Examining the influence of grain size on radiation tolerance in the nanocrystalline regime

DOE PAGES

Barr, Christopher M.; Li, Nan; Boyce, Brad L.; ...

2018-05-01

Here, nanocrystalline materials have been proposed as superior radiation tolerant materials in comparison to coarse grain counterparts. However, there is still a limited understanding whether a particular nanocrystalline grain size is required to obtain significant improvements in key deleterious effects resulting from energetic irradiation. This work employs the use of in-situ heavy ion irradiation transmission electron microscopy experiments coupled with quantitative defect characterization and precession electron diffraction to explore the sensitivity of defect size and density within the nanocrystalline regime in platinum. Under the explored experimental conditions, no significant change in either the defect size or density between grain sizesmore » of 20 and 100 nm was observed. Furthermore, the in-situ transmission electron microscopy irradiations illustrate stable sessile defect clusters of 1–3 nm adjacent to most grain boundaries, which are traditionally treated as strong defect sinks. The stability of these sessile defects observed in-situ in small, 20–40 nm, grains is the proposed primary mechanism for a lack of defect density trends. Lastly, this scaling breakdown in radiation improvement with decreasing grain size has practical importance on nanoscale grain boundary engineering approaches for proposed radiation tolerant alloys.« less

Examining the influence of grain size on radiation tolerance in the nanocrystalline regime

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

Barr, Christopher M.; Li, Nan; Boyce, Brad L.

Here, nanocrystalline materials have been proposed as superior radiation tolerant materials in comparison to coarse grain counterparts. However, there is still a limited understanding whether a particular nanocrystalline grain size is required to obtain significant improvements in key deleterious effects resulting from energetic irradiation. This work employs the use of in-situ heavy ion irradiation transmission electron microscopy experiments coupled with quantitative defect characterization and precession electron diffraction to explore the sensitivity of defect size and density within the nanocrystalline regime in platinum. Under the explored experimental conditions, no significant change in either the defect size or density between grain sizesmore » of 20 and 100 nm was observed. Furthermore, the in-situ transmission electron microscopy irradiations illustrate stable sessile defect clusters of 1–3 nm adjacent to most grain boundaries, which are traditionally treated as strong defect sinks. The stability of these sessile defects observed in-situ in small, 20–40 nm, grains is the proposed primary mechanism for a lack of defect density trends. Lastly, this scaling breakdown in radiation improvement with decreasing grain size has practical importance on nanoscale grain boundary engineering approaches for proposed radiation tolerant alloys.« less

Defect interactions with stepped CeO₂/SrTiO₃ interfaces: implications for radiation damage evolution and fast ion conduction.

PubMed

Dholabhai, Pratik P; Aguiar, Jeffery A; Misra, Amit; Uberuaga, Blas P

2014-05-21

Due to reduced dimensions and increased interfacial content, nanocomposite oxides offer improved functionalities in a wide variety of advanced technological applications, including their potential use as radiation tolerant materials. To better understand the role of interface structures in influencing the radiation damage tolerance of oxides, we have conducted atomistic calculations to elucidate the behavior of radiation-induced point defects (vacancies and interstitials) at interface steps in a model CeO2/SrTiO3 system. We find that atomic-scale steps at the interface have substantial influence on the defect behavior, which ultimately dictate the material performance in hostile irradiation environments. Distinctive steps react dissimilarly to cation and anion defects, effectively becoming biased sinks for different types of defects. Steps also attract cation interstitials, leaving behind an excess of immobile vacancies. Further, defects introduce significant structural and chemical distortions primarily at the steps. These two factors are plausible origins for the enhanced amorphization at steps seen in our recent experiments. The present work indicates that comprehensive examination of the interaction of radiation-induced point defects with the atomic-scale topology and defect structure of heterointerfaces is essential to evaluate the radiation tolerance of nanocomposites. Finally, our results have implications for other applications, such as fast ion conduction.

Performance of defect-tolerant set-associative cache memories

NASA Technical Reports Server (NTRS)

Frenzel, J. F.

1991-01-01

The increased use of on-chip cache memories has led researchers to investigate their performance in the presence of manufacturing defects. Several techniques for yield improvement are discussed and results are presented which indicate that set-associativity may be used to provide defect tolerance as well as improve the cache performance. Tradeoffs between several cache organizations and replacement strategies are investigated and it is shown that token-based replacement may be a suitable alternative to the widely-used LRU strategy.

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

Lu, Chenyang; Niu, Liangliang; Chen, Nanjun

A grand challenge in material science is to understand the correlation between intrinsic properties and defect dynamics. Radiation tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Unlike traditional approaches that rely on microstructural and nanoscale features to mitigate radiation damage, this study demonstrates enhancement of radiation tolerance with the suppression of void formation by two orders magnitude at elevated temperatures in equiatomic single-phase concentrated solid solution alloys, and more importantly, reveals its controlling mechanism through a detailed analysis of the depth distribution of defect clusters and an atomistic computer simulation. The enhancedmore » swelling resistance is attributed to the tailored interstitial defect cluster motion in the alloys from a long-range one-dimensional mode to a short-range three-dimensional mode, which leads to enhanced point defect recombination. Finally, the results suggest design criteria for next generation radiation tolerant structural alloys.« less

Variation and Defect Tolerance for Nano Crossbars

NASA Astrophysics Data System (ADS)

Tunc, Cihan

With the extreme shrinking in CMOS technology, quantum effects and manufacturing issues are getting more crucial. Hence, additional shrinking in CMOS feature size seems becoming more challenging, difficult, and costly. On the other hand, emerging nanotechnology has attracted many researchers since additional scaling down has been demonstrated by manufacturing nanowires, Carbon nanotubes as well as molecular switches using bottom-up manufacturing techniques. In addition to the progress in manufacturing, developments in architecture show that emerging nanoelectronic devices will be promising for the future system designs. Using nano crossbars, which are composed of two sets of perpendicular nanowires with programmable intersections, it is possible to implement logic functions. In addition, nano crossbars present some important features as regularity, reprogrammability, and interchangeability. Combining these features, researchers have presented different effective architectures. Although bottom-up nanofabrication can greatly reduce manufacturing costs, due to low controllability in the manufacturing process, some critical issues occur. Bottom- up nanofabrication process results in high variation compared to conventional top- down lithography used in CMOS technology. In addition, an increased failure rate is expected. Variation and defect tolerance methods used for conventional CMOS technology seem inadequate for adapting to emerging nano technology because the variation and the defect rate for emerging nano technology is much more than current CMOS technology. Therefore, variations and defect tolerance methods for emerging nano technology are necessary for a successful transition. In this work, in order to tolerate variations for crossbars, we introduce a framework that is established based on reprogrammability and interchangeability features of nano crossbars. This framework is shown to be applicable for both FET-based and diode-based nano crossbars. We present a characterization testing method which requires minimal number of test vectors. We formulate the variation optimization problem using Simulated Annealing with different optimization goals. Furthermore, we extend the framework for defect tolerance. Experimental results and comparison of proposed framework with exhaustive methods confirm its effectiveness for both variation and defect tolerance.

On the monitoring and implications of growing damages caused by manufacturing defects in composite structures

NASA Astrophysics Data System (ADS)

Schagerl, M.; Viechtbauer, C.; Hörrmann, S.

2015-07-01

Damage tolerance is a classical safety concept for the design of aircraft structures. Basically, this approach considers possible damages in the structure, predicts the damage growth under applied loading conditions and predicts the following decrease of the structural strength. As a fundamental result the damage tolerance approach yields the maximum inspection interval, which is the time a damage grows from a detectable to a critical level. The above formulation of the damage tolerance safety concept targets on metallic structures where the damage is typically a simple fatigue crack. Fiber-reinforced polymers show a much more complex damage behavior, such as delaminationsin laminated composites. Moreover, progressive damage in composites is often initiated by manufacturing defects. The complex manufacturing processes for composite structures almost certainly yield parts with defects, e.g. pores in the matrix or undulations of fibers. From such defects growing damages may start after a certain time of operation. The demand to simplify or even avoid the inspection of composite structures has therefore led to a comeback of the traditional safe-life safety concept. The aim of the so-called safe-life flaw tolerance concept is a structure that is capable of carrying the static loads during operation, despite significant damages and after a representative fatigue load spectrum. A structure with this property does not need to be inspected, respectively monitored at all during its service life. However, its load carrying capability is thereby not fully utilized. This article presents the possible refinement of the state-of-the-art safe-life flaw tolerance concept for composite structures towards a damage tolerance approach considering also the influence of manufacturing defects on damage initiation and growth. Based on fundamental physical relations and experimental observations the challenges when developing damage growth and residual strength curves are discussed.

PSO/ACO algorithm-based risk assessment of human neural tube defects in Heshun County, China.

PubMed

Liao, Yi Lan; Wang, Jin Feng; Wu, Ji Lei; Wang, Jiao Jiao; Zheng, Xiao Ying

2012-10-01

To develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world. The region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects (NTDs). A hybrid particle swarm optimization/ant colony optimization (PSO/ACO) algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes. The algorithm was easy to apply, with the accuracy of the results being 69.5%±7.02% at the 95% confidence level. The proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations. Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Defect formation energy in pyrochlore: the effect of crystal size

NASA Astrophysics Data System (ADS)

Wang, Jianwei; Ewing, Rodney C.; Becker, Udo

2014-09-01

Defect formation energies of point defects of two pyrochlores Gd2Ti2O7 and Gd2Zr2O7 as a function of crystal size were calculated. Density functional theory with plane-wave basis sets and the projector-augmented wave method were used in the calculations. The results show that the defect formation energies of the two pyrochlores diverge as the size decreases to the nanometer range. For Gd2Ti2O7 pyrochlore, the defect formation energy is higher at nanometers with respect to that of the bulk, while it is lower for Gd2Zr2O7. The lowest defect formation energy for Gd2Zr2O7 is found at 15-20 Å. The different behaviors of the defect formation energies as a function of crystal size are caused by different structural adjustments around the defects as the size decreases. For both pyrochlore compositions at large sizes, the defect structures are similar to those of the bulk. As the size decreases, for Gd2Ti2O7, additional structure distortions appear at the surfaces, which cause the defect formation energy to increase. For Gd2Zr2O7, additional oxygen Frenkel pair defects are introduced, which reduce the defect formation energy. As the size further decreases, increased structure distortions occur at the surfaces, which cause the defect formation energy to increase. Based on a hypothesis that correlates the energetics of defect formation and radiation response for complex oxides, the calculated results suggest that at nanometer range Gd2Ti2O7 pyrochlore is expected to have a lower radiation tolerance, and those of Gd2Zr2O7 pyrochlore to have a higher radiation tolerance. The highest radiation tolerance for Gd2Zr2O7 pyrochlore is expected to be found at ˜2 nanometers.

Searching for “Defect-Tolerant” Photovoltaic Materials: Combined Theoretical and Experimental Screening

DOE PAGES

Brandt, Riley E.; Poindexter, Jeremy R.; Gorai, Prashun; ...

2017-05-09

Recently, we and others have proposed screening criteria for 'defect-tolerant' photovoltaic (PV) absorbers, identifying several classes of semiconducting compounds with electronic structures similar to those of hybrid lead-halide perovskites. In this work, we reflect on the accuracy and prospects of these new design criteria through a combined experimental and theoretical approach. We construct a model to extract photoluminescence lifetimes of six of these candidate PV absorbers, including four (InI, SbSI, SbSeI, and BiOI) for which time-resolved photoluminescence has not been previously reported. The lifetimes of all six candidate materials exceed 1 ns, a threshold for promising early stage PV devicemore » performance. However, there are variations between these materials, and none achieve lifetimes as high as those of the hybrid lead-halide perovskites, suggesting that the heuristics for defect-tolerant semiconductors are incomplete. Here, we explore this through first-principles point defect calculations and Shockley-Read-Hall recombination models to describe the variation between the measured materials. In light of these insights, we discuss the evolution of screening criteria for defect tolerance and high-performance PV materials.« less

Competition of tolerant strategies in the spatial public goods game

NASA Astrophysics Data System (ADS)

Szolnoki, Attila; Perc, Matjaž

2016-08-01

Tolerance implies enduring trying circumstances with a fair and objective attitude. To determine whether evolutionary advantages might be stemming from diverse levels of tolerance in a population, we study a spatial public goods game, where in addition to cooperators, defectors, and loners, tolerant players are also present. Depending on the number of defectors within a group, a tolerant player can either cooperate in or abstain from a particular instance of the game. We show that the diversity of tolerance can give rise to synergistic effects, wherein players with a different threshold in terms of the tolerated number of defectors in a group compete most effectively against defection and default abstinence. Such synergistic associations can stabilise states of full cooperation where otherwise defection would dominate. We observe complex pattern formation that gives rise to an intricate phase diagram, where invisible yet stable strategy alliances require outmost care lest they are overlooked. Our results highlight the delicate importance of diversity and tolerance for the provisioning of public goods, and they reveal fascinating subtleties of the spatiotemporal dynamics that is due to the competition of subsystem solutions in structured populations.

Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model.

PubMed

Mrozik, Krzysztof Marek; Wada, Naohisa; Marino, Victor; Richter, Ward; Shi, Songtao; Wheeler, Donna L; Gronthos, Stan; Bartold, P Mark

2013-11-01

To investigate the capacity of allogeneic periodontal ligament stem cells (PDLSCs) to regenerate periodontal tissues using an ovine periodontal defect model. Surgically created zero-wall dehiscence periodontal defects created in Merino sheep were filled with 1 × 10(7) allogeneic PDLSCs attached to Gelfoam(®), Gelfoam alone or left untreated. After 4 weeks, histological analysis was performed to assess periodontal regeneration. Allogeneic PDLSCs were well tolerated by recipient animals. The mean area of new alveolar bone was significantly greater in the PDLSC + Gelfoam treatment group compared with the defect-alone group. The PDLSC + Gelfoam and Gelfoam-only treatment groups displayed significantly greater length of new cementum and percentage of cementum regrowth compared with the defect-alone group. New Sharpey's fibers were generally more organized and significantly thicker within the PDLSC + Gelfoam treatment group. The PDLSC + Gelfoam treatment group also showed a trend of increased Sharpey's fiber attachment length compared with the Gelfoam-only and defect-alone groups. These studies support the potential use of allogeneic PDLSC preparations as viable therapies for periodontal regeneration in the clinical setting.

Progressive Fracture of Fiber Composite Thin Shell Structures Under Internal Pressure and Axial Loads

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, Christos C.; Minnetyan, Levon

1996-01-01

Graphite/epoxy composite thin shell structures were simulated to investigate damage and fracture progression due to internal pressure and axial loading. Defective and defect-free structures (thin cylinders) were examined. The three different laminates examined had fiber orientations of (90/0/+/-0)(sub s), where 0 is 45, 60, and 75 deg. CODSTRAN, an integrated computer code that scales up constituent level properties to the structural level and accounts for all possible failure modes, was used to simulate composite degradation under loading. Damage initiation, growth, accumulation, and propagation to fracture were included in the simulation. Burst pressures for defective and defect-free shells were compared to evaluate damage tolerance. The results showed that damage initiation began with matrix failure whereas damage and/or fracture progression occurred as a result of additional matrix failure and fiber fracture. In both thin cylinder cases examined (defective and defect-free), the optimum layup configuration was (90/0/+/-60)(sub s) because it had the best damage tolerance with respect to the burst pressure.

Defects-tolerant Co-Cr-Mo dental alloys prepared by selective laser melting.

PubMed

Qian, B; Saeidi, K; Kvetková, L; Lofaj, F; Xiao, C; Shen, Z

2015-12-01

CrCoMo alloy specimens were successfully fabricated using selective laser melting (SLM). The aim of this study was to carefully investigate microstructure of the SLM specimens in order to understand the influence of their structural features inter-grown on different length scales ranging from nano- to macro-levels on their mechanical properties. Two different sets of processing parameters developed for building the inner part (core) and the surface (skin) of dental prostheses were tested. Microstructures were characterized by SEM, EBSD and XRD analysis. The elemental distribution was assessed by EDS line profile analysis under TEM. The mechanical properties of the specimens were measured. The microstructures of both specimens were characterized showing formation of grains comprised of columnar sub-grains with Mo-enrichment at the sub-grain boundaries. Clusters of columnar sub-grains grew coherently along one common crystallographic direction forming much larger single crystal grains which are intercrossing in different directions forming an overall dendrite-like microstructure. Three types of microstructural defects were occasionally observed; small voids (<10 μm), fine cracks at grain boundaries (<10 μm) and cracks at weld line boundaries (>10 μm). Despite the presence of these defects, the yield and the ultimate tensile strength (UTS) were 870 and 430MPa and 1300MPa and 1160MPa, respectively, for the skin and core specimens which are higher than casted dental alloy. Although the formation of microstructural defects is hard to be avoided during the SLM process, the SLM CoCrMo alloys can achieve improved mechanical properties than their casted counterparts, implying they are "defect-tolerant". Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

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

Brandt, Riley E.; Poindexter, Jeremy R.; Gorai, Prashun

Recently, we and others have proposed screening criteria for 'defect-tolerant' photovoltaic (PV) absorbers, identifying several classes of semiconducting compounds with electronic structures similar to those of hybrid lead-halide perovskites. In this work, we reflect on the accuracy and prospects of these new design criteria through a combined experimental and theoretical approach. We construct a model to extract photoluminescence lifetimes of six of these candidate PV absorbers, including four (InI, SbSI, SbSeI, and BiOI) for which time-resolved photoluminescence has not been previously reported. The lifetimes of all six candidate materials exceed 1 ns, a threshold for promising early stage PV devicemore » performance. However, there are variations between these materials, and none achieve lifetimes as high as those of the hybrid lead-halide perovskites, suggesting that the heuristics for defect-tolerant semiconductors are incomplete. Here, we explore this through first-principles point defect calculations and Shockley-Read-Hall recombination models to describe the variation between the measured materials. In light of these insights, we discuss the evolution of screening criteria for defect tolerance and high-performance PV materials.« less

In situ heavy ion irradiation studies of nanopore shrinkage and enhanced radiation tolerance of nanoporous Au

DOE PAGES

Li, Jin; Fan, Cuncai; Ding, Jie; ...

2017-01-03

High energy particle radiations induce severe microstructural damage in metallic materials. Nanoporous materials with a giant surface-to-volume ratio may alleviate radiation damage in irradiated metallic materials as free surface are defect sinks. We show, by using in situ Kr ion irradiation in a transmission electron microscope at room temperature, that nanoporous Au indeed has significantly improved radiation tolerance comparing with coarse-grained, fully dense Au. In situ studies show that nanopores can absorb and eliminate a large number of radiation-induced defect clusters. Meanwhile, nanopores shrink (self-heal) during radiation, and their shrinkage rate is pore size dependent. Furthermore, the in situ studiesmore » show dose-rate-dependent diffusivity of defect clusters. Our study sheds light on the design of radiation-tolerant nanoporous metallic materials for advanced nuclear reactor applications.« less

Nature of the chemical bond and prediction of radiation tolerance in pyrochlore and defect fluorite compounds

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

Lumpkin, Gregory R.; Institute of Materials and Engineering Science, Australian Nuclear Science and Technology Organisation, Private Mail Bag 1, Menai, NSW 2234; Pruneda, Miguel

2007-04-15

The radiation tolerance of synthetic pyrochlore and defect fluorite compounds has been studied using ion irradiation. We show that the results can be quantified in terms of the critical temperature for amorphization, structural parameters, classical Pauling electronegativity difference, and disorder energies. Our results demonstrate that radiation tolerance is correlated with a change in the structure from pyrochlore to defect fluorite, a smaller unit cell dimension, and lower cation-anion disorder energy. Radiation tolerance is promoted by an increase in the Pauling cation-anion electronegativity difference or, in other words, an increase in the ionicity of the chemical bonds. A further analysis ofmore » the data indicates that, of the two possible cation sites in ideal pyrochlore, the smaller B-site cation appears to play the major role in bonding. This result is supported by ab initio calculations of the structure and bonding, showing a correlation between the Mulliken overlap populations of the B-site cation and the critical temperature. - Graphical abstract: Three-dimensional representation of the predicted critical amorphization temperature in pyrochlores.« less

A novel one-shot circular stapler closure for atrial septal defect in a beating-heart porcine model.

PubMed

Tarui, Tatsuya; Tomita, Shigeyuki; Ishikawa, Norihiko; Ohtake, Hiroshi; Watanabe, Go

2015-02-01

In surgical atrial septal defect (ASD) closure, there are no techniques or devices that can close the ASD accurately in a short time under a beating heart. We have developed a simple and automatic ASD closure technique using a circular stapler. This study assessed the feasibility and efficacy of a new circular stapler closure for ASD. Under a continuous beating heart, hand-sewn patch plasty ASD closure was performed in 6 pigs (group A) and circular stapler ASD closure was performed in 6 pigs (group B). The time to close the ASD and the effectiveness of the closure were compared. Closure was significantly faster in group B (10.5 ± 1.0 seconds) than in group A (664 ± 10 seconds; p < 0.05). There was no leakage at the closure site, and sufficient tolerance was confirmed. A circular stapler can be used to treat ASD faster than hand-sewn patch plasty, with sufficient pressure tolerance in a beating heart porcine model. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

High Tolerance to Iron Contamination in Lead Halide Perovskite Solar Cells

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

Poindexter, Jeremy R.; Hoye, Robert L. Z.; Nienhaus, Lea

The relationship between charge-carrier lifetime and the tolerance of lead halide perovskite (LHP) solar cells to intrinsic point defects has drawn much attention by helping to explain rapid improvements in device efficiencies. However, little is known about how charge-carrier lifetime and solar cell performance in LHPs are affected by extrinsic defects (i.e., impurities), including those that are common in manufacturing environments and known to introduce deep levels in other semiconductors. Here, we evaluate the tolerance of LHP solar cells to iron introduced via intentional contamination of the feedstock and examine the root causes of the resulting efficiency losses. We findmore » that comparable efficiency losses occur in LHPs at feedstock iron concentrations approximately 100 times higher than those in p-type silicon devices. Photoluminescence measurements correlate iron concentration with nonradiative recombination, which we attribute to the presence of deep-level iron interstitials, as calculated from first-principles, as well as iron-rich particles detected by synchrotron-based X-ray fluorescence microscopy. At moderate contamination levels, we witness prominent recovery of device efficiencies to near-baseline values after biasing at 1.4 V for 60 s in the dark. We theorize that this temporary effect arises from improved charge-carrier collection enhanced by electric fields strengthened from ion migration toward interfaces. Lastly, our results demonstrate that extrinsic defect tolerance contributes to high efficiencies in LHP solar cells, which inspires further investigation into potential large-scale manufacturing cost savings as well as the degree of overlap between intrinsic and extrinsic defect tolerance in LHPs and 'perovskite-inspired' lead-free stable alternatives.« less

High Tolerance to Iron Contamination in Lead Halide Perovskite Solar Cells

DOE PAGES

Poindexter, Jeremy R.; Hoye, Robert L. Z.; Nienhaus, Lea; ...

2017-06-28

The relationship between charge-carrier lifetime and the tolerance of lead halide perovskite (LHP) solar cells to intrinsic point defects has drawn much attention by helping to explain rapid improvements in device efficiencies. However, little is known about how charge-carrier lifetime and solar cell performance in LHPs are affected by extrinsic defects (i.e., impurities), including those that are common in manufacturing environments and known to introduce deep levels in other semiconductors. Here, we evaluate the tolerance of LHP solar cells to iron introduced via intentional contamination of the feedstock and examine the root causes of the resulting efficiency losses. We findmore » that comparable efficiency losses occur in LHPs at feedstock iron concentrations approximately 100 times higher than those in p-type silicon devices. Photoluminescence measurements correlate iron concentration with nonradiative recombination, which we attribute to the presence of deep-level iron interstitials, as calculated from first-principles, as well as iron-rich particles detected by synchrotron-based X-ray fluorescence microscopy. At moderate contamination levels, we witness prominent recovery of device efficiencies to near-baseline values after biasing at 1.4 V for 60 s in the dark. We theorize that this temporary effect arises from improved charge-carrier collection enhanced by electric fields strengthened from ion migration toward interfaces. Lastly, our results demonstrate that extrinsic defect tolerance contributes to high efficiencies in LHP solar cells, which inspires further investigation into potential large-scale manufacturing cost savings as well as the degree of overlap between intrinsic and extrinsic defect tolerance in LHPs and 'perovskite-inspired' lead-free stable alternatives.« less

7 CFR 51.307 - Application of tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS) United States Standards for Grades of Apples Application of Tolerances § 51.307 Application of... least one apple which is seriously damaged by insects or affected by decay or internal breakdown may be... have more than 3 times the tolerance specified, except that at least three defective apples may be...

7 CFR 51.307 - Application of tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS) United States Standards for Grades of Apples Application of Tolerances § 51.307 Application of... least one apple which is seriously damaged by insects or affected by decay or internal breakdown may be... have more than 3 times the tolerance specified, except that at least three defective apples may be...

7 CFR 51.307 - Application of tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS) United States Standards for Grades of Apples Application of Tolerances § 51.307 Application of... least one apple which is seriously damaged by insects or affected by decay or internal breakdown may be... have more than 3 times the tolerance specified, except that at least three defective apples may be...

Fault tolerant system based on IDDQ testing

NASA Astrophysics Data System (ADS)

Guibane, Badi; Hamdi, Belgacem; Mtibaa, Abdellatif; Bensalem, Brahim

2018-06-01

Offline test is essential to ensure good manufacturing quality. However, for permanent or transient faults that occur during the use of the integrated circuit in an application, an online integrated test is needed as well. This procedure should ensure the detection and possibly the correction or the masking of these faults. This requirement of self-correction is sometimes necessary, especially in critical applications that require high security such as automotive, space or biomedical applications. We propose a fault-tolerant design for analogue and mixed-signal design complementary metal oxide (CMOS) circuits based on the quiescent current supply (IDDQ) testing. A defect can cause an increase in current consumption. IDDQ testing technique is based on the measurement of power supply current to distinguish between functional and failed circuits. The technique has been an effective testing method for detecting physical defects such as gate-oxide shorts, floating gates (open) and bridging defects in CMOS integrated circuits. An architecture called BICS (Built In Current Sensor) is used for monitoring the supply current (IDDQ) of the connected integrated circuit. If the measured current is not within the normal range, a defect is signalled and the system switches connection from the defective to a functional integrated circuit. The fault-tolerant technique is composed essentially by a double mirror built-in current sensor, allowing the detection of abnormal current consumption and blocks allowing the connection to redundant circuits, if a defect occurs. Spices simulations are performed to valid the proposed design.

Damage Tolerance Behavior of Friction Stir Welds in Aluminum Alloys

NASA Technical Reports Server (NTRS)

McGill, Preston; Burkholder, Jonathan

2012-01-01

Friction stir welding is a solid state welding process used in the fabrication of various aerospace structures. Self-reacting and conventional friction stir welding are variations of the friction stir weld process employed in the fabrication of cryogenic propellant tanks which are classified as pressurized structure in many spaceflight vehicle architectures. In order to address damage tolerance behavior associated with friction stir welds in these safety critical structures, nondestructive inspection and proof testing may be required to screen hardware for mission critical defects. The efficacy of the nondestructive evaluation or the proof test is based on an assessment of the critical flaw size. Test data describing fracture behavior, residual strength capability, and cyclic mission life capability of friction stir welds at ambient and cryogenic temperatures have been generated and will be presented in this paper. Fracture behavior will include fracture toughness and tearing (R-curve) response of the friction stir welds. Residual strength behavior will include an evaluation of the effects of lack of penetration on conventional friction stir welds, the effects of internal defects (wormholes) on self-reacting friction stir welds, and an evaluation of the effects of fatigue cycled surface cracks on both conventional and selfreacting welds. Cyclic mission life capability will demonstrate the effects of surface crack defects on service load cycle capability. The fracture data will be used to evaluate nondestructive inspection and proof test requirements for the welds.

Fatigue Behavior of Long and Short Cracks in Wrought and Powder Aluminum Alloys.

DTIC Science & Technology

1983-05-01

physically small (i.e., : 1 mm), must be considered as one of the major factors limiting the application of defect-tolerant fatigue design for airframe and...compared to the scale of local plasticity or simply physically small (i.e., 1 nm), must be considered as one of the major factors limiting the application ...particularly at near-threshold levels, a major limitation in the application of such information to defect-tolerant design must be regarded as the

Asymmetric interaction of point defects and heterophase interfaces in ZrN/TaN multilayered nanofilms.

PubMed

Lao, Yuanxia; Hu, Shuanglin; Shi, Yunlong; Deng, Yu; Wang, Fei; Du, Hao; Zhang, Haibing; Wang, Yuan

2017-01-05

Materials with a high density of heterophase interfaces, which are capable of absorbing and annihilating radiation-induced point defects, can exhibit a superior radiation tolerance. In this paper, we investigated the interaction behaviors of point defects and heterophase interfaces by implanting helium atoms into the ZrN/TaN multilayered nanofilms. It was found that the point defect-interface interaction on the two sides of the ZrN/TaN interface was asymmetric, likely due to the difference in the vacancy formation energies of ZrN and TaN. The helium bubbles could migrate from the ZrN layers into the TaN layers through the heterophase interfaces, resulting in a better crystallinity of the ZrN layers and a complete amorphization of the TaN layers. The findings provided some clues to the fundamental behaviors of point defects near the heterophase interfaces, which make us re-examine the design rules of advanced radiation-tolerant materials.

Asymmetric interaction of point defects and heterophase interfaces in ZrN/TaN multilayered nanofilms

NASA Astrophysics Data System (ADS)

Lao, Yuanxia; Hu, Shuanglin; Shi, Yunlong; Deng, Yu; Wang, Fei; Du, Hao; Zhang, Haibing; Wang, Yuan

2017-01-01

Materials with a high density of heterophase interfaces, which are capable of absorbing and annihilating radiation-induced point defects, can exhibit a superior radiation tolerance. In this paper, we investigated the interaction behaviors of point defects and heterophase interfaces by implanting helium atoms into the ZrN/TaN multilayered nanofilms. It was found that the point defect-interface interaction on the two sides of the ZrN/TaN interface was asymmetric, likely due to the difference in the vacancy formation energies of ZrN and TaN. The helium bubbles could migrate from the ZrN layers into the TaN layers through the heterophase interfaces, resulting in a better crystallinity of the ZrN layers and a complete amorphization of the TaN layers. The findings provided some clues to the fundamental behaviors of point defects near the heterophase interfaces, which make us re-examine the design rules of advanced radiation-tolerant materials.

Asymmetric interaction of point defects and heterophase interfaces in ZrN/TaN multilayered nanofilms

PubMed Central

Lao, Yuanxia; Hu, Shuanglin; Shi, Yunlong; Deng, Yu; Wang, Fei; Du, Hao; Zhang, Haibing; Wang, Yuan

2017-01-01

Materials with a high density of heterophase interfaces, which are capable of absorbing and annihilating radiation-induced point defects, can exhibit a superior radiation tolerance. In this paper, we investigated the interaction behaviors of point defects and heterophase interfaces by implanting helium atoms into the ZrN/TaN multilayered nanofilms. It was found that the point defect-interface interaction on the two sides of the ZrN/TaN interface was asymmetric, likely due to the difference in the vacancy formation energies of ZrN and TaN. The helium bubbles could migrate from the ZrN layers into the TaN layers through the heterophase interfaces, resulting in a better crystallinity of the ZrN layers and a complete amorphization of the TaN layers. The findings provided some clues to the fundamental behaviors of point defects near the heterophase interfaces, which make us re-examine the design rules of advanced radiation-tolerant materials. PMID:28053307

7 CFR 51.346 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples for Processing Tolerances § 51.346 Tolerances. When a lot of apples is required to meet one of the U.S. grades, the apples shall not be further...) For defects. 10 percent for apples which fail to meet the requirements of the grade: Provided, That...

7 CFR 51.346 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples for Processing Tolerances § 51.346 Tolerances. When a lot of apples is required to meet one of the U.S. grades, the apples shall not be further...) For defects. 10 percent for apples which fail to meet the requirements of the grade: Provided, That...

7 CFR 51.1439 - Tolerances for defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... foreign material; (2) 3 percent for portions of kernels which are “dark amber” or darker color, or darker... percent for portions of kernels which fail to meet the remaining requirements of the grade, including... of this tolerance may be applied to increase the tolerance for kernels which are “dark amber” or...

7 CFR 51.1439 - Tolerances for defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... foreign material; (2) 3 percent for portions of kernels which are “dark amber” or darker color, or darker... of this tolerance may be applied to increase the tolerance for kernels which are “dark amber” or darker color, or darker than any specified lighter color classification. (b) U.S. Commercial Halves, U.S...

