orientation becomes more important. The larger the beacon is at the home site, the greater is the distance over which it is used as a directional cue. As mice head towards their nest, they demonstrate a tendency to home by means of distal landmarks at large distances, and by means of path integration or guided beacon integration at smaller distances. This space related sequence in the use of orientation mechanisms is the reverse from the temporal sequence (stages) of learning mechanisms employed when first learning to navigate home (Alyan and Jander, 1994).

  1. Direct correlation of single-molecule properties with bulk mechanical performance for the biomimetic design of polymers.

    PubMed

    Chung, Jaeyoon; Kushner, Aaron M; Weisman, Adam C; Guan, Zhibin

    2014-11-01

    For rational design of advanced polymeric materials, it is critical to establish a clear mechanistic link between the molecular structure of a polymer and the emergent bulk mechanical properties. Despite progress towards this goal, it remains a major challenge to directly correlate the bulk mechanical performance to the nanomechanical properties of individual constituent macromolecules. Here, we show a direct correlation between the single-molecule nanomechanical properties of a biomimetic modular polymer and the mechanical characteristics of the resulting bulk material. The multi-cyclic single-molecule force spectroscopy (SMFS) data enabled quantitative derivation of the asymmetric potential energy profile of individual module rupture and re-folding, in which a steep dissociative pathway accounted for the high plateau modulus, while a shallow associative well explained the energy-dissipative hysteresis and dynamic, adaptive recovery. These results demonstrate the potential for SMFS to serve as a guide for future rational design of advanced multifunctional materials.

  2. Antenna Controller Replacement Software

    NASA Technical Reports Server (NTRS)

    Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza; Wert, Michael; Leung, Patrick

    2010-01-01

    The Antenna Controller Replacement (ACR) software accurately points and monitors the Deep Space Network (DSN) 70-m and 34-m high-efficiency (HEF) ground-based antennas that are used to track primarily spacecraft and, periodically, celestial targets. To track a spacecraft, or other targets, the antenna must be accurately pointed at the spacecraft, which can be very far away with very weak signals. ACR s conical scanning capability collects the signal in a circular pattern around the target, calculates the location of the strongest signal, and adjusts the antenna pointing to point directly at the spacecraft. A real-time, closed-loop servo control algorithm performed every 0.02 second allows accurate positioning of the antenna in order to track these distant spacecraft. Additionally, this advanced servo control algorithm provides better antenna pointing performance in windy conditions. The ACR software provides high-level commands that provide a very easy user interface for the DSN operator. The operator only needs to enter two commands to start the antenna and subreflector, and Master Equatorial tracking. The most accurate antenna pointing is accomplished by aligning the antenna to the Master Equatorial, which because of its small size and sheltered location, has the most stable pointing. The antenna has hundreds of digital and analog monitor points. The ACR software provides compact displays to summarize the status of the antenna, subreflector, and the Master Equatorial. The ACR software has two major functions. First, it performs all of the steps required to accurately point the antenna (and subreflector and Master Equatorial) at the spacecraft (or celestial target). This involves controlling the antenna/ subreflector/Master-Equatorial hardware, initiating and monitoring the correct sequence of operations, calculating the position of the spacecraft relative to the antenna, executing the real-time servo control algorithm to maintain the correct position, and

  3. Replacing a Missing Tooth

    MedlinePlus

    ... majority of patients with clefts will require full orthodontic treatment, especially if the cleft has passed through ... later replacement of the missing lateral incisor. During orthodontic treatment, an artificial tooth may be attached to ...

  4. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  5. Kidney Replacement Therapy

    MedlinePlus

    ... their function with either dialysis or a transplant. Dialysis Dialysis, the more common form of kidney-replacement ... the result of diabetes, not of hemodialysis. Peritoneal dialysis Another form of dialysis is called peritoneal dialysis. ...

  6. Artificial Disc Replacement

    MedlinePlus

    ... treat this condition, alternatives to disc replacement include fusion, nonoperative care or no treatment. Typically, surgery is ... operative treatment for disc pain has been spinal fusion. This is a surgical procedure in which disc ...

  7. Hurricane intensity and eyewall replacement.

    PubMed

    Houze, Robert A; Chen, Shuyi S; Smull, Bradley F; Lee, Wen-Chau; Bell, Michael M

    2007-03-01

    Observations made during the historic 2005 hurricane season document a case of "eyewall replacement." Clouds outside the hurricane eyewall coalesce to form a new eyewall at a greater radius from the storm center, and the old eyewall dies. The winds in the new eyewall are initially weaker than those in the original eyewall, but as the new eyewall contracts, the storm reintensifies. Understanding this replacement mechanism is vital to forecasting variations in hurricane intensity. Processes in the "moat" region between the new and old eyewall have been particularly unclear. Aircraft data now show that the moat becomes dynamically similar to the eye and thus is converted into a region inimical to survival of the inner eyewall. We suggest that targeting aircraft to key parts of the storm to gain crucial input to high-resolution numerical models can lead to improvements in forecasting hurricane intensity.

  8. Cryogenic mechanical property testing system directly cooled by G-M cryocooler

    NASA Astrophysics Data System (ADS)

    Huang, R. J.; Liu, Q.; Li, L. F.; Gong, L. H.; Liu, H. M.; Xu, D.

    2014-01-01

    Cryogenic mechanical properties are generally considered to be some of the most important parameters in cryogenic engineering. Therefore, it is very important to test and investigate mechanical properties at low temperatures. Most systems for cryogenic mechanical property testing are cooled using liquid nitrogen (300 K-77 K) or liquid helium (77 K-4.2 K). As we know, liquid helium is relatively rare and thus expensive. In this study, to attain accurate and stable intermediate temperatures and reduce testing cost, a cryogenic mechanical property testing system cooled by a G-M cryocooler was studied and developed. In this system, the sample can be cooled down to 10.5 K after about 10 hours of running. The tension, bending and compression testing (load range up to 50 kN) can be carried out.

  9. Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin

    PubMed Central

    Garcia-Manyes, Sergi; Dougan, Lorna; Badilla, Carmen L.; Brujić, Jasna; Fernández, Julio M.

    2009-01-01

    Statistical theories of protein folding have long predicted plausible mechanisms for reducing the vast conformational space through distinct ensembles of structures. However, these predictions have remained untested by bulk techniques, because the conformational diversity of folding molecules has been experimentally unapproachable. Owing to recent advances in single molecule force-clamp spectroscopy, we are now able to probe the structure and dynamics of the small protein ubiquitin by measuring its length and mechanical stability during each stage of folding. Here, we discover that upon hydrophobic collapse, the protein rapidly selects a subset of minimum energy structures that are mechanically weak and essential precursors of the native fold. From this much reduced ensemble, the native state is acquired through a barrier-limited transition. Our results support the validity of statistical mechanics models in describing the folding of a small protein on biological timescales. PMID:19541635

  10. Application of Three Unit-Cells Models on Mechanical Analysis of 3D Five-Directional and Full Five-Directional Braided Composites

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Xu, Xiwu; Chen, Kang

    2013-10-01

    As new lightweight textile material, 3D five directional and full five directional braided composites (5DBC and F5DBC) have tremendous potential applications in the aerospace industry. Before they are used in primary loading-bearing structures, a rational characterization of their mechanical properties is essential. In this paper, three types of unit-cell models corresponding to the interior, surface and corner regions of 5DBC and F5DBC are proposed. By introducing the reasonable boundary conditions, the effective stiffness properties of these two materials are predicted and compared by the three unit-cells models. The detailed mechanical response characteristic of the three unit-cell models is presented and analyzed in various loading cases. Numerical results show good agreement with experiment data, thus validates the proposed simulation method. Moreover, a parametric study is carried out for analyzing the effects of braiding angle and fiber volume fraction on the elastic properties of 5DBC and F5DBC. The obtained results can help designers to optimize the braided composite structures.

  11. Comorbidity between Type 2 Diabetes and Depression in the Adult Population: Directions of the Association and Its Possible Pathophysiological Mechanisms

    PubMed Central

    Berge, Line Iden; Riise, Trond

    2015-01-01

    Type 2 diabetes and depression are regarded as comorbid conditions, and three possible directions of the association between the diseases can underlie this observation of comorbidity. First, common etiology can increase a person's risk of both diseases; second, persons with type 2 diabetes have increased prevalence or risk of future development of depression; or third, persons with depression have increased prevalence or risk of development of type 2 diabetes. This review gives an overview over possible pathophysiological mechanisms for each of the directions of the association between type 2 diabetes and depression and further discusses epigenetics as an additional, direction independent approach. We argue that unspecific pathophysiological mechanisms involved in the stress response might, at least to some extent, explain each of the directions of the association between type 2 diabetes and depression, while changes in brain structure and function among persons with diabetes and possible increased risk of development of type 2 diabetes after use of antidepressant agents could represent more disease specific mechanisms underlying the comorbidity. PMID:26457080

  12. Rapid growth and formation mechanism of ultrafine structural oxide eutectic ceramics by laser direct forming

    NASA Astrophysics Data System (ADS)

    Su, H. J.; Zhang, J.; Liu, L.; Eckert, J.; Fu, H. Z.

    2011-11-01

    Melt growth of oxide eutectic is an important and fast-growing research topic in the fields of both applied physics and materials science. Rapid one-step fabrication of melt-grown oxide ceramics with large size is developed using laser direct forming. The near 100% density of Al2O3/YAG eutectic ceramic in situ composite free of pore and cracks is rapidly melted/solidified directly from Al2O3-Y2O3 powder without any preforming or sintering. Uniform three-dimensional network of ultrafine nanostructured eutectic microstructure is obtained. The direct experimental evidence of faceted-nonfaceted eutectic transition at high growth rate is presented and the physical model of the microstructural formation based on atom cluster elementary process is proposed. This technology provides a rapid freeform fabrication of high-performance complex shaped ceramics for various applications.

  13. Augmented intrinsic activity of Factor VIIa by replacement of residues 305, 314, 337 and 374: evidence of two unique mutational mechanisms of activity enhancement.

    PubMed

    Persson, Egon; Bak, Helle; Østergaard, Anette; Olsen, Ole H

    2004-04-15

    Coagulation Factor VIIa (FVIIa) lacks the ability to spontaneously complete the conversion to a fully active enzyme after specific cleavage of an internal peptide bond (Arg152-Ile153) in the zymogen. Recently, several variants of FVIIa with enhanced intrinsic activity have been constructed. The in vitro characterization of these variants has shed light on molecular determinants that put restrictions on FVIIa in favour of a zymogen-like conformation and warrants continued efforts. Here we describe a new FVIIa variant with high intrinsic activity containing the mutations Leu305-->Val, Ser314-->Glu, Lys337-->Ala, and Phe374-->Tyr. The variant, called FVIIa(VEAY), processes a tripeptidyl substrate very efficiently because of an unprecedented, 5.5-fold lowering of the K(m) value. Together with a 4-fold higher substrate turnover rate this gives the variant a catalytic efficiency 22 times that of wild-type FVIIa, which is reflected in a considerably enhanced susceptibility to inhibition by antithrombin and other inhibitors. For instance, the affinity of FVIIa(VEAY) for the S1 probe and inhibitor p -aminobenzamidine is represented by an 8-fold lower K(i) value compared with that of FVIIa. Activation of Factor X in solution occurs about 10 times faster with FVIIa(VEAY) than with FVIIa, due virtually exclusively to an increased kcat value. The high activity of FVIIa(VEAY) is not accompanied by an increased burial of the N-terminus of the protease domain. A comparison of the kinetic parameters and molecular properties of FVIIa(VEAY) with those of the previously described mutant V158D/E296V/M298Q-FVIIa (FVIIa(IIa)), and the locations of the substitutions in the two variants, reveals what appear to be two profoundly different structural mechanisms dictating improvements in enzymic performance. PMID:14686879

  14. Direct observation of mineral-organic composite formation reveals occlusion mechanism.

    PubMed

    Rae Cho, Kang; Kim, Yi-Yeoun; Yang, Pengcheng; Cai, Wei; Pan, Haihua; Kulak, Alexander N; Lau, Jolene L; Kulshreshtha, Prashant; Armes, Steven P; Meldrum, Fiona C; De Yoreo, James J

    2016-01-01

    Manipulation of inorganic materials with organic macromolecules enables organisms to create biominerals such as bones and seashells, where occlusion of biomacromolecules within individual crystals generates superior mechanical properties. Current understanding of this process largely comes from studying the entrapment of micron-size particles in cooling melts. Here, by investigating micelle incorporation in calcite with atomic force microscopy and micromechanical simulations, we show that different mechanisms govern nanoscale occlusion. By simultaneously visualizing the micelles and propagating step edges, we demonstrate that the micelles experience significant compression during occlusion, which is accompanied by cavity formation. This generates local lattice strain, leading to enhanced mechanical properties. These results give new insight into the formation of occlusions in natural and synthetic crystals, and will facilitate the synthesis of multifunctional nanocomposite crystals. PMID:26732046

  15. Direct observation of mineral–organic composite formation reveals occlusion mechanism

    PubMed Central

    Rae Cho, Kang; Kim, Yi-Yeoun; Yang, Pengcheng; Cai, Wei; Pan, Haihua; Kulak, Alexander N.; Lau, Jolene L.; Kulshreshtha, Prashant; Armes, Steven P.; Meldrum, Fiona C.; De Yoreo, James J.

    2016-01-01

    Manipulation of inorganic materials with organic macromolecules enables organisms to create biominerals such as bones and seashells, where occlusion of biomacromolecules within individual crystals generates superior mechanical properties. Current understanding of this process largely comes from studying the entrapment of micron-size particles in cooling melts. Here, by investigating micelle incorporation in calcite with atomic force microscopy and micromechanical simulations, we show that different mechanisms govern nanoscale occlusion. By simultaneously visualizing the micelles and propagating step edges, we demonstrate that the micelles experience significant compression during occlusion, which is accompanied by cavity formation. This generates local lattice strain, leading to enhanced mechanical properties. These results give new insight into the formation of occlusions in natural and synthetic crystals, and will facilitate the synthesis of multifunctional nanocomposite crystals. PMID:26732046

  16. Direct observation of mineral–organic composite formation reveals occlusion mechanism

    DOE PAGESBeta

    Cho, Kang Rae; Kim, Yi -Yeoun; Yang, Pengcheng; Cai, Wei; Pan, Haihua; Kulak, Alexander N.; Lau, Jolene L.; Kulshreshtha, Prashant; Armes, Steven P.; Meldrum, Fiona C.; et al

    2016-01-06

    Manipulation of inorganic materials with organic macromolecules enables organisms to create biominerals such as bones and seashells, where occlusion of biomacromolecules within individual crystals generates superior mechanical properties. Current understanding of this process largely comes from studying the entrapment of micron-size particles in cooling melts. Here, by investigating micelle incorporation in calcite with atomic force microscopy and micromechanical simulations, we show that different mechanisms govern nanoscale occlusion. By simultaneously visualizing the micelles and propagating step edges, we demonstrate that the micelles experience significant compression during occlusion, which is accompanied by cavity formation. This generates local lattice strain, leading to enhancedmore » mechanical properties. Furthermore, these results give new insight into the formation of occlusions in natural and synthetic crystals, and will facilitate the synthesis of multifunctional nanocomposite crystals.« less

  17. Neuropathic mechanisms in the pathophysiology of burns pruritus: redefining directions for therapy and research.

    PubMed

    Goutos, Ioannis

    2013-01-01

    Pruritus in burn wounds is a common symptom affecting patient rehabilitation. Over the last decades, there has been a resurgence of interest into more effective strategies to combat this distressing problem; nevertheless, no reports exist in the literature to propose pathophysiological mechanisms responsible for the generation and persistence of pruritic symptoms in the late phases of burns rehabilitation. Neuronal pathways mediating pruritic and painful stimuli share striking similarities, which allows the comparative exploration of the less extensively studied pruritic mechanisms using pain models. Furthermore, emerging anatomical, neurophysiological, and pharmacological evidence supports the involvement of neuropathic mechanisms in chronic burns pruritus. This work updates the conceptual framework for the pathophysiology of burns itch by embracing the contribution of the central nervous system in the maintenance of symptoms into a chronic state. The proposed pathophysiological model paves new avenues in burns pruritus research and is likely to have implications in the quest for more effective therapeutic regimens in clinical practice.

  18. Comparison of Mechanical Properties of Fiber-Reinforced Sand under Triaxial Compression and Direct Shear

    NASA Astrophysics Data System (ADS)

    Noorzad, Reza; Zarinkolaei, Seyed Taher Ghoreyshi

    2015-10-01

    This research investigates the behavior of sand reinforced with polypropylene fiber. To do this, 40 direct shear tests and 40 triaxial tests were performed on the coastal beaches of Babolsar, a city in the North of Iran. The effect of parameters such as fiber content, length of fiber and normal or confining pressure on the behavior of Babolsar sand have been studied. In this study, four various fiber contents (0, 0.25, 0.5 and 1 percent), three different lengths of fiber (6, 12 and 18 mm) and four normal or confining pressures (50, 100, 200 and 400 kPa) have been employed. The test results show that fiber inclusion has a significant effect on the behavior of sand. In both direct shear and triaxial tests, the addition of fibers improved shear strength parameters (C, '), increased peak shear strength and axial strain at failure, and also limited the amount of post-peak reduction in shear resistance. The comparison of the test results revealed that due to better fiber orientation toward the direction of principal tensile strain in triaxial test as compared to direct shear tests, the fiber efficiency and its effect on soil behavior is much more significant in triaxial specimens.

  19. Directional Solidification and Mechanical Properties of NiAl-NiAlTa Alloys

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Chen, X. F.; Oliver, B. F.; Noebe, R. D.; Whittenberger, J. D.

    1995-01-01

    Directional solidification of eutectic alloys is a promising technique for producing in-situ composite materials exhibiting a balance of properties. Consequently, the microstructure, creep strength and fracture toughness of directionally solidified NiAl-NiAlTa alloys were investigated. Directional solidification was performed by containerless processing techniques to minimize alloy contamination. The eutectic composition was found to be NiAl-15.5 at% Ta and well-aligned microstructures were produced at this composition. A near-eutectic alloy of NiAl-14.5Ta was also investigated. Directional solidification of the near-eutectic composition resulted in microstructures consisting of NiAl dendrites surrounded by aligned eutectic regions. The off-eutectic alloy exhibited promising compressive creep strengths compared to other NiAl-based intermetallics, while preliminary testing indicated that the eutectic alloy was competitive with Ni-base single crystal superalloys. The room temperature toughness of these two-phase alloys was similar to that of polycrystalline NiAl even with the presence of the brittle Laves phase NiAlTa.

  20. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement system must meet all conditions of initial approval of a mechanized claims processing and information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement system...

  1. Direct laser manipulation reveals the mechanics of cell contacts in vivo

    PubMed Central

    Bambardekar, Kapil; Clément, Raphaël; Blanc, Olivier; Chardès, Claire; Lenne, Pierre-François

    2015-01-01

    Cell-generated forces produce a variety of tissue movements and tissue shape changes. The cytoskeletal elements that underlie these dynamics act at cell–cell and cell–ECM contacts to apply local forces on adhesive structures. In epithelia, force imbalance at cell contacts induces cell shape changes, such as apical constriction or polarized junction remodeling, driving tissue morphogenesis. The dynamics of these processes are well-characterized; however, the mechanical basis of cell shape changes is largely unknown because of a lack of mechanical measurements in vivo. We have developed an approach combining optical tweezers with light-sheet microscopy to probe the mechanical properties of epithelial cell junctions in the early Drosophila embryo. We show that optical trapping can efficiently deform cell–cell interfaces and measure tension at cell junctions, which is on the order of 100 pN. We show that tension at cell junctions equilibrates over a few seconds, a short timescale compared with the contractile events that drive morphogenetic movements. We also show that tension increases along cell interfaces during early tissue morphogenesis and becomes anisotropic as cells intercalate during germ-band extension. By performing pull-and-release experiments, we identify time-dependent properties of junctional mechanics consistent with a simple viscoelastic model. Integrating this constitutive law into a tissue-scale model, we predict quantitatively how local deformations propagate throughout the tissue. PMID:25605934

  2. Terrain and Direction Classification of Locomotion Transitions Using Neuromuscular and Mechanical Input.

    PubMed

    Joshi, Deepak; Hahn, Michael E

    2016-04-01

    To perform seamless transitions in powered lower limb prostheses, accurate classification of transition type is required a priori. We propose a structure to detect direction (ascent or descent) and terrain (ramp or stairs) patterns when a person transitions from over ground to stairs or ramp locomotion. We compared electromyography (EMG) and accelerometry performance with an emphasis on sensor fusion for improving classification. Seven healthy subjects were recruited for this initial study. Data were collected with accelerometers and EMG electrodes on the dominant leg, while subjects transitioned from over ground to ramp (ascent and descent) and stair (ascent and descent) locomotion. Linear discriminant analysis and support vector machine approaches were used as classifiers using feature spaces of both sensor types. The results indicate that transitions are better classified as terrain type than direction type (p < 0.001), suggesting a terrain focused approach for an efficient structure. We also show that EMG and accelerometry data sources are complementary across the transitional gait cycle, suggesting sensor fusion for robust classification. These findings suggest that a terrain and direction focused classification approach will be useful for inclusion in classification approaches utilized in lower limb amputee samples.

  3. Design and application of permanent magnet flux sources for mechanical testing of magnetoactive elastomers at variable field directions

    NASA Astrophysics Data System (ADS)

    Hiptmair, F.; Major, Z.; Haßlacher, R.; Hild, S.

    2015-08-01

    Magnetoactive elastomers (MAEs) are a class of smart materials whose mechanical properties can be rapidly and reversibly changed by an external magnetic field. Due to this tunability, they are useable for actuators or in active vibration control applications. An extensive magnetomechanical characterization is necessary for MAE material development and requires experiments under cyclic loading in uniform but variable magnetic fields. MAE testing apparatus typically rely on fields of adjustable strength, but fixed (transverse) direction, often provided by electromagnets. In this work, two permanent magnet flux sources were developed as an add-on for a modular test stand, to allow for mechanical testing in uniform fields of variable direction. MAE specimens, based on a silicone matrix with isotropic and anisotropic carbonyl iron particle distributions, were subjected to dynamic mechanical analysis under different field and loading configurations. The magneto-induced increase of stiffness and energy dissipation was determined by the change of the hysteresis loop area and dynamic modulus values. A distinct influence of the composite microstructure and the loading state was observed. Due to the very soft and flexible matrix used for preparing the MAE samples, the material stiffness and damping behavior could be varied over a wide range via the applied field direction and intensity.

  4. Design and application of permanent magnet flux sources for mechanical testing of magnetoactive elastomers at variable field directions.

    PubMed

    Hiptmair, F; Major, Z; Haßlacher, R; Hild, S

    2015-08-01

    Magnetoactive elastomers (MAEs) are a class of smart materials whose mechanical properties can be rapidly and reversibly changed by an external magnetic field. Due to this tunability, they are useable for actuators or in active vibration control applications. An extensive magnetomechanical characterization is necessary for MAE material development and requires experiments under cyclic loading in uniform but variable magnetic fields. MAE testing apparatus typically rely on fields of adjustable strength, but fixed (transverse) direction, often provided by electromagnets. In this work, two permanent magnet flux sources were developed as an add-on for a modular test stand, to allow for mechanical testing in uniform fields of variable direction. MAE specimens, based on a silicone matrix with isotropic and anisotropic carbonyl iron particle distributions, were subjected to dynamic mechanical analysis under different field and loading configurations. The magneto-induced increase of stiffness and energy dissipation was determined by the change of the hysteresis loop area and dynamic modulus values. A distinct influence of the composite microstructure and the loading state was observed. Due to the very soft and flexible matrix used for preparing the MAE samples, the material stiffness and damping behavior could be varied over a wide range via the applied field direction and intensity. PMID:26329233

  5. Cellular and Molecular Mechanisms of Action of Transcranial Direct Current Stimulation: Evidence from In Vitro and In Vivo Models

    PubMed Central

    Pelletier, Simon J.

    2015-01-01

    Transcranial direct current stimulation is a noninvasive technique that has been experimentally tested for a number of psychiatric and neurological conditions. Preliminary observations suggest that this approach can indeed influence a number of cellular and molecular pathways that may be disease relevant. However, the mechanisms of action underlying its beneficial effects are largely unknown and need to be better understood to allow this therapy to be used optimally. In this review, we summarize the physiological responses observed in vitro and in vivo, with a particular emphasis on cellular and molecular cascades associated with inflammation, angiogenesis, neurogenesis, and neuroplasticity recruited by direct current stimulation, a topic that has been largely neglected in the literature. A better understanding of the neural responses to transcranial direct current stimulation is critical if this therapy is to be used in large-scale clinical trials with a view of being routinely offered to patients suffering from various conditions affecting the central nervous system. PMID:25522391

  6. Toxicology of chlorofluorocarbon replacements.

    PubMed Central

    Dekant, W

    1996-01-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements. PMID:8722112

  7. Toxicology of chlorofluorocarbon replacements.

    PubMed

    Dekant, W

    1996-03-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.

  8. Enhancement of the mechanical properties of directly spun CNT fibers by chemical treatment.

    PubMed

    Boncel, Slawomir; Sundaram, Rajyashree M; Windle, Alan H; Koziol, Krzysztof K K

    2011-12-27

    Translating the remarkable mechanical properties of individual carbon nanotubes to macroscopic assemblies presents a unique challenge in maximizing the potential of these remarkable entities for new materials. Infinitely long individual nanotubes would represent the ideal molecular building blocks; however, in the case of length-limited nanotubes, typically in the range of micro- and millimeters, an alternative strategy could be based on the improvement of the mechanical coherency between bundles assembling the macroscopic materials, like fibers or films. Here, we present a method to enhance the mechanical performance of fibers continuously spun from a CVD reactor, by a postproduction processing methodology utilizing a chemical agent aided by UV irradiation. The treatment results in an increase of 100% in specific strength and 300% in toughness of the fibers with strength values rocketing to as high as 3.5 GPa SG(-1). An attempt has been made to explore the nature of the chemical modifications introduced in the fiber and the consequential effects on its properties.

  9. Performance of mechanical filters and respirators for capturing nanoparticles--limitations and future direction.

    PubMed

    Mostofi, Reza; Wang, Bei; Haghighat, Fariborz; Bahloul, Ali; Jaime, Lara

    2010-01-01

    There is an increasing concern about the health hazard posed to workers exposed to inhalation of nanoparticles. Inhaling nanoparticles possess an occupational hazard due to elevated amount emitted to the atmosphere and working environment. Nanoparticles have potential toxic properties: the high particle surface area, number concentration, and surface reactivity. Inhalation, the most common route of nanoparticle exposure, has been shown to cause adverse effects on pulmonary functions and the deposited particles in the lung can be translocated to the blood system by passing through the pulmonary protection barriers. Filtration is the simplest and most common method of aerosol control. It is widely used in mechanical ventilation and respiratory protection. However, concerns have been raised regarding the effectiveness of the filters for capturing nanoparticles. This paper reviews the literature on the filtration performance of mechanical filters and respirators against nanoparticles. It includes the discussion about filtration mechanisms, theoretical models, affecting factors of the filtration efficiency, and testing protocols for respirator and filter certification. PMID:20562505

  10. Direct Measurement of the Mechanical Properties of Lipid Phases in Supported Bilayers

    PubMed Central

    Picas, Laura; Rico, Felix; Scheuring, Simon

    2012-01-01

    Biological membranes define not only the cell boundaries but any compartment within the cell. To some extent, the functionality of membranes is related to the elastic properties of the lipid bilayer and the mechanical and hydrophobic matching with functional membrane proteins. Supported lipid bilayers (SLBs) are valid biomimetic systems for the study of membrane biophysical properties. Here, we acquired high-resolution topographic and quantitative mechanics data of phase-separated SLBs using a recent atomic force microscopy (AFM) imaging mode based on force measurements. This technique allows us to quantitatively map at high resolution the mechanical differences of lipid phases at different loading forces. We have applied this approach to evaluate the contribution of the underlying hard support in the determination of the elastic properties of SLBs and to determine the adequate indentation range for obtaining reliable elastic moduli values. At ∼200 pN, elastic forces dominated the force-indentation response and the sample deformation was <20% of the bilayer thickness, at which the contribution of the support was found to be negligible. The obtained Young's modulus (E) of 19.3 MPa and 28.1 MPa allowed us to estimate the area stretch modulus (kA) as 106 pN/nm and 199 pN/nm and the bending stiffness (kc) as 18 kBT and 57 kBT for the liquid and gel phases, respectively. PMID:22225813

  11. Triple Starr Valve Replacement

    PubMed Central

    Braimbridge, M. V.; Clement, A. J.; Brown, A. Hedley; Sabar, E.; Mendel, D.

    1969-01-01

    Of nine patients who have had triple valve replacements for organic rheumatic triple valve disease two died in the postoperative period from inadequate myocardial reserve, and a third died four months later from cerebral embolism originating from clot on the left atrial wall. The remainder are well and, except for one, leading normal lives. Though cardiac transplantation has been recommended and used successfully for triple valve disease by Cooley, it is suggested that the long-term outlook today of triple valve replacement is likely to be better than that of transplantation. ImagesFig. 1Fig. 2Fig. 3 PMID:5809243

  12. Mechanisms governing the direct removal of wastes from the Waste Isolation Pilot Plant repository caused by exploratory drilling

    SciTech Connect

    Berglund, J.W.