7 CFR 51.1439 - Tolerances for defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... foreign material; (2) 3 percent for portions of kernels which are “dark amber” or darker color, or darker... of this tolerance may be applied to increase the tolerance for kernels which are “dark amber” or darker color, or darker than any specified lighter color classification. (b) U.S. Commercial Halves, U.S...

T-bet Down-Modulation in Tolerized Th1 Effector CD4 Cells Confers a TCR-Distal Signaling Defect That Selectively Impairs IFN-γ Expression1

PubMed Central

Long, Meixiao; Slaiby, Aaron M.; Hagymasi, Adam T.; Mihalyo, Marianne A.; Lichtler, Alexander C.; Reiner, Steven L.; Adler, Adam J.

2010-01-01

When Th1 effector CD4 cells encounter tolerizing Ag in vivo, their capacity to express the effector cytokines IFN-γ and TNF-α is lost more rapidly than noneffector functions such as IL-2 production and proliferation. To localize the relevant intracellular signaling defects, cytokine expression was compared following restimulation with Ag vs agents that bypass TCR-proximal signaling. IFN-γ and TNF-α expression were both partially rescued when TCR-proximal signaling was bypassed, indicating that both TCR-proximal and -distal signaling defects impair the expression of these two effector cytokines. In contrast, bypassing TCR-proximal signaling fully rescued IL-2 expression. T-bet, a transcription and chromatin remodeling factor that is required to direct the differentiation of naive CD4 cells into IFN-γ -expressing Th1 effectors, was partially down-modulated in tolerized Th1 effectors. Enforcing T-bet expression during tolerization selectively rescued the ability to express IFN-γ, but not TNF-α. Conversely, expression of a dominant-negative T-bet in Th1 effectors selectively impaired the ability to express IFN-γ, but not TNF-α. Analysis of histone acetylation at the IFN-γ promoter further suggested that down-modulation of T-bet expression during Th1 effector CD4 cell tolerization does not impair IFN-γ expression potential through alterations in chromatin structure. PMID:16393991

A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants

PubMed Central

Zhang, Shengxue; Yang, Xuewen; Chen, Rongrong; Zhang, Yuwen; Lu, Wei; Liu, Yan; Wang, Jianhua; Lin, Min; Wang, Guoying

2012-01-01

A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops. PMID:22715408

Band Gap Tuning and Defect Tolerance of Atomically Thin Two-Dimensional Organic-Inorganic Halide Perovskites.

PubMed

Pandey, Mohnish; Jacobsen, Karsten W; Thygesen, Kristian S

2016-11-03

Organic-inorganic halide perovskites have proven highly successful for photovoltaics but suffer from low stability, which deteriorates their performance over time. Recent experiments have demonstrated that low dimensional phases of the hybrid perovskites may exhibit improved stability. Here we report first-principles calculations for isolated monolayers of the organometallic halide perovskites (C 4 H 9 NH 3 ) 2 MX 2 Y 2 , where M = Pb, Ge, Sn and X,Y = Cl, Br, I. The band gaps computed using the GLLB-SC functional are found to be in excellent agreement with experimental photoluminescence data for the already synthesized perovskites. Finally, we study the effect of different defects on the band structure. We find that the most common defects only introduce shallow or no states in the band gap, indicating that these atomically thin 2D perovskites are likely to be defect tolerant.

Effect of Buckling Modes on the Fatigue Life and Damage Tolerance of Stiffened Structures

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Bisagni, Chiara; Rose, Cheryl A.

2015-01-01

The postbuckling response and the collapse of composite specimens with a co-cured hat stringer are investigated experimentally and numerically. These specimens are designed to evaluate the postbuckling response and the effect of an embedded defect on the collapse load and the mode of failure. Tests performed using controlled conditions and detailed instrumentation demonstrate that the damage tolerance, fatigue life, and collapse loads are closely tied with the mode of the postbuckling deformation, which can be different between two nominally identical specimens. Modes that tend to open skin/stringer defects are the most damaging to the structure. However, skin/stringer bond defects can also propagate under shearing modes. In the proposed paper, the effects of initial shape imperfections on the postbuckling modes and the interaction between different postbuckling deformations and the propagation of skin/stringer bond defects under quasi-static or fatigue loads will be examined.

Cariogenic properties of Streptococcus mutans clinical isolates with sortase defects.

PubMed

Lapirattanakul, Jinthana; Takashima, Yukiko; Tantivitayakul, Pornpen; Maudcheingka, Thaniya; Leelataweewud, Pattarawadee; Nakano, Kazuhiko; Matsumoto-Nakano, Michiyo

2017-09-01

In Streptococcus mutans, a Gram-positive pathogen of dental caries, several surface proteins are anchored by the activity of sortase enzyme. Although various reports have shown that constructed S. mutans mutants deficient of sortase as well as laboratory reference strains with a sortase gene mutation have low cariogenic potential, no known studies have investigated clinical isolates with sortase defects. Here, we examined the cariogenic properties of S. mutans clinical isolates with sortase defects as well as caries status in humans harboring such defective isolates. Sortase-defective clinical isolates were evaluated for biofilm formation, sucrose-dependent adhesion, stress-induced dextran-dependent aggregation, acid production, and acid tolerance. Additionally, caries indices of subjects possessing such defective isolates were determined. Our in vitro results indicated that biofilm with a lower quantity was formed by sortase-defective as compared to non-defective isolates. Moreover, impairments of sucrose-dependent adhesion and stress-induced dextran-dependent aggregation were found among the isolates with defects, whereas no alterations were seen in regard to acid production or tolerance. Furthermore, glucan-binding protein C, a surface protein anchored by sortase activity, was predominantly detected in culture supernatants of all sortase-defective S. mutans isolates. Although the sortase-defective isolates showed lower cariogenic potential because of a reduction in some cariogenic properties, deft/DMFT indices revealed that all subjects harboring those isolates had caries experience. Our findings suggest the impairment of cariogenic properties in S. mutans clinical isolates with sortase defects, though the detection of these defective isolates seemed not to imply low caries risk in the subjects harboring them. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atomic scale simulations of pyrochlore oxides with a tight-binding variable-charge model: implications for radiation tolerance.

PubMed

Sattonnay, G; Tétot, R

2014-02-05

Atomistic simulations with new interatomic potentials derived from a tight-binding variable-charge model were performed in order to investigate the lattice properties and the defect formation energies in Gd2Ti2O7 and Gd2Zr2O7 pyrochlores. The main objective was to determine the role played by the defect stability on the radiation tolerance of these compounds. Calculations show that the titanate has a more covalent character than the zirconate. Moreover, the properties of oxygen Frenkel pairs, cation antisite defects and cation Frenkel pairs were studied. In Gd2Ti2O7 the cation antisite defect and the Ti-Frenkel pair are not stable: they evolve towards more stable defect configurations during the atomic relaxation process. This phenomenon is driven by a decrease of the Ti coordination number down to five which leads to a local atomic reorganization and strong structural distortions around the defects. These kinds of atomic rearrangements are not observed around defects in Gd2Zr2O7. Therefore, the defect stability in A2B2O7 depends on the ability of B atoms to accommodate high coordination number (higher than six seems impossible for Ti). The accumulation of structural distortions around Ti-defects due to this phenomenon could drive the Gd2Ti2O7 amorphization induced by irradiation.

In situ observation of defect annihilation in Kr ion-irradiated bulk Fe/amorphous-Fe 2 Zr nanocomposite alloy

DOE PAGES

Yu, K. Y.; Fan, Z.; Chen, Y.; ...

2014-08-26

Enhanced irradiation tolerance in crystalline multilayers has received significant attention lately. However, little is known on the irradiation response of crystal/amorphous nanolayers. We report on in situ Kr ion irradiation studies of a bulk Fe 96Zr 4 nanocomposite alloy. Irradiation resulted in amorphization of Fe 2Zr and formed crystal/amorphous nanolayers. α-Fe layers exhibited drastically lower defect density and size than those in large α-Fe grains. In situ video revealed that mobile dislocation loops in α-Fe layers were confined by the crystal/amorphous interfaces and kept migrating to annihilate other defects. This study provides new insights on the design of irradiation-tolerant crystal/amorphousmore » nanocomposites.« less

Design of reliable universal QCA logic in the presence of cell deposition defect

NASA Astrophysics Data System (ADS)

Sen, Bibhash; Mukherjee, Rijoy; Mohit, Kumar; Sikdar, Biplab K.

2017-08-01

The emergence of Quantum-dot Cellular Automata (QCA) has resulted in being identified as a promising alternative to the currently prevailing techniques of very large scale integration. QCA can provide low-power nanocircuit with high device density. Keeping aside the profound acceptance of QCA, the challenge that it is facing can be quoted as susceptibility to high error rate. The work produced in this article aims towards the design of a reliable universal logic gate (r-ULG) in QCA (r-ULG along with the single clock zone and r-ULG-II along with multiple clock zones). The design would include hybrid orientation of cells that would realise majority and minority, functions and high fault tolerance simultaneously. The characterisation of the defective behaviour of r-ULGs under different kinds of cell deposition defects is investigated. The outcomes of the investigation provide an indication that the proposed r-ULG provides a fault tolerance of 75% under single clock zone and a fault tolerance of 100% under dual clock zones. The high functional aspects of r-ULGs in the implementation of different logic functions successfully under cell deposition defects are affirmed by the experimental results. The high-level logic around the multiplexer is synthesised, which helps to extend the design capability to the higher-level circuit synthesis.

Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus

PubMed Central

Powe, Camille E.; Allard, Catherine; Battista, Marie-Claude; Doyon, Myriam; Bouchard, Luigi; Ecker, Jeffrey L.; Perron, Patrice; Florez, Jose C.; Thadhani, Ravi

2016-01-01

OBJECTIVE To characterize physiologic subtypes of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS Insulin sensitivity and secretion were estimated in 809 women at 24–30 weeks' gestation, using oral glucose tolerance test–based indices. In women with GDM (8.3%), defects in insulin sensitivity or secretion were defined below the 25th percentile in women with normal glucose tolerance (NGT). GDM subtypes were defined based on the defect(s) present. RESULTS Relative to women with NGT, women with predominant insulin sensitivity defects (51% of GDM) had higher BMI and fasting glucose, larger infants (birth weight z score 0.57 [−0.01 to 1.37] vs. 0.03 [−0.53 to 0.52], P = 0.001), and greater risk of GDM-associated adverse outcomes (57.6 vs. 28.2%, P = 0.003); differences were independent of BMI. Women with predominant insulin secretion defects (30% of GDM) had BMI, fasting glucose, infant birth weights, and risk of adverse outcomes similar to those in women with NGT. CONCLUSIONS Heterogeneity of physiologic processes underlying hyperglycemia exists among women with GDM. GDM with impaired insulin sensitivity confers a greater risk of adverse outcomes. PMID:27208340

Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys.

PubMed

Lu, Chenyang; Jin, Ke; Béland, Laurent K; Zhang, Feifei; Yang, Taini; Qiao, Liang; Zhang, Yanwen; Bei, Hongbin; Christen, Hans M; Stoller, Roger E; Wang, Lumin

2016-02-01

Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross-sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters far exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri-vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance.

Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys

PubMed Central

Lu, Chenyang; Jin, Ke; Béland, Laurent K.; Zhang, Feifei; Yang, Taini; Qiao, Liang; Zhang, Yanwen; Bei, Hongbin; Christen, Hans M.; Stoller, Roger E.; Wang, Lumin

2016-01-01

Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross-sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters far exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri-vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance. PMID:26829570

Progressive Fracture of Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2001-01-01

This report includes the results of a research in which the COmposite Durability STRuctural ANalysis (CODSTRAN) computational simulation capabilities were augmented and applied to various structures for demonstration of the new features and verification. The first chapter of this report provides an introduction to the computational simulation or virtual laboratory approach for the assessment of damage and fracture progression characteristics in composite structures. The second chapter outlines the details of the overall methodology used, including the failure criteria and the incremental/iterative loading procedure with the definitions of damage, fracture, and equilibrium states. The subsequent chapters each contain an augmented feature of the code and/or demonstration examples. All but one of the presented examples contains laminated composite structures with various fiber/matrix constituents. For each structure simulated, damage initiation and progression mechanisms are identified and the structural damage tolerance is quantified at various degradation stages. Many chapters contain the simulation of defective and defect free structures to evaluate the effects of existing defects on structural durability.

Intraoperative three-dimensional transesophageal echocardiography for assessing the defect geometries of mitral prosthetic paravalvular leak during transcatheter closure.

PubMed

Wei, Jeng; Yin, Wei-Hsian; Lee, Yung-Tsai; Hsiung, Ming C; Tsai, Shen-Kou; Chuang, Yi Cheng; Ou, Ching-Huei; Chou, Yi-Pen

2015-03-01

Paravalvular leaks (PVLs) are a common complication of prosthetic valve replacement. Use of the transcatheter intervention technique is a suitable alternative in high-risk patients who may not tolerate repeat surgery. Common reasons for failure of this demanding intervention include poor imaging quality and unsuitable anatomy. The purpose of this study was to assess the usefulness and the incremental value of real-time three-dimensional (RT 3D) transesophageal echocardiography (TEE) over two-dimensional (2D) TEE findings in the evaluation of the geometry and track of mitral PVLs during transcatheter closure. Five patients with six mitral PVLs at high risk for repeat surgery underwent transcatheter leak closure. Intraoperative RT 3DTEE was used to assess the location, shape, number, and size of the defects. Transapical approaches were used in all cases with fluoroscopic and RT 3D TEE guidance of the wire and catheter, device positioning, and assessment of residual leak after the procedure. In all of the cases, defects with irregular crescent shapes and distorted tracks were clearly delineated by RT 3D TEE. This was compared to those results obtained through 2D TEE, which was unable to characterize the defects. Three cases showed small leaks, which were completely occluded with a patent ductus arteriosus (PDA) device in two cases, and a muscular ventricular septal defect (mVSD) occluder combined with coil devices in one case. One case involved a large leak and early device embolization of the muscular VSD occluder, which was removed surgically, and demonstrated a crescent-shaped defect. One patient had two releaks 2 months subsequent to the procedure due to two new extended leaks at the tails of the crescent-shaped defect. RT 3D TEE can clearly delineate the geometries of defects in their entirety, including shape, size, and location of the defect and track canal. It would also appear that RT 3D TEE is superior to 2D TEE in the process of guiding the wire through the difficult canal anatomy, facilitating the overall procedure. The small mitral PVLs can be completely occluded, but subsequent complications occurred with large defect closures because of embolization or releak. Therefore, transcatheter closure of PVLs seems to be an attractive alternative for these patients, but newer occluder designs that better conform to leak geometry will be required to improve outcomes. Copyright © 2014. Published by Elsevier Taiwan.

Restoring balance to B cells in ADA deficiency.

PubMed

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

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

Li, Jin; Fan, Cuncai; Ding, Jie

High energy particle radiations induce severe microstructural damage in metallic materials. Nanoporous materials with a giant surface-to-volume ratio may alleviate radiation damage in irradiated metallic materials as free surface are defect sinks. We show, by using in situ Kr ion irradiation in a transmission electron microscope at room temperature, that nanoporous Au indeed has significantly improved radiation tolerance comparing with coarse-grained, fully dense Au. In situ studies show that nanopores can absorb and eliminate a large number of radiation-induced defect clusters. Meanwhile, nanopores shrink (self-heal) during radiation, and their shrinkage rate is pore size dependent. Furthermore, the in situ studiesmore » show dose-rate-dependent diffusivity of defect clusters. Our study sheds light on the design of radiation-tolerant nanoporous metallic materials for advanced nuclear reactor applications.« less

Some Examples of the Relations Between Processing and Damage Tolerance

NASA Technical Reports Server (NTRS)

Nettles, Alan T.

2012-01-01

Most structures made of laminated polymer matrix composites (PMCs) must be designed to some damage tolerance requirement that includes foreign object impact damage. Thus from the beginning of a part s life, impact damage is assumed to exist in the material and the part is designed to carry the required load with the prescribed impact damage present. By doing this, some processing defects may automatically be accounted for in the reduced design allowable due to these impacts. This paper will present examples of how a given level of impact damage and certain processing defects affect the compression strength of a laminate that contains both. Knowledge of the impact damage tolerance requirements, before processing begins, can broaden material options and processing techniques since the structure is not being designed to pristine properties.

Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

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

Shutthanandan, Vaithiyalingam; Choudhury, Samrat; Manandhar, Sandeep

To understand how variations in interface properties such as misfit-dislocation density and local chemistry affect radiation-induced defect absorption and recombination, we have explored a model system of CrxV1-x alloy epitaxial films deposited on MgO single crystals. By controlling film composition, the lattice mismatch with MgO was adjusted so that the misfit-dislocation density varies at the interface. These interfaces were exposed to irradiation and in situ results show that the film with a semi-coherent interface (Cr) withstands irradiation while V film, which has similar semi-coherent interface like Cr, showed the largest damage. Theoretical calculations indicate that, unlike at metal/metal interfaces, themore » misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry, and the precise location of the misfit-dislocation density relative to the interface, drives defect behavior. Together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials.« less

Role of the Transcription Factor Sox4 in Insulin Secretion and Impaired Glucose Tolerance

PubMed Central

Goldsworthy, Michelle; Hugill, Alison; Freeman, Helen; Horner, Emma; Shimomura, Kenju; Bogani, Debora; Pieles, Guido; Mijat, Vesna; Arkell, Ruth; Bhattacharya, Shoumo; Ashcroft, Frances M.; Cox, Roger D.

2008-01-01

OBJECTIVES— To identify, map, clone, and functionally validate a novel mouse model for impaired glucose tolerance and insulin secretion. RESEARCH DESIGN AND METHODS— Haploinsufficiency of the insulin receptor and associated mild insulin resistance has been used to sensitize an N-ethyl-N-nitrosourea (ENU) screen to identify novel mutations resulting in impaired glucose tolerance and diabetes. The new impaired glucose tolerance 4 (IGT4) model was selected using an intraperitoneal glucose tolerance test and inheritance of the phenotype confirmed by generation of backcross progeny. Segregation of the phenotype was correlated with genotype information to map the location of the gene and candidates sequenced for mutations. The function of the SRY-related high mobility group (HMG)-box 4 (Sox4) gene in insulin secretion was tested using another ENU allele and by small interfering RNA silencing in insulinoma cells. RESULTS— We describe two allelic autosomal dominant mutations in the highly conserved HMG box of the transcription factor Sox4. Previously associated with pancreas development, Sox4 mutations in the adult mouse result in an insulin secretory defect, which exhibits impaired glucose tolerance in association with insulin receptor+/−–induced insulin resistance. Elimination of the Sox4 transcript in INS1 and Min6 cells resulted in the abolition of glucose-stimulated insulin release similar to that observed for silencing of the key metabolic enzyme glucokinase. Intracellular calcium measurements in treated cells indicate that this defect lies downstream of the ATP-sensitive K+ channel (KATP channel) and calcium influx. CONCLUSIONS— IGT4 represents a novel digenic model of insulin resistance coupled with an insulin secretory defect. The Sox4 gene has a role in insulin secretion in the adult β-cell downstream of the KATP channel. PMID:18477811

A Theoretical Simulation of the Radiation Responses of Si, Ge, and Si/Ge Superlattice to Low-Energy Irradiation.

PubMed

Jiang, Ming; Xiao, Haiyan; Peng, Shuming; Yang, Guixia; Liu, Zijiang; Qiao, Liang; Zu, Xiaotao

2018-05-02

In this study, the low-energy radiation responses of Si, Ge, and Si/Ge superlattice are investigated by an ab initio molecular dynamics method and the origins of their different radiation behaviors are explored. It is found that the radiation resistance of the Ge atoms that are around the interface of Si/Ge superlattice is comparable to bulk Ge, whereas the Si atoms around the interface are more difficult to be displaced than the bulk Si, showing enhanced radiation tolerance as compared with the bulk Si. The mechanisms for defect generation in the bulk and superlattice structures show somewhat different character, and the associated defects in the superlattice are more complex. Defect formation and migration calculations show that in the superlattice structure, the point defects are more difficult to form and the vacancies are less mobile. The enhanced radiation tolerance of the Si/Ge superlattice will benefit for its applications as electronic and optoelectronic devices under radiation environment.

A Theoretical Simulation of the Radiation Responses of Si, Ge, and Si/Ge Superlattice to Low-Energy Irradiation

NASA Astrophysics Data System (ADS)

Jiang, Ming; Xiao, Haiyan; Peng, Shuming; Yang, Guixia; Liu, Zijiang; Qiao, Liang; Zu, Xiaotao

2018-05-01

In this study, the low-energy radiation responses of Si, Ge, and Si/Ge superlattice are investigated by an ab initio molecular dynamics method and the origins of their different radiation behaviors are explored. It is found that the radiation resistance of the Ge atoms that are around the interface of Si/Ge superlattice is comparable to bulk Ge, whereas the Si atoms around the interface are more difficult to be displaced than the bulk Si, showing enhanced radiation tolerance as compared with the bulk Si. The mechanisms for defect generation in the bulk and superlattice structures show somewhat different character, and the associated defects in the superlattice are more complex. Defect formation and migration calculations show that in the superlattice structure, the point defects are more difficult to form and the vacancies are less mobile. The enhanced radiation tolerance of the Si/Ge superlattice will benefit for its applications as electronic and optoelectronic devices under radiation environment.

Investigation on size tolerance of pore defect of girth weld pipe.

PubMed

Li, Yan; Shuai, Jian; Xu, Kui

2018-01-01

Welding quality control is an important parameter for safe operation of oil and gas pipes, especially for high-strength steel pipes. Size control of welding defect is a bottleneck problem for current pipe construction. As a key part of construction procedure for butt-welding of pipes, pore defects in girth weld is difficult to ignore. A three-dimensional non-linear finite element numerical model is established to study applicability of size control indices based on groove shape and softening phenomenon of material in heat-affected zone of practical pipe girth weld. Taking design criteria of pipe as the basis, basic tensile, extremely tensile and extremely compressive loading conditions are determined for pipe stress analysis, and failure criteria based on flow stress is employed to perform stress analysis for pipe girth weld with pore defect. Results show that pipe girth welding stresses of pores at various radial locations are similar. Whereas, stress for pores of different sharpness varied significantly. Besides, tolerance capability of API 5L X90 grade pipe to pore defect of girth weld is lower than that of API 5L X80 grade pipe, and size control index of 3 mm related to pore defect in current standards is applicable to API 5L X80 and X90 grade girth welded pipes with radially non-sharp pore defects.

Investigation on size tolerance of pore defect of girth weld pipe

PubMed Central

Shuai, Jian; Xu, Kui

2018-01-01

Welding quality control is an important parameter for safe operation of oil and gas pipes, especially for high-strength steel pipes. Size control of welding defect is a bottleneck problem for current pipe construction. As a key part of construction procedure for butt-welding of pipes, pore defects in girth weld is difficult to ignore. A three-dimensional non-linear finite element numerical model is established to study applicability of size control indices based on groove shape and softening phenomenon of material in heat-affected zone of practical pipe girth weld. Taking design criteria of pipe as the basis, basic tensile, extremely tensile and extremely compressive loading conditions are determined for pipe stress analysis, and failure criteria based on flow stress is employed to perform stress analysis for pipe girth weld with pore defect. Results show that pipe girth welding stresses of pores at various radial locations are similar. Whereas, stress for pores of different sharpness varied significantly. Besides, tolerance capability of API 5L X90 grade pipe to pore defect of girth weld is lower than that of API 5L X80 grade pipe, and size control index of 3 mm related to pore defect in current standards is applicable to API 5L X80 and X90 grade girth welded pipes with radially non-sharp pore defects. PMID:29364986

Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys

DOE PAGES

Lu, Chenyang; Jin, Ke; Béland, Laurent K.; ...

2016-02-01

We report that energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross-sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters farmore » exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri-vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance.« less

Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

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

Shutthanandan, Vaithiyalingam; Choudhury, Samrat; Manandhar, Sandeep

The interaction of radiation with materials controls the performance, reliability, and safety of many structures in nuclear power systems. Revolutionary improvements in radiation damage resistance may be attainable if methods can be found to manipulate interface properties to give optimal interface stability and point defect recombination capability. To understand how variations in interface properties such as misfit dislocation density and local chemistry affect radiation-induced defect absorption and recombination, a model system of metallic Cr xV 1-x (0 ≤ x ≤ 1) epitaxial films deposited on MgO(001) single crystal substrates has been explored in this paper. By controlling film composition, themore » lattice mismatch between the film and MgO is adjusted to vary the misfit dislocation density at the metal/oxide interface. The stability of these interfaces under various irradiation conditions is studied experimentally and theoretically. The results indicate that, unlike at metal/metal interfaces, the misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry and the location of the misfit dislocation extra half-plane (in the metal or the oxide) drive radiation-induced defect behavior. Finally, together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials for next-generation nuclear power plants.« less

Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

DOE PAGES

Shutthanandan, Vaithiyalingam; Choudhury, Samrat; Manandhar, Sandeep; ...

2017-04-24

The interaction of radiation with materials controls the performance, reliability, and safety of many structures in nuclear power systems. Revolutionary improvements in radiation damage resistance may be attainable if methods can be found to manipulate interface properties to give optimal interface stability and point defect recombination capability. To understand how variations in interface properties such as misfit dislocation density and local chemistry affect radiation-induced defect absorption and recombination, a model system of metallic Cr xV 1-x (0 ≤ x ≤ 1) epitaxial films deposited on MgO(001) single crystal substrates has been explored in this paper. By controlling film composition, themore » lattice mismatch between the film and MgO is adjusted to vary the misfit dislocation density at the metal/oxide interface. The stability of these interfaces under various irradiation conditions is studied experimentally and theoretically. The results indicate that, unlike at metal/metal interfaces, the misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry and the location of the misfit dislocation extra half-plane (in the metal or the oxide) drive radiation-induced defect behavior. Finally, together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials for next-generation nuclear power plants.« less

Effects of chemical alternation on damage accumulation in concentrated solid-solution alloys

DOE PAGES

Ullah, Mohammad W.; Xue, Haizhou; Velisa, Gihan; ...

2017-06-23

Single-phase concentrated solid-solution alloys (SP-CSAs) have recently gained unprecedented attention due to their promising properties. To understand effects of alloying elements on irradiation-induced defect production, recombination and evolution, an integrated study of ion irradiation, ion beam analysis and atomistic simulations are carried out on a unique set of model crystals with increasing chemical complexity, from pure Ni to Ni 80Fe 20, Ni 50Fe 50, and Ni 80Cr 20 binaries, and to a more complex Ni 40Fe 40Cr 20 alloy. Both experimental and simulation results suggest that the binary and ternary alloys exhibit higher radiation resistance than elemental Ni. The modelingmore » work predicts that Ni 40Fe 40Cr 20 has the best radiation tolerance, with the number of surviving Frenkel pairs being factors of 2.0 and 1.4 lower than pure Ni and the 80:20 binary alloys, respectively. While the reduced defect mobility in SP-CSAs is identified as a general mechanism leading to slower growth of large defect clusters, the effect of specific alloying elements on suppression of damage accumulation is clearly demonstrated. This work suggests that concentrated solid-solution provides an effective way to enhance radiation tolerance by creating elemental alternation at the atomic level. The demonstrated chemical effects on defect dynamics may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.« less

7 CFR 51.3150 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 12 percent for nectarines... which are affected by decay. (2) For defects en route or at destination. 12 percent for nectarines which...

7 CFR 51.3150 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 12 percent for nectarines... which are affected by decay. (2) For defects en route or at destination. 12 percent for nectarines which...

Fault and Defect Tolerant Computer Architectures: Reliable Computing with Unreliable Devices

DTIC Science & Technology

2006-08-31

supply voltage, the delay of the inverter increases parabolically . 2.2.2.5 High Field Effects. A consequence of maintaining a higher Vdd than...be explained by dispro- portionate scaling of QCRIT with respect to collector efficiency. 78 Technology trends, then, indicate a moderate increase in...using clustered defects, a compounding procedure is used. Compounding considers λ as a random variable rather than a constant. Let l be this defect

Statistical shear lag model - unraveling the size effect in hierarchical composites.

PubMed

Wei, Xiaoding; Filleter, Tobin; Espinosa, Horacio D

2015-05-01

Numerous experimental and computational studies have established that the hierarchical structures encountered in natural materials, such as the brick-and-mortar structure observed in sea shells, are essential for achieving defect tolerance. Due to this hierarchy, the mechanical properties of natural materials have a different size dependence compared to that of typical engineered materials. This study aimed to explore size effects on the strength of bio-inspired staggered hierarchical composites and to define the influence of the geometry of constituents in their outstanding defect tolerance capability. A statistical shear lag model is derived by extending the classical shear lag model to account for the statistics of the constituents' strength. A general solution emerges from rigorous mathematical derivations, unifying the various empirical formulations for the fundamental link length used in previous statistical models. The model shows that the staggered arrangement of constituents grants composites a unique size effect on mechanical strength in contrast to homogenous continuous materials. The model is applied to hierarchical yarns consisting of double-walled carbon nanotube bundles to assess its predictive capabilities for novel synthetic materials. Interestingly, the model predicts that yarn gauge length does not significantly influence the yarn strength, in close agreement with experimental observations. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contribution a l'inspection automatique des pieces flexibles a l'etat libre sans gabarit de conformation

NASA Astrophysics Data System (ADS)

Sattarpanah Karganroudi, Sasan

The competitive industrial market demands manufacturing companies to provide the markets with a higher quality of production. The quality control department in industrial sectors verifies geometrical requirements of products with consistent tolerances. These requirements are presented in Geometric Dimensioning and Tolerancing (GD&T) standards. However, conventional measuring and dimensioning methods for manufactured parts are time-consuming and costly. Nowadays manual and tactile measuring methods have been replaced by Computer-Aided Inspection (CAI) methods. The CAI methods apply improvements in computational calculations and 3-D data acquisition devices (scanners) to compare the scan mesh of manufactured parts with the Computer-Aided Design (CAD) model. Metrology standards, such as ASME-Y14.5 and ISO-GPS, require implementing the inspection in free-state, wherein the part is only under its weight. Non-rigid parts are exempted from the free-state inspection rule because of their significant geometrical deviation in a free-state with respect to the tolerances. Despite the developments in CAI methods, inspection of non-rigid parts still remains a serious challenge. Conventional inspection methods apply complex fixtures for non-rigid parts to retrieve the functional shape of these parts on physical fixtures; however, the fabrication and setup of these fixtures are sophisticated and expensive. The cost of fixtures has doubled since the client and manufacturing sectors require repetitive and independent inspection fixtures. To eliminate the need for costly and time-consuming inspection fixtures, fixtureless inspection methods of non-rigid parts based on CAI methods have been developed. These methods aim at distinguishing flexible deformations of parts in a free-state from defects. Fixtureless inspection methods are required to be automatic, reliable, reasonably accurate and repeatable for non-rigid parts with complex shapes. The scan model, which is acquired as point clouds, represent the shape of a part in a free-state. Afterward, the inspection of defects is performed by comparing the scan and CAD models, but these models are presented in different coordinate systems. Indeed, the scan model is presented in the measurement coordinate system whereas the CAD model is introduced in the designed coordinate system. To accomplish the inspection and facilitate an accurate comparison between the models, the registration process is required to align the scan and CAD models in a common coordinate system. The registration includes a virtual compensation for the flexible deformation of the parts in a free-state. Then, the inspection is implemented as a geometrical comparison between the CAD and scan models. This thesis focuses on developing automatic and accurate fixtureless CAI methods for non-rigid parts along with assessing the robustness of the methods. To this end, an automatic fixtureless CAI method for non-rigid parts based on filtering registration points is developed to identify and quantify defects more accurately on the surface of scan models. The flexible deformation of parts in a free-state in our developed automatic fixtureless CAI method is compensated by applying FE non-rigid Registration (FENR) to deform the CAD model towards the scan mesh. The displacement boundary conditions (BCs) for FENR are determined based on the corresponding sample points, which are generated by the Generalized Numerical Inspection Fixture (GNIF) method on the CAD and scan models. These corresponding sample points are evenly distributed on the surface of the models. The comparison between this deformed CAD model and the scan mesh intend to evaluate and quantify the defects on the scan model. However, some sample points can be located close or on defect areas which result in an inaccurate estimation of defects. These sample points are automatically filtered out in our CAI method based on curvature and von Mises stress criteria. Once filtered out, the remaining sample points are used in a new FENR, which allows an accurate evaluation of defects with respect to the tolerances. The performance and robustness of all CAI methods are generally required to be assessed with respect to the actual measurements. This thesis also introduces a new validation metric for Verification and Validation (V&V) of CAI methods based on ASME recommendations. The developed V&V approach uses a nonparametric statistical hypothesis test, namely the Kolmogorov-Smirnov (K-S) test. In addition to validating the defects size, the K-S test allows a deeper evaluation based on distance distribution of defects. The robustness of CAI method with respect to uncertainties such as scanning noise is quantitatively assessed using the developed validation metric. Due to the compliance of non-rigid parts, a geometrically deviated part can still be assembled in the assembly-state. This thesis also presents a fixtureless CAI method for geometrically deviated (presenting defects) non-rigid parts to evaluate the feasibility of mounting these parts in the functional assembly-state. Our developed Virtual Mounting Assembly-State Inspection (VMASI) method performs a non-rigid registration to virtually mount the scan mesh in assembly-state. To this end, the point clouds of scan model representing the part in a free-state is deformed to meet the assembly constraints such as fixation position (e.g. mounting holes). In some cases, the functional shape of a deviated part can be retrieved by applying assembly loads, which are limited to permissible loads, on the surface of the part. The required assembly loads are estimated through our developed Restraining Pressures Optimization (RPO) aiming at displacing the deviated scan model to achieve the tolerance for mounting holes. Therefore, the deviated scan model can be assembled if the mounting holes on the predicted functional shape of scan model attain the tolerance range. Different industrial parts are used to evaluate the performance of our developed methods in this thesis. The automatic inspection for identifying different types of small (local) and big (global) defects on the parts results in an accurate evaluation of defects. The robustness of this inspection method is also validated with respect to different levels of scanning noise, which shows promising results. Meanwhile, the VMASI method is performed on various parts with different types of defects, which concludes that in some cases the functional shape of deviated parts can be retrieved by mounting them on a virtual fixture in assembly-state under restraining loads.

Damage-tolerant nanotwinned metals with nanovoids under radiation environments

PubMed Central

Chen, Y.; Yu, K Y.; Liu, Y.; Shao, S.; Wang, H.; Kirk, M. A.; Wang, J.; Zhang, X.

2015-01-01

Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from high density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials. PMID:25906997

Damage-tolerant nanotwinned metals with nanovoids under radiation environments.

PubMed

Chen, Y; Yu, K Y; Liu, Y; Shao, S; Wang, H; Kirk, M A; Wang, J; Zhang, X

2015-04-24

Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from high density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials.

Damage-tolerant nanotwinned metals with nanovoids under radiation environments

DOE PAGES

Chen, Y.; Yu, K. Y.; Liu, Y.; ...

2015-04-24

Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from highmore » density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials.« less

7 CFR 51.1151 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to... percent shall be for decay or wormy fruit. (ii) For defects en route or at destination. Not more than 12...

7 CFR 51.2336 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or.... (2) For defects en route or at destination. 12 percent for fruit which fail to meet the requirements...

7 CFR 51.2336 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 12 percent for fruit which fail to meet... internal breakdown or decay. (2) For defects en route or at destination. 12 percent for fruit which fail to...

7 CFR 51.2336 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or.... (2) For defects en route or at destination. 12 percent for fruit which fail to meet the requirements...

7 CFR 51.1214 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 14... not more than 1 percent for peaches which are affected by decay. (2) For defects en route or at...

7 CFR 51.1214 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 14 percent for peaches in any lot that... are affected by decay. (2) For defects en route or at destination. 14 percent for peaches in any lot...

7 CFR 51.1151 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not... defects en route or at destination. Not more than 12 percent of the fruit which fail to meet the...

7 CFR 51.760 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route.... (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to meet...

7 CFR 51.1214 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 14... not more than 1 percent for peaches which are affected by decay. (2) For defects en route or at...

7 CFR 51.1820 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not... defects en route or at destination. Not more than 12 percent of the fruit which fail to meet the...

7 CFR 51.1214 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 14 percent for peaches in any lot that... are affected by decay. (2) For defects en route or at destination. 14 percent for peaches in any lot...

7 CFR 51.1151 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not... defects en route or at destination. Not more than 12 percent of the fruit which fail to meet the...

7 CFR 51.2336 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route or at destination. 12 percent for fruit which fail to meet... internal breakdown or decay. (2) For defects en route or at destination. 12 percent for fruit which fail to...

7 CFR 51.760 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not more than 12... this amount not more than 1 percent shall be for decay or wormy fruit. (ii) For defects en route or at...

7 CFR 51.760 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route.... (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to meet...

7 CFR 51.1820 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not... defects en route or at destination. Not more than 12 percent of the fruit which fail to meet the...

7 CFR 51.1151 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to... percent shall be for decay or wormy fruit. (ii) For defects en route or at destination. Not more than 12...

7 CFR 51.1820 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route.... (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to meet...

7 CFR 51.760 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route or at destination. Not more than 12... this amount not more than 1 percent shall be for decay or wormy fruit. (ii) For defects en route or at...

7 CFR 51.1820 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (ii) For defects en route.... (ii) For defects en route or at destination. Not more than 12 percent of the fruit which fail to meet...

7 CFR 51.3150 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route...) For defects en route or at destination. 12 percent for nectarines which fail to meet the requirements...

7 CFR 51.3150 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... producing area or at port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the continental United States, the port of entry into the United States. (2) For defects en route...) For defects en route or at destination. 12 percent for nectarines which fail to meet the requirements...

Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

PubMed Central

Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

2008-01-01

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

Specialists Meeting on Impact Damage Tolerance of Structures

DTIC Science & Technology

1976-01-01

example, fatigue, timl-de tectIable initial defects and in-fliglht d amalt such aS that inflicted by miilitary weapons or by debris from ’n din tegra t...relative to many types of damaging mechanisms, lncludlig for example: I. Fat Igue 2. Non-detectable Initial defects 3. In-flight damage, such as Inflicted...undetected flaw or defect . In both cases, the benefits of successful design are Improved safety and economics. With respect to In-flight darvqe, tre

Irradiation-induced damage evolution in concentrated Ni-based alloys

DOE PAGES

Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou; ...

2017-06-06

Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less

Irradiation-induced damage evolution in concentrated Ni-based alloys

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

Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou

Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less

Location, location & size: defects close to surfaces dominate fatigue crack initiation

NASA Astrophysics Data System (ADS)

Serrano-Munoz, Itziar; Buffiere, Jean-Yves; Mokso, Rajmund; Verdu, Catherine; Nadot, Yves

2017-03-01

Metallic cast components inevitably contain defects such as shrinkage cavities which are inherent to the solidification process. Those defects are known to significantly alter the fatigue life of components. Yet very little is known, quantitatively, on the dangerosity of internal casting defects compared to surface ones. In this study, fatigue specimens containing controlled internal defects (shrinkage pores) are used to foster internal cracking. In situ fatigue tests monitored by X ray synchrotron tomography revealed that the internal nucleation and propagation of cracks was systematically overran by surface cracking initiated at castings defects up to ten times smaller than the internal ones. These findings indicate that the presence of internal defects in cast components can be tolerated to a larger extent than is allowed by nowadays standards

Location, location &size: defects close to surfaces dominate fatigue crack initiation.

PubMed

Serrano-Munoz, Itziar; Buffiere, Jean-Yves; Mokso, Rajmund; Verdu, Catherine; Nadot, Yves

2017-03-27

Metallic cast components inevitably contain defects such as shrinkage cavities which are inherent to the solidification process. Those defects are known to significantly alter the fatigue life of components. Yet very little is known, quantitatively, on the dangerosity of internal casting defects compared to surface ones. In this study, fatigue specimens containing controlled internal defects (shrinkage pores) are used to foster internal cracking. In situ fatigue tests monitored by X ray synchrotron tomography revealed that the internal nucleation and propagation of cracks was systematically overran by surface cracking initiated at castings defects up to ten times smaller than the internal ones. These findings indicate that the presence of internal defects in cast components can be tolerated to a larger extent than is allowed by nowadays standards.

Location, location & size: defects close to surfaces dominate fatigue crack initiation

PubMed Central

Serrano-Munoz, Itziar; Buffiere, Jean-Yves; Mokso, Rajmund; Verdu, Catherine; Nadot, Yves

2017-01-01

Metallic cast components inevitably contain defects such as shrinkage cavities which are inherent to the solidification process. Those defects are known to significantly alter the fatigue life of components. Yet very little is known, quantitatively, on the dangerosity of internal casting defects compared to surface ones. In this study, fatigue specimens containing controlled internal defects (shrinkage pores) are used to foster internal cracking. In situ fatigue tests monitored by X ray synchrotron tomography revealed that the internal nucleation and propagation of cracks was systematically overran by surface cracking initiated at castings defects up to ten times smaller than the internal ones. These findings indicate that the presence of internal defects in cast components can be tolerated to a larger extent than is allowed by nowadays standards PMID:28345599

Damage Tolerance Assessment of Friction Pull Plug Welds in an Aluminum Alloy

NASA Technical Reports Server (NTRS)

McGill, Preston; Burkholder, Jonathan

2012-01-01

Friction stir welding is a solid state welding process used in the fabrication of cryogenic propellant tanks. Self-reacting friction stir welding is one variation of the friction stir weld process being developed for manufacturing tanks. Friction pull plug welding is used to seal the exit hole that remains in a circumferential self-reacting friction stir weld. A friction plug weld placed in a self-reacting friction stir weld results in a non-homogenous weld joint where the initial weld, plug weld, their respective heat affected zones and the base metal all interact. The welded joint is a composite plastically deformed material system with a complex residual stress field. In order to address damage tolerance concerns associated with friction plug welds in safety critical structures, such as propellant tanks, nondestructive inspection and proof testing may be required to screen hardware for mission critical defects. The efficacy of the nondestructive evaluation or the proof test is based on an assessment of the critical flaw size. Test data relating residual strength capability to flaw size in an aluminum alloy friction plug weld will be presented.

Radiation tolerance of boron doped dendritic web silicon solar cells

NASA Technical Reports Server (NTRS)

Rohatgi, A.

1980-01-01

The potential of dendritic web silicon for giving radiation hard solar cells is compared with the float zone silicon material. Solar cells with n(+)-p-P(+) structure and approximately 15% (AMl) efficiency were subjected to 1 MeV electron irradiation. Radiation tolerance of web cell efficiency was found to be at least as good as that of the float zone silicon cell. A study of the annealing behavior of radiation-induced defects via deep level transient spectroscopy revealed that E sub v + 0.31 eV defect, attributed to boron-oxygen-vacancy complex, is responsible for the reverse annealing of the irradiated cells in the temperature range of 150 to 350 C.

Identification and classification of genes required for tolerance to freeze-thaw stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains.

PubMed

Ando, Akira; Nakamura, Toshihide; Murata, Yoshinori; Takagi, Hiroshi; Shima, Jun

2007-03-01

Yeasts used in bread making are exposed to freeze-thaw stress during frozen-dough baking. To clarify the genes required for freeze-thaw tolerance, genome-wide screening was performed using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 58 gene deletions that conferred freeze-thaw sensitivity. These genes were then classified based on their cellular function and on the localization of their products. The results showed that the genes required for freeze-thaw tolerance were frequently involved in vacuole functions and cell wall biogenesis. The highest numbers of gene products were components of vacuolar H(+)-ATPase. Next, the cross-sensitivity of the freeze-thaw-sensitive mutants to oxidative stress and to cell wall stress was studied; both of these are environmental stresses closely related to freeze-thaw stress. The results showed that defects in the functions of vacuolar H(+)-ATPase conferred sensitivity to oxidative stress and to cell wall stress. In contrast, defects in gene products involved in cell wall assembly conferred sensitivity to cell wall stress but not to oxidative stress. Our results suggest the presence of at least two different mechanisms of freeze-thaw injury: oxidative stress generated during the freeze-thaw process, and defects in cell wall assembly.

Influence of ECG measurement accuracy on ECG diagnostic statements.

PubMed

Zywietz, C; Celikag, D; Joseph, G

1996-01-01

Computer analysis of electrocardiograms (ECGs) provides a large amount of ECG measurement data, which may be used for diagnostic classification and storage in ECG databases. Until now, neither error limits for ECG measurements have been specified nor has their influence on diagnostic statements been systematically investigated. An analytical method is presented to estimate the influence of measurement errors on the accuracy of diagnostic ECG statements. Systematic (offset) errors will usually result in an increase of false positive or false negative statements since they cause a shift of the working point on the receiver operating characteristics curve. Measurement error dispersion broadens the distribution function of discriminative measurement parameters and, therefore, usually increases the overlap between discriminative parameters. This results in a flattening of the receiver operating characteristics curve and an increase of false positive and false negative classifications. The method developed has been applied to ECG conduction defect diagnoses by using the proposed International Electrotechnical Commission's interval measurement tolerance limits. These limits appear too large because more than 30% of false positive atrial conduction defect statements and 10-18% of false intraventricular conduction defect statements could be expected due to tolerated measurement errors. To assure long-term usability of ECG measurement databases, it is recommended that systems provide its error tolerance limits obtained on a defined test set.

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging.

PubMed

Kim, Jiwon; Di Franco, Antonino; Seoane, Tania; Srinivasan, Aparna; Kampaktsis, Polydoros N; Geevarghese, Alexi; Goldburg, Samantha R; Khan, Saadat A; Szulc, Massimiliano; Ratcliffe, Mark B; Levine, Robert A; Morgan, Ashley E; Maddula, Pooja; Rozenstrauch, Meenakshi; Shah, Tara; Devereux, Richard B; Weinsaft, Jonathan W

2016-11-01

Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction. © 2016 American Heart Association, Inc.

7 CFR 51.2954 - Tolerances for grade defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... damaged by mold or insects or seriously damaged by other means, of which not more than 5/6 or 5 pct may be damaged by insects, but no part of any tolerance shall be allowed for walnuts containing live insects No... adhering hulls 15 pct total, by count, including not more than 8 pct which are damaged by mold or insects...

Endoanal ultrasonography in fecal incontinence: Current and future perspectives.

PubMed

Albuquerque, Andreia

2015-06-10

Fecal incontinence has a profound impact in a patient's life, impairing quality of life and carrying a substantial economic burden due to health costs. It is an underdiagnosed condition because many affected patients are reluctant to report it and also clinicians are usually not alert to it. Patient evaluation with a detailed clinical history and examination is very important to indicate the type of injury that is present. Endoanal ultrasonography is currently the gold standard for sphincter evaluation in fecal incontinence and is a simple, well-tolerated and non-expensive technique. Most studies revealed 100% sensitivity in identifying sphincter defect. It is better than endoanal magnetic resonance imaging for internal anal sphincter defects, equivalent for the diagnosis of external anal sphincter defects, but with a lower capacity for assessment of atrophy of this sphincter. The most common cause of fecal incontinence is anal sphincter injury related to obstetric trauma. Only a small percentage of women are diagnosed with sphincter tears immediately after vaginal delivery, but endoanal ultrasonography shows that one third of these women have occult sphincter defects. Furthermore, in patients submitted to primary repair of these tears, ultrasound revealed a high frequency of persistent sphincter defects after surgery. Three-dimensional endoanal ultrasonography is currently largely used and accepted for sphincter evaluation in fecal incontinence, improving diagnostic accuracy and our knowledge of physiologic and pathological sphincters alterations. Conversely, there is currently no evidence to support the use of elastography in fecal incontinence evaluation.

Achromobacter denitrificans Strain YD35 Pyruvate Dehydrogenase Controls NADH Production To Allow Tolerance to Extremely High Nitrite Levels

PubMed Central

Doi, Yuki; Shimizu, Motoyuki; Fujita, Tomoya; Nakamura, Akira; Takizawa, Noboru

2014-01-01

We identified the extremely nitrite-tolerant bacterium Achromobacter denitrificans YD35 that can grow in complex medium containing 100 mM nitrite (NO2−) under aerobic conditions. Nitrite induced global proteomic changes and upregulated tricarboxylate (TCA) cycle enzymes as well as antioxidant proteins in YD35. Transposon mutagenesis generated NO2−-hypersensitive mutants of YD35 that had mutations at genes for aconitate hydratase and α-ketoglutarate dehydrogenase in the TCA cycle and a pyruvate dehydrogenase (Pdh) E1 component, indicating the importance of TCA cycle metabolism to NO2− tolerance. A mutant in which the pdh gene cluster was disrupted (Δpdh mutant) could not grow in the presence of 100 mM NO2−. Nitrite decreased the cellular NADH/NAD+ ratio and the cellular ATP level. These defects were more severe in the Δpdh mutant, indicating that Pdh contributes to upregulating cellular NADH and ATP and NO2−-tolerant growth. Exogenous acetate, which generates acetyl coenzyme A and then is metabolized by the TCA cycle, compensated for these defects caused by disruption of the pdh gene cluster and those caused by NO2−. These findings demonstrate a link between NO2− tolerance and pyruvate/acetate metabolism through the TCA cycle. The TCA cycle mechanism in YD35 enhances NADH production, and we consider that this contributes to a novel NO2−-tolerating mechanism in this strain. PMID:24413603

The relationship between grain boundary structure, defect mobility, and grain boundary sink efficiency

PubMed Central

Uberuaga, Blas Pedro; Vernon, Louis J.; Martinez, Enrique; Voter, Arthur F.

2015-01-01

Nanocrystalline materials have received great attention due to their potential for improved functionality and have been proposed for extreme environments where the interfaces are expected to promote radiation tolerance. However, the precise role of the interfaces in modifying defect behavior is unclear. Using long-time simulations methods, we determine the mobility of defects and defect clusters at grain boundaries in Cu. We find that mobilities vary significantly with boundary structure and cluster size, with larger clusters exhibiting reduced mobility, and that interface sink efficiency depends on the kinetics of defects within the interface via the in-boundary annihilation rate of defects. Thus, sink efficiency is a strong function of defect mobility, which depends on boundary structure, a property that evolves with time. Further, defect mobility at boundaries can be slower than in the bulk, which has general implications for the properties of polycrystalline materials. Finally, we correlate defect energetics with the volumes of atomic sites at the boundary. PMID:25766999

The relationship between grain boundary structure, defect mobility, and grain boundary sink efficiency

DOE PAGES

Uberuaga, Blas Pedro; Vernon, Louis J.; Martinez, Enrique; ...

2015-03-13

Nanocrystalline materials have received great attention due to their potential for improved functionality and have been proposed for extreme environments where the interfaces are expected to promote radiation tolerance. However, the precise role of the interfaces in modifying defect behavior is unclear. Using long-time simulations methods, we determine the mobility of defects and defect clusters at grain boundaries in Cu. We find that mobilities vary significantly with boundary structure and cluster size, with larger clusters exhibiting reduced mobility, and that interface sink efficiency depends on the kinetics of defects within the interface via the in-boundary annihilation rate of defects. Thus,more » sink efficiency is a strong function of defect mobility, which depends on boundary structure, a property that evolves with time. Further, defect mobility at boundaries can be slower than in the bulk, which has general implications for the properties of polycrystalline materials. Finally, we correlate defect energetics with the volumes of atomic sites at the boundary.« less

Role of Sink Density in Nonequilibrium Chemical Redistribution in Alloys

DOE PAGES

Martinez, Enrique Saez; Senninger, Oriane; Caro, Alfredo; ...

2018-03-08

Nonequilibrium chemical redistribution in open systems submitted to external forces, such as particle irradiation, leads to changes in the structural properties of the material, potentially driving the system to failure. Such redistribution is controlled by the complex interplay between the production of point defects, atomic transport rates, and the sink character of the microstructure. In this work, we analyze this interplay by means of a kinetic Monte Carlo (KMC) framework with an underlying atomistic model for the Fe-Cr model alloy to study the effect of ideal defect sinks on Cr concentration profiles, with a particular focus on the role ofmore » interface density. We observe that the amount of segregation decreases linearly with decreasing interface spacing. Within the framework of the thermodynamics of irreversible processes, a general analytical model is derived and assessed against the KMC simulations to elucidate the structure-property relationship of this system. Interestingly, in the kinetic regime where elimination of point defects at sinks is dominant over bulk recombination, the solute segregation does not directly depend on the dose rate but only on the density of sinks. Furthermore, this model provides new insight into the design of microstructures that mitigate chemical redistribution and improve radiation tolerance.« less

Role of Sink Density in Nonequilibrium Chemical Redistribution in Alloys

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

Martinez, Enrique Saez; Senninger, Oriane; Caro, Alfredo

Nonequilibrium chemical redistribution in open systems submitted to external forces, such as particle irradiation, leads to changes in the structural properties of the material, potentially driving the system to failure. Such redistribution is controlled by the complex interplay between the production of point defects, atomic transport rates, and the sink character of the microstructure. In this work, we analyze this interplay by means of a kinetic Monte Carlo (KMC) framework with an underlying atomistic model for the Fe-Cr model alloy to study the effect of ideal defect sinks on Cr concentration profiles, with a particular focus on the role ofmore » interface density. We observe that the amount of segregation decreases linearly with decreasing interface spacing. Within the framework of the thermodynamics of irreversible processes, a general analytical model is derived and assessed against the KMC simulations to elucidate the structure-property relationship of this system. Interestingly, in the kinetic regime where elimination of point defects at sinks is dominant over bulk recombination, the solute segregation does not directly depend on the dose rate but only on the density of sinks. Furthermore, this model provides new insight into the design of microstructures that mitigate chemical redistribution and improve radiation tolerance.« less

Role of Sink Density in Nonequilibrium Chemical Redistribution in Alloys

NASA Astrophysics Data System (ADS)

Martínez, Enrique; Senninger, Oriane; Caro, Alfredo; Soisson, Frédéric; Nastar, Maylise; Uberuaga, Blas P.

2018-03-01

Nonequilibrium chemical redistribution in open systems submitted to external forces, such as particle irradiation, leads to changes in the structural properties of the material, potentially driving the system to failure. Such redistribution is controlled by the complex interplay between the production of point defects, atomic transport rates, and the sink character of the microstructure. In this work, we analyze this interplay by means of a kinetic Monte Carlo (KMC) framework with an underlying atomistic model for the Fe-Cr model alloy to study the effect of ideal defect sinks on Cr concentration profiles, with a particular focus on the role of interface density. We observe that the amount of segregation decreases linearly with decreasing interface spacing. Within the framework of the thermodynamics of irreversible processes, a general analytical model is derived and assessed against the KMC simulations to elucidate the structure-property relationship of this system. Interestingly, in the kinetic regime where elimination of point defects at sinks is dominant over bulk recombination, the solute segregation does not directly depend on the dose rate but only on the density of sinks. This model provides new insight into the design of microstructures that mitigate chemical redistribution and improve radiation tolerance.

Regulation of extrarenal potassium homeostasis by adrenal hormones in rats.

PubMed

Bia, M J; Tyler, K A; DeFronzo, R A

1982-06-01

The effect of chronic (7-10 days) adrenal insufficiency on extrarenal potassium tolerance was examined by infusing potassium into rats after acute nephrectomy. The increment in plasma potassium concentration was significantly higher in glucocorticoid-replaced adrenalectomized rats versus controls (max delta PK 3.59 +/-0.11 vs. 2.93 +/- 0.08 meq/liter; P less than 0.001). The impairment in extrarenal potassium tolerance in adrenalectomized rats could not be attributed to acidemia, hypotension, changes in plasma insulin or glucose concentration, or potassium retention prior to study. Acute replacement with aldosterone resulted in significant improvement in the rise in plasma potassium after KCl (max delta PK 3.18 +/- 0.06 meq/liter; P less than 0.005 compared with aldosterone-deficient adrenalectomized rats but higher than in controls, P less than 0.02). If given on a chronic basis, aldosterone replacement led to a complete correction of the defect (max delta PK = 2.89 +/- 0.08 meq/liter). Acute epinephrine replacement in adrenalectomized rats also returned potassium tolerance to normal (max delta PK = 3.02 +/- 0.10 meq/liter). The results demonstrate that extrarenal potassium tolerance is impaired in chronic adrenal insufficiency and suggest that both aldosterone and epinephrine deficiency may contribute to the defect, since replacement with either hormone returns potassium tolerance toward normal. Accordingly, both aldosterone and epinephrine have important extrarenal mechanisms of action.

Implications of permeation through intrinsic defects in graphene on the design of defect-tolerant membranes for gas separation.

PubMed

Boutilier, Michael S H; Sun, Chengzhen; O'Hern, Sean C; Au, Harold; Hadjiconstantinou, Nicolas G; Karnik, Rohit

2014-01-28

Gas transport through intrinsic defects and tears is a critical yet poorly understood phenomenon in graphene membranes for gas separation. We report that independent stacking of graphene layers on a porous support exponentially decreases flow through defects. On the basis of experimental results, we develop a gas transport model that elucidates the separate contributions of tears and intrinsic defects on gas leakage through these membranes. The model shows that the pore size of the porous support and its permeance critically affect the separation behavior, and reveals the parameter space where gas separation can be achieved regardless of the presence of nonselective defects, even for single-layer membranes. The results provide a framework for understanding gas transport in graphene membranes and guide the design of practical, selectively permeable graphene membranes for gas separation.

The Design of Fault Tolerant Quantum Dot Cellular Automata Based Logic

NASA Technical Reports Server (NTRS)

Armstrong, C. Duane; Humphreys, William M.; Fijany, Amir

2002-01-01

As transistor geometries are reduced, quantum effects begin to dominate device performance. At some point, transistors cease to have the properties that make them useful computational components. New computing elements must be developed in order to keep pace with Moore s Law. Quantum dot cellular automata (QCA) represent an alternative paradigm to transistor-based logic. QCA architectures that are robust to manufacturing tolerances and defects must be developed. We are developing software that allows the exploration of fault tolerant QCA gate architectures by automating the specification, simulation, analysis and documentation processes.

Progressive Fracture and Damage Tolerance of Composite Pressure Vessels

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Gotsis, Pascal K.; Minnetyan, Levon

1997-01-01

Structural performance (integrity, durability and damage tolerance) of fiber reinforced composite pressure vessels, designed for pressured shelters for planetary exploration, is investigated via computational simulation. An integrated computer code is utilized for the simulation of damage initiation, growth, and propagation under pressure. Aramid fibers are considered in a rubbery polymer matrix for the composite system. Effects of fiber orientation and fabrication defect/accidental damages are investigated with regard to the safety and durability of the shelter. Results show the viability of fiber reinforced pressure vessels as damage tolerant shelters for planetary colonization.

Enhanced damage resistance and novel defect structure of CrFeCoNi under in situ electron irradiation

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

He, Mo -Rigen; Wang, Shuai; Jin, Ke

Defect production and growth in CrFeCoNi, a single-phase concentrated solid solution alloy, is characterized using in situ electron irradiation inside a transmission electron microscope operated at 400–1250 kV and 400 °C. All observed defects are interstitial-type, either elliptical Frank loops or polygonal (mostly rhombus) perfect loops. Both forms of loops in CrFeCoNi exhibit a sublinear power law of growth that is > 40 times slower than the linear defect growth in pure Ni. Lastly, this result shows how compositional complexity impacts the production of Frenkel pairs and the agglomeration of interstitials into loops, and, thus, enhances the radiation tolerance.

Recognizing defects in carbon-fiber reinforced plastics

NASA Technical Reports Server (NTRS)

Schuetze, R.; Hillger, W.

1982-01-01

The damage tolerance of structures made of carbon-fiber-reinforced plastic is tested under various loads. Test laminate (73/1/1, 24/9/1, 1465 A) specimens of thickness 1.5-3.2 mm with various defects were subjected to static and dynamic loads. Special attention was given to delamination, and ultrasonic C-scans were made on the specimens. It was shown that cracks from even small defects are detected with great accuracy. The same probes were also X rayed; defects that could not be detected under ordinary X rays were bored and studied under vacuum by a contrast technique. The nondestructive ultrasonic and X ray tests were controlled by partially destructive tests, and good agreement was observed.

Enhanced damage resistance and novel defect structure of CrFeCoNi under in situ electron irradiation

DOE PAGES

He, Mo -Rigen; Wang, Shuai; Jin, Ke; ...

2016-07-25

Defect production and growth in CrFeCoNi, a single-phase concentrated solid solution alloy, is characterized using in situ electron irradiation inside a transmission electron microscope operated at 400–1250 kV and 400 °C. All observed defects are interstitial-type, either elliptical Frank loops or polygonal (mostly rhombus) perfect loops. Both forms of loops in CrFeCoNi exhibit a sublinear power law of growth that is > 40 times slower than the linear defect growth in pure Ni. Lastly, this result shows how compositional complexity impacts the production of Frenkel pairs and the agglomeration of interstitials into loops, and, thus, enhances the radiation tolerance.

Nanofiltration across Defect-Sealed Nanoporous Monolayer Graphene

DOE PAGES

O'Hern, Sean C.; Jang, Doojoon; Bose, Suman; ...

2015-04-27

Monolayer nanoporous graphene represents an ideal membrane for molecular separations, but its practical realization is impeded by leakage through defects in the ultrathin graphene. Here, we report a multiscale leakage-sealing process that exploits the nonpolar nature and impermeability of pristine graphene to selectively block defects, resulting in a centimeter-scale membrane that can separate two fluid reservoirs by an atomically thin layer of graphene. After introducing subnanometer pores in graphene, the membrane exhibited rejection of multivalent ions and small molecules and water flux consistent with prior molecular dynamics simulations. The results indicate the feasibility of constructing defect-tolerant monolayer graphene membranes formore » nanofiltration, desalination, and other separation processes.« less

Oxidation at through-hole defects in fused slurry silicide coated columbium alloys FS-85 and Cb-752

NASA Technical Reports Server (NTRS)

Levine, S. R.

1973-01-01

Metal recession and interstitial contamination at 0.08-centimeter-diameter through-hole intentional defects in fused slurry silicide coated FS-85 and Cb-752 columbium alloys were studied to determine the tolerance of these materials to coating defects. Five external pressure reentry simulation exposures to 1320 C and 4.7 x 1,000 N/sq m (maximum pressure) resulted in a consumed metal zone having about twice the initial defect diameter for both alloys with an interstitial contamination zone extending about three to four initial defect diameters. Self-healing occurred in the 1.33 x 10 N/sq m, 1320 C exposures and to a lesser extent in internal pressure reentry cycles to 1320 C and 1.33 x 100 N/sq m (maximum pressure).

Achieving Radiation Tolerance through Non-Equilibrium Grain Boundary Structures.

PubMed

Vetterick, Gregory A; Gruber, Jacob; Suri, Pranav K; Baldwin, Jon K; Kirk, Marquis A; Baldo, Pete; Wang, Yong Q; Misra, Amit; Tucker, Garritt J; Taheri, Mitra L

2017-09-25

Many methods used to produce nanocrystalline (NC) materials leave behind non-equilibrium grain boundaries (GBs) containing excess free volume and higher energy than their equilibrium counterparts with identical 5 degrees of freedom. Since non-equilibrium GBs have increased amounts of both strain and free volume, these boundaries may act as more efficient sinks for the excess interstitials and vacancies produced in a material under irradiation as compared to equilibrium GBs. The relative sink strengths of equilibrium and non-equilibrium GBs were explored by comparing the behavior of annealed (equilibrium) and as-deposited (non-equilibrium) NC iron films on irradiation. These results were coupled with atomistic simulations to better reveal the underlying processes occurring on timescales too short to capture using in situ TEM. After irradiation, NC iron with non-equilibrium GBs contains both a smaller number density of defect clusters and a smaller average defect cluster size. Simulations showed that excess free volume contribute to a decreased survival rate of point defects in cascades occurring adjacent to the GB and that these boundaries undergo less dramatic changes in structure upon irradiation. These results suggest that non-equilibrium GBs act as more efficient sinks for defects and could be utilized to create more radiation tolerant materials in future.

Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1

PubMed Central

Landegren, Nils; Sharon, Donald; Freyhult, Eva; Hallgren, Åsa; Eriksson, Daniel; Edqvist, Per-Henrik; Bensing, Sophie; Wahlberg, Jeanette; Nelson, Lawrence M.; Gustafsson, Jan; Husebye, Eystein S.; Anderson, Mark S.; Snyder, Michael; Kämpe, Olle

2016-01-01

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE’s selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance. PMID:26830021

Outcome of influenza infection managed with oseltamivir in lung transplant recipients.