    1992-12-01

    Two processes are identified that can influence the quantity of wastes brought to the ground surface when a waste disposal room of the Waste Isolation Pilot Plant is inadvertently penetrated by an exploratory borehole. The first mechanism is due to the erosion of the borehole wall adjacent to the waste caused by the flowing drilling fluid (mud); a quantitative computational model based upon the flow characteristics of the drilling fluid (laminar or turbulent) and other drilling parameters is developed and example results shown. The second mechanism concerns the motion of the waste and borehole spall caused by the flow of waste-generated gas to the borehole. Some of the available literature concerning this process is discussed, and a number of elastic and elastic-plastic finite-difference and finite-element calculations are described that confirm the potential importance of this process in directly removing wastes from the repository to the ground surface. Based upon the amount of analysis performed to date, it is concluded that it is not unreasonable to expect that volumes of waste several times greater than that resulting from direct cutting of a gauge borehole could eventually reach the ground surface. No definitive quantitative model for waste removal as a result of the second mechanism is presented; it is concluded that decomposed waste constitutive data must be developed and additional experiments performed to assess further the full significance of this latter mechanism.

  13. Structural perspective on the direct inhibition mechanism of EGCG on mammalian histidine decarboxylase and DOPA decarboxylase.

    PubMed

    Ruiz-Pérez, M Victoria; Pino-Ángeles, Almudena; Medina, Miguel A; Sánchez-Jiménez, Francisca; Moya-García, Aurelio A

    2012-01-23

    Histidine decarboxylase (HDC) and l-aromatic amino acid decarboxylase (DDC) are homologous enzymes that are responsible for the synthesis of important neuroactive amines related to inflammatory, neurodegenerative, and neoplastic diseases. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, has been shown to target histamine-producing cells and to promote anti-inflammatory, antitumor, and antiangiogenic effects. Previous experimental work has demonstrated that EGCG has a direct inhibitory effect on both HDC and DDC. In this study, we investigated the binding modes of EGCG to HDC and DDC as a first step for designing new polyphenol-based HDC/DDC-specific inhibitors. PMID:22107329

  14. Mechanical behavior of the directionally solidified gamma/gamma prime - delta eutectic alloy

    NASA Technical Reports Server (NTRS)

    Barkalow, R. H.; Jackson, J. J.; Gell, M.; Leverant, G. R.

    1975-01-01

    The eutectic alloy Ni-20.0%Cb-2.5%Al-6.0%Cr was tested in short-term creep and long-term exposure to service conditions to assess its suitability for high temperature turbine blade applications. Long-time exposure showed the lamellar microstructure of the alloy to be exceptionally stable. Other properties tested were notch sensitivity, isothermal and thermomechanical fatigue strength, shear strength, and transverse ductility. It was shown that this alloy is superior to the best currently available directionally solidified superalloys over the temperature/stress conditions encountered in turbine airfoils.

  15. Mariner 9 celestial mechanics experiment - Gravity field and pole direction of Mars.

    NASA Technical Reports Server (NTRS)

    Lorell, J.; Born, G. H.; Christensen, E. J.; Jordan, J. F.; Laing, P. A.; Martin, W. L.; Sjogren, W. L.; Shapiro, I. I.; Reasenberg, R. D.; Slater, G. L.

    1972-01-01

    Analysis of the Mariner 9 radio-tracking data shows that the Martian gravity field is rougher than that of earth or the moon, and that the accepted direction of the Mars rotation axis is in error by about 0.5 deg. Contours of equivalent surface heights deduced from a sixth-degree solution for the Martian gravity field are presented. These contours represent the deviations from sphericity of a uniformly dense body with an external potential which is given by the first sixth-degree solution. In addition to Doppler observations, ranging or group-delay measurements have been made regularly since orbit insertion.

  16. Dynamic analysis of propulsion mechanism directly driven by wave energy for marine mobile buoy

    NASA Astrophysics Data System (ADS)

    Yu, Zhenjiang; Zheng, Zhongqiang; Yang, Xiaoguang; Chang, Zongyu

    2016-07-01

    Marine mobile buoy(MMB) have many potential applications in the maritime industry and ocean science. Great progress has been made, however the technology in this area is far from maturity in theory and faced with many difficulties in application. A dynamic model of the propulsion mechanism is very necessary for optimizing the parameters of the MMB, especially with consideration of hydrodynamic force. The principle of wave-driven propulsion mechanism is briefly introduced. To set a theory foundation for study on the MMB, a dynamic model of the propulsion mechanism of the MMB is obtained. The responses of the motion of the platform and the hydrofoil are obtained by using a numerical integration method to solve the ordinary differential equations. A simplified form of the motion equations is reached by omitting terms with high order small values. The relationship among the heave motion of the buoy, stiffness of the elastic components, and the forward speed can be obtained by using these simplified equations. The dynamic analysis show the following: The angle of displacement of foil is fairly small with the biggest value around 0.3 rad; The speed of mobile buoy and the angle of hydrofoil increased gradually with the increase of heave motion of buoy; The relationship among heaven motion, stiffness and attack angle is that heave motion leads to the angle change of foil whereas the item of speed or push function is determined by vertical velocity and angle, therefore, the heave motion and stiffness can affect the motion of buoy significantly if the size of hydrofoil is kept constant. The proposed model is provided to optimize the parameters of the MMB and a foundation is laid for improving the performance of the MMB.

  17. Dynamic analysis of propulsion mechanism directly driven by wave energy for marine mobile buoy

    NASA Astrophysics Data System (ADS)

    Yu, Zhenjiang; Zheng, Zhongqiang; Yang, Xiaoguang; Chang, Zongyu

    2016-05-01

    Marine mobile buoy(MMB) have many potential applications in the maritime industry and ocean science. Great progress has been made, however the technology in this area is far from maturity in theory and faced with many difficulties in application. A dynamic model of the propulsion mechanism is very necessary for optimizing the parameters of the MMB, especially with consideration of hydrodynamic force. The principle of wave-driven propulsion mechanism is briefly introduced. To set a theory foundation for study on the MMB, a dynamic model of the propulsion mechanism of the MMB is obtained. The responses of the motion of the platform and the hydrofoil are obtained by using a numerical integration method to solve the ordinary differential equations. A simplified form of the motion equations is reached by omitting terms with high order small values. The relationship among the heave motion of the buoy, stiffness of the elastic components, and the forward speed can be obtained by using these simplified equations. The dynamic analysis show the following: The angle of displacement of foil is fairly small with the biggest value around 0.3 rad; The speed of mobile buoy and the angle of hydrofoil increased gradually with the increase of heave motion of buoy; The relationship among heaven motion, stiffness and attack angle is that heave motion leads to the angle change of foil whereas the item of speed or push function is determined by vertical velocity and angle, therefore, the heave motion and stiffness can affect the motion of buoy significantly if the size of hydrofoil is kept constant. The proposed model is provided to optimize the parameters of the MMB and a foundation is laid for improving the performance of the MMB.

  18. Mariner 9 celestial mechanics experiment: gravity field and pole direction of Mars.

    PubMed

    Lorell, J; Born, G H; Christensen, E J; Jordan, J F; Laing, P A; Martin, W L; Sjogren, W L; Shapiro, I I; Reasenberg, R D; Slater, G L

    1972-01-21

    Analysis of the Mariner 9 radio-tracking data shows that the Martian gravity field is rougher than that of Earth or the moon, and that the accepted direction of Mars's rotation axis is in error by about 0.5 degrees . The new value for the pole direction for the epoch 1971.9, referred to the mean equatorial system of 1950.0, is right ascension alpha= 317.3 degrees +/- 0.3 degrees , declination delta = 52.6 degrees +/- 0.2 degrees . The values found for the coefficients of the low-order harmonics of Mars's gravity field are as follows: J(2)=(1.96+/-0.01)x10(-3), referred to an equatorial radius of 3394 kilometers; C(22) = -(5 +/- 1) x 10(-5); and S(22) = (3 +/- 1) x 10(-5). The value for J(2) is in excellent agreement with the result from, Wilkins' analysis of the observations of Phobos. The other two coefficients imply a value of (2.5 +/- 0.5) x 10(-4) for the fractional difference in the principal equatorial moments of inertia; the axis of the minimum moment passes near 105 degrees W. PMID:17814540

  19. Mariner 9 celestial mechanics experiment: gravity field and pole direction of Mars.

    PubMed

    Lorell, J; Born, G H; Christensen, E J; Jordan, J F; Laing, P A; Martin, W L; Sjogren, W L; Shapiro, I I; Reasenberg, R D; Slater, G L

    1972-01-21

    Analysis of the Mariner 9 radio-tracking data shows that the Martian gravity field is rougher than that of Earth or the moon, and that the accepted direction of Mars's rotation axis is in error by about 0.5 degrees . The new value for the pole direction for the epoch 1971.9, referred to the mean equatorial system of 1950.0, is right ascension alpha= 317.3 degrees +/- 0.3 degrees , declination delta = 52.6 degrees +/- 0.2 degrees . The values found for the coefficients of the low-order harmonics of Mars's gravity field are as follows: J(2)=(1.96+/-0.01)x10(-3), referred to an equatorial radius of 3394 kilometers; C(22) = -(5 +/- 1) x 10(-5); and S(22) = (3 +/- 1) x 10(-5). The value for J(2) is in excellent agreement with the result from, Wilkins' analysis of the observations of Phobos. The other two coefficients imply a value of (2.5 +/- 0.5) x 10(-4) for the fractional difference in the principal equatorial moments of inertia; the axis of the minimum moment passes near 105 degrees W.

  20. Toward direct neural current imaging by resonant mechanisms at ultra-low field.

    PubMed

    Kraus, R H; Volegov, P; Matlachov, A; Espy, M

    2008-01-01

    A variety of techniques have been developed to noninvasively image human brain function that are central to research and clinical applications endeavoring to understand how the brain works and to detect pathology (e.g. epilepsy, schizophrenia, etc.). Current methods can be broadly divided into those that rely on hemodynamic responses as indicators of neural activity (e.g. fMRI, optical, and PET) and methods that measure neural activity directly (e.g. MEG and EEG). The approaches all suffer from poor temporal resolution, poor spatial localization, or indirectly measuring neural activity. It has been suggested that the proton spin population will be altered by neural activity resulting in a measurable effect on the NMR signal that can be imaged by MRI methods. We present here the physical basis and experimental evidence for the resonant interaction between magnetic fields such as those arising from neural activity, with the spin population in ultra-low field (microT) NMR experiments. We demonstrate through the use of current phantoms that, in the case of correlated zero-mean current distributions such as those one might expect to result from neural activity, resonant interactions will produce larger changes in the observed NMR signal than dephasing. The observed resonant interactions reported here might one day form the foundation of a new functional neuroimaging modality ultimately capable of simultaneous direct neural activity and brain anatomy tomography.

  1. Line Replaceable Unit Analysis

    NASA Technical Reports Server (NTRS)

    Oepomo, T.; Prouty, T. V.

    1982-01-01

    Shuttle LRU (Line Replaceable Unit) Analysis Program (SLAP) aids in evaluation of LRU interface voltages in Shuttle orbiter electrical system. Slap includes reduced model of Shuttle LRU circuit. Although primarily intended for analysis of Shuttle LRU's SLAP could be adapted for voltage analysis in other situations.

  2. Replacing America's Job Bank

    ERIC Educational Resources Information Center

    Vollman, Jim

    2009-01-01

    The Job Central National Labor Exchange (www.jobcentral.com) has become the effective replacement for America's Job Bank with state workforce agencies and, increasingly, with community colleges throughout the country. The American Association of Community Colleges (AACC) has formed a partnership with Job Central to promote its use throughout the…

  3. Python import replacement

    SciTech Connect

    2011-10-01

    SmartImport.py is a Python source-code file that implements a replacement for the standard Python module importer. The code is derived from knee.py, a file in the standard Python diestribution , and adds functionality to improve the performance of Python module imports in massively parallel contexts.

  4. Prioritizing equipment for replacement.

    PubMed

    Capuano, Mike

    2010-01-01

    It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

  5. Direct Binding of Ledipasvir to HCV NS5A: Mechanism of Resistance to an HCV Antiviral Agent

    PubMed Central

    Kwon, Hyock Joo; Xing, Weimei; Chan, Katie; Niedziela-Majka, Anita; Brendza, Katherine M.; Kirschberg, Thorsten; Kato, Darryl; Link, John O.; Cheng, Guofeng; Liu, Xiaohong; Sakowicz, Roman

    2015-01-01

    Ledipasvir, a direct acting antiviral agent (DAA) targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H) that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants. PMID:25856426

  6. Extracellular Electron Transfer to Fe(III) Oxides by the Hyperthermophilic Archaeon Geoglobus ahangari via a Direct Contact Mechanism

    PubMed Central

    Manzella, Michael P.; Reguera, Gemma

    2013-01-01

    The microbial reduction of Fe(III) plays an important role in the geochemistry of hydrothermal systems, yet it is poorly understood at the mechanistic level. Here we show that the obligate Fe(III)-reducing archaeon Geoglobus ahangari uses a direct-contact mechanism for the reduction of Fe(III) oxides to magnetite at 85°C. Alleviating the need to directly contact the mineral with the addition of a chelator or the electron shuttle anthraquinone-2,6-disulfonate (AQDS) stimulated Fe(III) reduction. In contrast, entrapment of the oxides within alginate beads to prevent cell contact with the electron acceptor prevented Fe(III) reduction and cell growth unless AQDS was provided. Furthermore, filtered culture supernatant fluids had no effect on Fe(III) reduction, ruling out the secretion of an endogenous mediator too large to permeate the alginate beads. Consistent with a direct contact mechanism, electron micrographs showed cells in intimate association with the Fe(III) mineral particles, which once dissolved revealed abundant curled appendages. The cells also produced several heme-containing proteins. Some of them were detected among proteins sheared from the cell's outer surface and were required for the reduction of insoluble Fe(III) oxides but not for the reduction of the soluble electron acceptor Fe(III) citrate. The results thus support a mechanism in which the cells directly attach and transfer electrons to the Fe(III) oxides using redox-active proteins exposed on the cell surface. This strategy confers on G. ahangari a competitive advantage for accessing and reducing Fe(III) oxides under the extreme physical and chemical conditions of hot ecosystems. PMID:23728807

  7. Short actin-based mechanism for light-directed chloroplast movement in Arabidopsis

    PubMed Central

    Kadota, Akeo; Yamada, Noboru; Suetsugu, Noriyuki; Hirose, Mana; Saito, Chieko; Shoda, Keiko; Ichikawa, Satoshi; Kagawa, Takatoshi; Nakano, Akihiko; Wada, Masamitsu

    2009-01-01

    Organelle movement is essential for proper function of living cells. In plants, these movements generally depend on actin filaments, but the underlying mechanism is unknown. Here, in Arabidopsis, we identify associations of short actin filaments along the chloroplast periphery on the plasma membrane side associated with chloroplast photorelocation and anchoring to the plasma membrane. We have termed these chloroplast-actin filaments (cp-actin filaments). Cp-actin filaments emerge from the chloroplast edge and exhibit rapid turnover. The presence of cp-actin filaments depends on an actin-binding protein, chloroplast unusual positioning1 (CHUP1), localized on the chloroplast envelope. chup1 mutant lacked cp-actin filaments but showed normal cytoplasmic actin filaments. When irradiated with blue light to induce chloroplast movement, cp-actin filaments relocalize to the leading edge of chloroplasts before and during photorelocation and are regulated by 2 phototropins, phot1 and phot2. Our findings suggest that plants evolved a unique actin-based mechanism for organelle movement. PMID:19620714

  8. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism.

    PubMed Central

    Klar, Amar J S

    2003-01-01

    Theories concerning the cause of right- or left-hand preference in humans vary from purely learned behavior, to solely genetics, to a combination of the two mechanisms. The cause of handedness and its relation to the biologically specified scalp hair-whorl rotation is determined here. The general public, consisting of mostly right-handers (RH), shows counterclockwise whorl rotation infrequently in 8.4% of individuals. Interestingly, non-right-handers (NRH, i.e., left-handers and ambidextrous) display a random mixture of clockwise and counterclockwise swirling patterns. Confirming this finding, in another independent sample of individuals chosen because of their counterclockwise rotation, one-half of them are NRH. These findings of coupling in RH and uncoupling in NRH unequivocally establish that these traits develop from a common genetic mechanism. Another result concerning handedness of the progeny of discordant monozygotic twins suggests that lefties are one gene apart from righties. Together, these results suggest (1) that a single gene controls handedness, whorl orientation, and twin concordance and discordance and (2) that neuronal and visceral (internal organs) forms of bilateral asymmetry are coded by separate sets of genetic pathways. The sociological impact of the study is discussed. PMID:14504234

  9. Strain-engineered direct-indirect band gap transition and its mechanism in two-dimensional phosphorene

    NASA Astrophysics Data System (ADS)

    Peng, Xihong; Wei, Qun; Copple, Andrew

    2014-08-01

    Recently fabricated two-dimensional phosphorene crystal structures have demonstrated great potential in applications of electronics. In this paper, strain effect on the electronic band structure of phosphorene was studied using first-principles methods including density functional theory (DFT) and hybrid functionals. It was found that phosphorene can withstand a tensile stress and strain up to 10 N/m and 30%, respectively. The band gap of phosphorene experiences a direct-indirect-direct transition when axial strain is applied. A moderate -2% compression in the zigzag direction can trigger this gap transition. With sufficient expansion (+11.3%) or compression (-10.2% strains), the gap can be tuned from indirect to direct again. Five strain zones with distinct electronic band structure were identified, and the critical strains for the zone boundaries were determined. Although the DFT method is known to underestimate band gap of semiconductors, it was proven to correctly predict the strain effect on the electronic properties with validation from a hybrid functional method in this work. The origin of the gap transition was revealed, and a general mechanism was developed to explain energy shifts with strain according to the bond nature of near-band-edge electronic orbitals. Effective masses of carriers in the armchair direction are an order of magnitude smaller than that of the zigzag axis, indicating that the armchair direction is favored for carrier transport. In addition, the effective masses can be dramatically tuned by strain, in which its sharp jump/drop occurs at the zone boundaries of the direct-indirect gap transition.

  10. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution.

    PubMed

    Renata, Hans; Wang, Z Jane; Arnold, Frances H

    2015-03-01

    High selectivity and exquisite control over the outcome of reactions entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature's known repertoire. In this Review, we outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progression has been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been exploited for chemical synthesis, with an emphasis on reactions that do not have natural counterparts. Non-natural activities can be improved by directed evolution, thus mimicking the process used by nature to create new catalysts. Finally, we describe the discovery of non-native catalytic functions that may provide future opportunities for the expansion of the enzyme universe.

  11. Direct path from microscopic mechanics to Debye shielding, Landau damping and wave-particle interaction

    NASA Astrophysics Data System (ADS)

    Escande, D. F.; Elskens, Yves; Doveil, F.

    2015-02-01

    The derivation of Debye shielding and Landau damping from the N-body description of plasmas is performed directly by using Newton’s second law for the N-body system. This is done in a few steps with elementary calculations using standard tools of calculus and no probabilistic setting. Unexpectedly, Debye shielding is encountered together with Landau damping. This approach is shown to be justified in the one-dimensional case when the number of particles in a Debye sphere becomes large. The theory is extended to accommodate a correct description of trapping and chaos due to Langmuir waves. On top of their well-known production of collisional transport, the repulsive deflections of electrons are shown to produce shielding, in such a way that each particle is shielded by all other ones, while keeping in uninterrupted motion.

  12. A soluble acid invertase is directed to the vacuole by a signal anchor mechanism.

    PubMed

    Rae, Anne L; Casu, Rosanne E; Perroux, Jai M; Jackson, Mark A; Grof, Christopher P L

    2011-06-15

    Enzyme activities in the vacuole have an important impact on the net concentration of sucrose. In sugarcane (Saccharum hybrid), immunolabelling demonstrated that a soluble acid invertase (β-fructofuranosidase; EC 3.2.1.26) is present in the vacuole of storage parenchyma cells during sucrose accumulation. Examination of sequences from sugarcane, barley and rice showed that the N-terminus of the invertase sequence contains a signal anchor and a tyrosine motif, characteristic of single-pass membrane proteins destined for lysosomal compartments. The N-terminal peptide from the barley invertase was shown to be capable of directing the green fluorescent protein to the vacuole in sugarcane cells. The results suggest that soluble acid invertase is sorted to the vacuole in a membrane-bound form.

  13. Direct observation of ClO from chlorine nitrate photolysis. [as mechanism of polar ozone depletion

    NASA Technical Reports Server (NTRS)

    Minton, Timothy K.; Nelson, Christine M.; Moore, Teresa A.; Okumura, Mitchio

    1992-01-01

    Chlorine nitrate photolysis has been investigated with the use of a molecular beam technique. Excitation at both 248 and 193 nanometers led to photodissociation by two pathways, ClONO2 yields ClO + NO2 and ClONO2 yields Cl + NO3, with comparable yields. This experiment provides a direct measurement of the ClO product channel and consequently raises the possibility of an analogous channel in ClO dimer photolysis. Photodissociation of the ClO dimer is a critical step in the catalytic cycle that is presumed to dominate polar stratospheric ozone destruction. A substantial yield of ClO would reduce the efficiency of this cycle.

  14. Will Finite Elements Replace Structural Mechanics?

    NASA Astrophysics Data System (ADS)

    Ojalvo, I. U.

    1984-01-01

    This paper presents a personal view regarding the need for a continued interest and activity in structural methods in general, while viewing finite elements and the computer as simply two specific tools for assisting in this endeavor. An attempt is made to provide some insight as to why finite element methods seem to have "won the war," and to give examples of their more (and less) intelligent use. Items addressed include a highlight of unnecessary limitations of many existing standard finite element codes and where it is felt that further development work is needed.

  15. Thrombostatin FM compounds: direct thrombin inhibitors - mechanism of action in vitro and in vivo

    SciTech Connect

    Nieman, M T; Burke, F; Warnock, M; Zhou, Y; Sweigart, J; Chen, A; Ricketts, D; Lucchesi, B R; Chen, Z; Cera, E Di; Hilfinger, J; Kim, J S; Mosberg, H I; Schmaier, A H

    2008-04-29

    Novel pentapeptides called Thrombostatin FM compounds consisting mostly of D-isomers and unusual amino acids were prepared based upon the stable angiotensin converting enzyme breakdown product of bradykinin - RPPGF. These peptides are direct thrombin inhibitors prolonging the thrombin clotting time, activated partial thromboplastin time, and prothrombin time at ≥0.78, 1.6, and 1.6 μm, respectively. They competitively inhibit α-thrombin-induced cleavage of a chromogenic substrate at 4.4--8.2 μm. They do not significantly inhibit plasma kallikrein, factor (F) XIIa, FXIa, FIXa, FVIIa-TF, FXa, plasmin or cathepsin G. One form, FM19 [rOicPaF(p-Me)], blocks α-thrombin-induced calcium flux in fibroblasts with an IC50 of 6.9 ± 1.2 μm. FM19 achieved 100% inhibition of threshold α- or γ-thrombin-induced platelet aggregation at 8.4 ± 4.7 μm and 16 ± 4 μm, respectively. The crystal structure of thrombin in complex with FM19 shows that the N-terminal D-Arg retrobinds into the S1 pocket, its second residue Oic interacts with His-57, Tyr-60a and Trp-60d, and its C-terminal p-methyl Phe engages thrombin's aryl binding site composed of Ile-174, Trp-215, and Leu-99. When administered intraperitoneal, intraduodenal, or orally to mice, FM19 prolongs thrombin clotting times and delays carotid artery thrombosis. FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add-on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current antiplatelet therapy still have reactive platelets.

  16. Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Flow Direction Reversal

    PubMed Central

    Heuslein, Joshua L.; Meisner, Joshua K.; Li, Xuanyue; Song, Ji; Vincentelli, Helena; Leiphart, Ryan J.; Ames, Elizabeth G.; Price, Richard J.

    2015-01-01

    Objective Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of flow direction reversal, occurring in numerous collateral artery segments after femoral artery ligation (FAL), is unknown. Our objective was to determine if flow direction reversal in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. Approach and Results Collateral segments experiencing flow reversal after FAL in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post-FAL) remodeling. Genome-wide transcriptional analyses on HUVECs exposed to flow reversal conditions mimicking those occurring in-vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (NFκB, VEGF, FGF2, TGFβ) and arteriogenic canonical pathways (PKA, PDE, MAPK). Augmented expression of key pro-arteriogenic molecules (KLF2, ICAM-1, eNOS) was also verified by qRT-PCR, leading us to test whether ICAM-1 and/or eNOS regulate amplified arteriogenesis in flow-reversed collateral segments in-vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after FAL in ICAM-1−/− mice; however, eNOS−/− mice showed no such differences. Conclusions Flow reversal leads to a broad amplification of pro-arteriogenic endothelial signaling and a sustained ICAM-1-dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by flow reversal may lead to more effective and durable therapeutic options for arterial

  17. Thrombostatin FM compounds: direct thrombin inhibitors – mechanism of action in vitro and in vivo

    PubMed Central

    Nieman, M. T.; Burke, F.; Warnock, M.; Zhou, Y.; Sweigart, J.; Chen, A.; Ricketts, D.; Lucchesi, B. R.; Chen, Z.; Di Cera, E.; Hilfinger, J.; Kim, J. S.; Mosberg, H. I.; Schmaier, A. H.

    2009-01-01

    Summary Background Novel pentapeptides called Thrombostatin FM compounds consisting mostly of D-isomers and unusual amino acids were prepared based upon the stable angiotensin converting enzyme breakdown product of bradykinin – RPPGF. Methods and Results These peptides are direct thrombin inhibitors prolonging the thrombin clotting time, activated partial thromboplastin time, and prothrombin time at ≥0.78, 1.6, and 1.6 µm, respectively. They competitively inhibit α-thrombin-induced cleavage of a chromogenic substrate at 4.4–8.2 µm. They do not significantly inhibit plasma kallikrein, factor (F) XIIa, FXIa, FIXa, FVIIa-TF, FXa, plasmin or cathepsin G. One form, FM19 [rOicPaF(p-Me)], blocks α-thrombin-induced calcium flux in fibroblasts with an IC50 of 6.9 ± 1.2 µm. FM19 achieved 100% inhibition of threshold α- or γ-thrombin-induced platelet aggregation at 8.4 ± 4.7 µm and 16 ± 4 µm, respectively. The crystal structure of thrombin in complex with FM19 shows that the N-terminal D-Arg retrobinds into the S1 pocket, its second residue Oic interacts with His-57, Tyr-60a and Trp-60d, and its C-terminal p-methyl Phe engages thrombin_s aryl binding site composed of Ile-174, Trp-215, and Leu-99. When administered intraperitoneal, intraduodenal, or orally to mice, FM19 prolongs thrombin clotting times and delays carotid artery thrombosis. Conclusion FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add-on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current antiplatelet therapy still have reactive platelets. PMID:18315550

  18. The ionization mechanisms in direct and dopant-assisted atmospheric pressure photoionization and atmospheric pressure laser ionization.

    PubMed

    Kauppila, Tiina J; Kersten, Hendrik; Benter, Thorsten

    2014-11-01

    A novel, gas-tight API interface for gas chromatography-mass spectrometry was used to study the ionization mechanism in direct and dopant-assisted atmospheric pressure photoionization (APPI) and atmospheric pressure laser ionization (APLI). Eight analytes (ethylbenzene, bromobenzene, naphthalene, anthracene, benzaldehyde, pyridine, quinolone, and acridine) with varying ionization energies (IEs) and proton affinities (PAs), and four common APPI dopants (toluene, acetone, anisole, and chlorobenzene) were chosen. All the studied compounds were ionized by direct APPI, forming mainly molecular ions. Addition of dopants suppressed the signal of the analytes with IEs above the IE of the dopant. For compounds with suitable IEs or Pas, the dopants increased the ionization efficiency as the analytes could be ionized through dopant-mediated gas-phase reactions, such as charge exchange, proton transfer, and other rather unexpected reactions, such as formation of [M + 77](+) in the presence of chlorobenzene. Experiments with deuterated toluene as the dopant verified that in case of proton transfer, the proton originated from the dopant instead of proton-bound solvent clusters, as in conventional open or non-tight APPI sources. In direct APLI using a 266 nm laser, a narrower range of compounds was ionized than in direct APPI, because of exceedingly high IEs or unfavorable two-photon absorption cross-sections. Introduction of dopants in the APLI system changed the ionization mechanism to similar dopant-mediated gas-phase reactions with the dopant as in APPI, which produced mainly ions of the same form as in APPI, and ionized a wider range of analytes than direct APLI.

  19. Microstructure and Mechanical Properties of Al-8 pct Si Alloy Prepared by Direct Chill Casting Under Electromagnetic and Ultrasonic Fields

    NASA Astrophysics Data System (ADS)

    Zhang, Yubo; Jie, Jinchuan; Wu, Li; Fu, Ying; Li, Mu; Lu, Yiping; Li, Tingju

    2014-04-01

    The intermediate frequency electromagnetic field and power ultrasonic field were applied during the direct chill (DC) casting process of Al-8 pct Si alloy. The effects of different physical fields on the solidification microstructure and mechanical properties were studied. The results show that compared to the conventional casting without any treatments, refined microstructures and improved mechanical properties can be obtained when the electromagnetic or ultrasonic field is applied individually. For the case of compound fields, the electromagnetic field can increase the ultrasonic treated region, while the ultrasonic field can enhance the refinement effect of electromagnetic field. Owing to the advantages of both electromagnetic and ultrasonic fields, the microstructure obtained under the compound fields is fine and uniform, leading to a remarkable enhancement of mechanical properties. The interaction mechanism between intermediate frequency electromagnetic field and power ultrasonic field was discussed. The present study may be useful for grain refinement and improvement of mechanical properties of alloys during the DC casting process which is now widely used in industry.

  20. Observation of direction-dependent mechanical properties in the human brain with multi-excitation MR elastography.

    PubMed

    Anderson, Aaron T; Van Houten, Elijah E W; McGarry, Matthew D J; Paulsen, Keith D; Holtrop, Joseph L; Sutton, Bradley P; Georgiadis, John G; Johnson, Curtis L

    2016-06-01

    Magnetic resonance elastography (MRE) has shown promise in noninvasively capturing changes in mechanical properties of the human brain caused by neurodegenerative conditions. MRE involves vibrating the brain to generate shear waves, imaging those waves with MRI, and solving an inverse problem to determine mechanical properties. Despite the known anisotropic nature of brain tissue, the inverse problem in brain MRE is based on an isotropic mechanical model. In this study, distinct wave patterns are generated in the brain through the use of multiple excitation directions in order to characterize the potential impact of anisotropic tissue mechanics on isotropic inversion methods. Isotropic inversions of two unique displacement fields result in mechanical property maps that vary locally in areas of highly aligned white matter. Investigation of the corpus callosum, corona radiata, and superior longitudinal fasciculus, three highly ordered white matter tracts, revealed differences in estimated properties between excitations of up to 33%. Using diffusion tensor imaging to identify dominant fiber orientation of bundles, relationships between estimated isotropic properties and shear asymmetry are revealed. This study has implications for future isotropic and anisotropic MRE studies of white matter tracts in the human brain. PMID:27032311

  1. Observation of direction-dependent mechanical properties in the human brain with multi-excitation MR elastography.

    PubMed

    Anderson, Aaron T; Van Houten, Elijah E W; McGarry, Matthew D J; Paulsen, Keith D; Holtrop, Joseph L; Sutton, Bradley P; Georgiadis, John G; Johnson, Curtis L

    2016-06-01

    Magnetic resonance elastography (MRE) has shown promise in noninvasively capturing changes in mechanical properties of the human brain caused by neurodegenerative conditions. MRE involves vibrating the brain to generate shear waves, imaging those waves with MRI, and solving an inverse problem to determine mechanical properties. Despite the known anisotropic nature of brain tissue, the inverse problem in brain MRE is based on an isotropic mechanical model. In this study, distinct wave patterns are generated in the brain through the use of multiple excitation directions in order to characterize the potential impact of anisotropic tissue mechanics on isotropic inversion methods. Isotropic inversions of two unique displacement fields result in mechanical property maps that vary locally in areas of highly aligned white matter. Investigation of the corpus callosum, corona radiata, and superior longitudinal fasciculus, three highly ordered white matter tracts, revealed differences in estimated properties between excitations of up to 33%. Using diffusion tensor imaging to identify dominant fiber orientation of bundles, relationships between estimated isotropic properties and shear asymmetry are revealed. This study has implications for future isotropic and anisotropic MRE studies of white matter tracts in the human brain.

  2. Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

    PubMed Central

    Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

    2014-01-01

    The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

  3. A novel mechanism for direct real-time polymerase chain reaction that does not require DNA isolation from prokaryotic cells.

    PubMed

    Soejima, Takashi; Xiao, Jin-Zhong; Abe, Fumiaki

    2016-06-23

    Typically, polymerase chain reaction (PCR) is performed after DNA isolation. Real-time PCR (qPCR), also known as direct qPCR in mammalian cells with weak membranes, is a common technique using crude samples subjected to preliminary boiling to elute DNA. However, applying this methodology to prokaryotic cells, which have solid cell walls, in contrast to mammalian cells which immediately burst in water, can result in poor detection. We successfully achieved PCR elongation with the addition of 1.3 cfu of Cronobacter muytjensii to a newly developed direct qPCR master mix without performing any crude DNA extraction (detection limit of 1.6 × 10(0) cfu/ml for the test sample compared with a detection limit of 1.6 × 10(3) cfu/ml primarily for crude (boiling) or classical DNA isolation). We revealed that the chromosomal DNA retained in prokaryotic cells can function as a PCR template, similarly to the mechanism in in situ PCR. Elucidating this reaction mechanism may contribute to the development of an innovative master mix for direct qPCR to detect genes in a single bacterium with solid cell walls and might lead to numerous novel findings in prokaryotic genomics research.

  4. A novel mechanism for direct real-time polymerase chain reaction that does not require DNA isolation from prokaryotic cells.

    PubMed

    Soejima, Takashi; Xiao, Jin-Zhong; Abe, Fumiaki

    2016-01-01

    Typically, polymerase chain reaction (PCR) is performed after DNA isolation. Real-time PCR (qPCR), also known as direct qPCR in mammalian cells with weak membranes, is a common technique using crude samples subjected to preliminary boiling to elute DNA. However, applying this methodology to prokaryotic cells, which have solid cell walls, in contrast to mammalian cells which immediately burst in water, can result in poor detection. We successfully achieved PCR elongation with the addition of 1.3 cfu of Cronobacter muytjensii to a newly developed direct qPCR master mix without performing any crude DNA extraction (detection limit of 1.6 × 10(0) cfu/ml for the test sample compared with a detection limit of 1.6 × 10(3) cfu/ml primarily for crude (boiling) or classical DNA isolation). We revealed that the chromosomal DNA retained in prokaryotic cells can function as a PCR template, similarly to the mechanism in in situ PCR. Elucidating this reaction mechanism may contribute to the development of an innovative master mix for direct qPCR to detect genes in a single bacterium with solid cell walls and might lead to numerous novel findings in prokaryotic genomics research. PMID:27334801

  5. A novel mechanism for direct real-time polymerase chain reaction that does not require DNA isolation from prokaryotic cells

    PubMed Central

    Soejima, Takashi; Xiao, Jin-zhong; Abe, Fumiaki

    2016-01-01

    Typically, polymerase chain reaction (PCR) is performed after DNA isolation. Real-time PCR (qPCR), also known as direct qPCR in mammalian cells with weak membranes, is a common technique using crude samples subjected to preliminary boiling to elute DNA. However, applying this methodology to prokaryotic cells, which have solid cell walls, in contrast to mammalian cells which immediately burst in water, can result in poor detection. We successfully achieved PCR elongation with the addition of 1.3 cfu of Cronobacter muytjensii to a newly developed direct qPCR master mix without performing any crude DNA extraction (detection limit of 1.6 × 100 cfu/ml for the test sample compared with a detection limit of 1.6 × 103 cfu/ml primarily for crude (boiling) or classical DNA isolation). We revealed that the chromosomal DNA retained in prokaryotic cells can function as a PCR template, similarly to the mechanism in in situ PCR. Elucidating this reaction mechanism may contribute to the development of an innovative master mix for direct qPCR to detect genes in a single bacterium with solid cell walls and might lead to numerous novel findings in prokaryotic genomics research. PMID:27334801

  6. Influence of Direct Quenching on Microstructure and Mechanical Properties of Steel Plate for Large Oil Storage Tanks

    NASA Astrophysics Data System (ADS)

    Xiao, Guizhi; di, Hongshuang; Zhu, Fuxian; Chen, Bingzhang; Qiu, Bing

    2010-08-01

    The influence of direct quenching on microstructure and mechanical properties of high performance steel plates for large oil storage tanks was studied. The direct quenched and tempered (DQ&T) steel plates were rolled at different finish rolling temperatures (1113 and 1173 K), and their microstructures and mechanical properties were compared with those of reheat quenched and tempered (RQ&T) steel plate. The optical microscopy of the DQ steel shows deformed grains elongated along the rolling direction, while complete equiaxed grains are visible in RQ steel. Transmission electron microscopy (TEM) of the DQ steel shows refined lath martensite with high density of dislocations, which acts as preferred precipitation sites for NbC or Nb(C,N) particles during tempering. In all the plates, strength decreases with increasing tempering temperature. The strength of RQ steel increased significantly compared with that of DQ steel at the higher tempering temperature, which leads to better tempering resistance in DQ steels. The optimum combination of strength and toughness (yield strength (YS) reaches 585 MPa, tensile strength (TS) 667 MPa, and Charpy impact energy at 253 K of 291 J) in the DQ steels is achieved by quenching at 1113 K and tempering at 923 K.

  7. On morphologies, microsegregation, and mechanical behavior of directionally solidified cobalt-base superalloy at medium cooling rate

    NASA Astrophysics Data System (ADS)

    Chu, Shuangjie; Li, Jianguo; Liu, Zhongyuan; Shi, Zhengxing; Fu, Hengzhi

    1994-03-01

    A newly developed experimental setup that can provide a temperature gradient of 1300 K/cm has been used in the research of the morphologies, microsegregation, and mechanical behavior of directionally solidified cobalt-base superalloy (known as K10 in PR China) at medium cooling rates from 38 to 60 K/s. Experimental results show that the primary and secondary dendrite spacings of K10 become less than one-fifth and one-eighth, respectively, of those obtainable with a conventional 100 K/cm temperature gradient and a cooling rate below 1 K/s: the carbides are directionally arrayed and the carbides’ morphology changes from islands of general cast state into worms; microsegregation is almost completely eliminated; the mechanical properties, as can be expected, are greatly superior to those obtainable with 100 K/cm temperature gradient; at 1073 K, creep-rupture strength increases from 167 to 196 MPa; endurance life is raised from 10 to 30 hours; the reduction in area increases from 12 to 52 pct; and the specific elongation increases from 17 to 46 pct. And with the increase of cooling rate, there are always corresponding improvements of mechanical properties of K10. Otherwise, the fractography of superfine columnar structure samples is high-toughness transgranular fracture, with cracks originating at the edge of carbides.

  8. An Investigation of Mechanically Tunable and Nanostructured Polymer Scaffolds for Directing Human Mesenchymal Stem Cell Development

    NASA Astrophysics Data System (ADS)

    Jaafar, Israd Hakim

    This work investigated the use of biomedically relevant, polymer substrates for in vitro human mesenchymal stem cell (hMSC)-substrate surface interaction. Two materials were identified: (i) Poly(glycerol-sebacate) (PGS), a novel biocompatible and biodegradable thermosetting rubber-like elastomer, and (ii) injection molded polystyrene (PS). PGS was selected because it has tunable mechanical properties within the range of biological tissue, and thus provides a useful model to determine the types of substrate mechanical cues that would elicit specific hMSC lineage specification and possible differentiation outcomes. PS is a relevant material for in vitro cell-substrate surface interaction analysis since it is typically the base material of cell culture dishes. Both these materials have also shown micro to nanoscale molding capabilities. Hence these materials would also serve as a model in determining topographical properties (and related mechanical properties) at the dimension-scale of the extracellular environment that modulates hMSC state and fate. The work characterized, designed, and manufactured substrates made of these materials, for in vitro hMSC culture. Micro/nanoscale PGS and PS surface features were manufactured using silicon (Si) based tooling technology. The response of hMSCs to PGS substrates of various Young.s moduli was examined. hMSC response to a nanoscale array of PS pegs was also investigated. PGS was observed to be a semi-crystalline thermosetting elastomer that is fully amorphous above 35°C. The material acquired increasing stiffness and density of photoresist-coated with increasing levels of curing temperature and duration of cure. hMSCs were observed to respond differently on PGS with elastic modulii of 0.11, 1.11, and 2.30 MPa. The cells spread and proliferate more, and develop a stretched cytoskeleton on the stiffer substrates. On the softest substrate (0.11 MPa) the cells developed a branched and filopodia-rich morphology with a diffused

  9. Probable new type of reaction mechanism: Double. cap alpha. direct transfer process

    SciTech Connect

    Xu Shu-wei; Wu Guo-hua; Miao Rong-zhi; Han Fei

    1983-10-01

    It is assumed that /sup 8/Be consists of two ..cap alpha.. particles which are close to each other in configuration space. A spectroscopic density of /sup 8/Be cluster in the residue nuclei is then obtained, which is proportional to the square of the preformation probability of ..cap alpha.. particle at nuclear surface. Using the improved method of parametrization of EFR-DWBA overlap integral,/sup 1//sup en-dash//sup 2/ we calculate the double differential energy spectra and angular distributions of ..cap alpha.. particles for the reactions /sup 209/Bi (/sup 12/C, ..cap alpha..) /sup 217/Fr and extract the preformation probability of ..cap alpha.. particle at the surface of /sup 217/Fr nuclei from fitting the experimental data. The agreement within the range of calculation error between the preformation probabilities extracted from transfer reactions and ..cap alpha.. decay suggests that the reaction /sup 209/Bi(/sup 12/C, ..cap alpha..) /sup 217/Fr may be explained as a double ..cap alpha.. direct transfer process.

  10. Neurological disease associated with Mycoplasma pneumoniae infection. PCR evidence against a direct invasive mechanism

    PubMed Central

    Fink, C G; Sillis, M; Read, S J; Butler, L; Pike, M

    1995-01-01

    Aims—To investigate the pathology in patients presenting with sudden onset neurological illnesses associated with Mycoplasma pneumoniae infection. Methods—M pneumoniae infection was diagnosed by a highly rigorous interpretation of serological markers initially using complement fixation, agglutination and IgM antibodies. Confirmation of the serological diagnosis was achieved using indirect immunofluorescence for IgM, IgA, and IgG. Serum and cerebrospinal fluid (CSF) samples from these patients were examined using the polymerase chain reaction to look for evidence of M pneumoniae DNA. Results—No M pneumoniae DNA was found in any serum or CSF samples. Diagnosis of M pneumoniae infection by agglutination and complement fixation antibodies was not always confirmed by indirect immunofluorescence. Conclusion—The neurological lesions in these patients do not appear to be caused by the direct invasion of M pneumoniae into the nervous system. The lesions may be an immune response to infection. Serological diagnosis of M pneumoniae continues to be a laboratory problem. PMID:16695976

  11. The mechanism of ϕC31 integrase directionality: experimental analysis and computational modelling

    PubMed Central

    Pokhilko, Alexandra; Zhao, Jia; Ebenhöh, Oliver; Smith, Margaret C. M.; Stark, W. Marshall; Colloms, Sean D.

    2016-01-01

    Serine integrases, DNA site-specific recombinases used by bacteriophages for integration and excision of their DNA to and from their host genomes, are increasingly being used as tools for programmed rearrangements of DNA molecules for biotechnology and synthetic biology. A useful feature of serine integrases is the simple regulation and unidirectionality of their reactions. Recombination between the phage attP and host attB sites is promoted by the serine integrase alone, giving recombinant attL and attR sites, whereas the ‘reverse’ reaction (between attL and attR) requires an additional protein, the recombination directionality factor (RDF). Here, we present new experimental data on the kinetics and regulation of recombination reactions mediated by ϕC31 integrase and its RDF, and use these data as the basis for a mathematical model of the reactions. The model accounts for the unidirectionality of the attP × attB and attL × attR reactions by hypothesizing the formation of structurally distinct, kinetically stable integrase–DNA product complexes, dependent on the presence or absence of RDF. The model accounts for all the available experimental data, and predicts how mutations of the proteins or alterations of reaction conditions might increase the conversion efficiency of recombination. PMID:27387286

  12. Effects of feral horses in Great Basin landscapes on soils and ants: Direct and indirect mechanisms

    USGS Publications Warehouse

    Beever, E.A.; Herrick, J.E.

    2006-01-01

    We compared soil-surface penetration resistance and abundance of ant mounds at 12 western Great Basin sites (composed of 19 plots) either grazed by feral horses (Equus caballus) or having had horses removed for the last 10–14 years. Across this broad spatial domain (3.03 million ha), we minimized confounding due to abiotic factors by selecting horse-occupied and horse-removed sites with similar aspect, slope, fire history, grazing pressure by cattle (minimal to none), and dominant vegetation (Artemisia tridentata). During both 1997 and 1998, we found 2.2–8.4 times greater abundance of ant mounds and 3.0–15.4 times lower penetration resistance in soil surfaces at horse-removed sites. In 1998, thatched Formica ant mounds, which existed predominately at high elevations, were 3.3 times more abundant at horse-removed sites, although abundance varied widely among sites within treatments. Several types of analyses suggested that horses rather than environmental variability were the primary source of treatment differences we observed in ecosystem components. Tests of several predictions suggest that alterations occurred through not only direct effects, but also indirect effects and potentially feedback loops. Free-roaming horses as well as domestic grazers should be considered in conservation planning and land management in the Great Basin, an ecoregion that represents both an outstanding conservation opportunity and challenge.

  13. Mechanical Recanalization of Subacute Vessel Occlusion in Peripheral Arterial Disease with a Directional Atherectomy Catheter

    SciTech Connect

    Massmann, Alexander Katoh, Marcus; Shayesteh-Kheslat, Roushanak; Buecker, Arno

    2012-10-15

    Purpose: To retrospectively examine the technical feasibility and safety of directional atherectomy for treatment of subacute infrainguinal arterial vessel occlusions. Methods: Five patients (one woman, four men, age range 51-81 years) with peripheral arterial disease who experienced sudden worsening of their peripheral arterial disease-related symptoms during the last 2-6 weeks underwent digital subtraction angiography, which revealed vessel occlusion in native popliteal artery (n = 4) and in-stent occlusion of the superficial femoral artery (n = 1). Subsequently, all patients were treated by atherectomy with the SilverHawk (ev3 Endovascular, USA) device. Results: The mean diameter of treated vessels was 5.1 {+-} 1.0 mm. The length of the occlusion ranged 2-14 cm. The primary technical success rate was 100%. One patient experienced a reocclusion during hospitalization due to heparin-induced thrombocytopenia. There were no further periprocedural complications, in particular no peripheral embolizations, until hospital discharge or during the follow-up period of 1 year. Conclusion: The recanalization of infrainguinal arterial vessel occlusions by atherectomy with the SilverHawk device is technically feasible and safe. In our limited retrospective study, it was associated with a high technical success rate and a low procedure-related complication rate.

  14. Microfluidic direct writer with integrated declogging mechanism for fabricating cell-laden hydrogel constructs.

    PubMed

    Ghorbanian, Setareh; Qasaimeh, Mohammad A; Akbari, Mohsen; Tamayol, Ali; Juncker, David

    2014-06-01

    Cell distribution and nutrient supply in 3D cell-laden hydrogel scaffolds are critical and should mimic the in vivo cellular environment, but been difficult to control with conventional fabrication methods. Here, we present a microfluidic direct writer (MFDW) to construct 3D cell-laden hydrogel structures with openings permitting media exchange. The MFDW comprises a monolithic microfluidic head, which delivers coaxial streams of cell-laden sodium alginate and calcium chloride solutions to form hydrogel fibers. Fiber diameter is controlled by adjusting the ratio of the volumetric flow rates. The MFDW head is mounted on a motorized stage, which is automatically controlled and moves at a speed synchronized with the speed of fiber fabrication. Head geometry, flow rates, and viscosity of the writing solutions were optimized to prevent the occurrence of curling and bulging. For continuous use, a highly reliable process is needed, which was accomplished with the integration of a declogging conduit supplying a solvent to dissolve the clogging gel. The MFDW was used for layer-by-layer fabrication of simple 3D structures with encapsulated cells. Assembly of 3D structures with distinct fibers is demonstrated by alternatively delivering two different alginate gel solutions. The MFDW head can be built rapidly and easily, and will allow 3D constructs for tissue engineering to be fabricated with multiple hydrogels and cell types.

  15. Direct observation of epitaxial organic film growth: temperature-dependent growth mechanisms and metastability.

    PubMed

    Marchetto, Helder; Schmidt, Thomas; Groh, Ullrich; Maier, Florian C; Lévesque, Pierre L; Fink, Rainer H; Freund, Hans-Joachim; Umbach, Eberhard

    2015-11-21

    The growth of the first ten layers of organic thin films on a smooth metallic substrate has been investigated in real-time using the model system PTCDA on Ag(111). The complex behaviour is comprehensively studied by electron microscopy, spectroscopy and diffraction in a combined PEEM/LEEM instrument revealing several new phenomena and yielding a consistent picture of this layer growth. PTCDA grows above room temperature in a Stranski-Krastanov mode, forming three-dimensional islands on a stable bi-layer, in competition with metastable 3rd and 4th layers. Around room temperature this growth mode changes into a quasi layer-by-layer growth, while at temperatures below about 250 K a Vollmer-Weber-like behaviour is observed. By means of laterally resolved soft X-ray absorption spectroscopy the orientation of all adsorbed molecules is found to be homogeneously flat lying on the surface, even during the growth process. The films grow epitaxially, showing long-range order with rotational domains. For the monolayer these domains could be directly analysed, showing an average size of several micrometers extending over substrate steps.

  16. Low-energy spectrum of iron-sulfur clusters directly from many-particle quantum mechanics

    NASA Astrophysics Data System (ADS)

    Sharma, Sandeep; Sivalingam, Kantharuban; Neese, Frank; Chan, Garnet Kin-Lic

    2014-10-01

    Iron-sulfur clusters are a universal biological motif. They carry out electron transfer, redox chemistry and even oxygen sensing, in diverse processes including nitrogen fixation, respiration and photosynthesis. Their low-lying electronic states are key to their remarkable reactivity, but they cannot be directly observed. Here, we present the first ever quantum calculation of the electronic levels of [2Fe-2S] and [4Fe-4S] clusters free from any model assumptions. Our results highlight the limitations of long-standing models of their electronic structure. In particular, we demonstrate that the widely used Heisenberg double exchange model underestimates the number of states by one to two orders of magnitude, which can conclusively be traced to the absence of Fe dd excitations, thought to be important in these clusters. Furthermore, the electronic energy levels of even the same spin are dense on the scale of vibrational fluctuations and this provides a natural explanation for the ubiquity of these clusters in catalysis in nature.

  17. Direct observation of epitaxial organic film growth: temperature-dependent growth mechanisms and metastability.

    PubMed

    Marchetto, Helder; Schmidt, Thomas; Groh, Ullrich; Maier, Florian C; Lévesque, Pierre L; Fink, Rainer H; Freund, Hans-Joachim; Umbach, Eberhard

    2015-11-21

    The growth of the first ten layers of organic thin films on a smooth metallic substrate has been investigated in real-time using the model system PTCDA on Ag(111). The complex behaviour is comprehensively studied by electron microscopy, spectroscopy and diffraction in a combined PEEM/LEEM instrument revealing several new phenomena and yielding a consistent picture of this layer growth. PTCDA grows above room temperature in a Stranski-Krastanov mode, forming three-dimensional islands on a stable bi-layer, in competition with metastable 3rd and 4th layers. Around room temperature this growth mode changes into a quasi layer-by-layer growth, while at temperatures below about 250 K a Vollmer-Weber-like behaviour is observed. By means of laterally resolved soft X-ray absorption spectroscopy the orientation of all adsorbed molecules is found to be homogeneously flat lying on the surface, even during the growth process. The films grow epitaxially, showing long-range order with rotational domains. For the monolayer these domains could be directly analysed, showing an average size of several micrometers extending over substrate steps. PMID:26462749

  18. Site directed mutagenesis of Drosophila flightin disrupts phosphorylation and impairs flight muscle structure and mechanics.

    PubMed

    Barton, Byron; Ayer, Gretchen; Maughan, David W; Vigoreaux, Jim O

    2007-01-01

    Flightin is a myosin rod binding protein that in Drosophila melanogaster is expressed exclusively in the asynchronous indirect flight muscles (IFM). Hyperphosphorylation of flightin coincides with the completion of myofibril assembly and precedes the emergence of flight competency in young adults. To investigate the role of flightin phosphorylation in vivo we generated three flightin null (fln(0)) Drosophila strains that express a mutant flightin transgene with two (Thr158, Ser 162), three (Ser139, Ser141, Ser145) or all five potential phosphorylation sites mutated to alanines. These amino acid substitutions result in lower than normal levels of flightin accumulation and transgenic strains that are unable to beat their wings. On two dimensional gels of IFM proteins, the transgenic strain with five mutant sites (fln(5STA)) is devoid of all phosphovariants, the transgenic strain with two mutant sites (fln(2TSA)) expresses only the two least acidic of the nine phosphovariants, and the transgenic strain with three mutant sites (fln(3SA)) expresses all nine phosphovariants, as the wild-type strain. These results suggest that phosphorylation of Thr158 and/or Ser162 is necessary for subsequent phosphorylation of other sites. All three transgenic strains show normal, albeit long, IFM sarcomeres in newly eclosed adults. In contrast, sarcomeres in fully mature fln(5STA) and fln(2TSA) adults show extensive breakdown while those in fln(3SA) are not as disordered. The fiber hypercontraction phenotype that characterizes fln(0) is fully evident in fln(5STA) and fln(2TSA) but partially rescued in fln(3SA). Mechanics on skinned fibers from newly eclosed flies show alterations in viscous modulus for fln(5STA) and fln(2TSA) that result in a significant reduction in oscillatory power output. Expression of fln(5STA) and fln(2TSA), but not fln(3SA), in a wild-type (fln(+)/fln(+)) background resulted in a dominant negative effect manifested as flight impairments and hypercontracted IFM

  19. Cytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639Gmechanical heart valve replacement

    PubMed Central

    Kaur, Anupriya; Khan, Farah; Agrawal, Suraksha S.; Kapoor, Aditya; Agarwal, Surendra K.; Phadke, Shubha R.

    2013-01-01

    Background & objectives: Studies have demonstrated the effect of CYP2C9 (cytochrome P450) and VKORC1 (vitamin K epoxide reductase complex) gene polymorphisms on the dose of acenocoumarol. The data from India about these gene polymorphisms and their effects on acenocoumarol dose are scarce. The aim of this study was to determine the occurrence of CYP2C9*2,*3 and VKORC 1 -1639G>A gene polymorphisms and to study their effects on the dose of acenocoumarol required to maintain a target International Normalized Ratio (INR) in patients with mechanical heart valve replacement. Methods: Patients from the anticoagulation clinic of a tertiary care hospital in north India were studied. The anticoagulation profile, INR (International Normalized Ratio) values and administered acenocoumarol dose were obtained from the clinical records of patients. Determination of the CYP2C9*2,*3 and VKORC1 -1639G>A genotypes was done by PCR-RFLP (restriction fragment length polymorphism). Results: A total of 111 patients were studied. The genotype frequencies of CYP2C9 *1/*1,*1/*2,*1/*3 were as 0.883, 0.072, 0.036 and that of VKORC1 -1639G>A for GG, AG, and AA genotypes were 0.883, 0.090, and 0.027, respectively. The percentage of patients carrying any of the variant alleles of CYP2C9 and VKORC1 in heterozygous or homozygous form was 34% among those receiving a low dose of ≤20 mg/wk while it was 13.8 per cent in those receiving >20 mg/wk (P=0.014). A tendency of lower dose requirements was seen among carriers of the studied polymorphisms. There was considerable variability in the dose requirements of patients with and without variant alleles. Interpretation & conclusions: The study findings point towards the role of CYP2C9 and VKORC1 gene polymorphisms in determining the inter-individual dose variability of acenocoumarol in the Indian patients with mechanical heart valve replacement. PMID:23481074

  20. Transdiagnostic dimensions of anxiety: Neural mechanisms, executive functions, and new directions.

    PubMed

    Sharp, Paul B; Miller, Gregory A; Heller, Wendy

    2015-11-01

    Converging neuroscientific and psychological evidence points to several transdiagnostic factors that cut across DSM-defined disorders, which both affect and are affected by executive dysfunction. Two of these factors, anxious apprehension and anxious arousal, have helped bridge the gap between psychological and neurobiological models of anxiety. The present integration of diverse findings advances an understanding of the relationships between these transdiagnostic anxiety dimensions, their interactions with each other and executive function, and their neural mechanisms. Additionally, a discussion is provided concerning how these constructs fit within the Research Domain Criteria (RDoC) matrix developed by the National Institutes of Mental Health and how they relate to other anxiety constructs studied with different methods and at other units of analysis. Suggestions for future research are offered, including how to (1) improve measurement and delineation of these constructs, (2) use new neuroimaging methods and theoretical approaches of how the brain functions to build neural mechanistic models of these constructs, and (3) advance understanding of the relationships of these constructs to diverse emotional phenomena and executive functions.