PubMed

Ison, Michael G; Sharma, Amita; Shepard, Jo-Anne O; Wain, John C; Ginns, Leo C

2008-03-01

Influenza causes significant morbidity and mortality in lung transplant recipients and likely predisposes to obliterative bronchiolitis. Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and the number of antibiotic-requiring complications in ambulatory immunocompetent patients, although the efficacy of these agents in lung transplant recipients has not been assessed previously. In this study, 9 lung transplant patients who were treated with oseltamivir for influenza infections were identified and analyzed retrospectively. Oseltamivir was well tolerated. Infection resolved in all patients and there were no deaths. Two patients developed pneumonia shortly after their influenza infection and both responded to antibiotic therapy. None of the patients had persistent abnormalities noted on chest imaging and most did not show significant changes on pulmonary function testing. Two patients with the lowest pulmonary function test (PFT) values pre-infection had persistent defects after infection. Oseltamivir is well tolerated in lung transplant recipients and may reduce the risk of complications, although further studies are warranted.

The regulation of autoreactive B cells during innate immune responses.

PubMed

Vilen, Barbara J; Rutan, Jennifer A

2008-01-01

Systemic lupus erythematosus (SLE) highlights the dangers of dysregulated B cells and the importance of initiating and maintaining tolerance. In addition to central deletion, receptor editing, peripheral deletion, receptor revision, anergy, and indifference, we have described a new mechanism of B cell tolerance wherein dendritic cells (DCs) and macrophages (MPhis) regulate autoreactive B cells during innate immune responses. In part, DCs and MPhis repress autoreactive B cells by releasing IL-6 and soluble CD40L (sCD40L). This mechanism is selective in that IL-6 and sCD40L do not affect Ig secretion by naïve cells during innate immune responses, allowing immunity in the absence of autoimmunity. In lupus-prone mice, DCs and MPhis are defective in secretion of IL-6 and sCD40L and cannot effectively repress autoantibody secretion suggesting that defects in DC/MPhi-mediated tolerance may contribute to the autoimmune phenotype. Further, these studies suggest that reconstituting DCs and MPhis in SLE patients might restore regulation of autoreactive B cells and provide an alternative to immunosuppressive therapies.

Protein Kinase Cδ Deficiency Causes Mendelian Systemic Lupus Erythematosus With B Cell–Defective Apoptosis and Hyperproliferation

PubMed Central

Belot, Alexandre; Kasher, Paul R.; Trotter, Eleanor W.; Foray, Anne-Perrine; Debaud, Anne-Laure; Rice, Gillian I.; Szynkiewicz, Marcin; Zabot, Marie-Therese; Rouvet, Isabelle; Bhaskar, Sanjeev S.; Daly, Sarah B.; Dickerson, Jonathan E.; Mayer, Josephine; O’Sullivan, James; Juillard, Laurent; Urquhart, Jill E.; Fawdar, Shameem; Marusiak, Anna A.; Stephenson, Natalie; Waszkowycz, Bohdan; Beresford, Michael W.; Biesecker, Leslie G.; Black, Graeme C. M.; René, Céline; Eliaou, Jean-François; Fabien, Nicole; Ranchin, Bruno; Cochat, Pierre; Gaffney, Patrick M.; Rozenberg, Flore; Lebon, Pierre; Malcus, Christophe; Crow, Yanick J.; Brognard, John; Bonnefoy, Nathalie

2014-01-01

Objective Systemic lupus erythematosus (SLE) is a prototype autoimmune disease that is assumed to occur via a complex interplay of environmental and genetic factors. Rare causes of monogenic SLE have been described, providing unique insights into fundamental mechanisms of immune tolerance. The aim of this study was to identify the cause of an autosomal-recessive form of SLE. Methods We studied 3 siblings with juvenile-onset SLE from 1 consanguineous kindred and used next-generation sequencing to identify mutations in the disease-associated gene. We performed extensive biochemical, immunologic, and functional assays to assess the impact of the identified mutations on B cell biology. Results We identified a homozygous missense mutation in PRKCD, encoding protein kinase δ (PKCδ), in all 3 affected siblings. Mutation of PRKCD resulted in reduced expression and activity of the encoded protein PKCδ (involved in the deletion of autoreactive B cells), leading to resistance to B cell receptor– and calcium-dependent apoptosis and increased B cell proliferation. Thus, as for mice deficient in PKCδ, which exhibit an SLE phenotype and B cell expansion, we observed an increased number of immature B cells in the affected family members and a developmental shift toward naive B cells with an immature phenotype. Conclusion Our findings indicate that PKCδ is crucial in regulating B cell tolerance and preventing self-reactivity in humans, and that PKCδ deficiency represents a novel genetic defect of apoptosis leading to SLE. PMID:23666743

In situ transmission electron microscopy He + implantation and thermal aging of nanocrystalline iron

DOE PAGES

Muntifering, Brittany R.; Fang, Youwu; Leff, Asher C.; ...

2016-10-04

Due to their high density of interfaces, nanostructured material are hypothesized to show a higher tolerance to radiation damage compared to conventional coarse-grained materials and are on interest for use in future nuclear reactors. In order to investigate the roles of vacancies, self-interstitials, and helium during defect accumulation, and the thermal evolution of such defects, a complex set of in situ TEM experiments were performed in nanocrystalline iron.

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

Maughan, Annalise E.; Ganose, Alex M.; Bordelon, Mitchell M.

Vacancy-ordered double perovskites of the general formula, A2BX6, are a family of perovskite derivatives composed of a face-centered lattice of nearly isolated [BX6] units with A-site cations occupying the cuboctahedral voids. Despite the presence of isolated octahedral units, the close-packed iodide lattice provides significant electronic dispersion, such that Cs2SnI6 has recently been explored for applications in photovoltaic devices. To elucidate the structure-property relationships of these materials, we have synthesized the solid solution Cs2Sn1-xTexI6. However, even though tellurium substitution increases electronic dispersion via closer I-I contact distances, the substitution experimentally yields insulating behavior from a significant decrease in carrier concentration andmore » mobility. Density functional calculations of native defects in Cs2SnI6 reveal that iodine vacancies exhibit a low enthalpy of formation and the defect energy level is a shallow donor to the conduction band, rendering the material tolerant to these defect states. The increased covalency of Te-I bonding renders the formation of iodine vacancy states unfavorable, and is responsible for the reduction in conductivity upon Te substitution. Additionally, Cs2TeI6 is intolerant to the formation of these defects, as the defect level occurs deep within the band gap and thus localizes potential mobile charge carriers. In these vacancy-ordered double perovskites, the close-packed lattice of iodine provides significant electronic dispersion, while the interaction of the B- and X-site ions dictates the properties as they pertain to electronic structure and defect tolerance. This simplified perspective -- based on extensive experimental and theoretical analysis -- provides a platform from which to understand structure-property relationships in functional perovskite halides.« less

Take a byte out of MEEF: VAMPIRE: Vehicle for Advanced Mask Pattern Inspection Readiness Evaluations

NASA Astrophysics Data System (ADS)

Badger, Karen D.; Rankin, Jed; Turley, Christina; Seki, Kazunori; Dechene, Dan J.; Abdelghany, Hesham

2016-09-01

MEEF, or Mask Error Enhancement Factor, is simply defined as the ratio of the change in printed wafer feature width to the change in mask feature width scaled to wafer level. It is important in chip manufacturing that leads to the amplification of mask errors, creating challenges with both achieving dimensional control tolerances and ensuring defect free masks, as measured by on-wafer image quality. As lithographic imaging continues to be stressed, using lower and lower k1 factor resolution enhancement techniques, the high MEEF areas present on advanced optical masks creates an environment where the need for increased mask defect sensitivity in high-MEEF areas becomes more and more critical. There are multiple approaches to mask inspection that may or may not provide enough sensitivity to detect all wafer-printable defects; the challenge in the application of these techniques is simultaneously maintaining an acceptable level of mask inspectability. The higher the MEEF, the harder the challenge will be to achieve and appropriate level of sensitivity while maintaining inspectability…and to do so on the geometries that matter. The predominant photomask fabrication inspection approach in use today compares the features on the reticle directly with the design database using high-NA optics. This approach has the ability to detect small defects, however, when inspecting aggressive OPC, it can lead to the over-detection of inconsequential, or nuisance defects. To minimize these nuisance detections, changing the sensitivity of the inspection can improve the inspectability of a mask inspected in high-NA mode, however, it leads to the inability to detect subtle, yet wafer-printable defects in High-MEEF geometry, due to the fact that this `desense' must be applied globally. There are also `lithography-emulating' approaches to inspection that use various means to provide high defect sensitivity and the ability to tolerate inconsequential, non-printing defects by using scanner-like conditions to determine which defects are wafer printable. This inspection technique is commonly referred to as being `lithography plane' or `litho plane,' since it's assessing the mask quality based on how the mask appears to the imaging optics during use, as proposed to traditional `reticle plane' inspection which is comparing the mask only with its target design. Regardless of how the defects are detected, the real question is when should they be detected? For larger technology nodes, defects are considered `statistical risks'…i.e., first they have to occur, and then they have to fall in high-MEEF areas in order to be of concern, and be below the detection limits of traditional reticle-plane inspection. In short, the `perfect storm' has to happen in order to miss printable defects using well-optimized traditional inspection approaches. The introduction of lithographic inspection techniques has revealed this statistical game is a much higher risk than originally estimated, in that very subtle waferprintable CD errors typically fall into the desense band for traditional reticle plane inspection. Because printability is largely influenced by MEEF, designs with high-MEEF values are at greater risk of traditional inspection missing printable CD errors. The question is… how high is high… and at what MEEF is optical inspection at the reticle plane sufficient? This paper will provide evaluation results for both reticle-plane and litho-plane inspections as they pertain to varying degrees of MEEF. A newly designed high-MEEF programmed defect test mask, named VAMPIRE, will be introduced. This test mask is based on 7 nm node technology and contains intentionally varying degrees of MEEF as well as a variety of programmed defects in high-MEEF environments…all of which have been verified for defect lithographic significance on a Zeiss AIMS system.

Tolerance-based punishment in continuous public goods game

NASA Astrophysics Data System (ADS)

Gao, Jia; Li, Zhi; Cong, Rui; Wang, Long

2012-08-01

Altruistic punishment for defectors is considered as a key motive for the explanation of cooperation. However, there is no clear border between the cooperative and defective behaviors in a continuous strategy game. We propose a model to study the effect of punishment on the evolution of cooperation in continuous public goods game, wherein individuals have the traits to punish the co-players based on social tolerance. We show that a reasonable punishment with a uniform tolerance can spur individuals to make more investments. Additionally, for a fixed punishment cost and a fixed fine, a moderate value of tolerance can result in the best promotion of cooperation. Furthermore, we investigate the coevolutionary dynamics of investment and tolerance. We find that the population splits into two branches: high-tolerance individuals who make high investments and low-tolerance individuals who make low investments. A dynamic equilibrium is achieved between these two types of individuals. Our work extends punishment to continuous cooperative behaviors and the results may enhance the understanding of altruistic punishment in the evolution of human cooperation.

Physiological differences between various types of Eisenmenger syndrome and relation to outcome.

PubMed

Moceri, Pamela; Kempny, Aleksander; Liodakis, Emmanouil; Alonso Gonzales, Rafael; Germanakis, Ioannis; Diller, Gerhard-Paul; Swan, Lorna; Marino, Philip S; Wort, Stephen J; Babu-Narayan, Sonya V; Ferrari, Emile; Gatzoulis, Michael A; Li, Wei; Dimopoulos, Konstantinos

2015-01-20

Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) related to congenital heart disease. Several studies have suggested that the presence and location of the shunt defines the natural history of these patients by influencing right ventricular adaptation to PAH. We aimed to echocardiographically assess differences in cardiac physiology and outcome between various types of ES. In this longitudinal cohort study, 191 patients with ES and non-complex congenital heart disease were recruited, 36 with pre-tricuspid and 155 with post-tricuspid shunts. Patients with pre-tricuspid shunts were older, had higher BNP concentrations and lower exercise tolerance compared to patients with post-tricuspid shunts. Right ventricular (RV) function was impaired in patients with atrial septal defects, with larger right ventricles, impaired systolic function and adaptation. The left ventricular eccentricity index was significantly higher in pre-tricuspid defects. Within post-tricuspid shunts, patients with atrio-ventricular septal defects had better right ventricular function compared to ventricular septal defects, while in those with a patent ductus arteriosus this was worse. There was a trend towards lower mortality in patients with post versus pre-tricuspid shunts, which was significant for patients above the age of 48 years. The presence of a post-tricuspid shunt appears to carry physiological and possibly prognostic benefits in ES compared to patients with pre-tricuspid shunts. This should be borne in mind when management decisions and advanced therapies are considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

7 CFR 51.2648 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... for ship stores or overseas shipment, or, in the case of shipments from outside the continental United... one-half of 1 percent for cherries affected by decay. (b) For defects en route or at destination—(1) U...

7 CFR 51.2648 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... for ship stores or overseas shipment, or, in the case of shipments from outside the continental United... one-half of 1 percent for cherries affected by decay. (b) For defects en route or at destination—(1) U...

[Clinical and ossification outcome of custom-made hydroxyapatite prothese for large skull defect].

PubMed

Hardy, H; Tollard, E; Derrey, S; Delcampe, P; Péron, J-M; Fréger, P; Proust, F

2012-02-01

Cranioplasty is an everyday concern in neurosurgery, especially in decompressive craniectomy cases. Our surgical team uses custom-made hydroxyapatite implants for large and/or complex defects. Eight patients had a custom-made prosthesis. Each of them has been reviewed by an independent observer. Each patient described his feeling of satisfaction, using a questionnaire, graduated from "A" (really satisfied) to "D" (unsatisfied). Each of them also underwent a CT-scan (helicoidal acquisition, 0.6mm thick for multiplanar reconstruction) to evaluate qualitatively the ossification graduated from "0" (no ossification) to "5" (continuous ossification). Maximal under-prosthetic bone thickness, intra-prosthetic calcic density were also reported. Supervision delay was 43.7 months [6-99 months], average defect surface was 85.5 cm(2) [27.6-137.6 cm(2)], the craniectomy etiologies were intracranial hypertension (seven patients) and calvarial invasion (one patient). Implant tolerance was reparted in "A" score (50%) and "B" score (50%). Concerning ossification, six patients (75%) had a score of "2" or less and two patients had a score of "3" or "4". Hydroxyapatite custom-made implants for cranioplasty appear to be ideal for good aesthetic and tolerance results, but their ossification is hardly analyzed due to the prosthesis density higher than the bone's density. This is why we recommend them for children and in cases of complex defects such as pterion location. Copyright © 2011. Published by Elsevier Masson SAS.

β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL.

PubMed

Nyirjesy, Sarah C; Sheikh, Saba; Hadjiliadis, Denis; De Leon, Diva D; Peleckis, Amy J; Eiel, Jack N; Kubrak, Christina; Stefanovski, Darko; Rubenstein, Ronald C; Rickels, Michael R; Kelly, Andrea

2018-06-08

Patients with pancreatic insufficient cystic fibrosis (PI-CF) meeting standard criteria for normal glucose tolerance display impaired β-cell secretory capacity and early-phase insulin secretion defects. We sought evidence of impaired β-cell secretory capacity, a measure of functional β-cell mass, among those with early glucose intolerance (EGI), defined as 1-hour oral glucose tolerance test (OGTT) glucose ≥155 mg/dL (8.6 mmol/L). A cross-sectional study was conducted in the Penn and CHOP Clinical & Translational Research Centers. PI-CF categorized by OGTT as normal (PI-NGT: 1-hour glucose <155 mg/dL and 2-hour <140 mg/dL [7.8 mmol/L]; n = 13), PI-EGI (1-hour ≥155 mg/dL and 2-hour <140 mg/dL; n = 13), impaired (PI-IGT: 2-hour ≥140 and <200 mg/dL [11.1 mmol/L]; n = 8), and diabetic (cystic fibrosis-related diabetes, CFRD: 2-hour ≥200 mg/dL; n = 8) participated. Post-prandial glucose tolerance and insulin secretion, and β-cell secretory capacity and demand were derived from mixed-meal tolerance tests (MMTTs), and glucose-potentiated arginine (GPA) tests, respectively. PI-EGI had elevated post-prandial glucose with reduced early-phase insulin secretion during MMTT compared to PI-NGT (P < .05). PI-EGI also exhibited impaired acute insulin and C-peptide responses to GPA (P < .01 vs PI-NGT), measures of β-cell secretory capacity. Proinsulin secretory ratios were higher under hyperglycemic clamp conditions in PI-IGT and CFRD (P < .05 vs PI-NGT), and correlated with 1-hour glucose in PI-CF (P < .01). PI-CF patients with 1-hour OGTT glucose ≥155 mg/dL already manifest impaired β-cell secretory capacity with associated early-phase insulin secretion defects. Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tolerance of a Phage Element by Streptococcus pneumoniae Leads to a Fitness Defect during Colonization

PubMed Central

DeBardeleben, Hilary K.; Lysenko, Elena S.; Dalia, Ankur B.

2014-01-01

The pathogenesis of the disease caused by Streptococcus pneumoniae begins with colonization of the upper respiratory tract. Temperate phages have been identified in the genomes of up to 70% of clinical isolates. How these phages affect the bacterial host during colonization is unknown. Here, we examined a clinical isolate that carries a novel prophage element, designated Spn1, which was detected in both integrated and episomal forms. Surprisingly, both lytic and lysogenic Spn1 genes were expressed under routine growth conditions. Using a mouse model of asymptomatic colonization, we demonstrate that the Spn1− strain outcompeted the Spn1+ strain >70-fold. To determine if Spn1 causes a fitness defect through a trans-acting factor, we constructed an Spn1+ mutant that does not become an episome or express phage genes. This mutant competed equally with the Spn1− strain, indicating that expression of phage genes or phage lytic activity is required to confer this fitness defect. In vitro, we demonstrate that the presence of Spn1 correlated with a defect in LytA-mediated autolysis. Furthermore, the Spn1+ strain displayed increased chain length and resistance to lysis by penicillin compared to the Spn− strain, indicating that Spn1 alters the cell wall physiology of its host strain. We posit that these changes in cell wall physiology allow for tolerance of phage gene products and are responsible for the relative defect of the Spn1+ strain during colonization. This study provides new insight into how bacteria and prophages interact and affect bacterial fitness in vivo. PMID:24816604

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

PubMed Central

Zhang, Yanwen; Stocks, G. Malcolm; Jin, Ke; Lu, Chenyang; Bei, Hongbin; Sales, Brian C.; Wang, Lumin; Béland, Laurent K.; Stoller, Roger E.; Samolyuk, German D.; Caro, Magdalena; Caro, Alfredo; Weber, William J.

2015-01-01

A grand challenge in materials research is to understand complex electronic correlation and non-equilibrium atomic interactions, and how such intrinsic properties and dynamic processes affect energy transfer and defect evolution in irradiated materials. Here we report that chemical disorder, with an increasing number of principal elements and/or altered concentrations of specific elements, in single-phase concentrated solid solution alloys can lead to substantial reduction in electron mean free path and orders of magnitude decrease in electrical and thermal conductivity. The subsequently slow energy dissipation affects defect dynamics at the early stages, and consequentially may result in less deleterious defects. Suppressed damage accumulation with increasing chemical disorder from pure nickel to binary and to more complex quaternary solid solutions is observed. Understanding and controlling energy dissipation and defect dynamics by altering alloy complexity may pave the way for new design principles of radiation-tolerant structural alloys for energy applications. PMID:26507943

Defect design of insulation systems for photovoltaic modules

NASA Technical Reports Server (NTRS)

Mon, G. R.

1981-01-01

A defect-design approach to sizing electrical insulation systems for terrestrial photovoltaic modules is presented. It consists of gathering voltage-breakdown statistics on various thicknesses of candidate insulation films where, for a designated voltage, module failure probabilities for enumerated thickness and number-of-layer film combinations are calculated. Cost analysis then selects the most economical insulation system. A manufacturing yield problem is solved to exemplify the technique. Results for unaged Mylar suggest using fewer layers of thicker films. Defect design incorporates effects of flaws in optimal insulation system selection, and obviates choosing a tolerable failure rate, since the optimization process accomplishes that. Exposure to weathering and voltage stress reduces the voltage-withstanding capability of module insulation films. Defect design, applied to aged polyester films, promises to yield reliable, cost-optimal insulation systems.

The Prediction of Long-Term Coating Performance from Short-Term Electrochemical Data. Part 2; Comparison of Electrochemical Data to Field Exposure Results for Coatings on Steel

NASA Technical Reports Server (NTRS)

Contu, F.; Taylor, S. R.; Calle, L. M.; Hintze, P. E.; Curran, J. P.; Li, W.

2009-01-01

The pace of coatings development is limited by the time required to assess their corrosion protection properties. This study takes a step f orward from Part I in that it correlates the corrosion performance of organic coatings assessed by a series of short-term electrochemical measurement with 18-month beachside exposure results of duplicate pan els. A series of 19 coating systems on A36 steel substrates were test ed in a completely blind study using the damage tolerance test (DTT). In the DTT, a through-film pinhole defect is created, and the electro chemical characteristics of the defect are then monitored over the ne xt 4 to 7 days while immersed in 0.SM NaCl. The open circuit potentia l, anodic potentiostatic polarization tests and electrochemical imped ance spectroscopy were used to study the corrosion behavior of the co ating systems. The beachside exposure tests were conducted at the Ken nedy Space Center according to ASTM D610-01. It was found that for 79 % of the coatings systems examined, the 18 month beachside exposure r esults could be predicted by two independent laboratory tests obtained within 7 days.

Ferroelectric large polarons

NASA Astrophysics Data System (ADS)

Miyata, Kiyoshi; Zhu, X.-Y.

2018-05-01

Kiyoshi Miyata and X.-Y. Zhu analyse the ferroelectric-like dielectric response of lead halide perovskites in the terahertz region and discuss the potential role of polar nanodomains in accounting for the defect tolerance and low recombination rates of these materials.

Fault Tolerant Cache Schemes

NASA Astrophysics Data System (ADS)

Tu, H.-Yu.; Tasneem, Sarah

Most of modern microprocessors employ on—chip cache memories to meet the memory bandwidth demand. These caches are now occupying a greater real es tate of chip area. Also, continuous down scaling of transistors increases the possi bility of defects in the cache area which already starts to occupies more than 50% of chip area. For this reason, various techniques have been proposed to tolerate defects in cache blocks. These techniques can be classified into three different cat egories, namely, cache line disabling, replacement with spare block, and decoder reconfiguration without spare blocks. This chapter examines each of those fault tol erant techniques with a fixed typical size and organization of L1 cache, through extended simulation using SPEC2000 benchmark on individual techniques. The de sign and characteristics of each technique are summarized with a view to evaluate the scheme. We then present our simulation results and comparative study of the three different methods.

Structural Integrity Evaluation of the Lear Fan 2100 Aircraft

NASA Technical Reports Server (NTRS)

Kan, H. P.; Dyer, T. A.

1996-01-01

An in-situ nondestructive inspection was conducted to detect manufacturing and assembly induced defects in the upper two wing surfaces (skin s) and upper fuselage skin of the Lear Fan 2100 aircraft E009. The effects of the defects, detected during the inspection, on the integrity of the structure was analytically evaluated. A systematic evaluation was also conducted to determine the damage tolerance capability of the upper wing skin against impact threats and assembly induced damage. The upper wing skin was divided into small regions for damage tolerance evaluations. Structural reliability, margin of safety, allowable strains, and allowable damage size were computed. The results indicated that the impact damage threat imposed on composite military aircraft structures is too severe for the Lear Fan 2100 upper wing skin. However, the structural integrity is not significantly degraded by the assembly induced damage for properly assembled structures, such as the E009 aircraft.

The RdDM Pathway Is Required for Basal Heat Tolerance in Arabidopsis

PubMed Central

Jonak, Claudia

2013-01-01

Heat stress affects epigenetic gene silencing in Arabidopsis. To test for a mechanistic involvement of epigenetic regulation in heat-stress responses, we analyzed the heat tolerance of mutants defective in DNA methylation, histone modifications, chromatin-remodeling, or siRNA-based silencing pathways. Plants deficient in NRPD2, the common second-largest subunit of RNA polymerases IV and V, and in the Rpd3-type histone deacetylase HDA6 were hypersensitive to heat exposure. Microarray analysis demonstrated that NRPD2 and HDA6 have independent roles in transcriptional reprogramming in response to temperature stress. The misexpression of protein-coding genes in nrpd2 mutants recovering from heat correlated with defective epigenetic regulation of adjacent transposon remnants which involved the loss of control of heat-stress-induced read-through transcription. We provide evidence that the transcriptional response to temperature stress, at least partially, relies on the integrity of the RNA-dependent DNA methylation pathway. PMID:23376771

Evaluation of cranial bone transport distraction with and without adipose grafting.

PubMed

Koch, Felix P; Yuhasz, Mikell M; Travieso, Rob; Wong, Kenneth; Clune, James; Zhuang, Zhen W; Van Houten, Joshua; Steinbacher, Derek M

2014-05-01

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

Transparency and damage tolerance of patternable omniphobic lubricated surfaces based on inverse colloidal monolayers

DOE PAGES

Vogel, Nicolas; Belisle, Rebecca A.; Hatton, Benjamin; ...

2013-07-31

A transparent coating that repels a wide variety of liquids, prevents staining, is capable of self-repair and is robust towards mechanical damage can have a broad technological impact, from solar cell coatings to self-cleaning optical devices. Here we employ colloidal templating to design transparent, nanoporous surface structures. A lubricant can be firmly locked into the structures and, owing to its fluidic nature, forms a defect-free, self-healing interface that eliminates the pinning of a second liquid applied to its surface, leading to efficient liquid repellency, prevention of adsorption of liquid-borne contaminants, and reduction of ice adhesion strength. We further show howmore » this method can be applied to locally pattern the repellent character of the substrate, thus opening opportunities to spatially confine any simple or complex fluids. The coating is highly defect-tolerant due to its interconnected, honeycomb wall structure, and repellency prevails after the application of strong shear forces and mechanical damage. The regularity of the coating allows us to understand and predict the stability or failure of repellency as a function of lubricant layer thickness and defect distribution based on a simple geometric model.« less

Strongly Enhanced Photovoltaic Performance and Defect Physics of Air-Stable Bismuth Oxyiodide (BiOI)

DOE PAGES

Hoye, Robert L. Z.; Lee, Lana C.; Kurchin, Rachel C.; ...

2017-07-17

Bismuth-based compounds have recently gained increasing attention as potentially nontoxic and defect-tolerant solar absorbers. However, many of the new materials recently investigated show limited photovoltaic performance. Herein, one such compound is explored in detail through theory and experiment: bismuth oxyiodide (BiOI). BiOI thin films are grown by chemical vapor transport and found to maintain the same tetragonal phase in ambient air for at least 197 d. The computations suggest BiOI to be tolerant to antisite and vacancy defects. All-inorganic solar cells (ITO|NiO x|BiOI|ZnO|Al) with negligible hysteresis and up to 80% external quantum efficiency under select monochromatic excitation are demonstrated. Themore » short-circuit current densities and power conversion efficiencies under AM 1.5G illumination are nearly double those of previously reported BiOI solar cells, as well as other bismuth halide and chalcohalide photovoltaics recently explored by many groups. Through a detailed loss analysis using optical characterization, photoemission spectroscopy, and device modeling, direction for future improvements in efficiency is provided. In conclusion, this work demonstrates that BiOI, previously considered to be a poor photocatalyst, is promising for photovoltaics.« less

Polarity-dependence of the defect formation in c-axis oriented ZnO by the irradiation of an 8 MeV proton beam

NASA Astrophysics Data System (ADS)

Koike, Kazuto; Yano, Mitsuaki; Gonda, Shun-ichi; Uedono, Akira; Ishibashi, Shoji; Kojima, Kazunobu; Chichibu, Shigefusa F.

2018-04-01

The polarity dependence of the radiation hardness of single-crystalline ZnO bulk crystals is studied by irradiating the Zn-polar and O-polar c-planes with an 8 MeV proton beam up to the fluence of 4.2 × 1016 p/cm2. To analyze the hardness, radiation-induced defects were evaluated using positron annihilation (PA) analysis, and the recovery by post-annealing was examined using continuous-wave photoluminescence (PL) and time-resolved photoluminescence (TRPL) measurements. It was suggested by the PA and PL analyses that the major defects in both polarities were VZnVO divacancies. While the PA data did not show the clear dependence on the polarity, the PL and TRPL results showed that the Zn-polar c-plane had a little higher radiation tolerance than that of the O-polar c-plane, which was consistent with the result that the increase in the electrical resistance by proton beam irradiation was smaller for the former one. Considering these results in total, the polarity dependence is considered to be not so large, but the Zn-polar c-plane has a little higher tolerance than that of the O-polar one.

Damage Tolerance Assessment of Friction Pull Plug Welds

NASA Technical Reports Server (NTRS)

McGill, Preston; Burkholder, Jonathan

2012-01-01

Friction stir welding is a solid state welding process developed and patented by The Welding Institute in Cambridge, England. Friction stir welding has been implemented in the aerospace industry in the fabrication of longitudinal welds in pressurized cryogenic propellant tanks. As the industry looks to implement friction stir welding in circumferential welds in pressurized cryogenic propellant tanks, techniques to close out the termination hole associated with retracting the pin tool are being evaluated. Friction pull plug welding is under development as a one means of closing out the termination hole. A friction pull plug weld placed in a friction stir weld results in a non-homogenous weld joint where the initial weld, plug weld, their respective heat affected zones and the base metal all interact. The welded joint is a composite, plastically deformed material system with a complex residual stress field. In order to address damage tolerance concerns associated with friction plug welds in safety critical structures, such as propellant tanks, nondestructive inspection and proof testing may be required to screen hardware for mission critical defects. The efficacy of the nondestructive evaluation or the proof test is based on an assessment of the critical flaw size in the test or service environments. Test data relating residual strength capability to flaw size in two aluminum alloy friction plug weld configurations is presented.

Detection of fuze defects by image-processing methods

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

Chung, M.J.

1988-03-01

This paper describes experimental studies of the detection of mechanical defects by the application of computer-processing methods to real-time radiographic images of fuze assemblies. The experimental results confirm that a new algorithm developed at Materials Research Laboratory has potential for the automatic inspection of these assemblies and of others that contain discrete components. The algorithm was applied to images that contain a range of grey levels and has been found to be tolerant to image variations encountered under simulated production conditions.

Defense Small Business Innovation Research Program (SBIR). Volume 3. Air Force Abstracts of Phase 1 Awards

DTIC Science & Technology

1990-01-01

THERE WILL BE A CONTINUING NEED FOR A SENSITIVE, RAPID, AND ECONOMICAL TESTING PROCEDURE CAPABLE OF DETECTING DEFECTS AND PROVIDING FEEDBACK FOR QUALITY...SOLUTIONS. THE DKF METHOD PROVIDES OPTIMAL OR NEAR-OPTIMAL ACCURACY, REDUCE PROCESSING BURDEN, AND IMPROVE FAULT TOLERANCE. THE DKF/MMAE ( DMAE ) TECHNIQUES...DEVICES FOR B-SiC IS TO BE ABLE TO CONSISTENTLY PRODUCE INTRINSIC FILMS WITH VERY LOW DEFECTS AND TO DEVELOP SCHOTTKY AND OHMIC CONTACT MATERIALS THAT WILL

Fault-tolerance thresholds for the surface code with fabrication errors

NASA Astrophysics Data System (ADS)

Auger, James M.; Anwar, Hussain; Gimeno-Segovia, Mercedes; Stace, Thomas M.; Browne, Dan E.

2017-10-01

The construction of topological error correction codes requires the ability to fabricate a lattice of physical qubits embedded on a manifold with a nontrivial topology such that the quantum information is encoded in the global degrees of freedom (i.e., the topology) of the manifold. However, the manufacturing of large-scale topological devices will undoubtedly suffer from fabrication errors—permanent faulty components such as missing physical qubits or failed entangling gates—introducing permanent defects into the topology of the lattice and hence significantly reducing the distance of the code and the quality of the encoded logical qubits. In this work we investigate how fabrication errors affect the performance of topological codes, using the surface code as the test bed. A known approach to mitigate defective lattices involves the use of primitive swap gates in a long sequence of syndrome extraction circuits. Instead, we show that in the presence of fabrication errors the syndrome can be determined using the supercheck operator approach and the outcome of the defective gauge stabilizer generators without any additional computational overhead or use of swap gates. We report numerical fault-tolerance thresholds in the presence of both qubit fabrication and gate fabrication errors using a circuit-based noise model and the minimum-weight perfect-matching decoder. Our numerical analysis is most applicable to two-dimensional chip-based technologies, but the techniques presented here can be readily extended to other topological architectures. We find that in the presence of 8 % qubit fabrication errors, the surface code can still tolerate a computational error rate of up to 0.1 % .

7 CFR 51.2648 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... in the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects en route or at destination—(1) U.S. No. 1. 12 percent for cherries in any lot which fail to meet...