  1. Direct observation and mechanism of increased emission sites in Fe-coated microcrystalline diamond films

    SciTech Connect

    Panda, Kalpataru; Sundaravel, B.; Panigrahi, B. K.; Huang, Pin-Chang; Shih, Wen-Ching; Chen, Huang-Chin; Lin, I-Nan

    2012-06-15

    The electron field emission (EFE) properties of microcrystalline diamond (MCD) films are significantly enhanced due to the Fe coating and post-annealing processes. The 900 Degree-Sign C post-annealed Fe coated diamond films exhibit the best EFE properties, with a turn on field (E{sub 0}) of 3.42 V/{mu}m and attain EFE current density (J{sub e}) of 170 {mu}A/cm{sup 2} at 7.5 V/{mu}m. Scanning tunnelling spectroscopy (STS) in current imaging tunnelling spectroscopy mode clearly shows the increased number density of emission sites in Fe-coated and post-annealed MCD films than the as-prepared ones. Emission is seen from the boundaries of the Fe (or Fe{sub 3}C) nanoparticles formed during the annealing process. In STS measurement, the normalized conductance (dI/dV/I/V) versus V curves indicate nearly metallic band gap, at the boundaries of Fe (or Fe{sub 3}C) nanoparticles. Microstructural analysis indicates that the mechanism for improved EFE properties is due to the formation of nanographite that surrounds the Fe (or Fe{sub 3}C) nanoparticles.

  2. Mechanism of direct current electrical charge conduction in p-toluenesulfonate doped polypyrrole/carbon composites

    SciTech Connect

    Kumar, Amit; Singh, Rajiv K.; Singh, Hari K.; Singh, Ramadhar; Srivastava, Pankaj

    2014-03-14

    Polypyrrole/carbon (PPy/C) composites have been synthesized using varying concentration of p-toluenesulfonate (pTS) dopant by surface initiated in-situ chemical oxidative polymerization. The synthesis and influence of pTS on the structure of the PPy/C composites are confirmed by Fourier transform infrared studies and the morphological features have been examined by scanning electron microscopy. X-ray photoelectron spectroscopy, employed to examine the surface composition and doping level of these composites, confirms the anionic doping into the polymer backbone. Electron spin resonance measurement has been carried out on these samples to identify the nature of the charge carriers and their concentration at different doping levels. The dc electrical conductivity of these composites has been measured in the temperature range ∼10–305 K. The observed results have been analyzed in the framework of existing theoretical models. Different Mott's parameters, such as characteristic temperature (T{sub 0}), density of states at the Fermi level (N(E{sub F})), average hopping distance (R), and average hopping energy (W), evaluated from dc conductivity data supports the applicability of Mott's three dimensional variable range hopping mechanism in this system.

  3. Matrix Composition and Mechanics Direct Proangiogenic Signaling from Mesenchymal Stem Cells

    PubMed Central

    Abdeen, Amr A.; Weiss, Jared B.; Lee, Junmin

    2014-01-01

    The secretion of trophic factors that promote angiogenesis from mesenchymal stem cells (MSCs) is a promising cell-based therapeutic treatment. However, clinical efficacy has proved variable, likely on account of ill-defined cell delivery formulations and the inherent complexity of cellular secretion. Here we show how controlling the mechanical properties and protein composition of the extracellular matrix (ECM) surrounding MSCs can guide proangiogenic signaling. Conditioned media from MSCs adherent to polyacrylamide hydrogel functionalized with fibronectin, collagen I, or laminin was applied to 3D matrigel cultures containing human microvascular endothelial cells (HMVECs). The degree of tubulogenesis in HMVECs is shown to depend on both the substrate rigidity and matrix protein composition. MSCs cultured on fibronectin-modified hydrogels show a stiffness dependence in proangiogenic signaling with maximum influence on tubulogenesis observed from 40 kPa conditioned media, twofold higher than commercially available cocktails of growth factors. Quantitative real-time–polymerase chain reaction reveals stiffness-dependent expression of multiple factors involved in angiogenesis that corroborate the functional tubulogenesis assay. Restricting cell spreading with micropatterned surfaces attenuates the conditioned media effects; however, small-molecule inhibitors of actomyosin contractility do not significantly reduce the functional outcome. This work demonstrates how controlling matrix rigidity and protein composition can influence the secretory profile of MSCs. Model systems that deconstruct the physical and biochemical cues involved in MSC secretion may assist in the design of hydrogel biomaterials for cell-based therapies. PMID:24701989

  4. Matrix composition and mechanics direct proangiogenic signaling from mesenchymal stem cells.

    PubMed

    Abdeen, Amr A; Weiss, Jared B; Lee, Junmin; Kilian, Kristopher A

    2014-10-01

    The secretion of trophic factors that promote angiogenesis from mesenchymal stem cells (MSCs) is a promising cell-based therapeutic treatment. However, clinical efficacy has proved variable, likely on account of ill-defined cell delivery formulations and the inherent complexity of cellular secretion. Here we show how controlling the mechanical properties and protein composition of the extracellular matrix (ECM) surrounding MSCs can guide proangiogenic signaling. Conditioned media from MSCs adherent to polyacrylamide hydrogel functionalized with fibronectin, collagen I, or laminin was applied to 3D matrigel cultures containing human microvascular endothelial cells (HMVECs). The degree of tubulogenesis in HMVECs is shown to depend on both the substrate rigidity and matrix protein composition. MSCs cultured on fibronectin-modified hydrogels show a stiffness dependence in proangiogenic signaling with maximum influence on tubulogenesis observed from 40 kPa conditioned media, twofold higher than commercially available cocktails of growth factors. Quantitative real-time-polymerase chain reaction reveals stiffness-dependent expression of multiple factors involved in angiogenesis that corroborate the functional tubulogenesis assay. Restricting cell spreading with micropatterned surfaces attenuates the conditioned media effects; however, small-molecule inhibitors of actomyosin contractility do not significantly reduce the functional outcome. This work demonstrates how controlling matrix rigidity and protein composition can influence the secretory profile of MSCs. Model systems that deconstruct the physical and biochemical cues involved in MSC secretion may assist in the design of hydrogel biomaterials for cell-based therapies.

  5. The production mechanisms of OH radicals in a pulsed direct current plasma jet

    SciTech Connect

    Liu, X. Y.; Pei, X. K.; Lu, X. P.; Liu, D. W.; Ostrikov, K.

    2014-09-15

    The production mechanism of OH radicals in a pulsed DC plasma jet is studied by a two-dimensional (2-D) plasma jet model and a one-dimensional (1-D) discharge model. For the plasma jet in the open air, electron-impact dissociation of H{sub 2}O, electron neutralization of H{sub 2}O{sup +}, as well as dissociation of H{sub 2}O by O(1D) are found to be the main reactions to generate the OH species. The contribution of the dissociation of H{sub 2}O by electron is more than the others. The additions of N{sub 2}, O{sub 2}, air, and H{sub 2}O into the working gas increase the OH density outside the tube slightly, which is attributed to more electrons produced by Penning ionization. On the other hand, the additions of O{sub 2} and H{sub 2}O into the working gas increase the OH density inside the tube substantially, which is attributed to the increased O (1D) and H{sub 2}O concentration, respectively. The gas flow will transport high density OH out of the tube during pulse off period. It is also shown that the plasma chemistry and reactivity can be effectively controlled by the pulse numbers. These results are supported by the laser induced fluorescence measurements and are relevant to several applications of atmospheric-pressure plasmas in health care, medicine, and materials processing.

  6. Direct coupling between charge current and spin polarization by extrinsic mechanisms in graphene

    NASA Astrophysics Data System (ADS)

    Huang, Chunli; Chong, Y. D.; Cazalilla, Miguel A.

    2016-08-01

    Spintronics—the all-electrical control of the electron spin for quantum or classical information storage and processing—is one of the most promising applications of the two-dimensional material graphene. Although pristine graphene has negligible spin-orbit coupling (SOC), both theory and experiment suggest that SOC in graphene can be enhanced by extrinsic means, such as functionalization by adatom impurities. We present a theory of transport in graphene that accounts for the spin-coherent dynamics of the carriers, including hitherto-neglected spin precession processes taking place during resonant scattering in the dilute impurity limit. We uncover an "anisotropic spin precession" (ASP) scattering process in graphene, which contributes a large current-induced spin polarization and modifies the standard spin Hall effect. ASP scattering arises from two dimensionality and extrinsic SOC, and apart from graphene, it can be present in other 2D materials or in the surface states of 3D materials with a fluctuating SOC. Our theory also yields a comprehensive description of the spin relaxation mechanisms present in adatom-decorated graphene, including Elliot-Yafet and D'yakonov-Perel relaxation rates, the latter of which can become an amplification process in a certain parameter regime of the SOC disorder potential. Our work provides theoretical foundations for designing future graphene-based integrated spintronic devices.

  7. TGF-β-Induced Regulatory T Cells Directly Suppress B Cell Responses through a Noncytotoxic Mechanism.

    PubMed

    Xu, Anping; Liu, Ya; Chen, Weiqian; Wang, Julie; Xue, Youqiu; Huang, Feng; Rong, Liming; Lin, Jin; Liu, Dahai; Yan, Mei; Li, Quan-Zhen; Li, Bin; Song, Jianxun; Olsen, Nancy; Zheng, Song Guo

    2016-05-01

    Foxp3(+) regulatory T cells (Treg) playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases consist of thymus-derived naturally occurring CD4(+)Foxp3(+) Treg cells (nTreg) and those that can be induced ex vivo with TGF-β (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. The role of iTreg in regulating B cells remains unclear so far. The suppression assays of Treg subsets on activation, proliferation, and Abs production of B cells were measured using a Treg and B cell coculture system in vitro. Transwell and Ab blockade experiments were performed to assess the roles of cell contact and soluble cytokines. Treg were adoptively transferred to lupus mice to assess in vivo effects on B cells. Like nTreg, iTreg subset also directly suppressed activation and proliferation of B cells. nTreg subset suppressed B cell responses through cytotoxic manner related to expression of granzyme A, granzyme B, and perforin, whereas the role of iTreg subset on B cells did not involve in cytotoxic action but depending on TGF-β signaling. Furthermore, iTreg subset can significantly suppress Ab produced by lupus B cells in vitro. Comparison experiments using autoantibodies microarrays demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo. Our data implicate a role and advantage of iTreg subset in treating B cell-mediated autoimmune diseases, boosting the translational potential of these findings. PMID:27001954

  8. ARRANGEMENT FOR REPLACING FILTERS

    DOEpatents

    Blomgren, R.A.; Bohlin, N.J.C.

    1957-08-27

    An improved filtered air exhaust system which may be continually operated during the replacement of the filters without the escape of unfiltered air is described. This is accomplished by hermetically sealing the box like filter containers in a rectangular tunnel with neoprene covered sponge rubber sealing rings coated with a silicone impregnated pneumatic grease. The tunnel through which the filters are pushed is normal to the exhaust air duct. A number of unused filters are in line behind the filters in use, and are moved by a hydraulic ram so that a fresh filter is positioned in the air duct. The used filter is pushed into a waiting receptacle and is suitably disposed. This device permits a rapid and safe replacement of a radiation contaminated filter without interruption to the normal flow of exhaust air.

  9. NARC Rayon Replacement Program

    NASA Technical Reports Server (NTRS)

    Wilson, Kenneth P.; McCool, Alex (Technical Monitor)

    2002-01-01

    This viewgraph presentation provides information on the search for a replacement product for the aerospace grade rayon formerly used in the reusable solid rocket motor (RSRM). The rayon used in RSRMs is no longer produced by the North American Rayon Corporation (NARC), though NASA has stockpiled rayon to be used until a suitable replacement is found to be used in the RSRM nozzle carbon cloth phenolic (CCP). The primary considerations are performance, process ability, variability, long term availability, and cost. The preference will be given to commercial off-the-shelf products as opposed to those which are custom made. The candidate materials have been tested in previous phases of this selection process, and Enka Textile Rayon has emerged as a possible fabric, though its availability is still in question.

  10. Mechanism of altruism approach to blood donor recruitment and retention: a review and future directions.

    PubMed

    Ferguson, E

    2015-08-01

    Why do people donate blood? Altruism is the common answer. However, altruism is a complex construct and to answer this question requires a systematic analysis of the insights from the biology, economics and psychology of altruism. I term this the mechanism of altruism (MOA) approach and apply it here for understanding blood donor motivation. The answer also has enormous implications for the type of interventions we choose to adopt as a society. A MOA approach so far shows that blood donors are a mixture of (i) warm-glow givers (donation is emotionally rewarding) and (ii) reluctant altruists (cooperate rather than defect when free-riding is high). Donors also show 'saintly sinning' with the extra 'moral currency' form blood donation allowing them to be less generous in other contexts. The MOA approach suggests why financial incentives, in terms of gifts/lottery tickets, are effective and suggests a number of novel interventions for donor recruitment: 'voluntary reciprocal altruism' and 'charitable incentivisation'. The MOA approach also highlights the need for an intervention developed specifically for recipients to allow them to show their gratitude to donors and for society to celebrate blood donation. It is suggests a 'Monument to Blood Donors' will achieve this. The approach suggests a number of novel research questions into (i) donor self-selection effects, (ii) conditional cooperation and (iii) construct overlap with Theory of Planned Behaviour (e.g. affective attitudes and warm-glow). The MOA offers a powerful way to understand blood donor motivations around altruism and develop theoretically driven interventions. PMID:26311129

  11. Mechanism of altruism approach to blood donor recruitment and retention: a review and future directions.

    PubMed

    Ferguson, E

    2015-08-01

    Why do people donate blood? Altruism is the common answer. However, altruism is a complex construct and to answer this question requires a systematic analysis of the insights from the biology, economics and psychology of altruism. I term this the mechanism of altruism (MOA) approach and apply it here for understanding blood donor motivation. The answer also has enormous implications for the type of interventions we choose to adopt as a society. A MOA approach so far shows that blood donors are a mixture of (i) warm-glow givers (donation is emotionally rewarding) and (ii) reluctant altruists (cooperate rather than defect when free-riding is high). Donors also show 'saintly sinning' with the extra 'moral currency' form blood donation allowing them to be less generous in other contexts. The MOA approach suggests why financial incentives, in terms of gifts/lottery tickets, are effective and suggests a number of novel interventions for donor recruitment: 'voluntary reciprocal altruism' and 'charitable incentivisation'. The MOA approach also highlights the need for an intervention developed specifically for recipients to allow them to show their gratitude to donors and for society to celebrate blood donation. It is suggests a 'Monument to Blood Donors' will achieve this. The approach suggests a number of novel research questions into (i) donor self-selection effects, (ii) conditional cooperation and (iii) construct overlap with Theory of Planned Behaviour (e.g. affective attitudes and warm-glow). The MOA offers a powerful way to understand blood donor motivations around altruism and develop theoretically driven interventions.

  12. Osteoclast Precursor Interaction with Bone Matrix Induces Osteoclast Formation Directly by an Interleukin-1-mediated Autocrine Mechanism*

    PubMed Central

    Yao, Zhenqiang; Xing, Lianping; Qin, Chunlin; Schwarz, Edward M.; Boyce, Brendan F.

    2008-01-01

    Interleukin-1 (IL-1) and tumor necrosis factor (TNF) mediate bone resorption in a variety of diseases affecting bone. Like TNF, IL-1 is secreted by osteoclast precursors (OCPs), but unlike TNF, it does not induce osteoclast formation directly from OCPs in vitro. TNF induces IL-1 expression and activates c-Fos, a transcription factor required in OCPs for osteoclast formation. Here, we examined whether IL-1 can induce osteoclast formation directly from OCPs overexpressing c-Fos and whether interaction with bone matrix affects OCP cytokine expression. We infected OCPs with c-Fos or green fluorescent protein retrovirus, cultured them with macrophage colony-stimulating factor and IL-1 on bone slices or plastic dishes, and assessed osteoclast and resorption pit formation and expression of IL-1 by OCPs. We used a Transwell assay to determine whether OCPs secrete IL-1 when they interact with bone matrix. IL-1 induced osteoclast formation directly from c-Fos-expressing OCPs on plastic. c-Fos-expressing OCPs formed osteoclasts spontaneously on bone slices without addition of cytokines. OCPs on bone secreted IL-1, which induced osteoclast formation from c-Fos-expressing OCPs in the lower Transwell dishes. The bone matrix proteins dentin sialoprotein and osteopontin, but not transforming growth factor-β, stimulated OCP expression of IL-1 and induced c-Fos-expressing OCP differentiation into osteoclasts. Osteoclasts eroding inflamed joints have higher c-Fos expression compared with osteoclasts inside bone. We conclude that OCPs expressing c-Fos may induce their differentiation directly into osteoclasts by an autocrine mechanism in which they produce IL-1 through interaction with bone matrix. TNF could induce c-Fos expression in OCPs at sites of inflammation in bone to promote this autocrine mechanism and thus amplify bone loss. PMID:18250170

  13. Biological Mechanisms Underlying the Relationship between Stress and Smoking: State of the Science and Directions for Future Work

    PubMed Central

    Richards, Jessica; Stipelman, Brooke A.; Bornovalova, Marina A.; Daughters, Stacey; Sinha, Rajita; Lejuez, C.W.

    2011-01-01

    Theories of addiction implicate stress as a crucial mechanism underlying initiation, maintenance, and relapse to cigarette smoking. Examinations of the biological stress systems, including functioning of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), have provided additional insights into the relationship between stress and smoking. To date, convergent data suggests that chronic cigarette smoking is associated with alterations in HPA and ANS functioning; however, less is known about the role of HPA and ANS functioning in smoking initiation and relapse following cessation. In order to organize existing findings and stimulate future research, the current paper summarizes the available literature on the roles of HPA axis and ANS functioning in the relationship between stress and cigarette smoking, highlights limitations within the existing literature, and suggests directions for future research to address unanswered questions in the extant literature on the biological mechanisms underlying the relationship between stress and smoking. PMID:21741435

  14. Total femoral replacement.

    PubMed

    Nerubay, J; Katznelson, A; Tichler, T; Rubinstein, Z; Morag, B; Bubis, J J

    1988-04-01

    Between 1973 and 1983, 19 patients with sarcoma of the femur were treated by adjuvant chemotherapy, excision of the entire femur, and replacement by a total femoral prosthesis. Five patients had excellent and nine had good functional results. Twelve patients died an average of 23 months after the procedure and seven are at present disease free. This limb-saving procedure permits rapid rehabilitation, prevents severe psychological problems, and improves the quality of life.

  15. The directed self-assembly of nanostructures: Electric pressure, dipole, double layer and cracking mechanisms

    NASA Astrophysics Data System (ADS)

    Salac, David

    2007-12-01

    This dissertation presents investigations into the self-assembly of a wide number of material systems. This research introduces the concept that electric fields oriented in the plane of a thin polymer film will induce surface instabilities which grow to form structures. This experimental result indicates that large scale fabrication of nano- and micro-structures in a polymer film can be affectively achieved in an easy to construct and maintain setup. Electrostatic interactions have also been presented as a possible controlling mechanism in forming nanometer sized structure in molecularly thin film. A theoretical and computational investigation presented here indicates that the use of dipolar multilayer system combined with a substrate containing embedded electrodes is capable of fabricating patterns which would be difficult to obtain otherwise. It was observed that subsequent layers in a multilayer system will undergo layer-by-layer alignment and feature size reduction. The result has been applied to the ''molecular car'' concept, by which molecules are able to migrate on a surface due to externally controllable electric field patterns. The scaling and ordering of metallic nanoclusters on semiconductor substrates has been explored computationally. Numerical techniques were implemented to calculate the total electrostatic and van der Waals energies for systems containing multiple disks. Observations show that interactions in charge clouds beneath the metallic disks led to an electrostatic repulsive force. Attraction was observed by the van der Waals energy. An energy barrier past which disk coalescence will not occur was observed. This has applications in the development of large-scale nanodot systems which require precise control over both dot location and size. Finally, this dissertation presents results of systematic investigation of nanocracking in thin films using numerical techniques. Using a level-set method to describe an arbitrary crack in a heterogeneous

  16. A review of micro-contact physics, materials, and failure mechanisms in direct-contact RF MEMS switches

    NASA Astrophysics Data System (ADS)

    Basu, A.; Adams, G. G.; McGruer, N. E.

    2016-10-01

    Direct contact, ohmic MEMS switches for RF applications have several advantages over other conventional switching devices. Advantages include lower insertion loss, higher isolation, and better switching figure-of-merit (cut-off frequency). The most important aspect of a direct-contact RF MEMS switch is the metal microcontact which can dictate the lifetime and reliability of the switch. Therefore, an understanding of contact reliability is essential for developing robust MEMS switches. This paper discusses and reviews the most important work done over the past couple of decades toward understanding ohmic micro-contacts. We initially discuss the contact mechanics and multi-physics models for studying Hertzian and multi-asperity contacts. We follow this with a discussion on models and experiments for studying adhesion. We then discuss experimental setups and the development of contact test stations by various groups for accelerated testing of microcontacts, as well as for analysis of contact reliability issues. Subsequently, we analyze a number of material transfer mechanisms in microcontacts under hot and cold switching conditions. We finally review the material properties that can help determine the selection of contact materials. A trade-off between contact resistance and high reliability is almost always necessary during selection of contact material; this paper discusses how the choice of materials can help address such trade-offs.

  17. Exploring the nitrous acid (HONO) formation mechanism in winter Beijing: direct emissions and heterogeneous production in urban and suburban areas.

    PubMed

    Tong, Shengrui; Hou, Siqi; Zhang, Ying; Chu, Biwu; Liu, Yongchun; He, Hong; Zhao, Pusheng; Ge, Maofa

    2016-07-18

    Continuous measurements of nitrous acid (HONO) were performed from December 12 to December 22, 2015 in both urban and suburban areas of Beijing to study the formation mechanism of HONO. The measurement campaign in both sites included a clean-haze-clean transformation process. HONO concentrations showed similar variations in the two sites, while they were always higher in the urban area. Moreover, correlations of HONO with NOx, NO2, NO, PM2.5 and relative humidity (RH) were studied to explore possible HONO formation pathways, and the contributions of direct emissions, heterogeneous reactions, and homogeneous reactions were also calculated. This showed that HONO in urban and suburban areas underwent totally different formation procedures, which were affected by meteorological conditions, PM2.5 concentrations, direct emissions, homogeneous reactions and heterogeneous reactions. PM2.5 concentrations and RH would influence the NO2 conversion efficiency. Heterogeneous reactions of NO2 were more efficient in suburban areas and in clean periods while direct emissions and homogeneous reactions contributed more in urban areas and in polluted periods when the concentrations of NOx and NO were at a high level. PMID:27081740

  18. Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina

    PubMed Central

    Pei, Zhe; Chen, Qiang; Koren, David; Giammarinaro, Benno; Acaron Ledesma, Hector

    2015-01-01

    Direction selectivity of direction-selective ganglion cells (DSGCs) in the retina results from patterned excitatory and inhibitory inputs onto DSGCs during motion stimuli. The inhibitory inputs onto DSGCs are directionally tuned to the antipreferred (null) direction and therefore potently suppress spiking during motion in the null direction. However, whether direction-selective inhibition is indispensable for direction selectivity is unclear. Here, we selectively eliminated the directional tuning of inhibitory inputs onto DSGCs by disrupting GABA release from the presynaptic interneuron starburst amacrine cell in the mouse retina. We found that, even without directionally tuned inhibition, direction selectivity can still be implemented in a subset of On-Off DSGCs by direction-selective excitation and a temporal offset between excitation and isotropic inhibition. Our results therefore demonstrate the concerted action of multiple synaptic mechanisms for robust direction selectivity in the retina. SIGNIFICANCE STATEMENT The direction-selective circuit in the retina has been a classic model to study neural computations by the brain. An important but unresolved question is how direction selectivity is implemented by directionally tuned excitatory and inhibitory mechanisms. Here we specifically removed the direction tuning of inhibition from the circuit. We found that direction tuning of inhibition is important but not indispensable for direction selectivity of DSGCs' spiking activity, and that the residual direction selectivity is implemented by direction-selective excitation and temporal offset between excitation and inhibition. Our results highlight the concerted actions of synaptic excitation and inhibition required for robust direction selectivity in the retina and provide critical insights into how patterned excitation and inhibition collectively implement sensory processing. PMID:26400950

  19. Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina.

    PubMed

    Pei, Zhe; Chen, Qiang; Koren, David; Giammarinaro, Benno; Acaron Ledesma, Hector; Wei, Wei

    2015-09-23

    Direction selectivity of direction-selective ganglion cells (DSGCs) in the retina results from patterned excitatory and inhibitory inputs onto DSGCs during motion stimuli. The inhibitory inputs onto DSGCs are directionally tuned to the antipreferred (null) direction and therefore potently suppress spiking during motion in the null direction. However, whether direction-selective inhibition is indispensable for direction selectivity is unclear. Here, we selectively eliminated the directional tuning of inhibitory inputs onto DSGCs by disrupting GABA release from the presynaptic interneuron starburst amacrine cell in the mouse retina. We found that, even without directionally tuned inhibition, direction selectivity can still be implemented in a subset of On-Off DSGCs by direction-selective excitation and a temporal offset between excitation and isotropic inhibition. Our results therefore demonstrate the concerted action of multiple synaptic mechanisms for robust direction selectivity in the retina. Significance statement: The direction-selective circuit in the retina has been a classic model to study neural computations by the brain. An important but unresolved question is how direction selectivity is implemented by directionally tuned excitatory and inhibitory mechanisms. Here we specifically removed the direction tuning of inhibition from the circuit. We found that direction tuning of inhibition is important but not indispensable for direction selectivity of DSGCs' spiking activity, and that the residual direction selectivity is implemented by direction-selective excitation and temporal offset between excitation and inhibition. Our results highlight the concerted actions of synaptic excitation and inhibition required for robust direction selectivity in the retina and provide critical insights into how patterned excitation and inhibition collectively implement sensory processing.

  20. Reflections on replacement.

    PubMed

    Ryder, N B

    1993-01-01

    In the United States, the total fertility rate is about 1.9 births per woman, down from a peak of 3.2 a generation ago and below the replacement level of 2.1 children. The proportion of women who will never have children has risen from 8% a generation ago to approximately 18% in 1993. The increase in the proportion of women in the labor force, a proximate explanation of the recent decline in intended fertility, is expected to continue. The demographic consequence is declining population with an older age structure. A pronatalist policy to alleviate this outcome, through monetary transfers from taxpayers to potential parents, is not only unlikely to succeed, it is politically unfeasible. An alternative solution, immediately effective but politically unpalatable, would be a generous immigration policy. Even with replacement level fertility, the population is destined to become much older. This inevitable aging of the population should be countered by appropriate institutional transformations: 1) with lower fertility, a larger proportion of women will be available to participate in the labor force to generate taxes needed to support a larger number of pensioners; 2) the institutional practice of ascribing a dependent status to anyone above a particular age can be changed; 3) concerns that an older labor force will have an obsolete education (and fewer years of it) can be countered by changing access to education. Yet, the most serious question is not merely the net reproduction rate, but producing adequate numbers of new adult citizens with responsibility and technical training in the modern world. The fundamental process of socializing children may be jeopardized by replacing the full-time parent with the hired care-giver, the peer group, and the television set. The attenuation of the bonds between parent and child may devalue the worth of childbearing itself. These portentous consequences deserve consideration. PMID:8313953

  1. Total ankle joint replacement.

    PubMed

    2016-02-01

    Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain-free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications.

  2. Direct monitoring of opto-mechanical switching of self-assembled monolayer films containing the azobenzene group

    PubMed Central

    Tirosh, Einat; Benassi, Enrico; Pipolo, Silvio; Mayor, Marcel; Valášek, Michal; Frydman, Veronica

    2011-01-01

    Summary The potential for manipulation and control inherent in molecule-based motors holds great scientific and technological promise. Molecules containing the azobenzene group have been heavily studied in this context. While the effects of the cis–trans isomerization of the azo group in such molecules have been examined macroscopically by a number of techniques, modulations of the elastic modulus upon isomerization in self-assembled films were not yet measured directly. Here, we examine the mechanical response upon optical switching of bis[(1,1'-biphenyl)-4-yl]diazene organized in a self-assembled film on Au islands, using atomic force microscopy. Analysis of higher harmonics by means of a torsional harmonic cantilever allowed real-time extraction of mechanical data. Quantitative analysis of elastic modulus maps obtained simultaneously with topographic images show that the modulus of the cis-form is approximately twice that of the trans-isomer. Quantum mechanical and molecular dynamics studies show good agreement with this experimental result, and indicate that the stiffer response in the cis-form comprises contributions both from the individual molecular bonds and from intermolecular interactions in the film. These results demonstrate the power and insights gained from cutting-edge AFM technologies, and advanced computational methods. PMID:22259768

  3. Direct Numerical Simulations in Solid Mechanics for Quantifying the Macroscale Effects of Microstructure and Material Model-Form Error

    NASA Astrophysics Data System (ADS)

    Bishop, Joseph E.; Emery, John M.; Battaile, Corbett C.; Littlewood, David J.; Baines, Andrew J.

    2016-05-01

    Two fundamental approximations in macroscale solid-mechanics modeling are (1) the assumption of scale separation in homogenization theory and (2) the use of a macroscopic plasticity material model that represents, in a mean sense, the multitude of inelastic processes occurring at the microscale. With the goal of quantifying the errors induced by these approximations on engineering quantities of interest, we perform a set of direct numerical simulations (DNS) in which polycrystalline microstructures are embedded throughout a macroscale structure. The largest simulations model over 50,000 grains. The microstructure is idealized using a randomly close-packed Voronoi tessellation in which each polyhedral Voronoi cell represents a grain. An face centered cubic crystal-plasticity model is used to model the mechanical response of each grain. The overall grain structure is equiaxed, and each grain is randomly oriented with no overall texture. The detailed results from the DNS simulations are compared to results obtained from conventional macroscale simulations that use homogeneous isotropic plasticity models. The macroscale plasticity models are calibrated using a representative volume element of the idealized microstructure. Ultimately, we envision that DNS modeling will be used to gain new insights into the mechanics of material deformation and failure.

  4. Direct numerical simulations in solid mechanics for quantifying the macroscale effects of microstructure and material model-form error

    DOE PAGESBeta

    Bishop, Joseph E.; Emery, John M.; Battaile, Corbett C.; Littlewood, David J.; Baines, Andrew J.

    2016-03-16

    Two fundamental approximations in macroscale solid-mechanics modeling are (1) the assumption of scale separation in homogenization theory and (2) the use of a macroscopic plasticity material model that represents, in a mean sense, the multitude of inelastic processes occurring at the microscale. With the goal of quantifying the errors induced by these approximations on engineering quantities of interest, we perform a set of direct numerical simulations (DNS) in which polycrystalline microstructures are embedded throughout a macroscale structure. The largest simulations model over 50,000 grains. The microstructure is idealized using a randomly close-packed Voronoi tessellation in which each polyhedral Voronoi cellmore » represents a grain. An face centered cubic crystal-plasticity model is used to model the mechanical response of each grain. The overall grain structure is equiaxed, and each grain is randomly oriented with no overall texture. The detailed results from the DNS simulations are compared to results obtained from conventional macroscale simulations that use homogeneous isotropic plasticity models. The macroscale plasticity models are calibrated using a representative volume element of the idealized microstructure. Furthermore, we envision that DNS modeling will be used to gain new insights into the mechanics of material deformation and failure.« less

  5. Physical mechanisms of SiN{sub x} layer structuring with ultrafast lasers by direct and confined laser ablation

    SciTech Connect

    Rapp, S.; Heinrich, G.; Wollgarten, M.; Huber, H. P.; Schmidt, M.

    2015-03-14

    In the production process of silicon microelectronic devices and high efficiency silicon solar cells, local contact openings in thin dielectric layers are required. Instead of photolithography, these openings can be selectively structured with ultra-short laser pulses by confined laser ablation in a fast and efficient lift off production step. Thereby, the ultrafast laser pulse is transmitted by the dielectric layer and absorbed at the substrate surface leading to a selective layer removal in the nanosecond time domain. Thermal damage in the substrate due to absorption is an unwanted side effect. The aim of this work is to obtain a deeper understanding of the physical laser-material interaction with the goal of finding a damage-free ablation mechanism. For this, thin silicon nitride (SiN{sub x}) layers on planar silicon (Si) wafers are processed with infrared fs-laser pulses. Two ablation types can be distinguished: The known confined ablation at fluences below 300 mJ/cm{sup 2} and a combined partial confined and partial direct ablation at higher fluences. The partial direct ablation process is caused by nonlinear absorption in the SiN{sub x} layer in the center of the applied Gaussian shaped laser pulses. Pump-probe investigations of the central area show ultra-fast reflectivity changes typical for direct laser ablation. Transmission electron microscopy results demonstrate that the Si surface under the remaining SiN{sub x} island is not damaged by the laser ablation process. At optimized process parameters, the method of direct laser ablation could be a good candidate for damage-free selective structuring of dielectric layers on absorbing substrates.

  6. Molecular replacement then and now

    SciTech Connect

    Scapin, Giovanna

    2013-11-01

    A brief overview, with examples, of the evolution of molecular-replacement methods and models over the past few years is presented. The ‘phase problem’ in crystallography results from the inability to directly measure the phases of individual diffracted X-ray waves. While intensities are directly measured during data collection, phases must be obtained by other means. Several phasing methods are available (MIR, SAR, MAD, SAD and MR) and they all rely on the premise that phase information can be obtained if the positions of marker atoms in the unknown crystal structure are known. This paper is dedicated to the most popular phasing method, molecular replacement (MR), and represents a personal overview of the development, use and requirements of the methodology. The first description of noncrystallographic symmetry as a tool for structure determination was explained by Rossmann and Blow [Rossmann & Blow (1962 ▶), Acta Cryst.15, 24–31]. The term ‘molecular replacement’ was introduced as the name of a book in which the early papers were collected and briefly reviewed [Rossmann (1972 ▶), The Molecular Replacement Method. New York: Gordon & Breach]. Several programs have evolved from the original concept to allow faster and more sophisticated searches, including six-dimensional searches and brute-force approaches. While careful selection of the resolution range for the search and the quality of the data will greatly influence the outcome, the correct choice of the search model is probably still the main criterion to guarantee success in solving a structure using MR. Two of the main parameters used to define the ‘best’ search model are sequence identity (25% or more) and structural similarity. Another parameter that may often be undervalued is the quality of the probe: there is clearly a relationship between the quality and the correctness of the chosen probe and its usefulness as a search model. Efforts should be made by all structural biologists to

  7. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self‐funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty‐three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  8. Cadmium plating replacements

    NASA Technical Reports Server (NTRS)

    Nelson, Mary J.; Groshart, Earl C.

    1995-01-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  9. Sutureless aortic valve replacement

    PubMed Central

    Phan, Kevin

    2015-01-01

    The increasing incidence of aortic stenosis and greater co-morbidities and risk profiles of the contemporary patient population has driven the development of minimally invasive aortic valve surgery and percutaneous transcatheter aortic valve implantation (TAVI) techniques to reduce surgical trauma. Recent technological developments have led to an alternative minimally invasive option which avoids the placement and tying of sutures, known as “sutureless” or rapid deployment aortic valves. Potential advantages for sutureless aortic prostheses include reducing cross-clamp and cardiopulmonary bypass (CPB) duration, facilitating minimally invasive surgery and complex cardiac interventions, whilst maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates. However, given its recent developments, the majority of evidence regarding sutureless aortic valve replacement (SU-AVR) is limited to observational studies and there is a paucity of adequately-powered randomized studies. Recently, the International Valvular Surgery Study Group (IVSSG) has formulated to conduct the Sutureless Projects, set to be the largest international collaborative group to investigate this technology. This keynote lecture will overview the use, the potential advantages, the caveats, and current evidence of sutureless and rapid deployment aortic valve replacement (AVR). PMID:25870807

  10. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University's aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  11. Power Plant Replacement Study

    SciTech Connect

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  12. Total disc replacement.

    PubMed

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. PMID:24412045

  13. A threshold of mechanical strain intensity for the direct activation of osteoblast function exists in a murine maxilla loading model.

    PubMed

    Suzuki, Natsuki; Aoki, Kazuhiro; Marcián, Petr; Borák, Libor; Wakabayashi, Noriyuki

    2016-10-01

    The response to the mechanical loading of bone tissue has been extensively investigated; however, precisely how much strain intensity is necessary to promote bone formation remains unclear. Combination studies utilizing histomorphometric and numerical analyses were performed using the established murine maxilla loading model to clarify the threshold of mechanical strain needed to accelerate bone formation activity. For 7 days, 191 kPa loading stimulation for 30 min/day was applied to C57BL/6J mice. Two regions of interest, the AWAY region (away from the loading site) and the NEAR region (near the loading site), were determined. The inflammatory score increased in the NEAR region, but not in the AWAY region. A strain intensity map obtained from [Formula: see text] images was superimposed onto the images of the bone formation inhibitor, sclerostin-positive cell localization. The number of sclerostin-positive cells significantly decreased after mechanical loading of more than [Formula: see text] in the AWAY region, but not in the NEAR region. The mineral apposition rate, which shows the bone formation ability of osteoblasts, was accelerated at the site of surface strain intensity, namely around [Formula: see text], but not at the site of lower surface strain intensity, which was around [Formula: see text] in the AWAY region, thus suggesting the existence of a strain intensity threshold for promoting bone formation. Taken together, our data suggest that a threshold of mechanical strain intensity for the direct activation of osteoblast function and the reduction of sclerostin exists in a murine maxilla loading model in the non-inflammatory region.

  14. Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans

    PubMed Central

    Liedtke, Wolfgang; Tobin, David M.; Bargmann, Cornelia I.; Friedman, Jeffrey M.

    2003-01-01

    All animals detect osmotic and mechanical stimuli, but the molecular basis for these responses is incompletely understood. The vertebrate transient receptor potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been suggested to be an osmo/mechanosensory channel. To assess its function in vivo, we expressed TRPV4 in Caenorhabditis elegans sensory neurons and examined its ability to generate behavioral responses to sensory stimuli. C. elegans ASH neurons function as polymodal sensory neurons that generate a characteristic escape behavior in response to mechanical, osmotic, or olfactory stimuli. These behaviors require the TRPV channel OSM-9 because osm-9 mutants do not avoid nose touch, high osmolarity, or noxious odors. Expression of mammalian TRPV4 in ASH neurons of osm-9 worms restored avoidance responses to hypertonicity and nose touch, but not the response to odorant repellents. Mutations known to reduce TRPV4 channel activity also reduced its ability to direct nematode avoidance behavior. TRPV4 function in ASH required the endogenous C. elegans osmotic and nose touch avoidance genes ocr-2, odr-3, osm-10, and glr-1, indicating that TRPV4 is integrated into the normal ASH sensory apparatus. The osmotic and mechanical avoidance responses of TRPV4-expressing animals were different in their sensitivity and temperature dependence from the responses of wild-type animals, suggesting that the TRPV4 channel confers its characteristic properties on the transgenic animals' behavior. These results provide evidence that TRPV4 can function as a component of an osmotic/mechanical sensor in vivo. PMID:14581619

  15. Rear actomyosin contractility-driven directional cell migration in three-dimensional matrices: a mechano-chemical coupling mechanism

    PubMed Central

    Chi, Qingjia; Yin, Tieying; Gregersen, Hans; Deng, Xiaoyan; Fan, Yubo; Zhao, Jingbo; Liao, Donghua; Wang, Guixue

    2014-01-01

    Cell migration is of vital importance in many biological processes, including organismal development, immune response and development of vascular diseases. For instance, migration of vascular smooth muscle cells from the media to intima is an essential part of the development of atherosclerosis and restenosis after stent deployment. While it is well characterized that cells use actin polymerization at the leading edge to propel themselves to move on two-dimensional substrates, the migration modes of cells in three-dimensional matrices relevant to in vivo environments remain unclear. Intracellular tension, which is created by myosin II activity, fulfils a vital role in regulating cell migration. We note that there is compelling evidence from theoretical and experimental work that myosin II accumulates at the cell rear, either isoform-dependent or -independent, leading to three-dimensional migration modes driven by posterior myosin II tension. The scenario is not limited to amoeboid migration, and it is also seen in mesenchymal migration in which a two-dimensional-like migration mode based on front protrusions is often expected, suggesting that there may exist universal underlying mechanisms. In this review, we aim to shed some light on how anisotropic myosin II localization induces cell motility in three-dimensional environments from a biomechanical view. We demonstrate an interesting mechanism where an interplay between mechanical myosin II recruitment and biochemical myosin II activation triggers directional migration in three-dimensional matrices. In the case of amoeboid three-dimensional migration, myosin II first accumulates at the cell rear to induce a slight polarization displayed as a uropod-like structure under the action of a tension-dependent mechanism. Subsequent biochemical signalling pathways initiate actomyosin contractility, producing traction forces on the adhesion system or creating prominent motile forces through blebbing activity, to drive cells

  16. ChIP-seq in studying epigenetic mechanisms of disease and promoting precision medicine: progresses and future directions.

    PubMed

    Yan, Huihuang; Tian, Shulan; Slager, Susan L; Sun, Zhifu

    2016-09-01

    Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used for mapping histone modifications, histone proteins, chromatin regulators, transcription factors and other DNA-binding proteins. It has played a significant role in our understanding of disease mechanisms and in exploring epigenetic changes for potential clinical applications. However, the conventional protocol requires large amounts of starting material and does not quantify the actual occupancy, limiting its applications in clinical settings. Herein we summarize the latest progresses in utilizing ChIP-seq to link epigenetic alterations to disease initiation and progression, and the implications in precision medicine. We provide an update on the newly developed ChIP-seq protocols, especially those suitable for scare clinical samples. Technical and analytical challenges are outlined together with recommendations for improvement. Finally, future directions in expediting ChIP-seq use in clinic are discussed.

  17. Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase.

    PubMed

    Roland, Bartholomew P; Graham, Todd R

    2016-08-01

    Phospholipid flippases in the type IV P-type ATPase (P4-ATPases) family establish membrane asymmetry and play critical roles in vesicular transport, cell polarity, signal transduction, and neurologic development. All characterized P4-ATPases flip glycerophospholipids across the bilayer to the cytosolic leaflet of the membrane, but how these enzymes distinguish glycerophospholipids from sphingolipids is not known. We used a directed evolution approach to examine the molecular mechanisms through which P4-ATPases discriminate substrate backbone. A mutagenesis screen in the yeast Saccharomyces cerevisiae has identified several gain-of-function mutations in the P4-ATPase Dnf1 that facilitate the transport of a novel lipid substrate, sphingomyelin. We found that a highly conserved asparagine (N220) in the first transmembrane segment is a key enforcer of glycerophospholipid selection, and specific substitutions at this site allow transport of sphingomyelin. PMID:27432949

  18. Do financial incentives trump clinical guidance? Hip Replacement in England and Scotland.

    PubMed

    Papanicolas, Irene; McGuire, Alistair

    2015-12-01

    Following devolution in 1999 England and Scotland's National Health Services diverged, resulting in major differences in hospital payment. England introduced a case payment mechanism from 2003/4, while Scotland continued to pay through global budgets. We investigate the impact this change had on activity for Hip Replacement. We examine the financial reimbursement attached to uncemented Hip Replacement in England, which has been more generous than for its cemented counterpart, although clinical guidance from the National Institute for Clinical Excellence recommends the later. In Scotland this financial differential does not exist. We use a difference-in-difference estimator, using Scotland as a control, to test whether the change in reimbursement across the two countries had an influence on treatment. Our results indicate that financial incentives are directly linked to the faster uptake of the more expensive, uncemented Hip Replacement in England, which ran against the clinical guidance.

  19. Direct measurement of human ankle stiffness during quiet standing: the intrinsic mechanical stiffness is insufficient for stability

    PubMed Central

    Loram, Ian D; Lakie, Martin

    2002-01-01

    During quiet standing the human ‘inverted pendulum’ sways irregularly. In previous work where subjects balanced a real inverted pendulum, we investigated what contribution the intrinsic mechanical ankle stiffness makes to achieve stability. Using the results of a plausible model, we suggested that intrinsic ankle stiffness is inadequate for providing stability. Here, using a piezo-electric translator we applied small, unobtrusive mechanical perturbations to the foot while the subject was standing freely. These short duration perturbations had a similar size and velocity to movements which occur naturally during quiet standing, and they produced no evidence of any stretch reflex response in soleus, or gastrocnemius. Direct measurement confirms our earlier conclusion; intrinsic ankle stiffness is not quite sufficient to stabilise the body or pendulum. On average the directly determined intrinsic stiffness is 91 ± 23 % (mean ± s.d.) of that necessary to provide minimal stabilisation. The stiffness was substantially constant, increasing only slightly with ankle torque. This stiffness cannot be neurally regulated in quiet standing. Thus we attribute this stiffness to the foot, Achilles’ tendon and aponeurosis rather than the activated calf muscle fibres. Our measurements suggest that the triceps surae muscles maintain balance via a spring-like element which is itself too compliant to guarantee stability. The implication is that the brain cannot set ankle stiffness and then ignore the control task because additional modulation of torque is required to maintain balance. We suggest that the triceps surae muscles maintain balance by predictively controlling the proximal offset of the spring-like element in a ballistic-like manner. PMID:12482906

  20. Patient-directed music therapy reduces anxiety and sedation exposure in mechanically-ventilated patients: a research critique.

    PubMed

    Gullick, Janice G; Kwan, Xiu Xian

    2015-05-01

    This research appraisal, guided by the CASP Randomised Controlled Trial Checklist, critiques a randomised, controlled trial of patient-directed music therapy compared to either noise-cancelling headphones or usual care. This study recruited 373 alert, mechanically-ventilated patients across five intensive care units in the United States. The Music Assessment Tool, administered by a music therapist, facilitated music selection by participants in the intervention group. Anxiety was measured using the VAS-A scale. Sedation exposure was measured by both sedation frequency and by sedation intensity using a daily sedation intensity score. Context for the data was supported by an environmental scan form recording unit activity and by written comments from nurses about the patient's responses to the protocol. Patient-directed music therapy allowed a significant reduction in sedation frequency compared to noise-cancelling headphones and usual care participants. Patient-directed music therapy led to significantly lower anxiety and sedation intensity compared to usual care, but not compared to noise-cancelling headphones. This is a robust study with clear aims and a detailed description of research methods and follow-up. While no participants were lost to follow-up, not all were included in the analysis: 37% did not have the minimum of two anxiety assessments for comparison and 23% were not included in sedation analysis. While some participants utilised the intervention or active control for many hours-per-day, half the music therapy participants listened for 12min or less per day and half of the noise-cancelling headphone participants did not appear to use them. While the results suggest that patient-directed music therapy and noise-cancelling headphones may be useful and cost-effective interventions that lead to an overall improvement in anxiety and sedation exposure, these may appeal to a subset of ICU patients. The self-directed use of music therapy and noise

  1. Antenna grout replacement system

    NASA Technical Reports Server (NTRS)

    Mcclung, C. E. (Inventor)

    1983-01-01

    An epoxy grout suitable for use in mounting and positioning bearing runner plates used in hydrostatic bearing assemblies for rotatably mounting large radio telescope structures to stationary support pedestals is described. The epoxy grout may be used in original mountings or may be used as part of a replacement system for repairing cavities in existing grout resulting from grout deterioration. The epoxy grout has a relatively short work life and cure time even in the presence of hydraulic oil. The epoxy grout cures without shrinking or sagging to form a grout which is sufficiently strong and durable to provide a grout especially well suited for use under the high pressure loading and close tolerance requirements of large hydrostatic bearing assemblies.

  2. Seeing is believing: Direct imaging of charge flow along pili proteins reveals new mechanism for bacterial electron transfer

    NASA Astrophysics Data System (ADS)

    Malvankar, Nikhil; Yalcin, Sibel Ebru; Adhikari, Ramesh; Tuominen, Mark; Lovley, Derek

    2015-03-01

    Visualization of charge flow on the nanoscale in proteins is crucial for a fundamental understanding of several life processes. Here, we report direct visualization of charge propagation along native pili of Geobacter sulfurreducens at nanometer resolution using electrostatic force microscopy. Surprisingly, charges injected at a single point into individual, untreated pili, still attached to cells, propagate over the entire filament. The charges propagate despite a lack of cytochromes on the pili, in contrast to the dominant biochemical model that proteins are electronically insulating and must incorporate redox-active cofactors in order to achieve electron transport functionality. The mobile charge density in pili is comparable to synthetic organic conductors, increasing with proton doping, and with temperature-dependence consistent with previously discovered metallic-like transport mechanism. Conductive pili enable syntrophic bacteria to share energy by directly exchanging electrons among each other. Measurements along individual pilus using nanoelectrodes showed ohmic behavior strongly dependent on the amino acid composition of pili. Electron transfer rate measurement revealed that the pili conductivity is the decisive factor in controlling the bacterial respiration rate. Funded by Office of Naval Research, DOE Genomic Sciences, NSF-NSEC CHM (CMMI-1025020) and Burroughs Wellcome Fund.

  3. Comparing the similarity of responses received from studies in Amazon's Mechanical Turk to studies conducted online and with direct recruitment.

    PubMed

    Bartneck, Christoph; Duenser, Andreas; Moltchanova, Elena; Zawieska, Karolina

    2015-01-01

    Computer and internet based questionnaires have become a standard tool in Human-Computer Interaction research and other related fields, such as psychology and sociology. Amazon's Mechanical Turk (AMT) service is a new method of recruiting participants and conducting certain types of experiments. This study compares whether participants recruited through AMT give different responses than participants recruited through an online forum or recruited directly on a university campus. Moreover, we compare whether a study conducted within AMT results in different responses compared to a study for which participants are recruited through AMT but which is conducted using an external online questionnaire service. The results of this study show that there is a statistical difference between results obtained from participants recruited through AMT compared to the results from the participant recruited on campus or through online forums. We do, however, argue that this difference is so small that it has no practical consequence. There was no significant difference between running the study within AMT compared to running it with an online questionnaire service. There was no significant difference between results obtained directly from within AMT compared to results obtained in the campus and online forum condition. This may suggest that AMT is a viable and economical option for recruiting participants and for conducting studies as setting up and running a study with AMT generally requires less effort and time compared to other frequently used methods. We discuss our findings as well as limitations of using AMT for empirical studies.

  4. An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells

    PubMed Central

    Kang, Jinjoo; Yoo, Jaehyuk; Lee, Sunju; Tang, Wanli; Aguilar, Berenice; Ramu, Swapnika; Choi, Inho; Otu, Hasan H.; Shin, Jay W.; Dotto, G. Paolo; Koh, Chester J.; Detmar, Michael

    2010-01-01

    Arteriovenous-lymphatic endothelial cell fates are specified by the master regulators, namely, Notch, COUP-TFII, and Prox1. Whereas Notch is expressed in the arteries and COUP-TFII in the veins, the lymphatics express all 3 cell fate regulators. Previous studies show that lymphatic endothelial cell (LEC) fate is highly plastic and reversible, raising a new concept that all 3 endothelial cell fates may coreside in LECs and a subtle alteration can result in a reprogramming of LEC fate. We provide a molecular basis verifying this concept by identifying a cross-control mechanism among these cell fate regulators. We found that Notch signal down-regulates Prox1 and COUP-TFII through Hey1 and Hey2 and that activated Notch receptor suppresses the lymphatic phenotypes and induces the arterial cell fate. On the contrary, Prox1 and COUP-TFII attenuate vascular endothelial growth factor signaling, known to induce Notch, by repressing vascular endothelial growth factor receptor-2 and neuropilin-1. We show that previously reported podoplanin-based LEC heterogeneity is associated with differential expression of Notch1 in human cutaneous lymphatics. We propose that the expression of the 3 cell fate regulators is controlled by an exquisite feedback mechanism working in LECs and that LEC fate is a consequence of the Prox1-directed lymphatic equilibrium among the cell fate regulators. PMID:20351309

  5. Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC

    PubMed Central

    Chen, Qiang; Kinde, Monica N.; Arjunan, Palaniappa; Wells, Marta M.; Cohen, Aina E.; Xu, Yan; Tang, Pei

    2015-01-01

    Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6′) and A244(13′). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6′ or 13′ support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs. PMID:26346220

  6. Açaí (Euterpe oleracea Mart.) Modulates Oxidative Stress Resistance in Caenorhabditis elegans by Direct and Indirect Mechanisms

    PubMed Central

    Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J.; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; de Paula Oliveira, Riva

    2014-01-01

    Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. PMID:24594796

  7. Mode- and Direction-Dependent Mechanical Energy Dissipation in Single-Crystal Resonators due to Anharmonic Phonon-Phonon Scattering

    NASA Astrophysics Data System (ADS)

    Iyer, Srikanth S.; Candler, Robert N.

    2016-03-01

    In this work, we determine the intrinsic mechanical energy dissipation limit for single-crystal resonators due to anharmonic phonon-phonon scattering in the Akhiezer (Ω τ ≪1 ) regime. The energy loss is derived using perturbation theory and the linearized Boltzmann transport equation for phonons, and includes the direction- and polarization-dependent mode-Grüneisen parameters in order to capture the strain-induced anharmonicity among phonon branches. This expression reveals the fundamental differences among the internal friction limits for different types of bulk-mode elastic waves. For cubic crystals, 2D-extensional modes have increased dissipation compared to width-extensional modes because the biaxial deformation opposes the natural Poisson contraction of the solid. Additionally, we show that shear-mode vibrations, which preserve volume, have significantly reduced energy loss because dissipative phonon-phonon scattering is restricted to pure-shear phonon branches, indicating that Lamé- or wineglass-mode resonators will have the highest upper limit on mechanical efficiency. Finally, we employ key simplifications to evaluate the quality factor limits for common mode shapes in single-crystal silicon devices, explicitly including the correct effective elastic storage moduli for different vibration modes and crystal orientations. Our expression satisfies the pressing need for a reliable analytical model that can predict the phonon-phonon dissipation limits for modern resonant microelectromechanical systems, where precise manufacturing techniques and accurate finite-element methods can be used to select particular vibrational mode shapes and crystal orientations.

  8. Development of a direct exposure system for studying the mechanisms of central neurotoxicity caused by volatile organic compounds

    PubMed Central

    KANEMITSU, Masanari; FUETA, Yukiko; ISHIDAO, Toru; AOU, Shuji; HORI, Hajime

    2015-01-01

    Many volatile organic compounds (VOCs) used in work places are neurotoxic. However, it has been difficult to study the cellular mechanisms induced by a direct exposure to neurons because of their high volatility. The objective of this study was to establish a stable system for exposing brain slices to VOCs. With a conventional recording system for brain slices, it is not possible to keep a constant bath concentration of relatively highly volatile solvents, e.g. 1-bromopropane (1-BP). Here we report a new exposure system for VOCs that we developed in which a high concentration of oxygen is dissolved to a perfused medium applying a gas-liquid equilibrium, and in which the tubing is made of Teflon, non adsorptive material. Using our system, the bath concentration of the perfused 1-BP remained stable for at least 2 h in the slice chamber. Both 6.4 and 2.2 mM of 1-BP did not change the paired-pulse response, but fully suppressed long-term potentiation in the dentate gyrus (DG) of hippocampal slices obtained from rats, suggesting that 1-BP decreases synaptic plasticity in the DG at the concentrations tested. Our new system can be applicable for investigating the underlying mechanisms of the neurotoxicity of VOCs at the cellular level. PMID:26320726

  9. Nashville Gas treads carefully to replace pipe

    SciTech Connect

    1997-06-01

    The private gas utility, Nashville Gas, was responsible for replacing damaged or inadequate 2- and 4-inch steel gas lines beneath Music City, USA. The line replacements required either size for size or upsizing. The first choice was directional drilling, which was quickly determined to be unpractical because of rocky soil conditions. The second option was open trenching. Undoubtedly, trenching would mean having to contend with angry residents and tourists, since gas lines ran beneath yards, mature trees, sidewalks, roadways, and railways. In addition to the negative social factors, trenching would require additional funds for substantial landscaping and pavement replacement. It at all possible, a no-dig alternative was desired. Nashville Gas found Grundomat piercing tools which create a bore, then pushes pipe back through it. These same tools can simultaneously pull in pipe. These tools were customized for the Nashville project.

  10. Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Ferro, Carlo; Rossi, Umberto G. Bovio, Giulio; Dahamane, M'Hamed; Centanaro, Monica

    2007-09-15

    A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT.

  11. Proposal of an Amide-Directed Carbocupration Mechanism for Copper-Catalyzed meta-Selective C—H Arylation of Acetanilides by Diaryliodonium Salts

    NASA Astrophysics Data System (ADS)

    Zhang, Song-lin; Ding, Yu-qiang

    2011-12-01

    We examined the puzzling mechanism for Cu-catalyzed meta-C—H arylation reaction of anilides by diaryliodonium salts through systematic theoretical analysis. The previously proposed anti-oxy-cupration mechanism featuring anti-1,2- or anti-1,4-addition of cuprate and oxygen to the phenyl ring generating a meta-cuprated intermediate was excluded due to the large activation barriers. Alternatively, a new amide-directed carbocupration mechanism was proposed which involves a critical rate- and regio-determining step of amide-directed addition of the Cu(III)-aryl bond across the phenyl C2=C3 double bond to form an ortho-cuprated, meta-arylated intermediate. This mechanism is kinetically the most favored among several possible mechanisms such as ortho- or para-cupration/migration mechanism, direct meta C—H bond cleavage mediated by Cu(III) or Cu(I), and Cu(III)-catalyzed ortho-directed C—H bond activation mechanism. Furthermore, the predicted regioselectivity based on this mechanism has been shown to favor the meta-arylation that is consistent with the experimental observations.