7 CFR 51.2648 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... in the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects en route or at destination—(1) U.S. No. 1. 12 percent for cherries in any lot which fail to meet...

Safety assessment for In-service Pressure Bending Pipe Containing Incomplete Penetration Defects

NASA Astrophysics Data System (ADS)

Wang, M.; Tang, P.; Xia, J. F.; Ling, Z. W.; Cai, G. Y.

2017-12-01

Incomplete penetration defect is a common defect in the welded joint of pressure pipes. While the safety classification of pressure pipe containing incomplete penetration defects, according to periodical inspection regulations in present, is more conservative. For reducing the repair of incomplete penetration defect, a scientific and applicable safety assessment method for pressure pipe is needed. In this paper, the stress analysis model of the pipe system was established for the in-service pressure bending pipe containing incomplete penetration defects. The local finite element model was set up to analyze the stress distribution of defect location and the stress linearization. And then, the applicability of two assessment methods, simplified assessment and U factor assessment method, to the assessment of incomplete penetration defects located at pressure bending pipe were analyzed. The results can provide some technical supports for the safety assessment of complex pipelines in the future.

Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group.

PubMed

1998-05-01

Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy.

Precision cancer therapy: profiting from tumor specific defects in the DNA damage tolerance system.

PubMed

Buoninfante, Olimpia Alessandra; Pilzecker, Bas; Aslam, Muhammad Assad; Zavrakidis, Ioannis; van der Wiel, Rianne; van de Ven, Marieke; van den Berk, Paul C M; Jacobs, Heinz

2018-04-10

DNA damage tolerance (DDT) enables replication to continue in the presence of a damaged template and constitutes a key step in DNA interstrand crosslink repair. In this way DDT minimizes replication stress inflicted by a wide range of endogenous and exogenous agents, and provides a critical first line defense against alkylating and platinating chemotherapeutics. Effective DDT strongly depends on damage-induced, site-specific PCNA-ubiquitination at Lysine (K) 164 by the E2/E3 complex (RAD6/18). A survey of The Cancer Genome Atlas (TCGA) revealed a high frequency of tumors presents RAD6/RAD18 bi-allelic inactivating deletions. For instance, 11% of renal cell carcinoma and 5% of pancreatic tumors have inactivating RAD18 -deletions and 7% of malignant peripheral nerve sheath tumors lack RAD6B . To determine the potential benefit for tumor-specific DDT defects, we followed a genetic approach by establishing unique sets of DDT-proficient Pcna K164 and -defective Pcna K164R lymphoma and breast cancer cell lines. In the absence of exogenous DNA damage, Pcna K164R tumors grew comparably to their Pcna K164 controls in vitro and in vivo . However, DDT-defective lymphomas and breast cancers were compared to their DDT-proficient controls hypersensitive to the chemotherapeutic drug cisplatin (CsPt), both in vitro and in vivo. CsPt strongly inhibited tumor growth and the overall survival of tumor bearing mice greatly improved in the DDT-defective condition. These insights open new therapeutic possibilities for precision cancer medicine with DNA damaging chemotherapeutics and optimize Next-Generation-Sequencing (NGS)-based cancer-diagnostics, -therapeutics, and -prognosis.

Precision cancer therapy: profiting from tumor specific defects in the DNA damage tolerance system

PubMed Central

Buoninfante, Olimpia Alessandra; Pilzecker, Bas; Aslam, Muhammad Assad; Zavrakidis, Ioannis; van der Wiel, Rianne; van de Ven, Marieke; van den Berk, Paul C.M.; Jacobs, Heinz

2018-01-01

DNA damage tolerance (DDT) enables replication to continue in the presence of a damaged template and constitutes a key step in DNA interstrand crosslink repair. In this way DDT minimizes replication stress inflicted by a wide range of endogenous and exogenous agents, and provides a critical first line defense against alkylating and platinating chemotherapeutics. Effective DDT strongly depends on damage-induced, site-specific PCNA-ubiquitination at Lysine (K) 164 by the E2/E3 complex (RAD6/18). A survey of The Cancer Genome Atlas (TCGA) revealed a high frequency of tumors presents RAD6/RAD18 bi-allelic inactivating deletions. For instance, 11% of renal cell carcinoma and 5% of pancreatic tumors have inactivating RAD18-deletions and 7% of malignant peripheral nerve sheath tumors lack RAD6B. To determine the potential benefit for tumor-specific DDT defects, we followed a genetic approach by establishing unique sets of DDT-proficient PcnaK164 and -defective PcnaK164R lymphoma and breast cancer cell lines. In the absence of exogenous DNA damage, PcnaK164R tumors grew comparably to their PcnaK164 controls in vitro and in vivo. However, DDT-defective lymphomas and breast cancers were compared to their DDT-proficient controls hypersensitive to the chemotherapeutic drug cisplatin (CsPt), both in vitro and in vivo. CsPt strongly inhibited tumor growth and the overall survival of tumor bearing mice greatly improved in the DDT-defective condition. These insights open new therapeutic possibilities for precision cancer medicine with DNA damaging chemotherapeutics and optimize Next-Generation-Sequencing (NGS)-based cancer-diagnostics, -therapeutics, and -prognosis. PMID:29721165

Regulation of K+ Transport in Tomato Roots by the TSS1 Locus. Implications in Salt Tolerance1

PubMed Central

Rubio, Lourdes; Rosado, Abel; Linares-Rueda, Adolfo; Borsani, Omar; García-Sánchez, María J.; Valpuesta, Victoriano; Fernández, José A.; Botella, Miguel A.

2004-01-01

The tss1 tomato (Lycopersicon esculentum) mutant exhibited reduced growth in low K+ and hypersensitivity to Na+ and Li+. Increased Ca2+ in the culture medium suppressed the Na+ hypersensitivity and the growth defect on low K+ medium of tss1 seedlings. Interestingly, removing NH4+ from the growth medium suppressed all growth defects of tss1, suggesting a defective NH4+-insensitive component of K+ transport. We performed electrophysiological studies to understand the contribution of the NH4+-sensitive and -insensitive components of K+ transport in wild-type and tss1 roots. Although at 1 mm Ca2+ we found no differences in affinity for K+ uptake between wild type and tss1 in the absence of NH4+, the maximum depolarization value was about one-half in tss1, suggesting that a set of K+ transporters is inactive in the mutant. However, these transporters became active by raising the external Ca2+ concentration. In the presence of NH4+, a reduced affinity for K+ was observed in both types of seedlings, but tss1 at 1 mm Ca2+ exhibited a 2-fold higher Km than wild type did. This defect was again corrected by raising the external concentration of Ca2+. Therefore, membrane potential measurements in root cells indicated that tss1 is affected in both NH4+-sensitive and -insensitive components of K+ transport at low Ca2+ concentrations and that this defective transport is rescued by increasing the concentration of Ca2+. Our results suggest that the TSS1 gene product is part of a crucial pathway mediating the beneficial effects of Ca2+ involved in K+ nutrition and salt tolerance. PMID:14684839

7 CFR 51.3150 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... entry into the United States. (2) For defects en route or at destination. 12 percent for nectarines...

The study of develop optimization to control various resist defect in Photomask fabrication

NASA Astrophysics Data System (ADS)

Lim, JongHoon; Kim, ByungJu; Son, JaeSik; Park, EuiSang; Kim, SangPyo; Yim, DongGyu

2015-07-01

To reduce the pattern size in photomask is an inevitable trend because of the minimization of chip size. So it makes a big challenge to control defects in photomask industry. Defects below a certain size that had not been any problem in previous technology node are becoming an issue as the patterns are smaller. Therefore, the acceptable tolerance levels for current defect size and quantity are dramatically reduced. Because these defects on photomask can be the sources of the repeating defects on wafer, small size defects smaller than 200nm should not be ignored any more. Generally, almost defects are generated during develop process and etch process. Especially it is difficult to find the root cause of defects formed during the develop process because of their various types and very small size. In this paper, we studied how these small defects can be eliminated by analyzing the defects and tuning the develop process. There are 3 types of resist defects which are named as follows. The first type is `Popcorn' defect which is mainly occurred in negative resist and exists on the dark features. The second type is `Frog eggs' defect which is occurred in 2nd process of HTPSM and exists on the wide space area. The last type is `Spot' defect which also exists on the wide space area. These defects are generally appeared on the entire area of a plate and the number of these defects is about several hundred. It is thought that the original source is the surface's hydrophilic state before develop process or the incongruity between resist and developer. This study shows that the optimizing the develop process can be a good solution for some resist defects.

Stabilization of the Chest Wall: Autologous and Alloplastic Reconstructions

PubMed Central

Mahabir, Raman Chaos; Butler, Charles E.

2011-01-01

The goals of chest wall stabilization include maintenance of a rigid airtight cavity, protection of the thoracic and abdominal contents, optimization of respiration, and, whenever possible, an aesthetic reconstruction. Evidence suggests that bony fixation results in reduced ventilator dependence, a shorter overall hospital stay, and improved upper extremity function. We prefer to accomplish this with autologous tissue alone (such as the pectoralis major, latissimus dorsi, or rectus abdominus muscle flaps) for small to moderate defects. En bloc resection of defects larger than 5 cm or containing four or more ribs will likely benefit from chest wall stabilization. For patients previously treated with radiation, even larger defects may be tolerated owing to fibrosis. For these larger defects, methyl methacrylate composite meshes are used and covered with vascularized tissue. Contaminated wounds are generally reconstructed with bioprosthetic mesh rather than synthetic mesh. Using these principles, the reconstructive plastic surgeon can devise a comprehensive and safe plan to repair tremendous defects of the chest wall. PMID:22294941

7 CFR 51.2336 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... the United States. (2) For defects en route or at destination. 12 percent for fruit which fail to meet...

7 CFR 51.1214 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... the United States. (2) For defects en route or at destination. 14 percent for peaches in any lot that...

Pharmacogenetic approach to losartan in Marfan patients: a starting point to improve dosing regimen?

PubMed

Falvella, Felicia Stefania; Marelli, Susan; Cheli, Stefania; Montanelli, Stefano; Viecca, Federico; Salvi, Lucia; Ferrara, Alfio; Clementi, Emilio; Trifirò, Giuliana; Pini, Alessandro

2016-09-01

Losartan is under evaluation for managing Marfan patients with aortic root dilatation. Cytochrome P450 (CYP) enzymes convert losartan to E3174 active metabolite. The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. We genotyped 53 paediatric Marfan patients treated with losartan. The rate of aortic root dilatation was evaluated using the delta z-score variation. Differences in tolerated losartan daily doses with respect to CYP metabolic classes were assessed through the Kruskal-Wallis test. The losartan daily dose spans from 0.16 to 2.50 mg/kg (median 1.10 mg/kg). As we expect from the pharmacokinetics pathway, we observe highest tolerated dose in CYP2C9 poor metabolisers (median 1.50 mg/kg, interquartile range 1.08-1.67 mg/kg); however, this difference is not statistically significant. The optimal dose of angiotensin receptor blocker is not known, and no data are available about losartan pharmacogenetic profile in Marfan syndrome; we have proposed a strategy to tackle this issue based on evaluating the major genetic polymorphisms involved in the losartan conversion into active carboxylic acid metabolite. Further studies are needed to support the use of genetic polymorphisms as predictors of the right dose of losartan.

The Vibrio parahaemolyticus ToxRS Regulator Is Required for Stress Tolerance and Colonization in a Novel Orogastric Streptomycin-Induced Adult Murine Model

PubMed Central

Whitaker, W. Brian; Parent, Michelle A.; Boyd, Aoife; Richards, Gary P.

2012-01-01

Vibrio parahaemolyticus, a marine bacterium, is the causative agent of gastroenteritis associated with the consumption of seafood. It contains a homologue of the toxRS operon that in V. cholerae is the key regulator of virulence gene expression. We examined a nonpolar mutation in toxRS to determine the role of these genes in V. parahaemolyticus RIMD2210633, an O3:K6 isolate, and showed that compared to the wild type, ΔtoxRS was significantly more sensitive to acid, bile salts, and sodium dodecyl sulfate stresses. We demonstrated that ToxRS is a positive regulator of ompU expression, and that the complementation of ΔtoxRS with ompU restores stress tolerance. Furthermore, we showed that ToxRS also regulates type III secretion system genes in chromosome I via the regulation of the leuO homologue VP0350. We examined the effect of ΔtoxRS in vivo using a new orogastric adult murine model of colonization. We demonstrated that streptomycin-treated adult C57BL/6 mice experienced prolonged intestinal colonization along the entire intestinal tract by the streptomycin-resistant V. parahaemolyticus. In contrast, no colonization occurred in non-streptomycin-treated mice. A competition assay between the ΔtoxRS and wild-type V. parahaemolyticus strains marked with the β-galactosidase gene lacZ demonstrated that the ΔtoxRS strain was defective in colonization compared to the wild-type strain. This defect was rescued by ectopically expressing ompU. Thus, the defect in stress tolerance and colonization in ΔtoxRS is solely due to OmpU. To our knowledge, the orogastric adult murine model reported here is the first showing sustained intestinal colonization by V. parahaemolyticus. PMID:22392925

Radiation tolerance of nanocrystalline ceramics: insights from Yttria Stabilized Zirconia.

PubMed

Dey, Sanchita; Drazin, John W; Wang, Yongqiang; Valdez, James A; Holesinger, Terry G; Uberuaga, Blas P; Castro, Ricardo H R

2015-01-13

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr(+), 400 keV) is inversely proportional to the grain size. HAADF images suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces.

Radiation Tolerance of Nanocrystalline Ceramics: Insights from Yttria Stabilized Zirconia

PubMed Central

Dey, Sanchita; Drazin, John W.; Wang, Yongqiang; Valdez, James A.; Holesinger, Terry G.; Uberuaga, Blas P.; Castro, Ricardo H. R.

2015-01-01

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr+, 400 keV) is inversely proportional to the grain size. HAADF images suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces. PMID:25582769

Strongly Enhanced Photovoltaic Performance and Defect Physics of Air-Stable Bismuth Oxyiodide (BiOI).

PubMed

Hoye, Robert L Z; Lee, Lana C; Kurchin, Rachel C; Huq, Tahmida N; Zhang, Kelvin H L; Sponseller, Melany; Nienhaus, Lea; Brandt, Riley E; Jean, Joel; Polizzotti, James Alexander; Kursumović, Ahmed; Bawendi, Moungi G; Bulović, Vladimir; Stevanović, Vladan; Buonassisi, Tonio; MacManus-Driscoll, Judith L

2017-09-01

Bismuth-based compounds have recently gained increasing attention as potentially nontoxic and defect-tolerant solar absorbers. However, many of the new materials recently investigated show limited photovoltaic performance. Herein, one such compound is explored in detail through theory and experiment: bismuth oxyiodide (BiOI). BiOI thin films are grown by chemical vapor transport and found to maintain the same tetragonal phase in ambient air for at least 197 d. The computations suggest BiOI to be tolerant to antisite and vacancy defects. All-inorganic solar cells (ITO|NiO x |BiOI|ZnO|Al) with negligible hysteresis and up to 80% external quantum efficiency under select monochromatic excitation are demonstrated. The short-circuit current densities and power conversion efficiencies under AM 1.5G illumination are nearly double those of previously reported BiOI solar cells, as well as other bismuth halide and chalcohalide photovoltaics recently explored by many groups. Through a detailed loss analysis using optical characterization, photoemission spectroscopy, and device modeling, direction for future improvements in efficiency is provided. This work demonstrates that BiOI, previously considered to be a poor photocatalyst, is promising for photovoltaics. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radiation tolerance of nanocrystalline ceramics: Insights from yttria stabilized zirconia

DOE PAGES

Dey, Sanchita; Drazin, John W.; Wang, Yongqiang; ...

2015-01-13

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr⁺, 400 keV) is inversely proportional to the grain size. HAADF imagesmore » suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces.« less

Detecting Submicron Pattern Defects On Optical Photomasks Using An Enhanced El-3 Electron-Beam Lithography Tool

NASA Astrophysics Data System (ADS)

Simpson, R. A.; Davis, D. E.

1982-09-01

This paper describes techniques to detect submicron pattern defects on optical photomasks with an enhanced direct-write, electron-beam lithographic tool. EL-3 is a third generation, shaped spot, electron-beam lithography tool developed by IBM to fabricate semiconductor devices and masks. This tool is being upgraded to provide 100% inspection of optical photomasks for submicron pattern defects, which are subsequently repaired. Fixed-size overlapped spots are stepped over the mask patterns while a signal derived from the back-scattered electrons is monitored to detect pattern defects. Inspection does not require pattern recognition because the inspection scan patterns are derived from the original design data. The inspection spot is square and larger than the minimum defect to be detected, to improve throughput. A new registration technique provides the beam-to-pattern overlay required to locate submicron defects. The 'guard banding" of inspection shapes prevents mask and system tolerances from producing false alarms that would occur should the spots be mispositioned such that they only partially covered a shape being inspected. A rescanning technique eliminates noise-related false alarms and significantly improves throughput. Data is accumulated during inspection and processed offline, as required for defect repair. EL-3 will detect 0.5 um pattern defects at throughputs compatible with mask manufacturing.

Treatment of prediabetes

PubMed Central

Kanat, Mustafa; DeFronzo, Ralph A; Abdul-Ghani, Muhammad A

2015-01-01

Progression of normal glucose tolerance (NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance (IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus (type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options (lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed. PMID:26464759

Impact Damage and Strain Rate Effects for Toughened Epoxy Composite Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Minnetyan, Levon

2006-01-01

Structural integrity of composite systems under dynamic impact loading is investigated herein. The GENOA virtual testing software environment is used to implement the effects of dynamic loading on fracture progression and damage tolerance. Combinations of graphite and glass fibers with a toughened epoxy matrix are investigated. The effect of a ceramic coating for the absorption of impact energy is also included. Impact and post impact simulations include verification and prediction of (1) Load and Impact Energy, (2) Impact Damage Size, (3) Maximum Impact Peak Load, (4) Residual Strength, (5) Maximum Displacement, (6) Contribution of Failure Modes to Failure Mechanisms, (7) Prediction of Impact Load Versus Time, and (8) Damage, and Fracture Pattern. A computer model is utilized for the assessment of structural response, progressive fracture, and defect/damage tolerance characteristics. Results show the damage progression sequence and the changes in the structural response characteristics due to dynamic impact. The fundamental premise of computational simulation is that the complete evaluation of composite fracture requires an assessment of ply and subply level damage/fracture processes as the structure is subjected to loads. Simulation results for the graphite/epoxy composite were compared with the impact and tension failure test data, correlation and verification was obtained that included: (1) impact energy, (2) damage size, (3) maximum impact peak load, (4) residual strength, (5) maximum displacement, and (6) failure mechanisms of the composite structure.

The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.

PubMed

Suzuki, S; Hinokio, Y; Ohtomo, M; Hirai, M; Hirai, A; Chiba, M; Kasuga, S; Satoh, Y; Akai, H; Toyota, T

1998-05-01

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes and Hepatic Steatosis in Obese Girls

PubMed Central

Cree-Green, Melanie; Xie, Danielle; Rahat, Haseeb; Garcia-Reyes, Yesenia; Bergman, Bryan C; Scherzinger, Ann; Diniz Behn, Cecilia; Chan, Christine L; Kelsey, Megan M; Pyle, Laura; Nadeau, Kristen J

2018-01-01

Abstract Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4(+) T-cells in respiratory allergies.

PubMed

Karaki, S; Garcia, G; Tcherakian, C; Capel, F; Tran, T; Pallardy, M; Humbert, M; Emilie, D; Godot, V

2014-05-01

Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4(+) T-cells (IL-10-Tregs ) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs . We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs . We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs . This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs . We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Benefits of tolerance in public goods games.

PubMed

Szolnoki, Attila; Chen, Xiaojie

2015-10-01

Leaving the joint enterprise when defection is unveiled is always a viable option to avoid being exploited. Although loner strategy helps the population not to be trapped into the tragedy of the commons state, it could offer only a modest income for nonparticipants. In this paper we demonstrate that showing some tolerance toward defectors could not only save cooperation in harsh environments but in fact results in a surprisingly high average payoff for group members in public goods games. Phase diagrams and the underlying spatial patterns reveal the high complexity of evolving states where cyclic dominant strategies or two-strategy alliances can characterize the final state of evolution. We identify microscopic mechanisms which are responsible for the superiority of global solutions containing tolerant players. This phenomenon is robust and can be observed both in well-mixed and in structured populations highlighting the importance of tolerance in our everyday life.

Characterization of calcium oxalate defective (cod) 3 mutant from Medicago truncatula

USDA-ARS?s Scientific Manuscript database

Many plants invest a considerable amount of resources and energy into the formation of calcium oxalate crystals. Assigned roles for plant crystal formation include functions in defense, calcium regulation, and aluminum tolerance. From a human health standpoint, oxalate present in edible plant tiss...

7 CFR 51.307 - Application of tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples Application of... less than 10 percent, except that at least one apple which is seriously damaged by insects or affected... at least three defective apples may be permitted in any package: Provided, That not more than three...

7 CFR 51.307 - Application of tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Grades of Apples Application of... less than 10 percent, except that at least one apple which is seriously damaged by insects or affected... at least three defective apples may be permitted in any package: Provided, That not more than three...

76 FR 74655 - Damage Tolerance and Fatigue Evaluation of Composite Rotorcraft Structures

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... and discrete flaws, and impact or other accidental damage (including the discrete source of the... discrete manufacturing defects or accidental damage, is avoided throughout the operational life or... and discrete flaws, and impact or other accidental damage (including the discrete source of the...

Software fault tolerance in computer operating systems

NASA Technical Reports Server (NTRS)

Iyer, Ravishankar K.; Lee, Inhwan

1994-01-01

This chapter provides data and analysis of the dependability and fault tolerance for three operating systems: the Tandem/GUARDIAN fault-tolerant system, the VAX/VMS distributed system, and the IBM/MVS system. Based on measurements from these systems, basic software error characteristics are investigated. Fault tolerance in operating systems resulting from the use of process pairs and recovery routines is evaluated. Two levels of models are developed to analyze error and recovery processes inside an operating system and interactions among multiple instances of an operating system running in a distributed environment. The measurements show that the use of process pairs in Tandem systems, which was originally intended for tolerating hardware faults, allows the system to tolerate about 70% of defects in system software that result in processor failures. The loose coupling between processors which results in the backup execution (the processor state and the sequence of events occurring) being different from the original execution is a major reason for the measured software fault tolerance. The IBM/MVS system fault tolerance almost doubles when recovery routines are provided, in comparison to the case in which no recovery routines are available. However, even when recovery routines are provided, there is almost a 50% chance of system failure when critical system jobs are involved.

Environmental systems biology of cold-tolerant phenotype in Saccharomyces species adapted to grow at different temperatures.

PubMed

Paget, Caroline Mary; Schwartz, Jean-Marc; Delneri, Daniela

2014-11-01

Temperature is one of the leading factors that drive adaptation of organisms and ecosystems. Remarkably, many closely related species share the same habitat because of their different temporal or micro-spatial thermal adaptation. In this study, we seek to find the underlying molecular mechanisms of the cold-tolerant phenotype of closely related yeast species adapted to grow at different temperatures, namely S. kudriavzevii CA111 (cryo-tolerant) and S. cerevisiae 96.2 (thermo-tolerant). Using two different systems approaches, i. thermodynamic-based analysis of a genome-scale metabolic model of S. cerevisiae and ii. large-scale competition experiment of the yeast heterozygote mutant collection, genes and pathways important for the growth at low temperature were identified. In particular, defects in lipid metabolism, oxidoreductase and vitamin pathways affected yeast fitness at cold. Combining the data from both studies, a list of candidate genes was generated and mutants for two predicted cold-favouring genes, GUT2 and ADH3, were created in two natural isolates. Compared with the parental strains, these mutants showed lower fitness at cold temperatures, with S. kudriavzevii displaying the strongest defect. Strikingly, in S. kudriavzevii, these mutations also significantly improve the growth at warm temperatures. In addition, overexpression of ADH3 in S. cerevisiae increased its fitness at cold. These results suggest that temperature-induced redox imbalances could be compensated by increased glycerol accumulation or production of cytosolic acetaldehyde through the deletion of GUT2 or ADH3, respectively. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Resistance to and killing by the sporicidal microbicide peracetic acid.

PubMed

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; Mcdonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2015-03-01

To elucidate the mechanisms of spore resistance to and killing by the oxidizing microbicide peracetic acid (PAA). Mutants of Bacillus subtilis lacking specific spore structures were used to identify resistance properties in spores and to understand the mechanism of action of PAA. We also assessed the effect of PAA treatment on a number of spore properties including heat tolerance, membrane integrity and germination. The spore coat is essential for spore PAA resistance as spores with defective coats were greatly sensitized to PAA treatment. Small acid-soluble spore proteins apparently provide no protection against PAA. Defects in spore germination, specifically in germination via the GerB and GerK but not the GerA germination receptors, as well as leakage of internal components suggest that PAA is active at the spore inner membrane. It is therefore likely that the inner membrane is the major site of PAA's sporicidal activity. PAA treatment targets the spore membrane, with some of its activity directed specifically against the GerB and GerK germination receptors. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

7 CFR 51.1404 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (2) For kernel defects, by count. (i) 12 percent for pecans with kernels which fail to meet the... kernels which are seriously damaged: Provided, That not more than six-sevenths of this amount, or 6 percent, shall be allowed for kernels which are rancid, moldy, decayed or injured by insects: And provided...

7 CFR 51.1439 - Tolerances for defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... for shell, center wall, and foreign material; (2) 3 percent for portions of kernels which are “dark amber” or darker color, or darker than any specified lighter color classification but which are not... which are “dark amber” or darker color, or darker than any specified lighter color classification. (b) U...

7 CFR 51.1439 - Tolerances for defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... for shell, center wall, and foreign material; (2) 3 percent for portions of kernels which are “dark amber” or darker color, or darker than any specified lighter color classification but which are not... which are “dark amber” or darker color, or darker than any specified lighter color classification. (b) U...

Production of xylitol by a Coniochaeta ligniaria strain tolerant of inhibitors and defective in xylose metabolism

USDA-ARS?s Scientific Manuscript database

In conversion of biomass to fuels or chemicals, inhibitory compounds arising from physical-chemical pretreatment of the feedstock can interfere with fermentation of the sugars to product. Fungal strain Coniochaeta ligniaria NRRL30616, metabolizes the furan aldehydes furfural and 5-hydroxymethylfurfu...

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

PubMed

Lee, Kang-Gon; Lee, Kang-Sik; Kang, Yu-Jeoung; Hwang, Jong-Hyun; Lee, Se-Hwan; Park, Sang-Hyug; Park, Yongdoo; Cho, Young-Sam; Lee, Bu-Kyu

2018-05-01

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

Specific features of defect and mass transport in concentrated fcc alloys

DOE PAGES

Osetsky, Yuri N.; Béland, Laurent K.; Stoller, Roger E.

2016-06-15

We report that diffusion and mass transport are basic properties that control materials performance, such as phase stability, solute decomposition and radiation tolerance. While understanding diffusion in dilute alloys is a mature field, concentrated alloys are much less studied. Here, atomic-scale diffusion and mass transport via vacancies and interstitial atoms are compared in fcc Ni, Fe and equiatomic Ni-Fe alloy. High temperature properties were determined using conventional molecular dynamics on the microsecond timescale, whereas the kinetic activation-relaxation (k-ART) approach was applied at low temperatures. The k-ART was also used to calculate transition states in the alloy and defect transport coefficients.more » The calculations reveal several specific features. For example, vacancy and interstitial defects migrate via different alloy components, diffusion is more sluggish in the alloy and, notably, mass transport in the concentrated alloy cannot be predicted on the basis of diffusion in its pure metal counterparts. Lastly, the percolation threshold for the defect diffusion in the alloy is discussed and it is suggested that this phenomenon depends on the properties and diffusion mechanisms of specific defects.« less

Integra-based Reconstruction of Large Scalp Wounds: A Case Report and Systematic Review of the Literature

PubMed Central

Johnson, Maxwell B.

2016-01-01

Background: Large complex scalp wounds that have traditionally required free vascularized tissue transfer have been successfully reconstructed with skin substitutes such as Integra. Although there are multiple reports of Integra-based reconstructions of scalp wounds, there has not been a comprehensive assessment of this body of literature that critically examines this method. Our goal was to conduct a systematic review to determine the effectiveness of Integra-based reconstructions of scalp wounds, with emphasis on large defects. Methods: A comprehensive systematic review was completed using key search terms, including Integra, dermal regeneration template, bovine collagen, skin substitute, forehead, and scalp. Selected articles reported characteristics of patients and their reconstructions. The primary outcome measures were wound complications and percent graft take. Results: Thirty-four articles were included in this systematic review. Wound sizes ranged from 5.7 to 610 cm2, with 35.3% of articles reporting a mean defect size >100 cm2. Thirty-two articles reported mean percent take of skin graft ≥90%. Sixteen articles reported a minor complication. There were no major complications associated with the reconstructions. Conclusions: There is a substantial evidence base for the use of Integra to reconstruct scalp wounds. To date, the dermal regeneration template is generally reserved for salvage procedures or when the patient cannot tolerate free tissue transfer. Based on the findings of this systematic review and the authors’ clinical experience, Integra can be used to achieve predictable results in large complex scalp defects. PMID:27826471

Identification of Two Loci in Tomato Reveals Distinct Mechanisms for Salt Tolerance

PubMed Central

Borsani, Omar; Cuartero, Jesus; Fernández, José A.; Valpuesta, Victoriano; Botella, Miguel A.

2001-01-01

Salt stress is one of the most serious environmental factors limiting the productivity of crop plants. To understand the molecular basis for salt responses, we used mutagenesis to identify plant genes required for salt tolerance in tomato. As a result, three tomato salt-hypersensitive (tss) mutants were isolated. These mutants defined two loci and were caused by single recessive nuclear mutations. The tss1 mutant is specifically hypersensitive to growth inhibition by Na+ or Li+ and is not hypersensitive to general osmotic stress. The tss2 mutant is hypersensitive to growth inhibition by Na+ or Li+ but, in contrast to tss1, is also hypersensitive to general osmotic stress. The TSS1 locus is necessary for K+ nutrition because tss1 mutants are unable to grow on a culture medium containing low concentrations of K+. Increased Ca2+ in the culture medium suppresses the growth defect of tss1 on low K+. Measurements of membrane potential in apical root cells were made with an intracellular microelectrode to assess the permeability of the membrane to K+ and Na+. K+-dependent membrane potential measurements indicate impaired K+ uptake in tss1 but not tss2, whereas no differences in Na+ uptake were found. The TSS2 locus may be a negative regulator of abscisic acid signaling, because tss2 is hypersensitive to growth inhibition by abscisic acid. Our results demonstrate that the TSS1 locus is essential for K+ nutrition and NaCl tolerance in tomato. Significantly, the isolation of the tss2 mutant demonstrates that abscisic acid signaling is also important for salt and osmotic tolerance in glycophytic plants. PMID:11283342

Anergic self-reactive B cells present self antigen and respond normally to CD40-dependent T-cell signals but are defective in antigen-receptor-mediated functions.

PubMed Central

Eris, J M; Basten, A; Brink, R; Doherty, K; Kehry, M R; Hodgkin, P D

1994-01-01

B-cell tolerance to soluble protein self antigens such as hen egg lysozyme (HEL) is mediated by clonal anergy. Anergic B cells fail to mount antibody responses even in the presence of carrier-primed T cells, suggesting an inability to activate or respond to T helper cells. To investigate the nature of this defect, B cells from tolerant HEL/anti-HEL double-transgenic mice were incubated with a membrane preparation from activated T-cell clones expressing the CD40 ligand. These membranes, together with interleukin 4 and 5 deliver the downstream antigen-independent CD40-dependent B-cell-activating signals required for productive T-B collaboration. Anergic B cells responded to this stimulus by proliferating and secreting antibody at levels comparable to or better than control B cells. Furthermore, anergic B cells presented HEL acquired in vivo and could present the unrelated antigen, conalbumin, targeted for processing via surface IgD. In contrast, the low immunoglobulin receptor levels on anergic B cells were associated with reduced de novo presentation of HEL and a failure to upregulate costimulatory ligands for CD28. These defects in immunoglobulin-receptor-mediated functions could be overcome in vivo, suggesting a number of mechanisms for induction of autoantibody responses. Images PMID:7514304

Modeling of defect tolerance of IMM multijunction photovoltaics for space application

NASA Astrophysics Data System (ADS)

Mehrotra, Akhil; Freundlich, Alex

2013-03-01

Reduction of defects by use of thick sophisticated graded metamorphic buffers in inverted metamorphic solar cells has been a requirement to obtain high efficiency devices. With increase in number of metamorphic junctions to obtain higher efficiencies, these graded buffers constitute a significant part of growth time and cost for manufacturer of the solar cells. It's been shown that ultrathin 3 and 4 junction IMM devices perform better in presence of dislocations or/and radiation harsh environment compared to conventional thick IMM devices. Thickness optimization of the device would result in better defect and radiation tolerant behavior of 0.7ev and 1.0ev InGaAs sub-cells which would in turn require thinner buffers with higher efficiencies, hence reducing the total device thickness. It is also shown that for 3 and 4 junc. IMM, with an equivalent 1015 cm-2 1 MeV electron fluence radiation, very high EOL efficiencies can be afforded with substantially higher dislocation densities (<2×107 cm-2) than those commonly perceived as acceptable for IMM devices with remaining power factor as high as 0.85. The irregular radiation degradation behavior in 4-junc IMM is also explained by back photon reflection from gold contacts and reduced by using thickness optimization of 0.7ev and 1.0ev InGaAs sub-cells.

Global and Local Mechanical Properties of Autogenously Laser Welded Ti-6Al-4V

NASA Astrophysics Data System (ADS)

Cao, Xinjin; Kabir, Abu Syed H.; Wanjara, Priti; Gholipour, Javad; Birur, Anand; Cuddy, Jonathan; Medraj, Mamoun

2014-03-01

Ti-6Al-4V sheets, 3.2-mm in thickness, were butt welded using a continuous wave 4 kW Nd:YAG laser welding system. The effect of two main process parameters, laser power and welding speed, on the joint integrity was characterized in terms of the joint geometry, defects, microstructure, hardness, and tensile properties. In particular, a digital image correlation technique was used to determine the local tensile properties of the welds. It was determined that a wide range of heat inputs can be used to fully penetrate the Ti-6Al-4V butt joints during laser welding. At high laser power levels, however, significant defects such as underfill and porosity, can occur and cause marked degradation in the joint integrity and performance. At low welding speeds, however, significant porosity occurs due to its growth and the potential collapse of instable keyholes. Intermediate to relatively high levels of heat input allow maximization of the joint integrity and performance by limiting the underfill and porosity defects. In considering the effect of the two main defects on the joint integrity, the underfill defect was found to be more damaging to the mechanical performance of the weldment than the porosity. Specifically, it was determined that the maximum tolerable underfill depth for Ti-6Al-4V is approximately 6 pct of the workpiece thickness, which is slightly stricter than the value of 7 pct specified in AWS D17.1 for fusion welding in aerospace applications. Hence, employing optimized laser process parameters allows the underfill depth to be maintained within the tolerable limit (6 pct), which in turn prevents degradation in both the weld strength and ductility. To this end, the ability to maintain weld ductility in Ti-6Al-4V by means of applying a high energy density laser welding process presents a significant advantage over conventional arc welding for the assembly of aerospace components.

Many-Body Theory of Proton-Generated Point Defects for Losses of Electron Energy and Photons in Quantum Wells

NASA Astrophysics Data System (ADS)

Huang, Danhong; Iurov, Andrii; Gao, Fei; Gumbs, Godfrey; Cardimona, D. A.

2018-02-01

The effects of point defects on the loss of either energies of ballistic electron beams or incident photons are studied by using a many-body theory in a multi-quantum-well system. This theory includes the defect-induced vertex correction to a bare polarization function of electrons within the ladder approximation, and the intralayer and interlayer screening of defect-electron interactions is also taken into account in the random-phase approximation. The numerical results of defect effects on both energy-loss and optical-absorption spectra are presented and analyzed for various defect densities, numbers of quantum wells, and wave vectors. The diffusion-reaction equation is employed for calculating distributions of point defects in a layered structure. For completeness, the production rate for Frenkel-pair defects and their initial concentration are obtained based on atomic-level molecular-dynamics simulations. By combining the defect-effect, diffusion-reaction, and molecular-dynamics models with an available space-weather-forecast model, it will be possible in the future to enable specific designing for electronic and optoelectronic quantum devices that will be operated in space with radiation-hardening protection and, therefore, effectively extend the lifetime of these satellite onboard electronic and optoelectronic devices. Specifically, this theory can lead to a better characterization of quantum-well photodetectors not only for high quantum efficiency and low dark current density but also for radiation tolerance or mitigating the effects of the radiation.

Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

PubMed

Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

2016-05-01

The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term.

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

DOE PAGES

Zhang, Yanwen; Stocks, George Malcolm; Jin, Ke; ...

2015-10-28

A long-standing objective in materials research is to understand how energy is dissipated in both the electronic and atomic subsystems in irradiated materials, and how related non-equilibrium processes may affect defect dynamics and microstructure evolution. Here we show that alloy complexity in concentrated solid solution alloys having both an increasing number of principal elements and altered concentrations of specific elements can lead to substantial reduction in the electron mean free path and thermal conductivity, which has a significant impact on energy dissipation and consequentially on defect evolution during ion irradiation. Enhanced radiation resistance with increasing complexity from pure nickel tomore » binary and to more complex quaternary solid solutions is observed under ion irradiation up to an average damage level of 1 displacement per atom. Understanding how materials properties can be tailored by alloy complexity and their influence on defect dynamics may pave the way for new principles for the design of radiation tolerant structural alloys.« less

Functional defect in regulatory T cells in myasthenia gravis

PubMed Central

Thiruppathi, Muthusamy; Rowin, Julie; Jiang, Qin Li; Sheng, Jian Rong; Prabhakar, Bellur S.; Meriggioli, Matthew N.

2012-01-01

Forkhead box P3 (FOXP3)+ is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance, and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules such as FOXP3 on isolated Treg cells and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and up-regulated FOXP3 expression. These findings indicate a clinically relevant Treg cell–intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. PMID:23252899

Jet and flash imprint defectivity: assessment and reduction for semiconductor applications

NASA Astrophysics Data System (ADS)

Malloy, Matt; Litt, Lloyd C.; Johnson, Steve; Resnick, Douglas J.; Lovell, David

2011-04-01

Defectivity has been historically identified as a leading technical roadblock to the implementation of nanoimprint lithography for semiconductor high volume manufacturing. The lack of confidence in nanoimprint's ability to meet defect requirements originates in part from the industry's past experiences with 1X lithography and the shortage in end-user generated defect data. SEMATECH has therefore initiated a defect assessment aimed at addressing these concerns. The goal is to determine whether nanoimprint, specifically Jet and Flash Imprint Lithography from Molecular Imprints, is capable of meeting semiconductor industry defect requirements. At this time, several cycles of learning have been completed in SEMATECH's defect assessment, with promising results. J-FIL process random defectivity of < 0.1 def/cm2 has been demonstrated using a 120nm half-pitch template, providing proof of concept that a low defect nanoimprint process is possible. Template defectivity has also improved significantly as shown by a pre-production grade template at 80nm pitch. Cycles of learning continue on feature sizes down to 22nm.

7 CFR 51.1525 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the... than Italian type prunes en route or at destination. 12 percent for fruit which fails to meet the... amount not more than one-half of 1 percent for decay. (4) For defects of Italian type prunes en route or...

7 CFR 51.1525 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... port of loading for ship stores or overseas shipment, or, in the case of shipments from outside the... than Italian type prunes en route or at destination. 12 percent for fruit which fails to meet the... amount not more than one-half of 1 percent for decay. (4) For defects of Italian type prunes en route or...

CMOL: A New Concept for Nanoelectronics

NASA Astrophysics Data System (ADS)

Likharev, Konstantin

2005-03-01

I will review the recent work on devices and architectures for future hybrid semiconductor/molecular integrated circuits, in particular those of ``CMOL'' variety [1]. Such circuits would combine an advanced CMOS subsystem fabricated by the usual lithographic patterning, two layers of parallel metallic nanowires formed, e.g., by nanoimprint, and two-terminal molecular devices self-assembled on the nanowire crosspoints. Estimates show that this powerful combination may allow CMOL circuits to reach an unparalleled density (up to 10^12 functions per cm^2) and ultrahigh rate of information processing (up to 10^20 operations per second on a single chip), at acceptable power dissipation. The main challenges on the way toward practical CMOL technology are: (i) reliable chemically-directed self-assembly of mid-size organic molecules, and (ii) the development of efficient defect-tolerant architectures for CMOL circuits. Our recent work has shown that such architectures may be developed not only for terabit-scale memories and naturally defect-tolerant mixed-signal neuromorphic networks, but (rather unexpectedly) also for FPGA-style digital Boolean circuits. [1] For details, see http://rsfq1.physics.sunysb.edu/˜likharev/nano/Springer04.pdf

Reduced TCR signaling potential impairs negative selection but does not result in autoimmune disease

PubMed Central

Hwang, SuJin; Song, Ki-Duk; Lesourne, Renaud; Lee, Jan; Pinkhasov, Julia; Li, LiQi; El-Khoury, Dalal

2012-01-01

Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, and both require high-affinity interactions between the T cell receptor (TCR) and self-ligands. However, it remains unclear if they are similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) of the TCR ζ chain gene encoding a mutant protein lacking signaling capability whose expression is controlled by endogenous ζ regulatory sequences. Although negative selection was defective in 6F/6F mice, leading to the survival of autoreactive T cells, 6F/6F mice did not develop autoimmune disease. We found that 6F/6F mice generated increased numbers of thymus-derived T reg cells. We show that attenuation of TCR signaling potential selectively impacts downstream signaling responses and that this differential effect favors Foxp3 expression and T reg cell lineage commitment. These results identify a potential compensatory pathway for the enforcement of immune tolerance in response to defective negative selection caused by reduced TCR signaling capability. PMID:22945921

Design of novel materials for additive manufacturing - Isotropic microstructure and high defect tolerance.

PubMed

Günther, J; Brenne, F; Droste, M; Wendler, M; Volkova, O; Biermann, H; Niendorf, T

2018-01-22

Electron Beam Melting (EBM) is a powder-bed additive manufacturing technology enabling the production of complex metallic parts with generally good mechanical properties. However, the performance of powder-bed based additively manufactured materials is governed by multiple factors that are difficult to control. Alloys that solidify in cubic crystal structures are usually affected by strong anisotropy due to the formation of columnar grains of preferred orientation. Moreover, processing induced defects and porosity detrimentally influence static and cyclic mechanical properties. The current study presents results on processing of a metastable austenitic CrMnNi steel by EBM. Due to multiple phase transformations induced by intrinsic heat-treatment in the layer-wise EBM process the material develops a fine-grained microstructure almost without a preferred crystallographic grain orientation. The deformation-induced phase transformation yields high damage tolerance and, thus, excellent mechanical properties less sensitive to process-induced inhomogeneities. Various scan strategies were applied to evaluate the width of an appropriate process window in terms of microstructure evolution, porosity and change of chemical composition.

In vitro comparison of two widely used surgical sealants for treating alveolar air leak.

PubMed

Zhang, Ruoyu; Bures, Maximilian; Höffler, Klaus; Jonigk, Danny; Haverich, Axel; Krueger, Marcus

2014-12-01

Controversies surrounding the efficacy of sealants against alveolar air leak (AAL) are abundant in the literature. We sought to test the widely used sealants, TachoSil (Takeda Pharmaceutical Company Limited, Osaka, Japan) and BioGlue (CryoLife Europa Ltd., Surrey, United Kingdom) in an in vitro model. Materials and After creation of a focal superficial defect (40 × 25 mm) in swine lungs (n=40), AAL was assessed with increasing inspired tidal volume (TVi). Upon sealant application in a randomized order, AAL was assessed in the same way until sealant burst. At TVi =400, 500, 600, and 700 mL, BioGlue achieved sealing in 19, 19, 16, and 14 tests, while TachoSil sealed in 19, 14, 4, and no test, respectively. The maximally tolerated pressure of BioGlue was higher than TachoSil (40.3 ± 3.0 vs. 36.0 ± 4.9 cm H2O, p=0.003). Cohesive and adhesive failures were found in 10 and 1 tests of BioGlue, respectively, while all burst failures of TachoSil were adhesive. Concerning elasticity, TachoSil allowed more expansion of the covered defect than BioGlue (6.3 ± 3.9 vs. 1.4 ± 1.0 mm, p<0.001). The tested sealants demonstrated high sealing efficacy. While BioGlue was superior in resisting higher ventilation pressure, TachoSil possessed better elasticity. Georg Thieme Verlag KG Stuttgart · New York.

Robust manipulation of light using topologically protected plasmonic modes.

PubMed

Liu, Chenxu; Gurudev Dutt, M V; Pekker, David

2018-02-05

We propose using a topological plasmonic crystal structure composed of an array of nearly parallel nanowires with unequal spacing for manipulating light. In the paraxial approximation, the Helmholtz equation that describes the propagation of light along the nanowires maps onto the Schrödinger equation of the Su-Schrieffer-Heeger (SSH) model. Using a full three-dimensional finite difference time domain solution of the Maxwell equations, we verify the existence of topological defect modes, with sub-wavelength localization, bound to domain walls of the plasmonic crystal. We show that by manipulating domain walls we can construct spatial mode filters that couple bulk modes to topological defect modes, and topological beam-splitters that couple two topological defect modes. Finally, we show that the structures are tolerant to fabrication errors with an inverse length-scale smaller than the topological band gap.

Recent thymic emigrants are tolerized in the absence of inflammation

PubMed Central

Friesen, Travis J.; Ji, Qingyong

2016-01-01

T cell development requires a period of postthymic maturation. Why this is the case has remained a mystery, particularly given the rigors of intrathymic developmental checkpoints, successfully traversed by only ∼5% of thymocytes. We now show that the first few weeks of T cell residence in the lymphoid periphery define a period of heightened susceptibility to tolerance induction to tissue-restricted antigens (TRAs), the outcome of which depends on the context in which recent thymic emigrants (RTEs) encounter antigen. After encounter with TRAs in the absence of inflammation, RTEs exhibited defects in proliferation, diminished cytokine production, elevated expression of anergy-associated genes, and diminished diabetogenicity. These properties were mirrored in vitro by enhanced RTE susceptibility to regulatory T cell–mediated suppression. In the presence of inflammation, RTEs and mature T cells were, in contrast, equally capable of inducing diabetes, proliferating, and producing cytokines. Thus, recirculating RTEs encounter TRAs during a transitional developmental stage that facilitates tolerance induction, but inflammation converts antigen-exposed, tolerance-prone RTEs into competent effector cells. PMID:27139493

Ab initio study of irradiation tolerance for different M{sub n+1}AX{sub n} phases: Ti{sub 3}SiC{sub 2} and Ti{sub 3}AlC{sub 2}

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

Zhao, Shijun; Xue, Jianming, E-mail: jmxue@pku.edu.cn; Wang, Yugang

2014-01-14

Layered ternary M{sub n+1}AX{sub n} (MAX) materials are recently proposed to be promising candidates for future fission and fusion programmes because of their unique properties inherited from both ceramics and metals. However, different M{sub n+1}AX{sub n} materials demonstrate different behaviors when exposed to energetic neutron or ion irradiations. Based on first-principles calculations, we have investigated the irradiation tolerance of two typical M{sub n+1}AX{sub n} materials: Ti{sub 3}SiC{sub 2} and Ti{sub 3}AlC{sub 2} from two aspects. First, we make a detailed analysis on the interatomic bonding characters, which are believed to be responsible for the resistance to radiation-induced amorphization. Second, themore » formation energies of various intrinsic and antisite defects in these two compounds are calculated in order to elucidate their amorphization mechanism. Our results show that the absence of orbitals overlap of Al-C in Ti{sub 3}AlC{sub 2} renders it more resistant to amorphization compared to Ti{sub 3}SiC{sub 2}. In addition, the antisite defects Al{sub Ti(1)} and Al{sub Ti(2)} in Ti{sub 3}AlC{sub 2} have much lower formation energies compared to Si{sub Ti(1)} and Si{sub Ti(2)} in Ti{sub 3}SiC{sub 2}, which implies that the replacement of Ti with Al is easier than Si, thus providing an alternative way to accommodate the defects resulted from irradiation damage cascades. These results indicate that Ti{sub 3}AlC{sub 2} is more irradiation tolerant than Ti{sub 3}SiC{sub 2}, in accordance with experimental observations. Our results have profound implications for the choice of appropriate MAX phase with best performance to be used in next reaction reactors.« less

Off-pump repair of a post-infarct ventricular septal defect: the 'Hamburger procedure'

PubMed Central

Barker, Thomas A; Ng, Alexander; Morgan, Ian S

2006-01-01

We report a novel off-pump technique for the surgical closure of post-infarct ventricular septal defects (VSDs). The case report describes the peri-operative management of a 76 year old lady who underwent the 'Hamburger procedure' for closure of her apical VSD. Refractory cardiogenic shock meant that traditional patch repairs requiring cardiopulmonary bypass would be poorly tolerated. We show that echocardiography guided off-pump posterior-anterior septal plication is a safe, effective method for closing post-infarct VSDs in unstable patients. More experience is required to ascertain whether this technique will become an accepted alternative to patch repairs. PMID:16722552

Direct Observation of Sink-Dependent Defect Evolution in Nanocrystalline Iron under Irradiation

DOE PAGES

El Atwani, Osman; Nathaniel, James; Leff, Asher C.; ...

2017-05-12

Crystal defects generated during irradiation can result in severe changes in morphology and an overall degradation of mechanical properties in a given material. Nanomaterials have been proposed as radiation damage tolerant materials, due to the hypothesis that defect density decreases with grain size refinement due to the increase in grain boundary surface area. The lower defect density should arise from grain boundary-point defect absorption and enhancement of interstitial-vacancy annihilation. In this study, low energy helium ion irradiation on free-standing iron thin films were performed at 573 K. Interstitial loops of a 0 /2 [111] Burgers vector were directly observed asmore » a result of the displacement damage. Loop density trends with grain size demonstrated an increase in the nanocrystalline (<100 nm) regime, but scattered behavior in the transition from the nanocrystalline to the ultra-fine regime (100–500 nm). To examine the validity of such trends, loop density and area for different grains at various irradiation doses were compared and revealed efficient defect absorption in the nanocrystalline grain size regime, but loop coalescence in the ultra-fine grain size regime. Lastly, a relationship between the denuded zone formation, a measure of grain boundary absorption efficiency, grain size, grain boundary type and misorientation angle is determined.« less

Direct Observation of Sink-Dependent Defect Evolution in Nanocrystalline Iron under Irradiation

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

El Atwani, Osman; Nathaniel, James; Leff, Asher C.

Crystal defects generated during irradiation can result in severe changes in morphology and an overall degradation of mechanical properties in a given material. Nanomaterials have been proposed as radiation damage tolerant materials, due to the hypothesis that defect density decreases with grain size refinement due to the increase in grain boundary surface area. The lower defect density should arise from grain boundary-point defect absorption and enhancement of interstitial-vacancy annihilation. In this study, low energy helium ion irradiation on free-standing iron thin films were performed at 573 K. Interstitial loops of a 0 /2 [111] Burgers vector were directly observed asmore » a result of the displacement damage. Loop density trends with grain size demonstrated an increase in the nanocrystalline (<100 nm) regime, but scattered behavior in the transition from the nanocrystalline to the ultra-fine regime (100–500 nm). To examine the validity of such trends, loop density and area for different grains at various irradiation doses were compared and revealed efficient defect absorption in the nanocrystalline grain size regime, but loop coalescence in the ultra-fine grain size regime. Lastly, a relationship between the denuded zone formation, a measure of grain boundary absorption efficiency, grain size, grain boundary type and misorientation angle is determined.« less

[Renal glycosuria: dominant or recessive autosome anomaly? Mode of hereditary transmission based on the analysis of a 3-generation family tree].

PubMed

De Marchi, S; Proto, G; Jengo, A; Collinassi, P; Basile, A

1983-02-25

Assessment of the pedigree of 7 persons in 3 generations showed that interpretation of the transmission modality of renal glycosuria may be influenced by the diagnostic criteria employed. Analysis of renal glucose curves and evaluation of glycosuria after an oral glucose tolerance test made it clear that albeit slight detects could be detected in family members who would be regarded as healthy according to the criteria of Marble. Distribution of the character pointed to dominant transmission, as opposed to the recessive autosomal transmission favoured in the literature. Variations in the clinical gravity of the tubular defect may be ascribable to a difference in the expressiveness of the abnormal gene or to genetic heterogeneity. Persons homozygous and heterozygous for the gene were present in the pedigree concerned.

Computational Simulation of Damage Progression of Composite Thin Shells Subjected to Mechanical Loads

NASA Technical Reports Server (NTRS)

Gotsis, P. K.; Chamis, C. C.; Minnetyan, L.

1996-01-01

Defect-free and defected composite thin shells with ply orientation (90/0/+/-75) made of graphite/epoxy are simulated for damage progression and fracture due to internal pressure and axial loading. The thin shells have a cylindrical geometry with one end fixed and the other free. The applied load consists of an internal pressure in conjunction with an axial load at the free end, the cure temperature was 177 C (350 F) and the operational temperature was 21 C (70 F). The residual stresses due to the processing are taken into account. Shells with defect and without defects were examined by using CODSTRAN an integrated computer code that couples composite mechanics, finite element and account for all possible failure modes inherent in composites. CODSTRAN traces damage initiation, growth, accumulation, damage propagation and the final fracture of the structure. The results show that damage initiation started with matrix failure while damage/fracture progression occurred due to additional matrix failure and fiber fracture. The burst pressure of the (90/0/+/- 75) defected shell was 0.092% of that of the free defect. Finally the results of the damage progression of the (90/0/+/- 75), defective composite shell was compared with the (90/0/+/- theta, where theta = 45 and 60, layup configurations. It was shown that the examined laminate (90/0/+/- 75) has the least damage tolerant of the two compared defective shells with the (90/0/+/- theta), theta = 45 and 60 laminates.

The Development of Design Tools for Fault Tolerant Quantum Dot Cellular Automata Based Logic

NASA Technical Reports Server (NTRS)

Armstrong, Curtis D.; Humphreys, William M.

2003-01-01

We are developing software to explore the fault tolerance of quantum dot cellular automata gate architectures in the presence of manufacturing variations and device defects. The Topology Optimization Methodology using Applied Statistics (TOMAS) framework extends the capabilities of the A Quantum Interconnected Network Array Simulator (AQUINAS) by adding front-end and back-end software and creating an environment that integrates all of these components. The front-end tools establish all simulation parameters, configure the simulation system, automate the Monte Carlo generation of simulation files, and execute the simulation of these files. The back-end tools perform automated data parsing, statistical analysis and report generation.

Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV.

PubMed

Shankar, Manoharan; Hossain, Mohammad S; Biswas, Indranil

2017-04-15

Streptococcus mutans , an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque. S. mutans expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An S. mutans strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the S. mutans genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as sprV ( s treptococcal p leiotropic r egulator of v irulence). The transcript levels of several relevant genes in the sprV mutant corroborated the phenotypes observed upon sprV deletion. Owing to its highly conserved nature, inactivation of the sprV ortholog in Streptococcus gordonii also resulted in poor growth and defective UV tolerance and competence development as in the case of S. mutans Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the S. mutans biology. IMPORTANCE Streptococcus mutans employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded by S. mutans We show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production. Copyright © 2017 American Society for Microbiology.

Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV

PubMed Central

Shankar, Manoharan; Hossain, Mohammad S.

2017-01-01

ABSTRACT Streptococcus mutans, an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque. S. mutans expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An S. mutans strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the S. mutans genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as sprV (streptococcal pleiotropic regulator of virulence). The transcript levels of several relevant genes in the sprV mutant corroborated the phenotypes observed upon sprV deletion. Owing to its highly conserved nature, inactivation of the sprV ortholog in Streptococcus gordonii also resulted in poor growth and defective UV tolerance and competence development as in the case of S. mutans. Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the S. mutans biology. IMPORTANCE Streptococcus mutans employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded by S. mutans. We show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production. PMID:28167518

Radiation response of nanotwinned Cu under multiple-collision cascades

NASA Astrophysics Data System (ADS)

Wu, Lianping; Yu, Wenshan; Hu, Shuling; Shen, Shengping

2018-07-01

In this paper, multiple collision cascades (MCC) of nanotwinned (nt) Cu with three different twin spacings are performed to model the response of nt Cu upon a radiation dose of 1 displacements per atom (dpa). Considering the defects developed with high randomness in the material during a MCC process, each MCC in a nt Cu is conducted for eight times. This enables us to analyze some average properties of defect clusters in the radiated nt Cu with different twin spacings at the different radiation doses. We also analyze the microstructural evolution in the nt Cu during the MCC. Smaller size of defect clusters and lower defect density are seen in the nt Cu with smaller twin spacing. In addition, a number of defect clusters could be removed via their frequent interactions with the coherent twin boundaries (CTBs) during the MCC. This induces either the migration of CTBs or the healing of CTBs. Moreover, the potential formation and elimination mechanisms of stacking fault are found to be due to the climb of Frank partial dislocation and glide of Shockley partial dislocations. This study provides further evidence on the irradiation tolerance of CTBs and the self-healing capability of CTBs in response to radiation.

Assessment of cardiac single-photon emission computed tomography performance using a scanning linear observer

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

Lee, Chih-Jie; Kupinski, Matthew A.; Volokh, Lana

2013-01-15

Purpose: Single-photon emission computed tomography (SPECT) is widely used to detect myocardial ischemia and myocardial infarction. It is important to assess and compare different SPECT system designs in order to achieve the highest detectability of cardiac defects. Methods: Whitaker et al.'s study ['Estimating random signal parameters from noisy images with nuisance parameters: linear and scanning-linear methods,' Opt. Express 16(11), 8150-8173 (2008)] on the scanning linear observer (SLO) shows that the SLO can be used to estimate the location and size of signals. One major advantage of the SLO is that it can be used with projection data rather than withmore » reconstruction data. Thus, this observer model assesses the overall hardware performance independent of any reconstruction algorithm. In addition, the computation time of image quality studies is significantly reduced. In this study, three systems based on the design of the GE cadmium zinc telluride-based dedicated cardiac SPECT camera Discovery 530c were assessed. This design, which is officially named the Alcyone Technology: Discovery NM 530c, was commercialized in August, 2009. The three systems, GE27, GE19, and GE13, contain 27, 19, and 13 detectors, respectively. Clinically, a human heart can be virtually segmented into three coronary artery territories: the left-anterior descending artery, left-circumflex artery, and right coronary artery. One of the most important functions of a cardiac SPECT system is to produce images from which a radiologist can accurately predict in which territory the defect exists [http://www.asnc.org/media/PDFs/PPReporting081511.pdf, Guideline from American Society of Nuclear Cardiology]. A good estimation of the extent of the defect from the projection images is also very helpful for determining the seriousness of the myocardial ischemia. In this study, both the location and extent of defects were estimated by the SLO, and the system performance was assessed by localization receiver operating characteristic (LROC) [P. Khurd and G. Gindi, 'Decision strategies maximizing the area under the LROC curve,' Proc. SPIE 5749, 150-161 (2005)] or estimation receiver operating characteristic (EROC) [E. Clarkson, 'Estimation receiver operating characteristic curve and ideal observers for combined detection/estimation tasks,' J. Opt. Soc. Am. A 24, B91-B98 (2007)] curves. Results: The area under the LROC/EROC curve (AULC/AUEC) and the true positive fraction (TPF) at a specific false positive fraction (FPF) can be treated as the figures of merit. For radii estimation with a 1 mm tolerance, the AUEC values of the GE27, GE19, and GE13 systems are 0.8545, 0.8488, and 0.8329, and the TPF at FPF = 5% are 77.1%, 76.46%, and 73.55%, respectively. The assessment of all three systems revealed that the GE19 system yields estimated information and cardiac defect detectability very close to those of the GE27 system while using eight fewer detectors. Thus, 30% of the expensive detector units can be removed with confidence. Conclusions: As the results show, a combination of the SLO and LROC/EROC curves can determine the configuration that yields the most relevant estimation/detection information. Thus, this is a useful method for assessing cardiac SPECT systems.« less

7 CFR 51.1861 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... provided as specified: (a) U.S. No. 1—(1) For defects at shipping point. 2 Ten percent for tomatoes in any...) Five percent for tomatoes which are soft or affected by decay; (ii) Ten percent for tomatoes which are damaged by shoulder bruises or by discolored or sunken scars on any parts of the tomatoes; and, (iii) Ten...

7 CFR 51.1525 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects of plums or prunes other than Italian type prunes en route or at destination. 12 percent for fruit... Italian type prunes en route or at destination. Not more than a total of 18 percent of the fruit in any...

7 CFR 51.1525 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects of plums or prunes other than Italian type prunes en route or at destination. 12 percent for fruit... Italian type prunes en route or at destination. Not more than a total of 18 percent of the fruit in any...

Pyridoxal phosphate synthases PdxS/PdxT are required for Actinobacillus pleuropneumoniae viability, stress tolerance and virulence.

PubMed

Xie, Fang; Li, Gang; Wang, Yalei; Zhang, Yanhe; Zhou, Long; Wang, Chengcheng; Liu, Shuanghong; Liu, Siguo; Wang, Chunlai

2017-01-01

Pyridoxal 5'-phosphate (PLP) is an essential cofactor for numerous enzymes involved in a diversity of cellular processes in living organisms. Previous analysis of the Actinobacillus pleuropneumoniae S-8 genome sequence revealed the presence of pdxS and pdxT genes, which are implicated in deoxyxylulose 5-phosphate (DXP)-independent pathway of PLP biosynthesis; however, little is known about their roles in A. pleuropneumoniae pathogenicity. Our data demonstrated that A. pleuropneumoniae could synthesize PLP by PdxS and PdxT enzymes. Disruption of the pdxS and pdxT genes rendered the pathogen auxotrophic for PLP, and the defective growth as a result of these mutants was chemically compensated by the addition of PLP, suggesting the importance of PLP production for A. pleuropneumoniae growth and viability. Additionally, the pdxS and pdxT deletion mutants displayed morphological defects as indicated by irregular and aberrant shapes in the absence of PLP. The reduced growth of the pdxS and pdxT deletion mutants under osmotic and oxidative stress conditions suggests that the PLP synthases PdxS/PdxT are associated with the stress tolerance of A. pleuropneumoniae. Furthermore, disruption of the PLP biosynthesis pathway led to reduced colonization and attenuated virulence of A. pleuropneumoniae in the BALB/c mouse model. The data presented in this study reveal the critical role of PLP synthases PdxS/PdxT in viability, stress tolerance, and virulence of A. pleuropneumoniae.

Higher miRNA Tolerance in Immortal Li-Fraumeni Fibroblasts with Abrogated Interferon Signaling Pathway

PubMed Central

Li, Qunfang; Tainsky, Michael A.

2013-01-01

The IFN pathway is abrogated in fibroblasts from Li-Fraumeni syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Microarray profiling of differentially expressed microRNAs (miRNA) revealed that most miRNAs were upregulated in IFN pathway–defective MDAH087-10 fibroblasts compared with MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of IFN-stimulated genes in MDAH087-N cells resulting in significant cell death and reduced cell growth. Furthermore, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to changed IFN pathway activity. Dicer overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicertransfected MDAH087-10 cells. Therefore, cells with a defective IFN pathway have a higher miRNA tolerance than cells with normal IFN pathway. This work indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA upregulation to occur in early carcinogenesis. The IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation leads to cellular immortalization. PMID:21199806

Higher miRNA tolerance in immortal Li-Fraumeni fibroblasts with abrogated interferon signaling pathway.

PubMed

Li, Qunfang; Tainsky, Michael A

2011-01-01

The IFN pathway is abrogated in fibroblasts from Li-Fraumeni syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Microarray profiling of differentially expressed microRNAs (miRNA) revealed that most miRNAs were upregulated in IFN pathway-defective MDAH087-10 fibroblasts compared with MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of IFN-stimulated genes in MDAH087-N cells resulting in significant cell death and reduced cell growth. Furthermore, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to changed IFN pathway activity. Dicer overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicer-transfected MDAH087-10 cells. Therefore, cells with a defective IFN pathway have a higher miRNA tolerance than cells with normal IFN pathway. This work indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA upregulation to occur in early carcinogenesis. The IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation leads to cellular immortalization. © 2011 AACR.

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

PubMed

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

Differential regulation of peripheral CD4+ T cell tolerance induced by deletion and TCR revision.