  12. Mechanisms of direct inhibition of the respiratory sulfate-reduction pathway by (per)chlorate and nitrate

    PubMed Central

    Carlson, Hans K; Kuehl, Jennifer V; Hazra, Amrita B; Justice, Nicholas B; Stoeva, Magdalena K; Sczesnak, Andrew; Mullan, Mark R; Iavarone, Anthony T; Engelbrektson, Anna; Price, Morgan N; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

    2015-01-01

    We investigated perchlorate (ClO4−) and chlorate (ClO3−) (collectively (per)chlorate) in comparison with nitrate as potential inhibitors of sulfide (H2S) production by mesophilic sulfate-reducing microorganisms (SRMs). We demonstrate the specificity and potency of (per)chlorate as direct SRM inhibitors in both pure cultures and undefined sulfidogenic communities. We demonstrate that (per)chlorate and nitrate are antagonistic inhibitors and resistance is cross-inducible implying that these compounds share at least one common mechanism of resistance. Using tagged-transposon pools we identified genes responsible for sensitivity and resistance in Desulfovibrio alaskensis G20. We found that mutants in Dde_2702 (Rex), a repressor of the central sulfate-reduction pathway were resistant to both (per)chlorate and nitrate. In general, Rex derepresses its regulon in response to increasing intracellular NADH:NAD+ ratios. In cells in which respiratory sulfate reduction is inhibited, NADH:NAD+ ratios should increase leading to derepression of the sulfate-reduction pathway. In support of this, in (per)chlorate or nitrate-stressed wild-type G20 we observed higher NADH:NAD+ ratios, increased transcripts and increased peptide counts for genes in the core Rex regulon. We conclude that one mode of (per)chlorate and nitrate toxicity is as direct inhibitors of the central sulfate-reduction pathway. Our results demonstrate that (per)chlorate are more potent inhibitors than nitrate in both pure cultures and communities, implying that they represent an attractive alternative for controlling sulfidogenesis in industrial ecosystems. Of these, perchlorate offers better application logistics because of its inhibitory potency, solubility, relative chemical stability, low affinity for mineral cations and high mobility in environmental systems. PMID:25405978

  13. A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

    PubMed Central

    Bouzigues, Cedric; Holcman, David; Dahan, Maxime

    2010-01-01

    Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals. PMID:20179770

  14. Reaction Mechanism for Direct Propylene Epoxidation by Alumina-Supported Silver Aggregates. The Role of the Particle / Support Interface

    SciTech Connect

    Cheng, Lei; Yin, Chunrong; Mehmood, Faisal; Liu, Bin; Greeley, Jeffrey P.; Lee, Sungsik; Lee, Byeongdu; Seifert, Soenke; Winans, R. E.; Teschner, D.; Schlogl, Robert; Vajda, S.; Curtiss, Larry A.

    2013-11-21

    Sub-nanometer Ag aggregates on alumina supports have been found to be active toward direct propylene epoxidation to propylene oxide by molecular oxygen at low temperatures, with a negligible amount of carbon dioxide formation (Science 328, p. 224, 2010). In this work, we computationally and experimentally investigate the origin of the high reactivity of the sub-nanometer Ag aggregates. Computationally, we study O2 dissociation and propylene epoxidation on unsupported Ag19 and Ag20 clusters, as well as alumina-supported Ag19. The O2 dissociation and propylene epoxidation apparent barriers at the interface between the Ag aggregate and the alumina support are calculated to be 0.2 and 0.2~0.4 eV, respectively. These barriers are somewhat lower than those on sites away from the interface. The mechanism at the interface is similar to what was previously found for the silver trimer on alumina and can account for the high activity observed for the direct oxidation of propylene on the Ag aggregates. The barriers for oxygen dissociation on these model systems both at the interface and on the surfaces are small compared to crystalline surfaces, indicating that availability of oxygen will not be a rate limiting step for the aggregates, as in the case of the crystalline surfaces. Experimentally, we investigate Ultrananocrystalline Diamond (UNCD)-supported silver aggregates under reactive conditions of propylene partial oxidation. The UNCD-supported Ag clusters are found to be not measurably active toward propylene oxidation, in contrast to the alumina supported Ag clusters. This suggests that the lack of metal-oxide interfacial sites of the Ag-UNCD catalyst, limits the epoxidation catalytic activity. This combined computational and experimental study shows the importance of the metal-oxide interface as well as the non-crystalline nature of the alumina-supported sub-nanometer Ag aggregate catalysts for propylene epoxidation.

  15. World Health Organization's Innovative Direct Disbursement Mechanism for Payment of Grassroots Immunization Personnel and Operations in Nigeria: 2004–2015

    PubMed Central

    Yehualashet, Yared G.; Wadda, Alieu; Agblewonu, Koffi B.; Zhema, Theophilus; Ibrahim, Al-asi A.; Corr, Alhagie; Linkins, Jennifer; Mkanda, Pascal; Vaz, Rui G.; Nsubuga, Peter; Ashogbon, Daniel

    2016-01-01

    Background. Following the 1988 World Health Assembly resolution to eradicate polio, the government of Nigeria, with support from partners, has been implementing several rounds of supplementary immunization activities (SIAs) each year. In addition to the technical requirements, the success of the polio eradication initiative depends on timely provision of adequate financial resources. Disbursement of funds for SIAs and payment of allowances to numerous vaccination personnel at the grassroots level are enormous operational challenges in a country the size of Nigeria. Upon donors' request for a transparent and effective payment mechanism, the World Health Organization (WHO), in consultation with national counterparts, created the innovative direct disbursement mechanism (DDM) in 2004. The objective of the DDM was to timely deploy operational funds at the field level and directly pay vaccination personnel allowances at the grassroots level. Methods. A detailed operational guideline for funds disbursement was developed in close consultation with central and field stakeholders. Multiyear financial resource requirements and operational budgets for every campaign were produced by an interagency-coordinated finance subcommittee. The WHO engaged a bank and an accounting firm as DDM partners to support disbursement of and accounting for the SIA funds, respectively. The 37 WHO field offices were equipped with electronic financial systems to support the DDM process, and temporary payment sites were set up to facilitate payment to vaccination personnel at the grassroots level. Coordination meetings among DDM partners were held regularly to reconcile financial records and address operational challenges. Results. Between 2004 and 2014, DDM supported 99 polio and nonpolio vaccination campaigns, disbursing more than $370 million to about 16 million beneficiaries across 280 temporary payment sites. To mitigate security risks and reduce operational costs, the WHO and DDM

  16. Effect of pore architecture and stacking direction on mechanical properties of solid freeform fabrication-based scaffold for bone tissue engineering.

    PubMed

    Lee, Jung-Seob; Cha, Hwang Do; Shim, Jin-Hyung; Jung, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

    2012-07-01

    Fabrication of a three-dimensional (3D) scaffold with increased mechanical strength may be an essential requirement for more advanced bone tissue engineering scaffolds. Various material- and chemical-based approaches have been explored to enhance the mechanical properties of engineered bone tissue scaffolds. In this study, the effects of pore architecture and stacking direction on the mechanical and cell proliferation properties of a scaffold were investigated. The 3D scaffold was prepared using solid freeform fabrication technology with a multihead deposition system. Various types of scaffolds with different pore architectures (lattice, stagger, and triangle types) and stacking directions (horizontal and vertical directions) were fabricated with a blend of polycaprolactone and poly lactic-co-glycolic acid. In compression tests, the triangle-type scaffold was the strongest among the experimental groups. Stacking direction affected the mechanical properties of scaffolds. An in vitro cell counting kit-8 assay showed no significant differences in optical density depending on the different pore architectures and stacking directions. In conclusion, mechanical properties of scaffolds can be enhanced by controlling pore architecture and stacking direction.

  17. Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.

    PubMed

    Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R

    2012-01-01

    Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.

  18. Interconnection of thermal parameters, microstructure and mechanical properties in directionally solidified Sn–Sb lead-free solder alloys

    SciTech Connect

    Dias, Marcelino; Costa, Thiago; Rocha, Otávio; Spinelli, José E.; Cheung, Noé; Garcia, Amauri

    2015-08-15

    Considerable effort is being made to develop lead-free solders for assembling in environmental-conscious electronics, due to the inherent toxicity of Pb. The search for substitute alloys of Pb–Sn solders has increased in order to comply with different soldering purposes. The solder must not only meet the expected levels of electrical performance but may also have appropriate mechanical strength, with the absence of cracks in the solder joints. The Sn–Sb alloy system has a range of compositions that can be potentially included in the class of high temperature solders. This study aims to establish interrelations of solidification thermal parameters, microstructure and mechanical properties of Sn–Sb alloys (2 wt.%Sb and 5.5 wt.%Sb) samples, which were directionally solidified under cooling rates similar to those of reflow procedures in industrial practice. A complete high-cooling rate cellular growth is shown to be associated with the Sn–2.0 wt.%Sb alloy and a reverse dendrite-to-cell transition is observed for the Sn–5.5 wt.%Sb alloy. Strength and ductility of the Sn–2.0 wt.%Sb alloy are shown not to be affected by the cellular spacing. On the other hand, a considerable variation in these properties is associated with the cellular region of the Sn–5.5 wt.%Sb alloy casting. - Graphical abstract: Display Omitted - Highlights: • The microstructure of the Sn–2 wt.%Sb alloy is characterized by high-cooling rates cells. • Reverse dendrite > cell transition occurs for Sn–5.5 wt.%Sb alloy: cells prevail for cooling rates > 1.2 K/s. • Sn–5.5 wt.%Sb alloy: the dendritic region occurs for cooling rates < 0.9 K/s. • Sn–5.5 wt.%Sb alloy: tensile properties are improved with decreasing cellular spacing.

  19. Kinetics and Mechanisms of Thiol–Disulfide Exchange Covering Direct Substitution and Thiol Oxidation-Mediated Pathways

    PubMed Central

    2013-01-01

    Abstract Significance: Disulfides are important building blocks in the secondary and tertiary structures of proteins, serving as inter- and intra-subunit cross links. Disulfides are also the major products of thiol oxidation, a process that has primary roles in defense mechanisms against oxidative stress and in redox regulation of cell signaling. Although disulfides are relatively stable, their reduction, isomerisation, and interconversion as well as their production reactions are catalyzed by delicate enzyme machineries, providing a dynamic system in biology. Redox homeostasis, a thermodynamic parameter that determines which reactions can occur in cellular compartments, is also balanced by the thiol–disulfide pool. However, it is the kinetic properties of the reactions that best represent cell dynamics, because the partitioning of the possible reactions depends on kinetic parameters. Critical Issues: This review is focused on the kinetics and mechanisms of thiol–disulfide substitution and redox reactions. It summarizes the challenges and advances that are associated with kinetic investigations in small molecular and enzymatic systems from a rigorous chemical perspective using biological examples. The most important parameters that influence reaction rates are discussed in detail. Recent Advances and Future Directions: Kinetic studies of proteins are more challenging than small molecules, and quite often investigators are forced to sacrifice the rigor of the experimental approach to obtain the important kinetic and mechanistic information. However, recent technological advances allow a more comprehensive analysis of enzymatic systems via using the systematic kinetics apparatus that was developed for small molecule reactions, which is expected to provide further insight into the cell's machinery. Antioxid. Redox Signal. 18, 1623–1641. PMID:23075118

  20. Direct measures of mechanical energy for knife mill size reduction of switchgrass, wheat straw, and corn stover.

    PubMed

    Bitra, Venkata S P; Womac, Alvin R; Igathinathane, C; Miu, Petre I; Yang, Yuechuan T; Smith, David R; Chevanan, Nehru; Sokhansanj, Shahab

    2009-12-01

    Lengthy straw/stalk of biomass may not be directly fed into grinders such as hammer mills and disc refiners. Hence, biomass needs to be preprocessed using coarse grinders like a knife mill to allow for efficient feeding in refiner mills without bridging and choking. Size reduction mechanical energy was directly measured for switchgrass (Panicum virgatum L.), wheat straw (Triticum aestivum L.), and corn stover (Zea mays L.) in an instrumented knife mill. Direct power inputs were determined for different knife mill screen openings from 12.7 to 50.8 mm, rotor speeds between 250 and 500 rpm, and mass feed rates from 1 to 11 kg/min. Overall accuracy of power measurement was calculated to be +/-0.003 kW. Total specific energy (kWh/Mg) was defined as size reduction energy to operate mill with biomass. Effective specific energy was defined as the energy that can be assumed to reach the biomass. The difference is parasitic or no-load energy of mill. Total specific energy for switchgrass, wheat straw, and corn stover chopping increased with knife mill speed, whereas, effective specific energy decreased marginally for switchgrass and increased for wheat straw and corn stover. Total and effective specific energy decreased with an increase in screen size for all the crops studied. Total specific energy decreased with increase in mass feed rate, but effective specific energy increased for switchgrass and wheat straw, and decreased for corn stover at increased feed rate. For knife mill screen size of 25.4 mm and optimum speed of 250 rpm, optimum feed rates were 7.6, 5.8, and 4.5 kg/min for switchgrass, wheat straw, and corn stover, respectively, and the corresponding total specific energies were 7.57, 10.53, and 8.87 kWh/Mg and effective specific energies were 1.27, 1.50, and 0.24 kWh/Mg for switchgrass, wheat straw, and corn stover, respectively. Energy utilization ratios were calculated as 16.8%, 14.3%, and 2.8% for switchgrass, wheat straw, and corn stover, respectively. These

  1. [Octreotide acetate for persistent cylothorax after descending aorta replacement].

    PubMed

    Naganuma, Hirokuni; Kawahito, Koji; Matsumura, Yoko; Nakamura, Ken; Haijima, Norimasa

    2010-12-01

    Cylothorax is one of a hazardous complication after thoracic aorta replacement. In this paper, we report effectiveness of octreotide acetate for postoperative persistent cylothorax. A 59-year-old female was referred to our hospital for chest pain. Previously she underwent arch reconstruction following aortic root replacement due to aortic dissection. Computed tomography (CT) revealed acute dissection on dissected descending aorta. Urgent descending aorta replacement was performed. After surgery, massive chylothoracic pleural fluid was drainaged. Although conventional medical treatment was not effective, drainage of chylothoracic pleural fluid significantly decreased after administration of octreotide acetate. Although mechanism has not been fully investigated, octreotide acetate was effective for persistent cylothorax after descending aorta replacement.

  2. A preliminary mechanical property and stress corrosion evaluation of VIM-VAR work strengthened and direct aged Inconel 718 bar material

    NASA Technical Reports Server (NTRS)

    Montano, J. W.

    1987-01-01

    This report presents a preliminary mechanical property and stress corrosion evaluation of double melted (vacuum induction melted (VIM), and vacuum arc remelted (VAR)), solution treated, work strengthened and direct aged Inconel 718 alloy bar (5.50 in. (13.97 cm) diameter). Two sets of tensile specimens, one direct single aged and the other direct double aged, were tested at ambient temperature in both the longitudinal and transverse directions. Longitudinal tensile and yield strengths in excess of 200 ksi (1378.96 MPa) and 168 ksi (1158.33 MPa), respectively, were realized at ambient temperature, for the direct double aged specimen. No failures occurred in the single or double edged longitudinal and transverse tensile specimens stressed to 75 and 100 percent of their respective yield strengths and exposed to a salt fog environment for 180 days. Tensile tests performed after the stress corrosion test showed no mechanical property degradation.

  3. The chemical mechanism of the limonene ozonolysis reaction in the SOA formation: A quantum chemistry and direct dynamic study

    NASA Astrophysics Data System (ADS)

    Sun, Tingli; Wang, Yudong; Zhang, Chenxi; Sun, Xiaomin; Wang, Wenxing

    2011-03-01

    The ozonolysis of limonene is one of the most important processes for secondary organic aerosol formation and a detailed understanding of the atmospheric chemistry of d-limonene is highly urgent. In this paper, the reaction of d-limonene with O 3 has been studied using high level molecular orbital theory. A detailed description of the possible ozonolysis mechanism in the presence of H 2O or NO is provided. The main products obtained are keto-limonene, limononic acid and 7OH-lim, which are low vapor pressure compounds. On the basis of the quantum chemical information, the direct dynamic calculation is performed and the rate constants are calculated over a temperature range of 200˜800 K using the transition state theory and canonical varitional transition state theory with small-curvature tunneling effect. The four-parameter formula of rate constants with the temperature is fitted and the lifetimes of the reaction species in the troposphere are estimated according to the rate constants, which can provide helpful information to the model simulation study.

  4. Oral cancer: reviewing the present understanding of its molecular mechanism and exploring the future directions for its effective management.

    PubMed

    Nagpal, Jatin K; Das, Bibhu R

    2003-04-01

    The present review aims to analyze the information available regarding the molecular mechanisms of Oral Carcinogenesis and explore the future directions where the field of Cancer Biology is venturing. Oncologists have excellently followed the proverb "Necessity is the mother of Invention". The desire to be more precise and comprehensive in their studies has led to the invention of some of the most innovative techniques like laser capture microdissection, comparative genomic hybridization, microarrays, and protein chips etc. Various Biotech companies and Cancer Institutes are on a hunt for anti-cancer drugs and molecular markers for cancers. These revolutionary approaches and the new breed of Oncologists have made the field very exciting and have generated the hope that finally the war against cancer would be won. In the end it is urged that the lead taken in other cancers like colon, breast, leukemia will be emulated in oral cancer. This is expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of pre-neoplastic lesions, as well as novel targets for its pharmacological intervention. PMID:12618193

  5. Temperature-dependent phase-specific deformation mechanisms in a directionally solidified NiAl-Cr(Mo) lamellar composite

    SciTech Connect

    Yu, Dunji; An, Ke; Chen, Xu; Bei, Hongbin

    2015-10-09

    Phase-specific thermal expansion and mechanical deformation behaviors of a directionally solidified NiAl–Cr(Mo) lamellar in situ composite were investigated by using real-time in situ neutron diffraction during compression at elevated temperatures up to 800 °C. Tensile and compressive thermal residual stresses were found to exist in the NiAl phase and Crss (solid solution) phase, respectively. Then, based on the evolution of lattice spacings and phase stresses, the phase-specific deformation behavior was analyzed qualitatively and quantitatively. Moreover, estimates of phase stresses were derived by Hooke's law on the basis of a simple method for the determination of stress-free lattice spacing in in situ composites. During compressive loading, the NiAl phase yields earlier than the Crss phase. The Crss phase carries much higher stress than the NiAl phase, and displays consistent strain hardening at all temperatures. The NiAl phase exhibits strain hardening at relatively low temperatures and softening at high temperatures. During unloading, the NiAl phase yields in tension whereas the Crss phase unloads elastically. Additionally, post-test microstructural observations show phase-through cracks at room temperature, micro cracks along phase interfaces at 600 °C and intact lamellae kinks at 800 °C, which is due to the increasing deformability of both phases as temperature rises.

  6. Temperature-dependent phase-specific deformation mechanisms in a directionally solidified NiAl-Cr(Mo) lamellar composite

    DOE PAGESBeta

    Yu, Dunji; An, Ke; Chen, Xu; Bei, Hongbin

    2015-10-09

    Phase-specific thermal expansion and mechanical deformation behaviors of a directionally solidified NiAl–Cr(Mo) lamellar in situ composite were investigated by using real-time in situ neutron diffraction during compression at elevated temperatures up to 800 °C. Tensile and compressive thermal residual stresses were found to exist in the NiAl phase and Crss (solid solution) phase, respectively. Then, based on the evolution of lattice spacings and phase stresses, the phase-specific deformation behavior was analyzed qualitatively and quantitatively. Moreover, estimates of phase stresses were derived by Hooke's law on the basis of a simple method for the determination of stress-free lattice spacing in inmore » situ composites. During compressive loading, the NiAl phase yields earlier than the Crss phase. The Crss phase carries much higher stress than the NiAl phase, and displays consistent strain hardening at all temperatures. The NiAl phase exhibits strain hardening at relatively low temperatures and softening at high temperatures. During unloading, the NiAl phase yields in tension whereas the Crss phase unloads elastically. Additionally, post-test microstructural observations show phase-through cracks at room temperature, micro cracks along phase interfaces at 600 °C and intact lamellae kinks at 800 °C, which is due to the increasing deformability of both phases as temperature rises.« less

  7. Direct Renin Inhibition with Aliskiren Improves Ischemia-Induced Neovasculogenesis in Diabetic Animals via the SDF-1 Related Mechanism

    PubMed Central

    Chang, Ting-Ting; Wu, Tao-Cheng; Huang, Po-Hsun; Lin, Chih-Pei; Chen, Jia-Shiong; Lin, Liang-Yu; Lin, Shing-Jong; Chen, Jaw-Wen

    2015-01-01

    Objective Aliskiren is a direct renin inhibitor which is suggested to modify proangiogenic cells in addition to lower blood pressure. Given that angiogenesis is impaired in the presence of diabetes mellitus, we would like to investigate whether and how aliskiren enhances endothelial progenitor cells (EPCs) and improves ischemic-induced neovasculogenesis by an effect independent of blood pressure reduction in diabetic animals. Methods Streptozotocin-induced diabetic mice were administered with either aliskiren (5 or 25 mg/kg/day) using an osmotic pump or hydralazine (2 or 10 mg/kg/day) given in drinking water for two weeks prior to a hind-limb ischemia surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neovasculogenesis and the circulating levels of EPCs, respectively. Results In streptozotocin-induced diabetic mice, aliskiren enhanced the recovery of limb perfusion and capillary density, increased the number of circulating Sca-1+/Flk-1+ EPC-like cells, and elevated the levels of the plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α in a dose-dependent manner, whereas there were no such effects in hydralazine-treated mice. Intraperitoneal administration of anti-SDF-1 neutralizing monoclonal antibodies abolished the effects of aliskiren. Conclusions Independent of the reduction of blood pressure, aliskiren enhanced ischemia-induced neovasculogenesis in a dose-dependent manner via VEGF/SDF-1α related mechanisms in diabetic mice. PMID:26305217

  8. Reliable and cost effective design of intermetallic Ni2Si nanowires and direct characterization of its mechanical properties

    PubMed Central

    Han, Seung Zeon; Kang, Joonhee; Kim, Sung-Dae; Choi, Si-Young; Kim, Hyung Giun; Lee, Jehyun; Kim, Kwangho; Lim, Sung Hwan; Han, Byungchan

    2015-01-01

    We report that a single crystal Ni2Si nanowire (NW) of intermetallic compound can be reliably designed using simple three-step processes: casting a ternary Cu-Ni-Si alloy, nucleate and growth of Ni2Si NWs as embedded in the alloy matrix via designing discontinuous precipitation (DP) of Ni2Si nanoparticles and thermal aging, and finally chemical etching to decouple the Ni2Si NWs from the alloy matrix. By direct application of uniaxial tensile tests to the Ni2Si NW we characterize its mechanical properties, which were rarely reported in previous literatures. Using integrated studies of first principles density functional theory (DFT) calculations, high-resolution transmission electron microscopy (HRTEM), and energy-dispersive X-ray spectroscopy (EDX) we accurately validate the experimental measurements. Our results indicate that our simple three-step method enables to design brittle Ni2Si NW with high tensile strength of 3.0 GPa and elastic modulus of 60.6 GPa. We propose that the systematic methodology pursued in this paper significantly contributes to opening innovative processes to design various kinds of low dimensional nanomaterials leading to advancement of frontiers in nanotechnology and related industry sectors. PMID:26456769

  9. Degradation mechanisms and mitigation strategies of metal cations in recycled fuel for direct methanol fuel cell membrane electrode assembly

    NASA Astrophysics Data System (ADS)

    Yang, Min-Jee; Park, Ka-Young; Kim, Ki-Beum; Cho, Hyejung; Choi, Hanshin; Park, Jun-Young

    2013-11-01

    Some metal contaminants, such as Al3+, Ni+2, Fe2+ and Cr3+, are produced during reactions in heat exchangers, stacks, and other fuel/water management system components. Due to the gradual build-up of these contaminants generated in the system, direct methanol fuel cell (DMFC) membrane electrode assemblies (MEAs) deteriorate steadily with increasing operation time. Hence, this study systematically investigates the effects of metal cations by supplying various concentrations of metal solutions to the fuel stream at constant-current densities, with the aim of understanding the mechanism and influence of metal contamination on a DMFC MEA. Various electrochemical diagnostic techniques are used to determine the main cause of MEA degradation, including electrochemical impedance spectroscopy, electrode polarization, and methanol stripping voltammetry. In addition, the critical concentration of metal cations in methanol fuel is investigated for high DMFC MEA stability. Further, various novel methods for mitigating the influence of the metal contaminants on the performance of a DMFC are suggested and verified.

  10. Total Hip Joint Replacement Biotelemetry System

    NASA Technical Reports Server (NTRS)

    Boreham, J. F.; Postal, R. B.; Luntz, R. A.

    1981-01-01

    The development of a biotelemetry system that is hermetically sealed within a total hip replacement implant is reported. The telemetry system transmits six channels of stress data to reconstruct the major forces acting on the neck of the prosthesis and uses an induction power coupling technique to eliminate the need for internal batteries. The activities associated with the telemetry microminiaturization, data recovery console, hardware fabrications, power induction systems, electrical and mechanical testing and hermetic sealing test results are discussed.

  11. Using your shoulder after replacement surgery

    MedlinePlus

    Joint replacement surgery - using your shoulder; Shoulder replacement surgery - after ... You have had shoulder replacement surgery to replace the bones of your shoulder joint with artificial parts. The parts include a stem made of metal and a ...

  12. The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation

    PubMed Central

    Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

    2016-01-01

    Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all

  13. The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation.

    PubMed

    Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

    2016-01-01

    Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all

  14. The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation.

    PubMed

    Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

    2016-01-01

    Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all

  15. The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation

    PubMed Central

    Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

    2016-01-01

    Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all

  16. Replacement Cost of Domestic Crude

    1994-12-01

    The DEEPWATER model forecasts the replacement cost of domestic crude oil for 13 offshore regions in the lower 48 states. The replacement cost of domestic crude oil is the constant or levelized selling price that will recover the full expense of exploration, development, and productions with a reasonable return on capital.

  17. Dialogue Replacement for Student Productions.

    ERIC Educational Resources Information Center

    Hank, Stephen

    1997-01-01

    Argues that film students should be taught how dialog replacement fits into overall engineering of a sound track--replacing dialog offers advantages to the student filmmaker that can enhance a less than stellar performance. States that skills such as foley artistry, postsynchronization of sound effects, and sound track engineering are as important…

  18. Uni-directional Coupling between Tibiofemoral Frontal and Axial Plane Rotation Supports Valgus Collapse Mechanism of ACL Injury

    PubMed Central

    Kiapour, Ata M.; Kiapour, Ali; Goel, Vijay K.; Quatman, Carmen E.; Wordeman, Samuel C.; Hewett, Timothy E.; Demetropoulos, Contantine K.

    2015-01-01

    Despite general agreement on the effects of knee valgus and internal tibial rotation on anterior cruciate (ACL) loading, compelling debate persists on the interrelationship between these rotations and how they contribute to the multi-planar ACL injury mechanism. This study investigates coupling between knee valgus and internal tibial rotation and their effects on ACL strain as a quantifiable measure of injury risk. Nineteen instrumented cadaveric legs were imaged and tested under a range of knee valgus and internal tibial torques. Posterior tibial slope and the medial tibial depth, along with changes in tibiofemoral kinematics and ACL strain, were quantified. Valgus torque significantly increased knee valgus rotation and ACL strain (p<0.02), yet generated minimal coupled internal tibial rotation (p=0.537). Applied internal tibial torque significantly increased internal tibial rotation and ACL strain and generated significant coupled knee valgus rotation (p<0.001 for all comparisons). Similar knee valgus rotations (7.3° vs 7.4°) and ACL strain levels (4.4% vs 4.9%) were observed under 50 N-m of valgus and 20 N-m of internal tibial torques, respectively. Coupled knee valgus rotation under 20 N-m of internal tibial torque was significantly correlated with internal tibial rotation, lateral and medial tibial slopes, and medial tibial depth (R2>0.30; p<0.020). These findings demonstrate uni-directional coupling between knee valgus and internal tibial rotation in a cadaveric model. Although both knee valgus and internal tibial torques contribute to increased ACL strain, knee valgus rotation has the ultimate impact on ACL strain regardless of loading mode. PMID:26070647

  19. Uni-directional coupling between tibiofemoral frontal and axial plane rotation supports valgus collapse mechanism of ACL injury.

    PubMed

    Kiapour, Ata M; Kiapour, Ali; Goel, Vijay K; Quatman, Carmen E; Wordeman, Samuel C; Hewett, Timothy E; Demetropoulos, Constantine K

    2015-07-16

    Despite general agreement on the effects of knee valgus and internal tibial rotation on anterior cruciate ligament (ACL) loading, compelling debate persists on the interrelationship between these rotations and how they contribute to the multi-planar ACL injury mechanism. This study investigates coupling between knee valgus and internal tibial rotation and their effects on ACL strain as a quantifiable measure of injury risk. Nineteen instrumented cadaveric legs were imaged and tested under a range of knee valgus and internal tibial torques. Posterior tibial slope and the medial tibial depth, along with changes in tibiofemoral kinematics and ACL strain, were quantified. Valgus torque significantly increased knee valgus rotation and ACL strain (p<0.020), yet generated minimal coupled internal tibial rotation (p=0.537). Applied internal tibial torque significantly increased internal tibial rotation and ACL strain and generated significant coupled knee valgus rotation (p<0.001 for all comparisons). Similar knee valgus rotations (7.3° vs 7.4°) and ACL strain levels (4.4% vs 4.9%) were observed under 50 Nm of valgus and 20 Nm of internal tibial torques, respectively. Coupled knee valgus rotation under 20 Nm of internal tibial torque was significantly correlated with internal tibial rotation, lateral and medial tibial slopes, and medial tibial depth (R(2)>0.30; p<0.020). These findings demonstrate uni-directional coupling between knee valgus and internal tibial rotation in a cadaveric model. Although both knee valgus and internal tibial torques contribute to increased ACL strain, knee valgus rotation has the ultimate impact on ACL strain regardless of loading mode.