PubMed

Ali, Mohamed; Weinreich, Michael; Balcaitis, Stephanie; Cooper, Cristine J; Fink, Pamela J

2003-12-01

In Vbeta5 transgenic mice, mature Vbeta5(+)CD4(+) T cells are tolerized upon recognition of a self Ag, encoded by a defective endogenous retrovirus, whose expression is confined to the lymphoid periphery. Cells are driven by the tolerogen to enter one of two tolerance pathways, deletion or TCR revision. CD4(+) T cells entering the former pathway are rendered anergic and then eliminated. In contrast, TCR revision drives gene rearrangement at the endogenous TCR beta locus and results in the appearance of Vbeta5(-), endogenous Vbeta(+), CD4(+) T cells that are both self-tolerant and functional. An analysis of the molecules that influence each of these pathways was conducted to understand better the nature of the interactions that control tolerance induction in the lymphoid periphery. These studies reveal that deletion is efficient in reconstituted radiation chimeras and is B cell, CD28, inducible costimulatory molecule, Fas, CD4, and CD8 independent. In contrast, TCR revision is radiosensitive, B cell, CD28, and inducible costimulatory molecule dependent, Fas and CD4 influenced, and CD8 independent. Our data demonstrate the differential regulation of these two divergent tolerance pathways, despite the fact that they are both driven by the same tolerogen and restricted to mature CD4(+) T cells.

Defect tolerant transmission lithography mask

DOEpatents

Vernon, Stephen P.

2000-01-01

A transmission lithography mask that utilizes a transparent substrate or a partially transparent membrane as the active region of the mask. A reflective single layer or multilayer coating is deposited on the membrane surface facing the illumination system. The coating is selectively patterned (removed) to form transmissive (bright) regions. Structural imperfections and defects in the coating have negligible effect on the aerial image of the mask master pattern since the coating is used to reflect radiation out of the entrance pupil of the imaging system. Similarly, structural imperfections in the clear regions of the membrane have little influence on the amplitude or phase of the transmitted electromagnetic fields. Since the mask "discards," rather than absorbs, unwanted radiation, it has reduced optical absorption and reduced thermal loading as compared to conventional designs. For EUV applications, the mask circumvents the phase defect problem, and is independent of the thermal load during exposure.

Stable Metal–Organic Frameworks with Group 4 Metals: Current Status and Trends

PubMed Central

2018-01-01

Group 4 metal-based metal–organic frameworks (MIV-MOFs), including Ti-, Zr-, and Hf-based MOFs, are one of the most attractive classes of MOF materials owing to their superior chemical stability and structural tunability. Despite being a relatively new field, MIV-MOFs have attracted significant research attention in the past few years, leading to exciting advances in syntheses and applications. In this outlook, we start with a brief overview of the history and current status of MIV-MOFs, emphasizing the challenges encountered in their syntheses. The unique properties of MIV-MOFs are discussed, including their high chemical stability and strong tolerance toward defects. Particular emphasis is placed on defect engineering in Zr-MOFs which offers additional routes to tailor their functions. Photocatalysis of MIV-MOF is introduced as a representative example of their emerging applications. Finally, we conclude with the perspective of new opportunities in synthesis and defect engineering. PMID:29721526

Alleviation of proton toxicity by nitrate uptake specifically depends on nitrate transporter 1.1 in Arabidopsis.

PubMed

Fang, Xian Zhi; Tian, Wen Hao; Liu, Xing Xing; Lin, Xian Yong; Jin, Chong Wei; Zheng, Shao Jian

2016-07-01

Protons in acid soil are highly rhizotoxic to plants, but the mechanism of tolerance of plants to protons is largely unknown. Nitrate uptake by root cells is accompanied by the uptake of protons. Therefore, nitrate uptake transporters (NRTs) may be involved in plant tolerance to proton toxicity. We investigated the root nitrate uptake response to proton stress in Arabidopsis and its association with proton tolerance using NRT-related mutants and pharmacological methods. Lack of NRT1.1 in knockout nrt1.1 mutants led to impaired proton tolerance in nitrate-sufficient growth medium, whereas no difference was seen between wild-type plants and NRT1.2-, NRT2.1-, NRT2.2-, and NRT2.4-null mutants. Another nrt1.1 point mutant, which is defective in nitrate uptake but has a normal nitrate-sensing function, also had impaired proton tolerance compared with the wild-type plant. Furthermore, proton stress induced NRT1.1-mediated nitrate uptake. These results indicate that NRT1.1-conferred proton tolerance depends on nitrate uptake activity. In addition, the rooting medium was alkalified by wild-type plants, but not by knockout nrt1.1 mutants, and in pH-buffered medium, there were no differences in proton tolerance between wild-type plants and knockout nrt1.1 mutants. We conclude that NRT1.1-mediated nitrate uptake plays a crucial role in plant proton tolerance by alkalifying the rhizosphere. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Surveillance metrics sensitivity study.

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

Hamada, Michael S.; Bierbaum, Rene Lynn; Robertson, Alix A.

2011-09-01

In September of 2009, a Tri-Lab team was formed to develop a set of metrics relating to the NNSA nuclear weapon surveillance program. The purpose of the metrics was to develop a more quantitative and/or qualitative metric(s) describing the results of realized or non-realized surveillance activities on our confidence in reporting reliability and assessing the stockpile. As a part of this effort, a statistical sub-team investigated various techniques and developed a complementary set of statistical metrics that could serve as a foundation for characterizing aspects of meeting the surveillance program objectives. The metrics are a combination of tolerance limit calculationsmore » and power calculations, intending to answer level-of-confidence type questions with respect to the ability to detect certain undesirable behaviors (catastrophic defects, margin insufficiency defects, and deviations from a model). Note that the metrics are not intended to gauge product performance but instead the adequacy of surveillance. This report gives a short description of four metrics types that were explored and the results of a sensitivity study conducted to investigate their behavior for various inputs. The results of the sensitivity study can be used to set the risk parameters that specify the level of stockpile problem that the surveillance program should be addressing.« less

Surveillance Metrics Sensitivity Study

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

Bierbaum, R; Hamada, M; Robertson, A

2011-11-01

In September of 2009, a Tri-Lab team was formed to develop a set of metrics relating to the NNSA nuclear weapon surveillance program. The purpose of the metrics was to develop a more quantitative and/or qualitative metric(s) describing the results of realized or non-realized surveillance activities on our confidence in reporting reliability and assessing the stockpile. As a part of this effort, a statistical sub-team investigated various techniques and developed a complementary set of statistical metrics that could serve as a foundation for characterizing aspects of meeting the surveillance program objectives. The metrics are a combination of tolerance limit calculationsmore » and power calculations, intending to answer level-of-confidence type questions with respect to the ability to detect certain undesirable behaviors (catastrophic defects, margin insufficiency defects, and deviations from a model). Note that the metrics are not intended to gauge product performance but instead the adequacy of surveillance. This report gives a short description of four metrics types that were explored and the results of a sensitivity study conducted to investigate their behavior for various inputs. The results of the sensitivity study can be used to set the risk parameters that specify the level of stockpile problem that the surveillance program should be addressing.« less

Absence of MyD88 Signaling Induces Donor-Specific Kidney Allograft Tolerance

PubMed Central

Noordmans, Gerda A.; O’Brien, Maya R.; Ma, Jin; Zhao, Cathy Y.; Zhang, Geoff Y.; Kwan, Tony K.T.; Alexander, Stephen I.; Chadban, Steven J.

2012-01-01

Toll-like receptors (TLRs) play a fundamental role in innate immunity and provide a link between innate and adaptive responses to an allograft; however, whether the development of acute and chronic allograft rejection requires TLR signaling is unknown. Here, we studied TLR signaling in a fully MHC-mismatched, life-sustaining murine model of kidney allograft rejection. Mice deficient in the TLR adaptor protein MyD88 developed donor antigen-specific tolerance, which protected them from both acute and chronic allograft rejection and increased their survival after transplantation compared with wild-type controls. Administration of an anti-CD25 antibody to MyD88-deficient recipients depleted CD4+CD25+FoxP3+ cells and broke tolerance. In addition, defective development of Th17 immune responses to alloantigen both in vitro and in vivo occurred, resulting in an increased ratio of Tregs to Th17 effectors. Thus, MyD88 deficiency was associated with an altered balance of Tregs over Th17 cells, promoting tolerance instead of rejection. This study provides evidence that targeting innate immunity may be a clinically relevant strategy to facilitate transplantation tolerance. PMID:22878960

OsPRX2 contributes to stomatal closure and improves potassium deficiency tolerance in rice.

PubMed

Mao, Xiaohui; Zheng, Yanmei; Xiao, Kaizhuan; Wei, Yidong; Zhu, Yongsheng; Cai, Qiuhua; Chen, Liping; Xie, Huaan; Zhang, Jianfu

2018-01-01

Peroxiredoxins (Prxs) which are thiol-based peroxidases have been implicated in the toxic reduction and intracellular concentration regulation of hydrogen peroxide. In Arabidopsis thaliana At2-CysPrxB (At5g06290) has been demonstrated to be essential in maintaining the water-water cycle for proper H 2 O 2 scavenging. Although the mechanisms of 2-Cys Prxs have been extensively studied in Arabidopsis thaliana, the function of 2-Cys Prxs in rice is unclear. In this study, a rice homologue gene of At2-CysPrxB, OsPRX2 was investigated aiming to characterize the effect of 2-Cys Prxs on the K + -deficiency tolerance in rice. We found that OsPRX2 was localized in the chloroplast. Overexpressed OsPRX2 causes the stomatal closing and K + -deficiency tolerance increasing, while knockout of OsPRX2 lead to serious defects in leaves phenotype and the stomatal opening under the K + -deficiency tolerance. Detection of K + accumulation, antioxidant activity of transgenic plants under the starvation of potassium, further confirmed that OsPRX2 is a potential target for engineering plants with improved potassium deficiency tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of multi-drug tolerant persister cells in Streptococcus suis.

PubMed

Willenborg, Jörg; Willms, Daniela; Bertram, Ralph; Goethe, Ralph; Valentin-Weigand, Peter

2014-05-12

Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial 'bet-hedging' strategy and are of particular importance in pathogenic bacteria. We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis.

The dlt genes play a role in antimicrobial tolerance of Streptococcus mutans biofilms.

PubMed

Nilsson, Martin; Rybtke, Morten; Givskov, Michael; Høiby, Niels; Twetman, Svante; Tolker-Nielsen, Tim

2016-09-01

Microbial biofilms are tolerant to antibiotic treatment and therefore cause problematic infections. Knowledge about the molecular mechanisms underlying biofilm-associated antimicrobial tolerance will aid the development of antibiofilm drugs. Screening of a Streptococcus mutans transposon mutant library for genes that are important for biofilm-associated antimicrobial tolerance provided evidence that the dlt genes play a role in the tolerance of S. mutans biofilms towards gentamicin. The minimum bactericidal concentration for biofilm cells (MBC-B) for a dltA transposon mutant was eight-fold lower than that of the wild-type. The minimum bactericidal concentration for planktonic cells (MBC-P) was only slightly reduced, indicating that the mechanism involved in the observed antimicrobial tolerance has a predominant role specifically in biofilms. Experiments with a knockout dltA mutant and complemented strain confirmed that the dlt genes in S. mutans play a role in biofilm-associated tolerance to gentamicin. Confocal laser scanning microscopy analyses of biofilms grown on glass slides showed that the dltA mutant produced roughly the same amount of biofilm as the wild-type, indicating that the reduced antimicrobial tolerance of the dltA mutant is not due to a defect in biofilm formation. The products of the dlt genes have been shown to mediate alanylation of teichoic acids, and in accordance the dltA mutant showed a more negatively charged surface than the wild-type, which likely is an important factor in the reduced tolerance of the dltA mutant biofilms towards the positively charged gentamicin. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome

PubMed Central

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have. PMID:27570464

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome.

PubMed

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have.

On flaw tolerance of nacre: a theoretical study

PubMed Central

Shao, Yue; Zhao, Hong-Ping; Feng, Xi-Qiao

2014-01-01

As a natural composite, nacre has an elegant staggered ‘brick-and-mortar’ microstructure consisting of mineral platelets glued by organic macromolecules, which endows the material with superior mechanical properties to achieve its biological functions. In this paper, a microstructure-based crack-bridging model is employed to investigate how the strength of nacre is affected by pre-existing structural defects. Our analysis demonstrates that owing to its special microstructure and the toughening effect of platelets, nacre has a superior flaw-tolerance feature. The maximal crack size that does not evidently reduce the tensile strength of nacre is up to tens of micrometres, about three orders higher than that of pure aragonite. Through dimensional analysis, a non-dimensional parameter is proposed to quantify the flaw-tolerance ability of nacreous materials in a wide range of structural parameters. This study provides us some inspirations for optimal design of advanced biomimetic composites. PMID:24402917

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo.

PubMed

Lee-Young, R S; Ayala, J E; Fueger, P T; Mayes, W H; Kang, L; Wasserman, D H

2011-07-01

Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and α2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPKα2 is necessary to restore work tolerance. HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (P<0.05 versus chow). In chow-fed α2-KD mice, running speed and time were impaired ∼45 and ∼55%, respectively (P<0.05 versus WT chow); HF feeding further reduced running time ∼25% (P<0.05 versus α2-KD chow). In response to 5 weeks of exercise training, HF-fed WT and α2-KD mice increased maximum running speed ∼35% (P<0.05 versus pre-training) and maintained body weight at pre-training levels, whereas body weight increased in untrained HF WT and α2-KD mice. Exercise training restored running speed to levels seen in healthy, chow-fed mice. HF feeding impairs AMPKα2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed α2-KD mice show that AMPKα2-independent mechanisms are also involved. Importantly, α2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPKα2 activity.

Irradiation-induced grain growth and defect evolution in nanocrystalline zirconia with doped grain boundaries

DOE PAGES

Dey, Sanchita; Mardinly, John; Wang, Yongqiang; ...

2016-05-27

Grain boundaries are effective sinks for radiation-induced defects, ultimately impacting the radiation tolerance of nanocrystalline materials (dense materials with nanosized grains) against net defect accumulation. However, irradiation-induced grain growth leads to grain boundary area decrease, shortening potential benefits of nanostructures. A possible approach to mitigate this is the introduction of dopants to target a decrease in grain boundary mobility or a reduction in grain boundary energy to eliminate driving forces for grain growth (using similar strategies as to control thermal growth). Here, in this study, we tested this concept in nanocrystalline zirconia doped with lanthanum. Although the dopant is observedmore » to segregate to the grain boundaries, causing grain boundary energy decrease and promoting dragging forces for thermally activated boundary movement, irradiation induced grain growth could not be avoided under heavy ion irradiation, suggesting a different growth mechanism as compared to thermal growth. Furthermore, it is apparent that reducing the grain boundary energy reduced the effectiveness of the grain boundary as sinks, and the number of defects in the doped material is higher than in undoped (La-free) YSZ.« less

To repair or not to repair: with FAVOR there is no question

NASA Astrophysics Data System (ADS)

Garetto, Anthony; Schulz, Kristian; Tabbone, Gilles; Himmelhaus, Michael; Scheruebl, Thomas

2016-10-01

In the mask shop the challenges associated with today's advanced technology nodes, both technical and economic, are becoming increasingly difficult. The constant drive to continue shrinking features means more masks per device, smaller manufacturing tolerances and more complexity along the manufacturing line with respect to the number of manufacturing steps required. Furthermore, the extremely competitive nature of the industry makes it critical for mask shops to optimize asset utilization and processes in order to maximize their competitive advantage and, in the end, profitability. Full maximization of profitability in such a complex and technologically sophisticated environment simply cannot be achieved without the use of smart automation. Smart automation allows productivity to be maximized through better asset utilization and process optimization. Reliability is improved through the minimization of manual interactions leading to fewer human error contributions and a more efficient manufacturing line. In addition to these improvements in productivity and reliability, extra value can be added through the collection and cross-verification of data from multiple sources which provides more information about our products and processes. When it comes to handling mask defects, for instance, the process consists largely of time consuming manual interactions that are error prone and often require quick decisions from operators and engineers who are under pressure. The handling of defects itself is a multiple step process consisting of several iterations of inspection, disposition, repair, review and cleaning steps. Smaller manufacturing tolerances and features with higher complexity contribute to a higher number of defects which must be handled as well as a higher level of complexity. In this paper the recent efforts undertaken by ZEISS to provide solutions which address these challenges, particularly those associated with defectivity, will be presented. From automation of aerial image analysis to the use of data driven decision making to predict and propose the optimized back end of line process flow, productivity and reliability improvements are targeted by smart automation. Additionally the generation of the ideal aerial image from the design and several repair enhancement features offer additional capabilities to improve the efficiency and yield associated with defect handling.

The "Arabidopsis cax3" mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H(+)-ATPase activity

USDA-ARS?s Scientific Manuscript database

Perturbing CAX1, an "Arabidopsis" vacuolar H(+)/Ca(2+) antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among "cax1" and "ca...

OBIST methodology incorporating modified sensitivity of pulses for active analogue filter components

NASA Astrophysics Data System (ADS)

Khade, R. H.; Chaudhari, D. S.

2018-03-01

In this paper, oscillation-based built-in self-test method is used to diagnose catastrophic and parametric faults in integrated circuits. Sallen-Key low pass filter and high pass filter circuits with different gains are used to investigate defects. Variation in seven parameters of operational amplifier (OP-AMP) like gain, input impedance, output impedance, slew rate, input bias current, input offset current, input offset voltage and catastrophic as well as parametric defects in components outside OP-AMP are introduced in the circuit and simulation results are analysed. Oscillator output signal is converted to pulses which are used to generate a signature of the circuit. The signature and pulse count changes with the type of fault present in the circuit under test (CUT). The change in oscillation frequency is observed for fault detection. Designer has flexibility to predefine tolerance band of cut-off frequency and range of pulses for which circuit should be accepted. The fault coverage depends upon the required tolerance band of the CUT. We propose a modification of sensitivity of parameter (pulses) to avoid test escape and enhance yield. Result shows that the method provides 100% fault coverage for catastrophic faults.

K-RAS GTPase- and B-RAF kinase-mediated T-cell tolerance defects in rheumatoid arthritis.

PubMed

Singh, Karnail; Deshpande, Pratima; Li, Guangjin; Yu, Mingcan; Pryshchep, Sergey; Cavanagh, Mary; Weyand, Cornelia M; Goronzy, Jörg J

2012-06-19

Autoantibodies to common autoantigens and neoantigens, such as IgG Fc and citrullinated peptides, are immunological hallmarks of rheumatoid arthritis (RA). We examined whether a failure in maintaining tolerance is mediated by defects in T-cell receptor activation threshold settings. RA T cells responded to stimulation with significantly higher ERK phosphorylation (P < 0.001). Gene expression arrays of ERK pathway members suggested a higher expression of KRAS and BRAF, which was confirmed by quantitative PCR (P = 0.003), Western blot, and flow cytometry (P < 0.01). Partial silencing of KRAS and BRAF lowered activation-induced phosphorylated ERK levels (P < 0.01). In individual cells, levels of these signaling molecules correlated with ERK phosphorylation, attesting that their concentrations are functionally important. In confocal studies, B-RAF/K-RAS clustering was increased in RA T cells 2 min after T-cell receptor stimulation (P < 0.001). Overexpression of B-RAF and K-RAS in normal CD4 T cells amplified polyclonal T-cell proliferation and facilitated responses to citrullinated peptides. We propose that increased expression of B-RAF and K-RAS lowers T-cell activation thresholds in RA T cells, enabling responses to autoantigens.

Recent thymic emigrants are tolerized in the absence of inflammation.

PubMed

Friesen, Travis J; Ji, Qingyong; Fink, Pamela J

2016-05-30

T cell development requires a period of postthymic maturation. Why this is the case has remained a mystery, particularly given the rigors of intrathymic developmental checkpoints, successfully traversed by only ∼5% of thymocytes. We now show that the first few weeks of T cell residence in the lymphoid periphery define a period of heightened susceptibility to tolerance induction to tissue-restricted antigens (TRAs), the outcome of which depends on the context in which recent thymic emigrants (RTEs) encounter antigen. After encounter with TRAs in the absence of inflammation, RTEs exhibited defects in proliferation, diminished cytokine production, elevated expression of anergy-associated genes, and diminished diabetogenicity. These properties were mirrored in vitro by enhanced RTE susceptibility to regulatory T cell-mediated suppression. In the presence of inflammation, RTEs and mature T cells were, in contrast, equally capable of inducing diabetes, proliferating, and producing cytokines. Thus, recirculating RTEs encounter TRAs during a transitional developmental stage that facilitates tolerance induction, but inflammation converts antigen-exposed, tolerance-prone RTEs into competent effector cells. © 2016 Friesen et al.

The assessment of colour perception, naming and knowledge: a new test device with a case study.

PubMed

Pagani, Rossella; Bosco, Giovanna; Dalla Valle, Elisabetta; Capitani, Erminio; Laiacona, Marcella

2012-08-01

Besides ocular diseases, also cerebral damage may cause colour vision deficits; cerebral lesions may be associated with a variety of clinical conditions that impair colour processing. This study presents procedures and normative data for a rapid, comprehensive seven-test battery aimed at assessing colour perception, colour naming and object colour knowledge. The norms, obtained from 96 healthy Italian participants, allow normality/pathology judgements on the basis of one-sided tolerance limits, after adjusting the score of each test for the demographic variables of the proband subjects. We also report, as an example, use of the battery in a stroke patient; this patient was chosen because her lesion affected the left temporal-occipital cortex, an area sometimes associated with a deficit of colour processing. The patient resulted normal on colour perception and colour name retrieval, but defective on object colour knowledge probed using the stimulus name. For the sound definition of the functional locus of cognitive impairment at the single case level, a multi-faceted set of tasks is necessary.

Leveraging Genetic-Background Effects in Saccharomyces cerevisiae To Improve Lignocellulosic Hydrolysate Tolerance

DOE PAGES

Sardi, Maria; Rovinskiy, Nikolay; Zhang, Yaoping; ...

2016-07-22

We report a major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in different Saccharomyces cerevisiae (yeast)more » strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six different S. cerevisiae strains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Lastly, our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.« less

Relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism: assessment with breath-hold SPECT-CT pulmonary angiography fusion images.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Tokuda, Osamu; Matsunaga, Naofumi

2008-09-01

The relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism (PTE) was comprehensively assessed on deep-inspiratory breath-hold (DIBrH) perfusion SPECT-computed tomographic pulmonary angiography (CTPA) fusion images. Subjects were 34 acute PTE patients, who had successfully performed DIBrH perfusion SPECT using a dual-headed SPECT and a respiratory tracking system. Automated DIBrH SPECT-CTPA fusion images were used to assess the relation between lung perfusion defects and intravascular clots detected by CTPA. DIBrH SPECT visualized 175 lobar/segmental or subsegmental defects in 34 patients, and CTPA visualized 61 intravascular clots at variable locations in 30 (88%) patients, but no clots in four (12%) patients. In 30 patients with clots, the fusion images confirmed that 69 (41%) perfusion defects (20 segmental, 45 subsegmental and 4 lobar defects) of total 166 defects were located in lung territories without clots, although the remaining 97 (58%) defects were located in lung territories with clots. Perfusion defect was absent in lung territories with clots (one lobar branch and three segmental branches) in four (12%) of these patients. In four patients without clots, nine perfusion defects including four segmental ones were present. Because of unexpected dissociation between intravascular clots and lung perfusion defects, the present fusion images will be a useful adjunct to CTPA in the diagnosis of acute PTE.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

PubMed

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

HLA-E–restricted regulatory CD8+ T cells are involved in development and control of human autoimmune type 1 diabetes

PubMed Central

Jiang, Hong; Canfield, Steve M.; Gallagher, Mary P.; Jiang, Hong H.; Jiang, Yihua; Zheng, Zongyu; Chess, Leonard

2010-01-01

A key feature of the immune system is its ability to discriminate self from nonself. Breakdown in any of the mechanisms that maintain unresponsiveness to self (a state known as self-tolerance) contributes to the development of autoimmune conditions. Recent studies in mice show that CD8+ T cells specific for the unconventional MHC class I molecule Qa-1 bound to peptides derived from the signal sequence of Hsp60 (Hsp60sp) contribute to self/nonself discrimination. However, it is unclear whether they exist in humans and play a role in human autoimmune diseases. Here we have shown that CD8+ T cells specific for Hsp60sp bound to HLA-E (the human homolog of Qa-1) exist and play an important role in maintaining peripheral self-tolerance by discriminating self from nonself in humans. Furthermore, in the majority of type 1 diabetes (T1D) patients tested, there was a specific defect in CD8+ T cell recognition of HLA-E/Hsp60sp, which was associated with failure of self/nonself discrimination. However, the defect in the CD8+ T cells from most of the T1D patients tested could be corrected in vitro by exposure to autologous immature DCs loaded with the Hsp60sp peptide. These data suggest that HLA-E–restricted CD8+ T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D. PMID:20877010

Fenestrated Transcatheter ASD Closure in Adults with Diastolic Dysfunction and/or Pulmonary Hypertension: Case Series and Review of the Literature.

PubMed

Abdelkarim, Ayman; Levi, Daniel S; Tran, Bao; Ghobrial, Joanna; Aboulhosn, Jamil

2016-12-01

This study aims to evaluate the safety and efficacy of transcatheter fenestrated ASD closure and to summarize the literature regarding the published techniques and outcomes of transcatheter partial ASD closure. Patients with left ventricular diastolic dysfunction (LVDD) or right ventricular (RV) dysfunction and/or pulmonary hypertension (PHT) may suffer untoward consequences of complete closure of an ostium secundum atrial septal defect (ASD). Therefore, for patients that fall under these categories we suggest partial occlusion of the defect, which may be better tolerated than complete defect closure. After obtaining IRB approval, a search for patients that have undergone percutaneous ASD closure was performed in the Ahmanson/UCLA Adult Congenital Heart Disease Center database to identify which patients received a fenestrated ASD closure device. Eight consecutive patients ranging between 22 and 83 years of age (mean 48 years) with PHT and/or LVDD or RV dysfunction who underwent fenestrated transcatheter ASD closure at UCLA were identified. None of the subjects experienced complications related to the procedure. Postprocedure clinical evaluation showed improvement in symptoms and exercise capacity. Available follow-up transthoracic echocardiography data (mean 4 months, range 0-20 months) demonstrated patent fenestrations in four of eight patients. None of the patients had thromboembolic or infectious complications and there were no device migrations, erosions or embolizations. Partial ASD occlusion in patients with diastolic dysfunction or RV dysfunction and/or PHT is safe and may be better tolerated than complete ASD closure in selected patients. © 2016 Wiley Periodicals, Inc.

Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation1[OPEN

PubMed Central

Parker, Nicole; Wang, Yixing; Meinke, David

2016-01-01

Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes. PMID:27707889

DNA damage tolerance in hematopoietic stem and progenitor cells in mice

PubMed Central

Pilzecker, Bas; Buoninfante, Olimpia Alessandra; van den Berk, Paul; Lancini, Cesare; Song, Ji-Ying; Citterio, Elisabetta

2017-01-01

DNA damage tolerance (DDT) enables bypassing of DNA lesions during replication, thereby preventing fork stalling, replication stress, and secondary DNA damage related to fork stalling. Three modes of DDT have been documented: translesion synthesis (TLS), template switching (TS), and repriming. TLS and TS depend on site-specific PCNA K164 monoubiquitination and polyubiquitination, respectively. To investigate the role of DDT in maintaining hematopoietic stem cells (HSCs) and progenitors, we used PcnaK164R/K164R mice as a unique DDT-defective mouse model. Analysis of the composition of HSCs and HSC-derived multipotent progenitors (MPPs) revealed a significantly reduced number of HSCs, likely owing to increased differentiation of HSCs toward myeloid/erythroid-associated MPP2s. This skewing came at the expense of the number of lymphoid-primed MPP4s, which appeared to be compensated for by increased MPP4 proliferation. Furthermore, defective DDT decreased the numbers of MPP-derived common lymphoid progenitor (CLP), common myeloid progenitor (CMP), megakaryocyte-erythroid progenitor (MEP), and granulocyte-macrophage progenitor (GMP) cells, accompanied by increased cell cycle arrest in CMPs. The HSC and MPP phenotypes are reminiscent of premature aging and stressed hematopoiesis, and indeed progressed with age and were exacerbated on cisplatin exposure. Bone marrow transplantations revealed a strong cell intrinsic defect of DDT-deficient HSCs in reconstituting lethally irradiated mice and a strong competitive disadvantage when cotransplanted with wild-type HSCs. These findings indicate a critical role of DDT in maintaining HSCs and progenitor cells, and in preventing premature aging. PMID:28761001

Characterization of a Putative Spindle Assembly Checkpoint Kinase Mps1, Suggests Its Involvement in Cell Division, Morphogenesis and Oxidative Stress Tolerance in Candida albicans

PubMed Central

Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus. PMID:25025778

Characterization of a putative spindle assembly checkpoint kinase Mps1, suggests its involvement in cell division, morphogenesis and oxidative stress tolerance in Candida albicans.

PubMed

Kamthan, Mohan; Nalla, Vijaya Kumar; Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1 mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1 and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus.

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

Sardi, Maria; Rovinskiy, Nikolay; Zhang, Yaoping

We report a major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in different Saccharomyces cerevisiae (yeast)more » strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six different S. cerevisiae strains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Lastly, our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.« less

A cotton Raf-like MAP3K gene, GhMAP3K40, mediates reduced tolerance to biotic and abiotic stress in Nicotiana benthamiana by negatively regulating growth and development.

PubMed

Chen, Xiaobo; Wang, Ji; Zhu, Ming; Jia, Haihong; Liu, Dongdong; Hao, Lili; Guo, Xingqi

2015-11-01

Mitogen-activated protein kinase (MAPK) cascades mediate various responses in plants. As the top component, MAP3Ks deserve more attention; however, little is known about the role of MAP3Ks, especially in cotton, a worldwide economic crop. In this study, a gene encoding a putative Raf-like MAP3K, GhMAP3K40, was isolated. GhMAP3K40 expression was induced by stress and multiple signal molecules. The plants overexpressing GhMAP3K40 had an enhanced tolerance to drought and salt stress at the germination stage. However, at the seedling stage, the transgenic plants suffered more severe damage after drought, exposure to pathogens and oxidative stress. The defence-related genes and the antioxidant system were activated in transgenic palnts, suggesting that GhMAP3K40 positively regulate the defence response. The transgenic plants were less able to prevent pathogenic invasion, which was due to defects in the cell structure of the leaves. The root system of the control plants were stronger compared with the transgenic plants. These results indicated a negative role of GhMAP3K40 in growth and development and GhMAP3K40 possibly caused the defects by down-regulating the lignin biosynthesis. Overall, these results suggest that GhMAP3K40 may positively regulate defence response but cause reduced tolerance to biotic and abiotic stress by negatively regulating growth and development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessing tolerance for wildlife: Clarifying relations between concepts and measures

USGS Publications Warehouse

Bruskotter, Jeremy T.; Singh, Ajay; Fulton, David C.; Slagle, Kristina

2015-01-01

Two parallel lines of inquiry, tolerance for and acceptance of wildlife populations, have arisen in the applied literature on wildlife conservation to assess probability of successfully establishing or increasing populations of controversial species. Neither of these lines is well grounded in social science theory, and diverse measures have been employed to assess tolerance, which inhibits comparability across studies. We empirically tested behavioral measures of tolerance against self-reports of previous policy-relevant behavior and behavioral intentions. Both composite behavioral measures were strongly correlated (r > .70) with two attitudinal measures of tolerance commonly employed in the literature. The strong correlation between attitudinal and behavioral measures suggests existing attitudinal measures represent valid, parsimonious measures of tolerance that may be useful when behavioral measures are too cumbersome or misreporting of behavior is anticipated. Our results demonstrate how behavioral measures of tolerance provide additional, useful information beyond general attitudinal measures.

Microstructural evolution of nanochannel CrN films under ion irradiation at elevated temperature and post-irradiation annealing

NASA Astrophysics Data System (ADS)

Tang, Jun; Hong, Mengqing; Wang, Yongqiang; Qin, Wenjing; Ren, Feng; Dong, Lan; Wang, Hui; Hu, Lulu; Cai, Guangxu; Jiang, Changzhong

2018-03-01

High-performance radiation tolerance materials are crucial for the success of future advanced nuclear reactors. In this paper, we present a further investigation that the "vein-like" nanochannel films can enhance radiation tolerance under ion irradiation at high temperature and post-irradiation annealing. The chromium nitride (CrN) nanochannel films with different nanochannel densities and the compact CrN film are chosen as a model system for these studies. Microstructural evolution of these films were investigated using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Elastic Recoil Detection (ERD) and Grazing Incidence X-ray Diffraction (GIXRD). Under the high fluence He+ ion irradiation at 500 °C, small He bubbles with low bubble densities are observed in the irradiated nanochannel CrN films, while the aligned large He bubbles, blistering and texture reconstruction are found in the irradiated compact CrN film. For the heavy Ar2+ ion irradiation at 500 °C, the microstructure of the nanochannel CrN RT film is more stable than that of the compact CrN film due to the effective releasing of defects via the nanochannel structure. Under the He+ ion irradiation and subsequent annealing, compared with the compact film, the nanochannel films have excellent performance for the suppression of He bubble growth and possess the strong microstructural stability. Basing on the analysis on the sizes and number densities of bubbles as well as the concentrations of He retained in the nanochannel CrN films and the compact CrN film under different experimental conditions, potential mechanism for the enhanced radiation tolerance are discussed. Nanochannels play a crucial role on the release of He/defects under ion irradiation. We conclude that the tailored "vein-like" nanochannel structure may be used as advanced radiation tolerance materials for future nuclear reactors.