  20. Novel Annular and Subvalvular Enlargement in Congenital Mitral Valve Replacement.

    PubMed

    Carroll, Nels D; Beers, Kevin M; Maldonado, Elaine M; Calhoon, John H; Husain, S Adil

    2016-09-01

    Reparative procedures are not always feasible in congenitally abnormal mitral valves. Mechanical prosthesis has been accepted as the choice for valve replacement in the pediatric population. This report describes a case of congenital mitral valve disease requiring mitral valve replacement. The infant's mitral valve annulus was not amenable to placement of the smallest available mechanical prosthesis. The approach used here for annular and subvalvular enlargement facilitated implantation of a larger prosthesis for congenital mitral valve replacement. Five-year outcomes in a single patient may indicate broader applicability and avoidance of patient-prosthesis mismatch.

  1. Mineral replacement front propagation in deformed rocks

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Koehn, Daniel; Kelka, Ulrich

    2015-04-01

    Fluid migrations are a major agent of contaminant transport leading to mineral replacement in rocks, impacting their properties as porosity, permeability, and rheology. Understanding the physical and chemical mechanisms that govern mineralogical replacement during and after deformation is required to better understand complex interplays between fluid and rocks that are involved in faulting, seismic cycle, and resource distribution in the upper crust. Dolomitization process related to hydrothermal fluid flow is one of the most studied and debated replacement processes in earth sciences. Dolomitization of limestone is of economic importance as well, as it stands as unconventional oil reservoirs and is systematically observed in Mississippian-Valley Type ore deposit. Despite recent breakthrough about dolomitization processes at large-scale, the small-scale propagation of the reaction front remains unclear. It is poorly documented in the occurrence of stylolites and fractures in the medium while pressure-solution and fracture network development are the most efficient deformation accomodation mechanism in limestone from early compaction to layer-parallel shortening. Thus, the impact of such network on geometry of replaced bodies and on replacement front propagation deserves specific attention. This contribution illustrates the role of fracture and stylolites on the propagation of a reaction front. In a 2 dimensional numerical model we simulate the dolomitization front propagation in a heterogeneous porous medium. The propagation of the reaction front is governed by the competition between advection and diffusion processes, and takes into account reaction rates, disorder in the location of the potential replacement seeds, and permeability heterogeneities. We add stylolites and fractures that can act as barriers or drains to fluid flow according to their orientation and mineralogical content, which can or cannot react with the contaminant. The patterns produced from

  2. Physical activity and self-esteem: testing direct and indirect relationships associated with psychological and physical mechanisms

    PubMed Central

    Zamani Sani, Seyed Hojjat; Fathirezaie, Zahra; Brand, Serge; Pühse, Uwe; Holsboer-Trachsler, Edith; Gerber, Markus; Talepasand, Siavash

    2016-01-01

    In the present study, we investigated the relationship between physical activity (PA) and self-esteem (SE), while introducing body mass index (BMI), perceived physical fitness (PPF), and body image (BI) in adults (N =264, M =38.10 years). The findings indicated that PA was directly and indirectly associated with SE. BMI predicted SE neither directly nor indirectly, but was directly associated with PPF and both directly and indirectly with BI. Furthermore, PPF was directly related to BI and SE, and a direct association was found between BI and SE. The pattern of results suggests that among a sample of adults, PA is directly and indirectly associated with SE, PPF, and BI, but not with BMI. PA, PPF, and BI appear to play an important role in SE. Accordingly, regular PA should be promoted, in particular, among adults reporting lower SE. PMID:27789950

  3. Artificial vitreous replacements.

    PubMed

    Soman, N; Banerjee, R

    2003-01-01

    Vitreoretinal pathologies remain the significant leading cause of blindness, after cataract, throughout the world. Biomaterials as a whole, and vitreous substitutes in particular, have had a major role to play in vitreoretinal surgery. History has witnessed the advent of vitreous substitutes from collagen and hyaluronic acid to gases, silicone oils and perfluorocarbon liquids and now to polymer hydrogels. Such a long list only underscores the fact that we have been found wanting in our quest for an ideal vitreous substitute. This review focuses on the merits and demerits of various vitreous substitutes, which have been tried to date, clinical as well as experimental. The properties required of an ideal substitute and the performance of the vitreous substitutes with respect to these criteria have been described. Finally, the concluding note dwells on the future directions for biomaterial research in the posterior segment of the eye and undermines the role of tissue engineering in vitreoretinal regeneration.

  4. Direct Insulation-to-Conduction Transformation of Adhesive Catecholamine for Simultaneous Increases of Electrical Conductivity and Mechanical Strength of CNT Fibers.

    PubMed

    Ryu, Seongwoo; Chou, Jeffrey B; Lee, Kyueui; Lee, Dongju; Hong, Soon Hyung; Zhao, Rong; Lee, Haeshin; Kim, Sang-gook

    2015-06-01

    Increase in conductivity and mechanical properties of a carbon nanotube (CNT) fiber inspired by mussel-adhesion chemistry is described. Infiltration of polydopamine into an as-drawn CNT fiber followed by pyrolysis results in a direct insulation-to-conduction transformation of poly(dopamine) into pyrolyzed-poly(dopamine) (py-PDA), retaining the intrinsic adhesive function of catecholamine. The py-PDA enhances both the electrical conductivity and the mechanical strength of the CNT fibers. PMID:25899742

  5. Direct Insulation-to-Conduction Transformation of Adhesive Catecholamine for Simultaneous Increases of Electrical Conductivity and Mechanical Strength of CNT Fibers.

    PubMed

    Ryu, Seongwoo; Chou, Jeffrey B; Lee, Kyueui; Lee, Dongju; Hong, Soon Hyung; Zhao, Rong; Lee, Haeshin; Kim, Sang-gook

    2015-06-01

    Increase in conductivity and mechanical properties of a carbon nanotube (CNT) fiber inspired by mussel-adhesion chemistry is described. Infiltration of polydopamine into an as-drawn CNT fiber followed by pyrolysis results in a direct insulation-to-conduction transformation of poly(dopamine) into pyrolyzed-poly(dopamine) (py-PDA), retaining the intrinsic adhesive function of catecholamine. The py-PDA enhances both the electrical conductivity and the mechanical strength of the CNT fibers.

  6. Replacing the kilogram

    NASA Astrophysics Data System (ADS)

    Kibble, B. P.; Robinson, I. A.

    2003-08-01

    The kilogram is the last remaining SI unit defined by an artefact—the platinum-iridium cylinder kept at the International Bureau of Weights and Measures (BIPM). The artefact standard is subject to, admittedly very small, irreversible changes caused both by wear and by accretion of mass from atmospheric pollutants. In addition, the unit of mass can only be disseminated by comparison with the artefact held by the BIPM. Comparisons of its mass with other similar and equally carefully preserved cylinders show relative changes, over many tens of years, of several parts in 108. If a procedure was available to link mass to a fundamental constant, with a similar or better accuracy, the above limitations would be overcome, making the unit accessible to anyone caring to carry out the procedure and long term stability would be assured. Attempts to do this fall into two broad categories: the first relates the kilogram to atomic masses by measuring the number of atoms in a sample and the second relates the kilogram to Planck's constant, the metre and the second via the equivalence of mechanical and electrical energy. We summarize experiments in both these categories.

  7. Characterization of dislocation structures and deformation mechanisms in as-grown and deformed directionally solidified NiAl–Mo composites

    DOE PAGESBeta

    Kwon, J.; Bowers, M. L.; Brandes, M. C.; McCreary, V.; Robertson, Ian M.; Phani, P. Sudaharshan; Bei, H.; Gao, Y. F.; Pharr, George M.; George, Easo P.; et al

    2015-02-26

    In this paper, directionally solidified (DS) NiAl–Mo eutectic composites were strained to plastic strain values ranging from 0% to 12% to investigate the origin of the previously observed stochastic versus deterministic mechanical behaviors of Mo-alloy micropillars in terms of the development of dislocation structures at different pre-strain levels. The DS composites consist of long, [1 0 0] single-crystal Mo-alloy fibers with approximately square cross-sections embedded in a [1 0 0] single-crystal NiAl matrix. Scanning transmission electron microscopy (STEM) and computational stress state analysis were conducted for the current study. STEM of the as-grown samples (without pre-straining) reveal no dislocations inmore » the investigated Mo-alloy fibers. In the NiAl matrix, on the other hand, a(1 0 0)-type dislocations exist in two orthogonal orientations: along the [1 0 0] Mo fiber axis, and wrapped around the fiber axis. They presumably form to accommodate the different thermal contractions of the two phases during cool down after eutectic solidification. At intermediate pre-strain levels (4–8%), a/2(1 1 1)-type dislocations are present in the Mo-alloy fibers and the pre-existing dislocations in the NiAl matrix seem to be swept toward the interphase boundary. Some of the dislocations in the Mo-alloy fibers appear to be transformed from a(1 0 0)-type dislocations present in the NiAl matrix. Subsequently, the transformed dislocations in the fibers propagate through the NiAl matrix as a(1 1 1) dislocations and aid in initiating additional slip bands in adjacent fibers. Thereafter, co-deformation presumably occurs by (1 1 1) slip in both phases. With a further increase in the pre-strain level (>10%), multiple a/2(1 1 1)-type dislocations are observed in many locations in the Mo-alloy fibers. Interactions between these systems upon subsequent deformation could lead to stable junctions and persistent dislocation sources. Finally, the transition from stochastic to

  8. Structural, mechanical and in vitro characterization of individually structured Ti-6Al-4V produced by direct laser forming.

    PubMed

    Hollander, Dirk A; von Walter, Matthias; Wirtz, Tobias; Sellei, Richard; Schmidt-Rohlfing, Bernhard; Paar, Othmar; Erli, Hans-Josef

    2006-03-01

    Direct laser forming (DLF) is a rapid prototyping technique which enables prompt modelling of metal parts with high bulk density on the base of individual three-dimensional data, including computer tomography models of anatomical structures. In our project, we tested DLF-produced material on the basis of the titanium alloy Ti-6Al-4V for its applicability as hard tissue biomaterial. To this end, we investigated mechanical and structural properties of DLF-Ti-6Al-4V. While the tensile and yield strengths of untreated DLF alloy ranged beyond 1000 MPa, a breaking elongation of 6.5+/-0.6% was determined for this material. After an additional post-DLF annealing treatment, this parameter was increased two-fold to 13.0+/-0.6%, while tensile and yield strengths were reduced by approx. 8%. A Young's modulus of 118.000+/-2.300 MPa was determined for post-DLF annealed Ti-6Al-4V. All data gained from tensile testing of post-DLF annealed Ti-6Al-4V matched American Society of Testing and Materials (ASTM) specifications for the usage of this alloy as medical material. Rotating bending tests revealed that the fatigue profile of post-DLF annealed Ti-6Al-4V was comparable to casted/hot isostatic pressed alloy. We characterized the structure of non-finished DLF-Ti-6Al-4V by scanning electron microscopy and observed a surface-associated layer of particles, which was removable by sandblasting as a finishing step. We manufactured porous specimens with nominal pore diameters of 500, 700 and 1000 microm. The diameters were reduced by the used DLF processing by approx. 300 microm. In an in vitro investigation, we cultured human osteoblasts on non-porous and porous blasted DLF-Ti-6Al-4V specimens to study morphology, vitality, proliferation and differentiation of the cells. The cells spreaded and proliferated on DLF-Ti-6Al-4V over a culture time of 14 days. On porous specimens, osteoblasts grew along the rims of the pores and formed circle-shaped structures, as visualized by live

  9. Characterization of dislocation structures and deformation mechanisms in as-grown and deformed directionally solidified NiAl–Mo composites

    SciTech Connect

    Kwon, J.; Bowers, M. L.; Brandes, M. C.; McCreary, V.; Robertson, Ian M.; Phani, P. Sudaharshan; Bei, H.; Gao, Y. F.; Pharr, George M.; George, Easo P.; Mills, M. J.

    2015-02-26

    In this paper, directionally solidified (DS) NiAl–Mo eutectic composites were strained to plastic strain values ranging from 0% to 12% to investigate the origin of the previously observed stochastic versus deterministic mechanical behaviors of Mo-alloy micropillars in terms of the development of dislocation structures at different pre-strain levels. The DS composites consist of long, [1 0 0] single-crystal Mo-alloy fibers with approximately square cross-sections embedded in a [1 0 0] single-crystal NiAl matrix. Scanning transmission electron microscopy (STEM) and computational stress state analysis were conducted for the current study. STEM of the as-grown samples (without pre-straining) reveal no dislocations in the investigated Mo-alloy fibers. In the NiAl matrix, on the other hand, a(1 0 0)-type dislocations exist in two orthogonal orientations: along the [1 0 0] Mo fiber axis, and wrapped around the fiber axis. They presumably form to accommodate the different thermal contractions of the two phases during cool down after eutectic solidification. At intermediate pre-strain levels (4–8%), a/2(1 1 1)-type dislocations are present in the Mo-alloy fibers and the pre-existing dislocations in the NiAl matrix seem to be swept toward the interphase boundary. Some of the dislocations in the Mo-alloy fibers appear to be transformed from a(1 0 0)-type dislocations present in the NiAl matrix. Subsequently, the transformed dislocations in the fibers propagate through the NiAl matrix as a(1 1 1) dislocations and aid in initiating additional slip bands in adjacent fibers. Thereafter, co-deformation presumably occurs by (1 1 1) slip in both phases. With a further increase in the pre-strain level (>10%), multiple a/2(1 1 1)-type dislocations are observed in many locations in the Mo-alloy fibers. Interactions between these systems upon subsequent deformation could lead to stable junctions and persistent dislocation sources. Finally, the transition from stochastic to

  10. Microstructural development and mechanical properties of a near-eutectic directionally solidified Sn–Bi solder alloy

    SciTech Connect

    Silva, Bismarck Luiz; Reinhart, Guillaume; Nguyen-Thi, Henri; Mangelinck-Noël, Nathalie; Garcia, Amauri; Spinelli, José Eduardo

    2015-09-15

    Sn–Bi solders may be applied for electronic applications where low-temperature soldering is required, i.e., sensitive components, step soldering and soldering LEDs. In spite of their potential to cover such applications, the mechanical response of soldered joints of Sn–Bi alloys in some cases does not meet the strength requirements due to inappropriate resulting microstructures. Hence, careful examination and control of as-soldered microstructures become necessary with a view to pre-programming reliable final properties. The present study aims to investigate the effects of solidification thermal parameters (growth rate — V{sub L} and cooling rate — T-dot{sub L}) on the microstructure of the Sn–52 wt.%Bi solder solidified under unsteady-state conditions. Samples were obtained by upward directional solidification (DS), followed by characterization through metallography and scanning electron microscopy (SEM). The microstructures are shown to be formed by Sn-rich dendrites decorated with Bi precipitates surrounded by a complex regular eutectic mixture, with alternated Bi-rich and Sn-rich phases. Experimental correlations of primary (λ{sub 1}), secondary (λ{sub 2}), tertiary (λ{sub 3}) dendritic and eutectic spacings (λ{sub coarse} and λ{sub fine}) with cooling rate and growth rate are established. Two ranges of lamellar eutectic sizes were determined, described by two experimental equations λ = 1.1 V{sub L}{sup −1/2} and λ = 0.67 V{sub L}{sup −1/2}. The onset of tertiary branches within the dendritic array along the Sn–52 wt.%Bi alloy DS casting is shown to occur for cooling rates lower than 1.5 °C/s. - Highlights: • The Sn–52 wt.%Bi solder was shown to have two eutectic sizes. • The fishbone eutectic is preferably located adjacent to the Bi-rich lamellar phases. • The onset of tertiary dendritic branches in Sn–Bi is associated with T-dot{sub L} < 1.5 °C/s. • Higher eutectic fraction and λ{sub 3} provoked a reverse increase in

  11. Fracture After Total Hip Replacement

    MedlinePlus

    ... er Total Hip Replacement cont. • Dislocation • Limb length inequality • Poor fracture healing • Repeat fracture • Lack of in- ... Surgeons (AAOS). To learn more about your orthopaedic health, please visit orthoinfo.org. Page ( 5 ) AAOS does ...

  12. When to Replace a Prosthesis

    MedlinePlus

    Donate Fundraise Connect Contact Us Materiales en español Amputee Coalition Navigation HOME WHO WE ARE About Us ... Advisory Committee Connect With Us! STORE CALENDAR SEARCH Amputee Coalition > Limb Loss Resource Center > When to Replace ...

  13. Meal replacements and energy balance.

    PubMed

    Heymsfield, Steven B

    2010-04-26

    Induction and maintenance of a period of negative energy balance are required for overweight and obese subjects to lose weight. Meal replacements, particularly in beverage form, have now evolved as part of the "toolbox" used by researchers and clinicians to achieve negative energy balance. This overview traces the historical development of beverage meal replacements, reviews key studies supporting their clinical efficacy, and examines concerns related to their safe use. This collective information supports the view that meal replacements, particularly in beverage form, are now an effective and safe component for use in the clinical setting. Further studies are needed to identify those subjects most likely to benefit from use of meal replacements as part of their comprehensive weight control program.

  14. Prioritization Methodology for Chemical Replacement

    NASA Technical Reports Server (NTRS)

    Cruit, W.; Schutzenhofer, S.; Goldberg, B.; Everhart, K.

    1993-01-01

    This project serves to define an appropriate methodology for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weigh the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results are being implemented as a guideline for consideration for current NASA propulsion systems.

  15. Mechanically stable, hierarchically porous Cu3(btc)2 (HKUST-1) monoliths via direct conversion of copper(II) hydroxide-based monoliths.

    PubMed

    Moitra, Nirmalya; Fukumoto, Shotaro; Reboul, Julien; Sumida, Kenji; Zhu, Yang; Nakanishi, Kazuki; Furukawa, Shuhei; Kitagawa, Susumu; Kanamori, Kazuyoshi

    2015-02-28

    The synthesis of highly crystalline macro-meso-microporous monolithic Cu3(btc)2 (HKUST-1; btc(3-) = benzene-1,3,5-tricarboxylate) is demonstrated by direct conversion of Cu(OH)2-based monoliths while preserving the characteristic macroporous structure. The high mechanical strength of the monoliths is promising for possible applications to continuous flow reactors. PMID:25572361

  16. The CDM superfamily protein MBC directs myoblast fusion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk.

    PubMed

    Balagopalan, Lakshmi; Chen, Mei-Hui; Geisbrecht, Erika R; Abmayr, Susan M

    2006-12-01

    Myoblast city (mbc), a member of the CDM superfamily, is essential in the Drosophila melanogaster embryo for fusion of myoblasts into multinucleate fibers. Using germ line clones in which both maternal and zygotic contributions were eliminated and rescue of the zygotic loss-of-function phenotype, we established that mbc is required in the fusion-competent subset of myoblasts. Along with its close orthologs Dock180 and CED-5, MBC has an SH3 domain at its N terminus, conserved internal domains termed DHR1 and DHR2 (or "Docker"), and C-terminal proline-rich domains that associate with the adapter protein DCrk. The importance of these domains has been evaluated by the ability of MBC mutations and deletions to rescue the mbc loss-of-function muscle phenotype. We demonstrate that the SH3 and Docker domains are essential. Moreover, ethyl methanesulfonate-induced mutations that change amino acids within the MBC Docker domain to residues that are conserved in other CDM family members nevertheless eliminate MBC function in the embryo, which suggests that these sites may mediate interactions specific to Drosophila MBC. A functional requirement for the conserved DHR1 domain, which binds to phosphatidylinositol 3,4,5-triphosphate, implicates phosphoinositide signaling in myoblast fusion. Finally, the proline-rich C-terminal sites mediate strong interactions with DCrk, as expected. These sites are not required for MBC to rescue the muscle loss-of-function phenotype, however, which suggests that MBC's role in myoblast fusion can be carried out independently of direct DCrk binding.

  17. Computational mechanics - Advances and trends; Proceedings of the Session - Future directions of Computational Mechanics of the ASME Winter Annual Meeting, Anaheim, CA, Dec. 7-12, 1986

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K. (Editor)

    1986-01-01

    The papers contained in this volume provide an overview of the advances made in a number of aspects of computational mechanics, identify some of the anticipated industry needs in this area, discuss the opportunities provided by new hardware and parallel algorithms, and outline some of the current government programs in computational mechanics. Papers are included on advances and trends in parallel algorithms, supercomputers for engineering analysis, material modeling in nonlinear finite-element analysis, the Navier-Stokes computer, and future finite-element software systems.

  18. Replacing equipment due to obsolescence, fuel efficiency

    SciTech Connect

    Harbor, V.

    1982-08-23

    Southern Natural Gas' engine replacement program with regard to expansion problems, replacement justification, meeting requirements (e.g. FERC regulations), economics, and removal and replacement was examined. As a result of replacement, gas supplies are more plentiful; and due to increased load factors, the replacing of four 1,300-hp units is now under way.

  19. Numerical study of turbulence-influence mechanism on arc characteristics in an air direct current circuit breaker

    NASA Astrophysics Data System (ADS)

    Wu, Mingliang; Yang, Fei; Rong, Mingzhe; Wu, Yi; Qi, Yang; Cui, Yufei; Liu, Zirui; Guo, Anxiang

    2016-04-01

    This paper focuses on the numerical investigation of arc characteristics in an air direct current circuit breaker (air DCCB). Using magneto-hydrodynamics (MHD) theory, 3D laminar model and turbulence model are constructed and calculated. The standard k-epsilon model is utilized to consider the turbulence effect in the arc chamber of the DCCB. Several important phenomena are found: the arc column in the turbulence-model case is more extensive, moves much more slowly than the counterpart in the laminar-model case, and shows stagnation at the entrance of the chamber, unlike in the laminar-model case. Moreover, the arc voltage in the turbulence-model case is much lower than in the laminar-model case. However, the results in the turbulence-model case show a much better agreement with the results of the breaking experiments under DC condition than in the laminar-model case, which is contradictory to the previous conclusions from the arc researches of both the low-voltage circuit breaker and the sulfur hexafluoride (SF6) nozzle. First, in the previous air-arc research of the low-voltage circuit breaker, it is assumed that the air plasma inside the chamber is in the state of laminar, and the laminar-model application gives quite satisfactory results compared with the experiments, while in this paper, the laminar-model application works badly. Second, the turbulence-model application in the arc research of the SF6-nozzle performs much better and gives higher arc voltage than the laminar-model application does, whereas in this paper, the turbulence-model application predicts lower arc voltage than the laminar-model application does. Based on the analysis of simulation results in detail, the mechanism of the above phenomena is revealed. The transport coefficients are strongly changed by turbulence, which will enhance the arc diffusion and make the arc volume much larger. Consequently, the arc appearance and the distribution of Lorentz force in the turbulence-model case

  20. Peri-procedural imaging for transcatheter mitral valve replacement.

    PubMed

    Natarajan, Navin; Patel, Parag; Bartel, Thomas; Kapadia, Samir; Navia, Jose; Stewart, William; Tuzcu, E Murat; Schoenhagen, Paul

    2016-04-01

    Mitral regurgitation (MR) has a high prevalence in older patient populations of industrialized nations. Common etiologies are structural, degenerative MR and functional MR secondary to myocardial remodeling. Because of co-morbidities and associated high surgical risk, open surgical mitral repair/replacement is deferred in a significant percentage of patients. For these patients transcatheter repair/replacement are emerging as treatment options. Because of the lack of direct visualization, pre- and intra-procedural imaging is critical for these procedures. In this review, we summarize mitral valve anatomy, trans-catheter mitral valve replacement (TMVR) options, and imaging in the context of TMVR. PMID:27054104

  1. Peri-procedural imaging for transcatheter mitral valve replacement

    PubMed Central

    Natarajan, Navin; Patel, Parag; Bartel, Thomas; Kapadia, Samir; Navia, Jose; Stewart, William; Tuzcu, E. Murat

    2016-01-01

    Mitral regurgitation (MR) has a high prevalence in older patient populations of industrialized nations. Common etiologies are structural, degenerative MR and functional MR secondary to myocardial remodeling. Because of co-morbidities and associated high surgical risk, open surgical mitral repair/replacement is deferred in a significant percentage of patients. For these patients transcatheter repair/replacement are emerging as treatment options. Because of the lack of direct visualization, pre- and intra-procedural imaging is critical for these procedures. In this review, we summarize mitral valve anatomy, trans-catheter mitral valve replacement (TMVR) options, and imaging in the context of TMVR. PMID:27054104

  2. Experimental replacement of an obligate insect symbiont.

    PubMed

    Moran, Nancy A; Yun, Yueli

    2015-02-17

    Symbiosis, the close association of unrelated organisms, has been pivotal in biological diversification. In the obligate symbioses found in many insect hosts, organisms that were once independent are permanently and intimately associated, resulting in expanded ecological capabilities. The primary model for this kind of symbiosis is the association between the bacterium Buchnera and the pea aphid (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic changes underlying obligate symbioses has been the inability to experimentally disrupt and reconstitute symbiont-host partnerships. Our experiments show that Buchnera can be experimentally transferred between aphid matrilines and, furthermore, that Buchnera replacement has a massive effect on host fitness. Using a recipient pea aphid matriline containing Buchnera that are heat sensitive because of an allele eliminating the heat shock response of a small chaperone, we reduced native Buchnera through heat exposure and introduced a genetically distinct Buchnera from another matriline, achieving complete replacement and stable inheritance. This transfer disrupted 100 million years (∼ 1 billion generations) of continuous maternal transmission of Buchnera in its host aphids. Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in heat tolerance, directly demonstrating a strong effect of symbiont genotype on host ecology.

  3. Experimental replacement of an obligate insect symbiont.

    PubMed

    Moran, Nancy A; Yun, Yueli

    2015-02-17

    Symbiosis, the close association of unrelated organisms, has been pivotal in biological diversification. In the obligate symbioses found in many insect hosts, organisms that were once independent are permanently and intimately associated, resulting in expanded ecological capabilities. The primary model for this kind of symbiosis is the association between the bacterium Buchnera and the pea aphid (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic changes underlying obligate symbioses has been the inability to experimentally disrupt and reconstitute symbiont-host partnerships. Our experiments show that Buchnera can be experimentally transferred between aphid matrilines and, furthermore, that Buchnera replacement has a massive effect on host fitness. Using a recipient pea aphid matriline containing Buchnera that are heat sensitive because of an allele eliminating the heat shock response of a small chaperone, we reduced native Buchnera through heat exposure and introduced a genetically distinct Buchnera from another matriline, achieving complete replacement and stable inheritance. This transfer disrupted 100 million years (∼ 1 billion generations) of continuous maternal transmission of Buchnera in its host aphids. Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in heat tolerance, directly demonstrating a strong effect of symbiont genotype on host ecology. PMID:25561531

  4. Optimization of station battery replacement

    NASA Astrophysics Data System (ADS)

    Jancauskas, J. R.; Shook, D. A.

    1994-08-01

    During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability to quickly analyze proposed modifications and respond to internal and external audits.

  5. Homologous gene replacement in Physarum

    SciTech Connect

    Burland, T.G.; Pallotta, D.

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

  6. Transvalvular mitral regurgitation following mitral valve replacement a diagnostic dilemma

    PubMed Central

    Kumar, U. S. Dinesh; Nareppa, Umesh; Shetty, Shyam Prasad; Wali, Murugesh

    2015-01-01

    After mitral valve replacement with a prosthetic valve, the valve should be competent and there should not be any residual prosthetic valve regurgitation. Transvalvular residual prosthetic valve regurgitation are difficult to diagnose and quantify. we are reporting interesting TEE images as a diagnostic dilemma in a case of transvalvular mitral regurgitation following mitral valve replacement secondary to entrapment of sub-valvular apparatus in a Chitra mechanical heart valve. PMID:26440249

  7. Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer's Dementia: Possible Mechanisms, Current Evidence and Future Directions.

    PubMed

    Matura, Silke; Carvalho, André F; Alves, Gilberto S; Pantel, Johannes

    2016-01-01

    Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric or non-cognitive symptoms are common and often distressing features of Alzheimer's Dementia. BPSD significantly increase patient suffering, early institutionalization and caregiver's burden. The clinical management of BPSD is dominated by a pharmacological approach, although these medications often come with serious adverse side-effects. There are only few nonpharmacological treatment strategies for BPSD. A substantial amount of intervention studies that have investigated non-pharmacological treatment options for BPSD have focused on physical exercise. Although these studies are very heterogeneous in terms of type and severity of dementia, as well as type and duration of the exercise intervention, the overall picture shows a positive effect of physical exercise in alleviating BPSD. There is evidence that numerous mechanisms contribute to the positive effect of physical exercise on BPSD. No attempt has been undertaken so far to give an overview of the existing knowledge regarding these mechanisms. Therefore, the current review aims to integrate the existing evidence on psychological and neurobiological mechanisms that contribute to the beneficial effects of physical exercise in ameliorating BPSD in Alzheimer's dementia. A discussion of psychological mechanisms such as improved sleep and stress reduction will be followed by a discussion of neurobiological mechanisms including the exercise induced change in neurotransmitter concentrations, increased synthesis of neurotrophins and immune activation. The review closes with recommendations for future research to overcome the shortcomings of existing studies and broaden the current knowledge on the positive effects of physical exercise on BPSD.

  8. Trials and Tribulations with VH Replacement.

    PubMed

    Meng, Wenzhao; Jayaraman, Sahana; Zhang, Bochao; Schwartz, Gregory W; Daber, Robert D; Hershberg, Uri; Garfall, Alfred L; Carlson, Christopher S; Luning Prak, Eline T

    2014-01-01

    VH replacement (VHR) is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH) invades a pre-existing rearrangement (VDJ). In this Hypothesis and Theory article, we begin by reviewing the mechanism of VHR, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VHR versus other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, and include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VHR.

  9. Familial LCAT deficiency: from renal replacement to enzyme replacement.

    PubMed

    Stoekenbroek, R M; van den Bergh Weerman, M A; Hovingh, G K; Potter van Loon, B J; Siegert, C E H; Holleboom, A G

    2013-01-01

    Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy is available, yet enzyme replacement therapy is in development. PMID:23412821

  10. Molecular replacement: tricks and treats

    SciTech Connect

    Abergel, Chantal

    2013-11-01

    To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% of the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.

  11. A Direct Test of the Differentiation Mechanism: REM, BCDMEM, and the Strength-Based Mirror Effect in Recognition Memory

    ERIC Educational Resources Information Center

    Starns, Jeffrey J.; White, Corey N.; Ratcliff, Roger

    2010-01-01

    We explore competing explanations for the reduction in false alarm rate observed when studied items are strengthened. Some models, such as Retrieving Effectively from Memory (REM; Shiffrin & Steyvers, 1997), attribute the false alarm rate reduction to differentiation, a process in which strengthening memory traces at study directly reduces the…

  12. VH replacement in primary immunoglobulin repertoire diversification.

    PubMed

    Sun, Amy; Novobrantseva, Tatiana I; Coffre, Maryaline; Hewitt, Susannah L; Jensen, Kari; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B

    2015-02-01

    The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.

  13. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

    1995-01-01

    This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

  14. DEVELOPMENT OF REMOTE HANFORD CONNECTOR GASKET REPLACEMENT TOOLING FOR DWPF

    SciTech Connect

    Krementz, D.; Coughlin, Jeffrey

    2009-05-05

    The Defense Waste Processing Facility (DWPF) requested the Savannah River National Laboratory (SRNL) to develop tooling and equipment to remotely replace gaskets in mechanical Hanford connectors to reduce personnel radiation exposure as compared to the current hands-on method. It is also expected that radiation levels will continually increase with future waste streams. The equipment is operated in the Remote Equipment Decontamination Cell (REDC), which is equipped with compressed air, two master-slave manipulators (MSM's) and an electro-mechanical manipulator (EMM) arm for operation of the remote tools. The REDC does not provide access to electrical power, so the equipment must be manually or pneumatically operated. The MSM's have a load limit at full extension of ten pounds, which limited the weight of the installation tool. In order to remotely replace Hanford connector gaskets several operations must be performed remotely, these include: removal of the spent gasket and retaining ring (retaining ring is also called snap ring), loading the new snap ring and gasket into the installation tool and installation of the new gasket into the Hanford connector. SRNL developed and tested tools that successfully perform all of the necessary tasks. Removal of snap rings from horizontal and vertical connectors is performed by separate air actuated retaining ring removal tools and is manipulated in the cell by the MSM. In order install a new gasket, the snap ring loader is used to load a new snap ring into a groove in the gasket installation tool. A new gasket is placed on the installation tool and retained by custom springs. An MSM lifts the installation tool and presses the mounted gasket against the connector block. Once the installation tool is in position, the gasket and snap ring are installed onto the connector by pneumatic actuation. All of the tools are located on a custom work table with a pneumatic valve station that directs compressed air to the desired tool and

  15. Replaceable Sleeve Protects Welder Coil

    NASA Technical Reports Server (NTRS)

    Baker, W. L.; Simpson, C., E.

    1983-01-01

    New replaceable carbon insert for deflection coil in electron-beam welder promises to decrease maintenance costs. Inserts made from materials other than carbon (not yet tried) are less expensive, thus reducing costs even further. With carbon insert, deflection coils last longer and are easier to maintain.

  16. Will peanut hulls replace oil

    SciTech Connect

    Not Available

    1980-12-01

    A low-cost, fast-curing wood adhesive has been recently developed by the University of Georgia, in which up to 80% of the petroleum ingredients can be replaced with a substance extracted from peanut hulls. An outline of the process is given.

  17. Comparison of the direct burst pressure and the ring tensile test methods for mechanical characterization of tissue-engineered vascular substitutes.

    PubMed

    Laterreur, Véronique; Ruel, Jean; Auger, François A; Vallières, Karine; Tremblay, Catherine; Lacroix, Dan; Tondreau, Maxime; Bourget, Jean-Michel; Germain, Lucie

    2014-06-01

    Tissue engineering provides a promising alternative for small diameter vascular grafts, especially with the self-assembly method. It is crucial that these grafts possess mechanical properties that allow them to withstand physiological flow and pressure without being damaged. Therefore, an accurate assessment of their mechanical properties, especially the burst pressure, is essential prior to clinical release. In this study, the burst pressure of self-assembled tissue-engineered vascular substitutes was first measured by the direct method, which consists in pressurizing the construct with fluid until tissue failure. It was then compared to the burst pressure estimated by Laplace׳s law using data from a ring tensile test. The major advantage of this last method is that it requires a significantly smaller tissue sample. However, it has been reported as overestimating the burst pressure compared to a direct measurement. In the present report, it was found that an accurate estimation of the burst pressure may be obtained from a ring tensile test when failure internal diameter is used as the diameter parameter in Laplace׳s law. Overestimation occurs with the method previously reported, i.e. when the unloaded internal diameter is used for calculations. The estimation of other mechanical properties was also investigated. It was demonstrated that data from a ring tensile test provide an accurate estimate of the failure strain and the stiffness of the constructs when compared to measurements with the direct method.

  18. The Competition of Charge Remote and Charge Directed Fragmentation Mechanisms in Quaternary Ammonium Salt Derivatized Peptides—An Isotopic Exchange Study

    NASA Astrophysics Data System (ADS)

    Cydzik, Marzena; Rudowska, Magdalena; Stefanowicz, Piotr; Szewczuk, Zbigniew

    2011-12-01

    Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci. 2011, 17, 445 -453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms - charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms.

  19. Degradation mechanism of alachlor during direct ozonation and O(3)/H(2)O(2) advanced oxidation process.

    PubMed

    Qiang, Zhimin; Liu, Chao; Dong, Bingzhi; Zhang, Yalei

    2010-01-01

    The degradation of alachlor by direct ozonation and advanced oxidation process O(3)/H(2)O(2) was investigated in this study with focus on identification of degradation byproducts. The second-order reaction rate constant between ozone and alachlor was determined to be 2.5+/-0.1M(-1)s(-1) at pH 7.0 and 20 degrees C. Twelve and eight high-molecular-weight byproducts (with the benzene ring intact) from alachlor degradation were identified during direct ozonation and O(3)/H(2)O(2), respectively. The common degradation byproducts included N-(2,6-diethylphenyl)-methyleneamine, 8-ethyl-3,4-dihydro-quinoline, 8-ethyl-quinoline, 1-chloroacetyl-2-hydro-3-ketone-7-acetyl-indole, 2-chloro-2',6'-diacetyl-N-(methoxymethyl)acetanilide, 2-chloro-2'-acetyl-6'-ethyl-N-(methoxymethyl)-acetanilide, and two hydroxylated alachlor isomers. In direct ozonation, four more byproducts were also identified including 1-chloroacetyl-2,3-dihydro-7-ethyl-indole, 2-chloro-2',6'-ethyl-acetanilide, 2-chloro-2',6'-acetyl-acetanilide and 2-chloro-2'-ethyl-6'-acetyl-N-(methoxymethyl)-acetanilide. Degradation of alachlor by O(3) and O(3)/H(2)O(2) also led to the formation of low-molecular-weight byproducts including formic, acetic, propionic, monochloroacetic and oxalic acids as well as chloride ion (only detected in O(3)/H(2)O(2)). Nitrite and nitrate formation was negligible. Alachlor degradation occurred via oxidation of the arylethyl group, N-dealkylation, cyclization and cleavage of benzene ring. After O(3) or O(3)/H(2)O(2) treatment, the toxicity of alachlor solution examined by the Daphnia magna bioassay was slightly reduced. PMID:20022076

  20. A Hypothetical Perspective on the Relative Contributions of Strategic and Adaptive Control Mechanisms in Plastic Recalibration of Locomotor Heading Direction

    NASA Technical Reports Server (NTRS)

    Richards, J. T.; Mulavara, A. P.; Ruttley, T.; Peters, B. T.; Warren, L. E.; Bloomberg, J. J.

    2006-01-01

    We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of the control of position and trajectory during over-ground locomotion, which functionally reflects adaptive changes in the sensorimotor integration of visual, vestibular, and proprioceptive cues (Mulavara et al., 2005). The objective of this study was to investigate how strategic changes in torso control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping.

  1. On the protonation states, hydrogen bonding and catalytic mechanism of family 11 glycosidases: Direct visualization with neutrons

    SciTech Connect

    Fisher, Suzanne Zoe; Graham, David E.; Hanson, Leif; Kovalevskyi, Andrii Y.; Langan, Paul; Parks, Jerry M.; Wan, Qun; Ostermann, Andreas; Schrader, Tobias

    2015-10-06

    Most enzymatic reactions involve hydrogen or proton transfer among the enzyme, substrate, and water at physiological pH. Thus, enzyme catalysis cannot be fully understood without accurate mapping of hydrogen atom positions in these macromolecular catalysts. Direct information on the location of hydrogen atoms can be obtained using neutron crystallography. We used neutron crystallography and biomolecular simulation to characterize the initial stage of the glycoside hydrolysis reaction catalyzed by a family 11 glycoside hydrolase. We provide evidence that the catalytic glutamate residue alternates between two conformations bearing different basicities, first to obtain a proton from the bulk solvent, and then to deliver it to the glycosidic oxygen to initiate the hydrolysis reaction.

  2. Direct imaging of the magnetic polarity and reversal mechanism in individual Fe(3-x)O4 nanoparticles.

    PubMed

    Moya, Carlos; Iglesias-Freire, Óscar; Pérez, Nicolás; Batlle, Xavier; Labarta, Amilcar; Asenjo, Agustina

    2015-05-01

    This work reports on the experimental characterization of the magnetic domain configurations in cubic, isolated Fe3-xO4 nanoparticles with a lateral size of 25-30 nm. The magnetic polarity at remanence of single domain ferrimagnetic Fe3-xO4 nanoparticles deposited onto a carbon-silicon wafer is observed by magnetic force microscopy. The orientations of these domains provide a direct observation of the magneto-crystalline easy axes in each individual nanoparticle. Furthermore, the change in the domain orientation with an external magnetic field gives evidence of particle magnetization reversal mediated by a coherent rotation process that is also theoretically predicted by micromagnetic calculations.

  3. Displacement and Stress Analysis around the Artificial Acetabular Cup in a Total Hip Replacement

    NASA Astrophysics Data System (ADS)

    Kakunai, Satoshi; Tachibana, Hiroyuki; Sakamoto, Tohru; Abo, Masayoshi; Ikeda, Daisaku; Fujiwara, Hiroo

    In order to improve the service life of the artificial acetabular cup in a total hip replacement, it is important to determine the best material and design, and to assess the mechanical behavior around the cup. In this study, electronic speckle interferometry (ESPI) and the two-dimensional finite element method (FEM) are employed to investigate the mechanical behavior. The influence of the cancellous bone and cup thickness on mechanical behavior around the cup was investigated. Good agreement of the cup model was found between the ESPI measurements and FEM predictions. The following results were obtained. (1) Cancellous bone with a porous structure can be measured by the ESPI method. (2) There are discontinuities of the displacement distribution in the transverse direction in each boundary region of the cup, bone cement and cancellous bone. (3) The maximum shear stress exists in the boundary region of the cup and bone cement.

  4. Total ankle replacement – surgical treatment and rehabilitation

    PubMed Central

    Krogulec, Zbigniew; Turski, Piotr; Przepiórski, Emil; Małdyk, Paweł; Księżopolska-Orłowska, Krystyna

    2015-01-01

    Functions of the ankle joint are closely connected with the gait and ability to maintain an upright position. Degenerative lesions of the joint directly contribute to postural disorders and greatly restrict propulsion of the foot, thus leading to abnormal gait. Development of total ankle replacement is connected with the use of the method as an efficient treatment of joint injuries and continuation of achievements in hip and knee surgery. The total ankle replacement technique was introduced as an alternative to arthrodesis, i.e. surgical fixation, which made it possible to preserve joint mobility and to improve gait. Total ankle replacement is indicated in post-traumatic degenerative joint disease and joint destruction secondary to rheumatoid arthritis. In this paper, total ankle replacement and various types of currently used endoprostheses are discussed. The authors also describe principles of early postoperative rehabilitation as well as rehabilitation in the outpatient setting. PMID:27407223

  5. On the possibility that local mechanical forcing permits directionally-controlled long-range electron transfer along DNA-like molecular wires with no need of an external electric field. Mechanical control of electrons

    NASA Astrophysics Data System (ADS)

    Chetverikov, Alexander P.; Ebeling, Werner; Lakhno, Viktor D.; Shigaev, Alexey S.; Velarde, Manuel G.

    2016-04-01

    It is shown that in DNA-like molecules containing added, excess charges, such as electrons and holes (cation-radicals), it is possible by highly energetic, local, mechanical excitation at definite places of the chain to control the creation of breathers/bubbles and hence to control the long-range transfer of charges moving along the chain in a definite given direction with no external electric field needed.

  6. Noise-robust recognition of wide-field motion direction and the underlying neural mechanisms in Drosophila melanogaster

    PubMed Central

    Suzuki, Yoshinori; Ikeda, Hideaki; Miyamoto, Takuya; Miyakawa, Hiroyoshi; Seki, Yoichi; Aonishi, Toru; Morimoto, Takako

    2015-01-01

    Appropriate and robust behavioral control in a noisy environment is important for the survival of most organisms. Understanding such robust behavioral control has been an attractive subject in neuroscience research. Here, we investigated the processing of wide-field motion with random dot noise at both the behavioral and neuronal level in Drosophila melanogaster. We measured the head yaw optomotor response (OMR) and the activity of motion-sensitive neurons, horizontal system (HS) cells, with in vivo whole-cell patch clamp recordings at various levels of noise intensity. We found that flies had a robust sensation of motion direction under noisy conditions, while membrane potential changes of HS cells were not correlated with behavioral responses. By applying signal classification theory to the distributions of HS cell responses, however, we found that motion direction under noise can be clearly discriminated by HS cells, and that this discrimination performance was quantitatively similar to that of OMR. Furthermore, we successfully reproduced HS cell activity in response to noisy motion stimuli with a local motion detector model including a spatial filter and threshold function. This study provides evidence for the physiological basis of noise-robust behavior in a tiny insect brain. PMID:25974721

  7. Mechanism of induction and suppression of antiviral immunity directed by virus-derived small RNAs in Drosophila.

    PubMed

    Aliyari, Roghiyh; Wu, Qingfa; Li, Hong-Wei; Wang, Xiao-Hong; Li, Feng; Green, Lance D; Han, Cliff S; Li, Wan-Xiang; Ding, Shou-Wei

    2008-10-16

    The small RNA-directed viral immunity pathway in plants and invertebrates begins with the production by Dicer nuclease of virus-derived siRNAs (viRNAs), which guide specific antiviral silencing by Argonaute protein in an RNA-induced silencing complex (RISC). Molecular identity of the viral RNA precursor of viRNAs remains a matter of debate. Using Flock house virus (FHV) infection of Drosophila as a model, we show that replication of FHV positive-strand RNA genome produces an approximately 400 bp dsRNA from its 5' terminus that serves as the major Dicer-2 substrate. ViRNAs thus generated are loaded in Argonaute-2 and methylated at their 3' ends. Notably, FHV-encoded RNAi suppressor B2 protein interacts with both viral dsRNA and RNA replicase and inhibits production of the 5'-terminal viRNAs. Our findings, therefore, provide a model in which small RNA-directed viral immunity is induced during the initiation of viral progeny (+)RNA synthesis and suppressed by B2 inside the viral RNA replication complex.

  8. Direct observation of oil consumption mechanisms in a production spark ignition engine using fluorescence techniques. Master's thesis

    SciTech Connect

    Lusted, R.M.

    1994-05-01

    The oil consumption characteristics of a four cylinder, normally aspirated spark-ignition engine were investigated for different piston ring end-gap configurations. A radiotracer was used to perform direct measurement of the oil consumption while Laser-induced Fluorescence (LIF) was used to perform the oil film thickness measurements for consumption predictions using the 'Puddle Theory of Oil Consumption,' which relates oil consumption to second land film thickness and reverse flow through top ring gap. The consumption data was evaluated to determine the impact of top ring end-gap azimuthal location on oil consumption. The film thickness data was used to evaluate the extent to which the oil Puddle Theory predicts variations seen in the actual oil consumption. A tritium radiotracer oil consumption measurement system with an accuracy of 94.6% was designed and constructed. This was used to perform direct measurements of the test engine oil consumption in two different test matrices. The first evaluated a piston ring configuration with the rings free to rotate. The second evaluated configurations with the top ring and second piston rings pinned to fix the azimuthal location of the end-gap; the azimuth of the top ring was varied. In the second test matrix, the oil film thickness on the piston's second land was measured, and predictions were made on the basis of that measurement.

  9. Neuroimaging studies of pediatric social anxiety: paradigms, pitfalls and a new direction for investigating the neural mechanisms

    PubMed Central

    2013-01-01

    Social Anxiety Disorder (SAD) is a common and debilitating condition that typically manifests in adolescence. Here we describe cognitive factors engaged by brain-imaging tasks, which model the peer-based social interactions that evoke symptoms of SAD. We then present preliminary results from the Virtual School paradigm, a novel peer-based social interaction task. This paradigm is designed to investigate the neural mechanisms mediating individual differences in social response flexibility and in participants’ responses to uncertainty in social contexts. We discuss the utility of this new paradigm for research on brain function and developmental psychopathology. PMID:23849682

  10. The Process of Nanostructuring of Metal (Iron) Matrix in Composite Materials for Directional Control of the Mechanical Properties

    PubMed Central

    Zemtsova, Elena

    2014-01-01

    We justified theoretical and experimental bases of synthesis of new class of highly nanostructured composite nanomaterials based on metal matrix with titanium carbide nanowires as dispersed phase. A new combined method for obtaining of metal iron-based composite materials comprising the powder metallurgy processes and the surface design of the dispersed phase is considered. The following stages of material synthesis are investigated: (1) preparation of porous metal matrix; (2) surface structuring of the porous metal matrix by TiC nanowires; (3) pressing and sintering to give solid metal composite nanostructured materials based on iron with TiC nanostructures with size 1–50 nm. This material can be represented as the material type “frame in the frame” that represents iron metal frame reinforcing the frame of different chemical compositions based on TiC. Study of material functional properties showed that the mechanical properties of composite materials based on iron with TiC dispersed phase despite the presence of residual porosity are comparable to the properties of the best grades of steel containing expensive dopants and obtained by molding. This will solve the problem of developing a new generation of nanostructured metal (iron-based) materials with improved mechanical properties for the different areas of technology. PMID:24695459

  11. The process of nanostructuring of metal (iron) matrix in composite materials for directional control of the mechanical properties.

    PubMed

    Zemtsova, Elena; Yurchuk, Denis; Smirnov, Vladimir

    2014-01-01

    We justified theoretical and experimental bases of synthesis of new class of highly nanostructured composite nanomaterials based on metal matrix with titanium carbide nanowires as dispersed phase. A new combined method for obtaining of metal iron-based composite materials comprising the powder metallurgy processes and the surface design of the dispersed phase is considered. The following stages of material synthesis are investigated: (1) preparation of porous metal matrix; (2) surface structuring of the porous metal matrix by TiC nanowires; (3) pressing and sintering to give solid metal composite nanostructured materials based on iron with TiC nanostructures with size 1-50 nm. This material can be represented as the material type "frame in the frame" that represents iron metal frame reinforcing the frame of different chemical compositions based on TiC. Study of material functional properties showed that the mechanical properties of composite materials based on iron with TiC dispersed phase despite the presence of residual porosity are comparable to the properties of the best grades of steel containing expensive dopants and obtained by molding. This will solve the problem of developing a new generation of nanostructured metal (iron-based) materials with improved mechanical properties for the different areas of technology.

  12. Toll like receptor 9 antagonism modulates spinal cord neuronal function and survival: Direct versus astrocyte-mediated mechanisms.

    PubMed

    Acioglu, Cigdem; Mirabelli, Ersilia; Baykal, Ahmet Tarik; Ni, Li; Ratnayake, Ayomi; Heary, Robert F; Elkabes, Stella

    2016-08-01

    Toll like receptors (TLRs) are expressed by cells of the immune system and mediate the host innate immune responses to pathogens. However, increasing evidence indicates that they are important contributors to central nervous system (CNS) function in health and in pathological conditions involving sterile inflammation. In agreement with this idea, we have previously shown that intrathecal administration of a TLR9 antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), ameliorates the outcomes of spinal cord injury (SCI). Although these earlier studies showed a marked effect of CpG ODN 2088 on inflammatory cells, the expression of TLR9 in spinal cord (SC) neurons and astrocytes suggested that the antagonist exerts additional effects through direct actions on these cells. The current study was undertaken to assess the direct effects of CpG ODN 2088 on SC neurons, astrocytes and astrocyte-neuron interactions, in vitro. We report, for the first time, that inhibition of TLR9 in cultured SC neurons alters their function and confers protection against kainic acid (KA)-induced excitotoxic death. Moreover, the TLR9 antagonist attenuated the KA-elicited endoplasmic reticulum (ER) stress response in neurons, in vitro. CpG ODN 2088 also reduced the transcript levels and release of chemokine (C-X-C) motif ligand 1 (CXCL1) and monocyte chemotactic protein 1 (MCP-1) by astrocytes and it diminished interleukin-6 (IL-6) release without affecting transcript levels in vitro. Conditioned medium (CM) of CpG ODN 2088-treated astroglial cultures decreased the viability of SC neurons compared to CM of vehicle-treated astrocytes. However, this toxicity was not observed when astrocytes were co-cultured with neurons. Although CpG ODN 2088 limited the survival-promoting effects of astroglia, it did not reduce neuronal viability compared to controls grown in the absence of astrocytes. We conclude that the TLR9 antagonist acts directly on both SC neurons and astrocytes

  13. On the protonation states, hydrogen bonding and catalytic mechanism of family 11 glycosidases: Direct visualization with neutrons

    DOE PAGESBeta

    Fisher, Suzanne Zoe; Graham, David E.; Hanson, Leif; Kovalevskyi, Andrii Y.; Langan, Paul; Parks, Jerry M.; Wan, Qun; Ostermann, Andreas; Schrader, Tobias

    2015-10-06

    Most enzymatic reactions involve hydrogen or proton transfer among the enzyme, substrate, and water at physiological pH. Thus, enzyme catalysis cannot be fully understood without accurate mapping of hydrogen atom positions in these macromolecular catalysts. Direct information on the location of hydrogen atoms can be obtained using neutron crystallography. We used neutron crystallography and biomolecular simulation to characterize the initial stage of the glycoside hydrolysis reaction catalyzed by a family 11 glycoside hydrolase. We provide evidence that the catalytic glutamate residue alternates between two conformations bearing different basicities, first to obtain a proton from the bulk solvent, and then tomore » deliver it to the glycosidic oxygen to initiate the hydrolysis reaction.« less

  14. Direct observation and mechanism for enhanced field emission sites in platinum ion implanted/post-annealed ultrananocrystalline diamond films

    SciTech Connect

    Panda, Kalpataru E-mail: phy.kalpa@gmail.com; Inami, Eiichi; Sugimoto, Yoshiaki; Sankaran, Kamatchi J.; Tai, Nyan Hwa; Lin, I-Nan

    2014-10-20

    Enhanced electron field emission (EFE) properties for ultrananocrystalline diamond (UNCD) films upon platinum (Pt) ion implantation and subsequent post-annealing processes is reported, viz., low turn-on field of 4.17 V/μm with high EFE current density of 5.08 mA/cm{sup 2} at an applied field of 7.0 V/μm. Current imaging tunneling spectroscopy (CITS) mode in scanning tunneling spectroscopy directly revealed the increased electron emission sites density for Pt ion implanted/post-annealed UNCD films than the pristine one. The high resolution CITS mapping and local current–voltage characteristic curves demonstrated that the electrons are dominantly emitted from the diamond grain boundaries and Pt nanoparticles.

  15. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma

    PubMed Central

    Rheinbay, Esther; Boulay, Gaylor; Suvà, Mario L.; Rossetti, Nikki E.; Boonseng, Wannaporn E.; Oksuz, Ozgur; Cook, Edward B.; Formey, Aurélie; Patel, Anoop; Gymrek, Melissa; Thapar, Vishal; Deshpande, Vikram; Ting, David T.; Hornicek, Francis J.; Nielsen, G. Petur; Stamenkovic, Ivan; Aryee, Martin J.

    2015-01-01

    Summary The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma yet its molecular function is incompletely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators, while activating oncogenes and new potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation. PMID:25453903

  16. Community directed approach beyond ivermectin in Tanzania: a promising mechanism for the delivery of complex health interventions.

    PubMed

    Mutalemwa, P; Kisinza, W N; Kisoka, W J; Kilima, S; Njau, J; Tenu, F; Nkya, T; Magesa, S M

    2009-07-01

    The Community Directed Intervention (CDI) is currently used for Ivermectin distribution for the treatment of onchocerciasis in Africa. This study was carried out to determine the extent to which the CDI process can be used for the delivery of other health interventions with different degrees of complexity. The study was conducted in five districts of Kilosa, Muheza, Lushoto, Korogwe and Ulanga in Tanzania and involved communities, health facility and district healthcare providers. Implementation of CDI across these health interventions involved addressing six major processes, namely, stakeholder processes, health system dynamics, engaging communities, empowering communities, engaging CDI implementers and broader system effects. Community and health systems changes were triggered, such that the inherent value of community involvement and empowerment could be internalized by communities and health workers, leading to a more receptive health system. The CDI process was accepted at the community levels as many were willing and ready to adopt the approach. Health workers at community levels were readily available and supportive of the process. Additionally, noted were the verified willingness and ability of community implementers to deliver multiple interventions; confirmed efficiency of CDI leading to cost savings at health systems level; increasing interest of the health system in CDI; interest of health workers in the process of integrated planning. However, there were factors that may have a negative influence on the CDI process. Drug and supply policy for CDI process was lacking at the national and district levels and the presence of parallel community-based programmes that provide financial incentives for community members to run them discouraged Community-directed distributors who in most cases are volunteers. In conclusion, the results have clearly and evidently demonstrated the potential of CDI approach for effectively and efficiently control of other diseases

  17. Asymmetric control mechanisms of bimanual coordination: an application of directed connectivity analysis to kinematic and functional MRI data.

    PubMed

    Maki, Yohko; Wong, Kin Foon Kevin; Sugiura, Motoaki; Ozaki, Tohru; Sadato, Norihiro

    2008-10-01

    Mirror-symmetrical bimanual movement is more stable than parallel bimanual movement. This is well established at the kinematic level. We used functional MRI (fMRI) to evaluate the neural substrates of the stability of mirror-symmetrical bimanual movement. Right-handed participants (n=17) rotated disks with their index fingers bimanually, both in mirror-symmetrical and asymmetrical parallel modes. We applied the Akaike causality model to both kinematic and fMRI time-series data. We hypothesized that kinematic stability is represented by the extent of neural "cross-talk": as the fraction of signals that are common to controlling both hands increases, the stability also increases. The standard deviation of the phase difference for the mirror mode was significantly smaller than that for the parallel mode, confirming that the former was more stable. We used the noise-contribution ratio (NCR), which was computed using a multivariate autoregressive model with latent variables, as a direct measure of the cross-talk between both the two hands and the bilateral primary motor cortices (M1s). The mode-by-direction interaction of the NCR was significant in both the kinematic and fMRI data. Furthermore, in both sets of data, the NCR from the right hand (left M1) to the left (right M1) was more prominent than vice versa during the mirror-symmetrical mode, whereas no difference was observed during parallel movement or rest. The asymmetric interhemispheric interaction from the left M1 to the right M1 during symmetric bimanual movement might represent cortical-level cross-talk, which contributes to the stability of symmetric bimanual movements.

  18. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    PubMed

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  19. Replacement element for automobile thermostat

    SciTech Connect

    Ferrari, W.

    1988-06-07

    This patent describes a thermostat replacement element for use in a cooling system in which a continuous stream of coolant n