Self-assembled III-V quantum dots: potential for silicon optoelectronics

NASA Technical Reports Server (NTRS)

Leon, R.

2001-01-01

The basic optoelectronic properties of self-forming InGaAs/InAlAs QDs are examined in parallel with their device implementation. Recent results showing remarkably good tolerance to radiation induced point defects and good luminescence emission from InAs/InGaAs QDs grown on dislocationarrays are discussed in terms of an enabling technology which will allow optelectronics integration with silicon technology.

Using genotyping-by-sequencing to develop broccoli markers for construction of a high-density linkage map and to identify quantitative trait loci associated with heat tolerance

USDA-ARS?s Scientific Manuscript database

Heat stress reduces the yield and quality of broccoli heads imposing seasonal and geographic limits to broccoli production. For the most part, the risk of producing broccoli with head defects (uneven beads, bracts in heads, etc.) induced by high temperatures has restricted commercial production in t...

Characterization of multi-drug tolerant persister cells in Streptococcus suis

PubMed Central

2014-01-01

Background Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial ‘bet-hedging’ strategy and are of particular importance in pathogenic bacteria. Results We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Conclusions Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis. PMID:24885389

Long-term effect of latanoprost/timolol fixed combination in patients with glaucoma or ocular hypertension: A prospective, observational, noninterventional study

PubMed Central

2010-01-01

Background Prospective, observational studies that enroll large numbers of patients with few exclusion criteria may better reflect actual ongoing clinical experience than randomized clinical trials. Our purpose was to obtain efficacy and safety information from a cohort of subjects exposed to latanoprost/timolol fixed combination (FC) for ≥18 months using a prospective, observational design. Methods In all, 577 office-based ophthalmologists in Germany switched 2339 patients with glaucoma or ocular hypertension to latanoprost/timolol FC for medical reasons. Follow-up visits were scheduled for every 6 months over 24 months; physicians followed usual care routines. Intraocular pressure (IOP), visual field status, optic nerve head findings, and adverse events were recorded. Efficacy parameters were evaluated for the per protocol (PP) population; the safety population included subjects receiving ≥1 drop of FC. Physicians rated efficacy, tolerability, and subject compliance at month 24. Results Of the 2339 subjects switched to latanoprost/timolol FC (safety population), the primary reasons for switching were inadequate IOP reduction (78.2%) and desire to simplify treatment with once-daily dosing (29.4%; multiple reasons possible). In all, 1317 (56.3%) subjects completed the study, and 1028 (44.0%) were included in the PP population. Most discontinuations were due to loss to follow-up. Change in mean IOP from baseline to month 6 was -4.0 ± 4.31 mmHg, a reduction that was maintained throughout (P < 0.05 for change at all time points). By investigator assessments, optic disc parameters and visual field were stable over 24 months, and there was no relationship between IOP reduction over 24 months and development of a visual field defect. More than 90% of physicians rated latanoprost/timolol FC as "very good" or "good" for efficacy (PP population), tolerability, and compliance. The FC was safe and well tolerated. No change in iris color was reported by most subjects (83.1%) at month 24. Conclusions Over 24 months, latanoprost/timolol FC effectively lowers IOP levels and is well tolerated in patients with glaucoma or ocular hypertension who change from their previous ocular hypotensive therapy for medical reasons. Investigator assessments found optic disc parameters and visual field to be stable throughout 24 months of follow-up. PMID:20825668

Mouse models of mitochondrial DNA defects and their relevance for human disease

PubMed Central

Tyynismaa, Henna; Suomalainen, Anu

2009-01-01

Qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been shown to be common causes of inherited neurodegenerative and muscular diseases, and have also been implicated in ageing. These diseases can be caused by primary mtDNA mutations, or by defects in nuclear-encoded mtDNA maintenance proteins that cause secondary mtDNA mutagenesis or instability. Furthermore, it has been proposed that mtDNA copy number affects cellular tolerance to environmental stress. However, the mechanisms that regulate mtDNA copy number and the tissue-specific consequences of mtDNA mutations are largely unknown. As post-mitotic tissues differ greatly from proliferating cultured cells in their need for mtDNA maintenance, and as most mitochondrial diseases affect post-mitotic cell types, the mouse is an important model in which to study mtDNA defects. Here, we review recently developed mouse models, and their contribution to our knowledge of mtDNA maintenance and its role in disease. PMID:19148224

Effect of nickel on point defects diffusion in Fe – Ni alloys

DOE PAGES

Anento, Napoleon; Serra, Anna; Osetsky, Yury N.

2017-05-05

Iron-Nickel alloys are perspective alloys as nuclear energy structural materials because of their good radiation damage tolerance and mechanical properties. Understanding of experimentally observed features such as the effect of Ni content to radiation defects evolution is essential for developing predictive models of radiation. Recently an atomic-scale modelling study has revealed one particular mechanism of Ni effect related to the reduced mobility of clusters of interstitial atoms in Fe-Ni alloys. In this paper we present results of the microsecond-scale molecular dynamics study of point defects, i.e. vacancies and self-interstitial atoms, diffusion in Fe-Ni alloys. It is found that the additionmore » of Ni atoms affects diffusion processes: diffusion of vacancies is enhanced in the presence of Ni, whereas diffusion of interstitials is reduced and these effects increase at high Ni concentration and low temperature. As a result, the role of Ni solutes in radiation damage evolution in Fe-Ni alloys is discussed.« less

Arabidopsis thaliana phytochelatin synthase 2 is constitutively active in vivo and can rescue the growth defect of the PCS1-deficient cad1-3 mutant on Cd-contaminated soil.

PubMed

Kühnlenz, Tanja; Schmidt, Holger; Uraguchi, Shimpei; Clemens, Stephan

2014-08-01

Phytochelatins play a key role in the detoxification of metals in plants and many other eukaryotes. Their formation is catalysed by phytochelatin synthases (PCS) in the presence of metal excess. It appears to be common among higher plants to possess two PCS genes, even though in Arabidopsis thaliana only AtPCS1 has been demonstrated to confer metal tolerance. Employing a highly sensitive quantification method based on ultraperformance electrospray ionization quadrupole time-of-flight mass spectrometry, we detected AtPCS2-dependent phytochelatin formation. Overexpression of AtPCS2 resulted in constitutive phytochelatin accumulation, i.e. in the absence of metal excess, both in planta and in a heterologous system. This indicates distinct enzymatic differences between AtPCS1 and AtPCS2. Furthermore, AtPCS2 was able to partially rescue the Cd hypersensitivity of the AtPCS1-deficient cad1-3 mutant in a liquid seedling assay, and, more importantly, when plants were grown on soil spiked with Cd to a level that is close to what can be found in agricultural soils. No rescue was found in vertical-plate assays, the most commonly used method to assess metal tolerance. Constitutive AtPCS2-dependent phytochelatin synthesis suggests a physiological role of AtPCS2 other than metal detoxification. The differences observed between wild-type plants and cad1-3 on Cd soil demonstrated: (i) the essentiality of phytochelatin synthesis for tolerating levels of Cd contamination that can naturally be encountered by plants outside of metal-rich habitats, and (ii) a contribution to Cd accumulation under these conditions. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency

PubMed Central

Sauer, Aisha Vanessa; Brigida, Immacolata; Carriglio, Nicola; Aiuti, Alessandro

2012-01-01

Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties. PMID:22969765

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

PubMed

Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

2016-05-01

Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

Reliability analysis of magnetic logic interconnect wire subjected to magnet edge imperfections

NASA Astrophysics Data System (ADS)

Zhang, Bin; Yang, Xiaokuo; Liu, Jiahao; Li, Weiwei; Xu, Jie

2018-02-01

Nanomagnet logic (NML) devices have been proposed as one of the best candidates for the next generation of integrated circuits thanks to its substantial advantages of nonvolatility, radiation hardening and potentially low power. In this article, errors of nanomagnetic interconnect wire subjected to magnet edge imperfections have been evaluated for the purpose of reliable logic propagation. The missing corner defects of nanomagnet in the wire are modeled with a triangle, and the interconnect fabricated with various magnetic materials is thoroughly investigated by micromagnetic simulations under different corner defect amplitudes and device spacings. The results show that as the defect amplitude increases, the success rate of logic propagation in the interconnect decreases. More results show that from the interconnect wire fabricated with materials, iron demonstrates the best defect tolerance ability among three representative and frequently used NML materials, also logic transmission errors can be mitigated by adjusting spacing between nanomagnets. These findings can provide key technical guides for designing reliable interconnects. Project supported by the National Natural Science Foundation of China (No. 61302022) and the Scientific Research Foundation for Postdoctor of Air Force Engineering University (Nos. 2015BSKYQD03, 2016KYMZ06).

Intrinsic defect processes and elastic properties of Ti3AC2 (A = Al, Si, Ga, Ge, In, Sn) MAX phases

NASA Astrophysics Data System (ADS)

Christopoulos, S.-R. G.; Filippatos, P. P.; Hadi, M. A.; Kelaidis, N.; Fitzpatrick, M. E.; Chroneos, A.

2018-01-01

Mn+1AXn phases (M = early transition metal; A = group 13-16 element and X = C or N) have a combination of advantageous metallic and ceramic properties, and are being considered for structural applications particularly where high thermal conductivity and operating temperature are the primary drivers: for example in nuclear fuel cladding. Here, we employ density functional theory calculations to investigate the intrinsic defect processes and mechanical behaviour of a range of Ti3AC2 phases (A = Al, Si, Ga, Ge, In, Sn). Based on the intrinsic defect reaction, it is calculated that Ti3SnC2 is the more radiation-tolerant 312 MAX phase considered herein. In this material, the C Frenkel reaction is the lowest energy intrinsic defect mechanism with 5.50 eV. When considering the elastic properties of the aforementioned MAX phases, Ti3SiC2 is the hardest and Ti3SnC2 is the softest. All the MAX phases considered here are non-central force solids and brittle in nature. Ti3SiC2 is elastically more anisotropic and Ti3AlC2 is nearly isotropic.

Superalloy Lattice Block Structures

NASA Technical Reports Server (NTRS)

Nathal, M. V.; Whittenberger, J. D.; Hebsur, M. G.; Kantzos, P. T.; Krause, D. L.

2004-01-01

Initial investigations of investment cast superalloy lattice block suggest that this technology will yield a low cost approach to utilize the high temperature strength and environmental resistance of superalloys in lightweight, damage tolerant structural configurations. Work to date has demonstrated that relatively large superalloy lattice block panels can be successfully investment cast from both IN-718 and Mar-M247. These castings exhibited mechanical properties consistent with the strength of the same superalloys measured from more conventional castings. The lattice block structure also accommodates significant deformation without failure, and is defect tolerant in fatigue. The potential of lattice block structures opens new opportunities for the use of superalloys in future generations of aircraft applications that demand strength and environmental resistance at elevated temperatures along with low weight.

Vehicle response-based track geometry assessment using multi-body simulation

NASA Astrophysics Data System (ADS)

Kraft, Sönke; Causse, Julien; Coudert, Frédéric

2018-02-01

The assessment of the geometry of railway tracks is an indispensable requirement for safe rail traffic. Defects which represent a risk for the safety of the train have to be identified and the necessary measures taken. According to current standards, amplitude thresholds are applied to the track geometry parameters measured by recording cars. This geometry-based assessment has proved its value but suffers from the low correlation between the geometry parameters and the vehicle reactions. Experience shows that some defects leading to critical vehicle reactions are underestimated by this approach. The use of vehicle responses in the track geometry assessment process allows identifying critical defects and improving the maintenance operations. This work presents a vehicle response-based assessment method using multi-body simulation. The choice of the relevant operation conditions and the estimation of the simulation uncertainty are outlined. The defects are identified from exceedances of track geometry and vehicle response parameters. They are then classified using clustering methods and the correlation with vehicle response is analysed. The use of vehicle responses allows the detection of critical defects which are not identified from geometry parameters.

Photographic guide to selected external defect indicators and associated internal defects in black cherry

Treesearch

Everette D. Rast; John A. Beaton; John A. Beaton

1985-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development for black cherry. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in yellow birch

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow birch. Eleven types of external...

Photographic guide of selected external defect indicators and associated internal defects in sugar maple

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for sugar maple. Eleven types of external...

Photographic guide to selected external defect indicators and associated internal defects in black walnut

Treesearch

Everette D.Beaton John A. Rast; David L. Sonderman; David L. Sonderman

1988-01-01

To properly classify qr grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its develqpment for black walnut. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in white oak

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman; David L. Sonderman

1989-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development for white oak. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in yellow-poplar

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow-poplar. Twelve types of external...

Photographic guide of selected external defect indicators and associated internal defects in northern red oak

Treesearch

Everette D. Rast

1982-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development. It illustrates and describes eight types...

Thermotolerance and Human Performance: Role of Heat Shock Proteins

DTIC Science & Technology

2009-10-01

rats, hamsters, guinea pigs , rabbits, sheep, pigs , and monkeys (Edwards et al 2003). However, the type and severity of the fetal defects were dependent...begin to understand how to tolerate higher body temperatures, increase physical performance, and reduce the risk of severe heat injury and death ...overexpression of a family of Hsps and are thereby protected from cell death caused by various stresses (Figure 1). This suggests that the chaperonic

AGARD/SMP Review Damage Tolerance for Engine Structures. 2. Defects and Quantitative Materials Behaviour

DTIC Science & Technology

1988-10-01

TURBISTAN). En ce qui concerne les materiaux pour aubes de turbine la question reste ouverte. La caracterisation des materiaux pour... caracterisation mecanique. Face aux couts des caracterisations et qualifications de materiaux pour disques de lurbomachines, il importe de tenter...de concentrer ses propres forces : une solution possible est de constituer des plans standard de caracterisation . Federer au sein d’un groupe de

Mechanical response of dental cements as determined by nanoindentation and scanning electron microscopy.

PubMed

Saghiri, Mohammad Ali; Nazari, Amir; Garcia-Godoy, Franklin; Asatourian, Armen; Malekzadeh, Mansour; Elyasi, Maryam

2013-12-01

This study evaluated the effects of nanoindentation on the surface of white mineral trioxide aggregate (WMTA), Bioaggregate and Nano WMTA cements. Cements were mixed according to the manufacturer directions, condensed inside glass tubes, and randomly divided into three groups (n = 8). Specimens were soaked in synthetic tissue fluid (pH = 7.4) and incubated for 3 days. Cement pellets were subjected to nanoindentation tests and observed by scanning electron microscopy. Then, the images were processed and the number of cracks and total surface area of defects on the surface were calculated and analyzed using ImageJ. Data were submitted to one-way analysis of variance and a post hoc Tukey's test. The lowest number of cracks and total surface of defects were detected in Nano WMTA samples; however, it was not significantly different from WMTA samples (p = 0.588), while the highest values were noticed in Bioaggregate specimens that were significantly different from Nano WMTA and WMTA (p = 0.0001). The surface of WMTA and Nano WMTA showed more resistance after exposure to nano-compressive forces which indicated a better surface tolerance against these forces and crack formation. This suggests these substances are more tolerant cement materials which can predictably withstand loaded situations in a clinical scenario.

Irradiation Induced Microstructure Evolution in Nanostructured Materials: A Review

PubMed Central

Liu, Wenbo; Ji, Yanzhou; Tan, Pengkang; Zang, Hang; He, Chaohui; Yun, Di; Zhang, Chi; Yang, Zhigang

2016-01-01

Nanostructured (NS) materials may have different irradiation resistance from their coarse-grained (CG) counterparts. In this review, we focus on the effect of grain boundaries (GBs)/interfaces on irradiation induced microstructure evolution and the irradiation tolerance of NS materials under irradiation. The features of void denuded zones (VDZs) and the unusual behavior of void formation near GBs/interfaces in metals due to the interactions between GBs/interfaces and irradiation-produced point defects are systematically reviewed. Some experimental results and calculation results show that NS materials have enhanced irradiation resistance, due to their extremely small grain sizes and large volume fractions of GBs/interfaces, which could absorb and annihilate the mobile defects produced during irradiation. However, there is also literature reporting reduced irradiation resistance or even amorphization of NS materials at a lower irradiation dose compared with their bulk counterparts, since the GBs are also characterized by excess energy (compared to that of single crystal materials) which could provide a shift in the total free energy that will lead to the amorphization process. The competition of these two effects leads to the different irradiation tolerance of NS materials. The irradiation-induced grain growth is dominated by irradiation temperature, dose, ion flux, character of GBs/interface and nanoprecipitates, although the decrease of grain sizes under irradiation is also observed in some experiments. PMID:28787902

The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.

PubMed

Bowen, David G; Zen, Monica; Holz, Lauren; Davis, Thomas; McCaughan, Geoffrey W; Bertolino, Patrick

2004-09-01

Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram.

PubMed

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989-2002) and up to 5 years later (1989-2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery-Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants' relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability.

Annealing characteristics of irradiated hydrogenated amorphous silicon solar cells

NASA Technical Reports Server (NTRS)

Payson, J. S.; Abdulaziz, S.; Li, Y.; Woodyard, J. R.

1991-01-01

It was shown that 1 MeV proton irradiation with fluences of 1.25E14 and 1.25E15/sq cm reduces the normalized I(sub SC) of a-Si:H solar cell. Solar cells recently fabricated showed superior radiation tolerance compared with cells fabricated four years ago; the improvement is probably due to the fact that the new cells are thinner and fabricated from improved materials. Room temperature annealing was observed for the first time in both new and old cells. New cells anneal at a faster rate than old cells for the same fluence. From the annealing work it is apparent that there are at least two types of defects and/or annealing mechanisms. One cell had improved I-V characteristics following irradiation as compared to the virgin cell. The work shows that the photothermal deflection spectroscopy (PDS) and annealing measurements may be used to predict the qualitative behavior of a-Si:H solar cells. It was anticipated that the modeling work will quantitatively link thin film measurements with solar cell properties. Quantitative predictions of the operation of a-Si:H solar cells in a space environment will require a knowledge of the defect creation mechanisms, defect structures, role of defects on degradation, and defect passivation and annealing mechanisms. The engineering data and knowledge base for justifying space flight testing of a-Si:H alloy based solar cells is being developed.

Role of temperature in the radiation stability of yttria stabilized zirconia under swift heavy ion irradiation: A study from the perspective of nuclear reactor applications

NASA Astrophysics Data System (ADS)

Kalita, Parswajit; Ghosh, Santanu; Sattonnay, Gaël; Singh, Udai B.; Grover, Vinita; Shukla, Rakesh; Amirthapandian, S.; Meena, Ramcharan; Tyagi, A. K.; Avasthi, Devesh K.

2017-07-01

The search for materials that can withstand the harsh radiation environments of the nuclear industry has become an urgent challenge in the face of ever-increasing demands for nuclear energy. To this end, polycrystalline yttria stabilized zirconia (YSZ) pellets were irradiated with 80 MeV Ag6+ ions to investigate their radiation tolerance against fission fragments. To better simulate a nuclear reactor environment, the irradiations were carried out at the typical nuclear reactor temperature (850 °C). For comparison, irradiations were also performed at room temperature. Grazing incidence X-ray diffraction and Raman spectroscopy measurements reveal degradation in crystallinity for the room temperature irradiated samples. No bulk structural amorphization was however observed, whereas defect clusters were formed as indicated by transmission electron microscopy and supported by thermal spike simulation results. A significant reduction of the irradiation induced defects/damage, i.e., improvement in the radiation tolerance, was seen under irradiation at 850 °C. This is attributed to the fact that the rapid thermal quenching of the localized hot molten zones (arising from spike in the lattice temperature upon irradiation) is confined to 850 °C (i.e., attributed to the resistance inflicted on the rapid thermal quenching of the localized hot molten zones by the high temperature of the environment) thereby resulting in the reduction of the defects/damage produced. Our results present strong evidence for the applicability of YSZ as an inert matrix fuel in nuclear reactors, where competitive effects of radiation damage and dynamic thermal healing mechanisms may lead to a strong reduction in the damage production and thus sustain its physical integrity.

Assessment of rail long-pitch corrugation

NASA Astrophysics Data System (ADS)

Valehrach, Jan; Guziur, Petr; Riha, Tomas; Plasek, Otto

2017-09-01

The paper focuses on defects of the running surface of the rail, namely the rail corrugation defect and specifically long-pitch corrugation in curves of small radii. These defects cause a shorter life of the rails, greater maintenance costs and increase the noise and vibration pollution. Therefore, it is very important to understand the formation and development of the imperfection of the rails. In the paper, various sections of railway tracks in the Czech Republic are listed, each of them completed with comparison of defect development, the particular track superstructure, rolling stock, axle load, traffic load etc. Based on performed measurements, defect development has been proved as different on sections with similar (or even same) parameters. The paper assumes that a train velocity is the significant circumstance for defect development rates. Assessment of track section with under sleeper pads, which are expected to be the one of the possible ways to suppress the corrugation defect development, is included in evaluation.

Topical treatment of major omphalocoele: Acacia nilotica versus povidone-iodine: A randomised controlled study

PubMed Central

Eltayeb, Almoutaz A.; Mostafa, Mahmoud M.

2015-01-01

Background: Conservative management for major omphalocoele with topical agents as escharotics therapy is well established in practice. Different agents have been used in the past, including mercurochrome and alcohol, proved later to be unsafe. The aim of this study is to evaluate the efficacy and safety of the application of Acacia nilotica paste compared to povidone-iodine solution as a primary non-surgical treatment of major omphalocoele. Patients and Methods: A double-blind, randomised study was conducted on 24 cases of major omphalocoele where they were randomly divided into two equal groups; Group A treated with topical application of A. nilotica paste and Group B treated with topical application of povidone-iodine solution. Cases with gastroschisis, ruptured major omphalocoele or minor omphalocoele were excluded from the study. The evaluating parameters were size of the fascial defect in cm, period of mechanical ventilation if needed, time required for full oral feeding tolerance, duration of hospital stay and any short- or long-term complications. Results: There was no statistical significant difference between both groups regarding their gestational or post-natal age, weight and the mean umbilical port defect. Patients from Group A tolerated full oral feeding earlier and had shorter total hospital stay duration than those from Group B, but without a statistical significant difference (P = 0.347 and 0.242, respectively). The overall mortality rate was 33.3% without a statistical significant difference between both groups (P = 0.667). Conclusions: Application of A. nilotica is a safe and effective treatment of major omphalocoele as it was associated with rapid full enteral feeding tolerance, short duration of hospital stay and low mortality rate. PMID:26712288

Assessment of dynamic properties and stiffness of composite bridges with pavement defects

NASA Astrophysics Data System (ADS)

Kartopol'tsev, Vladimir; Kartopol'tsev, Andrei; Kolmakov, Boris

2017-01-01

This paper is aimed at assessing the dynamic properties and stiffness of the reinforced concrete roadway slab under live loads that impact composite bridge girders considering pavement defects. A special attention is paid to the reinforced concrete roadway slab as a transfer member of forced oscillations. The test results obtained for bridges with different spans ranging from 24 to 110 m are presented to assess the behavior of the reinforced concrete roadway slab and the dynamic stiffness of bridge span allowed for the pavement defects. Dynamic tests are carried out under controlled and random loads that simulate live load interaction with the span and the pavement with defects. The differential equations are presented for vertical oscillations of spans, pavement defect parameter, Eigen frequency and others. As a result of the experimental research the equation is derived to ascertain the dynamic stiffness of the vehicle-span system.

Safety of inadvertent anthrax vaccination during pregnancy: An analysis of birth defects in the U.S. military population, 2003-2010.

PubMed

Conlin, Ava Marie S; Sevick, Carter J; Gumbs, Gia R; Khodr, Zeina G; Bukowinski, Anna T

2017-08-03

Anthrax vaccine adsorbed (AVA) vaccination is compulsory for United States military servicemembers with operational indicators. As the number of female military servicemembers has increased, so has the chance of inadvertent AVA vaccination during pregnancy. Building upon past analyses assessing AVA vaccination during pregnancy and birth defects risk, this study sought to determine if inadvertent AVA vaccination during pregnancy is significantly associated with risk of birth defects after adjusting for other potential risk factors. The study population included 126,839 liveborn infants in the Department of Defense Birth and Infant Health Registry (2003-2010). Mothers were categorized by AVA vaccination exposure timing in relation to pregnancy. Infant medical records were assessed for birth defect diagnoses within the first year of life. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Infants of first trimester AVA vaccinated mothers versus receipt at any other time point (OR, 1.10; 95% CI, 0.93-1.29) were not at higher odds of birth defects in adjusted models. Infants of mothers vaccinated prepregnancy versus postpregnancy had a 1.11 (95% CI, 1.01-1.22) higher odds of having a birth defect. Vaccination postpregnancy versus never vaccinated revealed a 10% lower odds of birth defects (OR, 0.90; 95% CI, 0.83-0.99). No strong associations between inadvertent AVA vaccination during pregnancy and birth defects risk were observed. Marginal associations between prepregnancy vaccination or never vaccinated women and birth defects risk was observed when compared to postpregnancy vaccination. These findings may be due to self-selection and/or reverse causation bias when assessing comparisons with postpregnancy vaccination, and a "healthy worker" effect when assessing comparisons with women never vaccinated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reconstruction of maxillary defect with musculo-adipose rectus free flap.

PubMed

Low, Tsu-Hui Hubert; Lindsay, Andrew; Clark, Jonathan; Chai, Francis; Lewis, Richard

2017-02-01

The rectus myocutaneous free flap (RMFF) is used for medium to large maxillectomy defects. However, in patients with central obesity the inset could be difficult due to the bulk from excessive layer of adipose tissue. We describe a modification of the RMFF for patients with excessive central obesity with a flap consisting of adipose tissue with minimal rectus muscle; the musculo-adipose rectus free flap (MARF). Five cases of MARF reconstruction were performed between 2003 and 2013, with patients' body mass indexes ranging from 29.0 to 41.2 kg/m 2 . All patients had sinonasal tumor, of which three were adenoid cystic carcinoma, one squamous cell carcinoma, and one melanoma. Four patients had Codeiro IIIb defects and one had Codeiro II defect. Using the MARF technique, the maxillectomy defect was obliterated with vascularized adipose tissue overlying the rectus muscle and was trimmed to fit the maxillectomy defect. The adipose tissue was allowed to granulate and mucosalize. The volume of adipose tissue harvested was between 120 and 160 mL. All flaps survived with no requirement for re-exploration. Complete oro-nasal separation was achieved in all patients. The time to commencement of oral intake ranges from 5 to 15 days. One patient developed seroma and one developed wound breakdown on the donor site. The length of stay at the hospital ranges from 9 to 22 days. On follow-up ranging 7.5-32.8 months, two patients died from their malignancies. The other three patients were able to tolerate oral soft diet. The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017. © 2015 Wiley Periodicals, Inc.

HIRA, a Conserved Histone Chaperone, Plays an Essential Role in Low-dose Stress Response via Transcriptional Stimulation in Fission Yeast*

PubMed Central

Chujo, Moeko; Tarumoto, Yusuke; Miyatake, Koichi; Nishida, Eisuke; Ishikawa, Fuyuki

2012-01-01

Cells that have been pre-exposed to mild stress (priming stress) acquire transient resistance to subsequent severe stress even under different combinations of stresses. This phenomenon is called cross-tolerance. Although it has been reported that cross-tolerance occurs in many organisms, the molecular basis is not clear yet. Here, we identified slm9+ as a responsible gene for the cross-tolerance in the fission yeast Schizosaccharomyces pombe. Slm9 is a homolog of mammalian HIRA histone chaperone. HIRA forms a conserved complex and gene disruption of other HIRA complex components, Hip1, Hip3, and Hip4, also yielded a cross-tolerance-defective phenotype, indicating that the fission yeast HIRA is involved in the cross-tolerance as a complex. We also revealed that Slm9 was recruited to the stress-responsive gene loci upon stress treatment in an Atf1-dependent manner. The expression of stress-responsive genes under stress conditions was compromised in HIRA disruptants. Consistent with this, Pol II recruitment and nucleosome eviction at these gene loci were impaired in slm9Δ cells. Furthermore, we found that the priming stress enhanced the expression of stress-responsive genes in wild-type cells that were exposed to the severe stress. These observations suggest that HIRA functions in stress response through transcriptional regulation. PMID:22589550

Assessing the heat tolerance of 17 beef cattle genotypes

NASA Astrophysics Data System (ADS)

Gaughan, J. B.; Mader, T. L.; Holt, S. M.; Sullivan, M. L.; Hahn, G. L.

2010-11-01

Cattle production plays a significant role in terms of world food production. Nearly 82% of the world's 1.2 billion cattle can be found in developing countries. An increasing demand for meat in developing countries has seen an increase in intensification of animal industries, and a move to cross-bred animals. Heat tolerance is considered to be one of the most important adaptive aspects for cattle, and the lack of thermally-tolerant breeds is a major constraint on cattle production in many countries. There is a need to not only identify heat tolerant breeds, but also heat tolerant animals within a non-tolerant breed. Identification of heat tolerant animals is not easy under field conditions. In this study, panting score (0 to 4.5 scale where 0 = no stress and 4.5 = extreme stress) and the heat load index (HLI) [HLIBG<25°C = 10.66 + 0.28 × rh + 1.30 × BG - WS; and, HLI BG> 25°C = 8.62 + 0.38 × rh + 1.55 × BG - 0.5 × WS + e(2.4 - WS), where BG = black globe temperature (oC), rh = relative humidity (decimal form), WS = wind speed (m/s) and e is the base of the natural logarithm] were used to assess the heat tolerance of 17 genotypes (12,757 steers) within 13 Australian feedlots over three summers. The cattle were assessed under natural climatic conditions in which HLI ranged from thermonuetral (HLI < 70) to extreme (HLI > 96; black globe temperature = 40.2°C, relative humidity = 64%, wind speed = 1.58 m/s). When HLI > 96 a greater number ( P < 0.001) of pure bred Bos taurus and crosses of Bos taurus cattle had a panting score ≥ 2 compared to Brahman cattle, and Brahman-cross cattle. The heat tolerance of the assessed breeds was verified using panting scores and the HLI. Heat tolerance of cattle can be assessed under field conditions by using panting score and HLI.

Insulin sensitivity and secretion in Arab Americans with glucose intolerance.

PubMed

Salinitri, Francine D; Pinelli, Nicole R; Martin, Emily T; Jaber, Linda A

2013-12-01

This study examined the pathophysiological abnormalities in Arab Americans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin secretion (HOMA-%β), and the Matsuda Insulin Sensitivity Index composite (ISIcomposite) were calculated from the fasting and stimulated glucose and insulin concentrations measured during the oral glucose tolerance test in a population-based, representative, cross-sectional sample of randomly selected Arab Americans. In total, 497 individuals (42±14 years old; 40% males; body mass index [BMI], 29±6 kg/m(2)) were studied. Multivariate linear regression models were performed to compare HOMA-IR, HOMA-%β, and ISIcomposite among individuals with normal glucose tolerance (NGT) (n=191) versus isolated IFG (n=136), isolated IGT (n=22), combined IFG/IGT (n=43), and diabetes (n=105). Compared with individuals with NGT (2.9±1.6), HOMA-IR progressively increased in individuals with isolated IFG (4.8±2.7, P<0.001), combined IFG/IGT (6.0±4.3, P<0.001), and diabetes (9.7±8.3, P<0.001) but not in those with isolated IGT (3.0±1.7, P=0.87). After adjustment for sex and BMI, these associations remained unchanged. Whole-body insulin sensitivity as measured by ISIcomposite was significantly lower in individuals with isolated IFG (3.9±2.3, P<0.001), isolated IGT (2.8±1.5, P<0.001), combined IFG/IGT (1.9±1.1, P<0.001), and diabetes (1.6±1.1, P<0.001) compared with those with NGT (6.1±3.5). HOMA-%β was significantly lower in diabetes (113.7±124.9, P<0.001) compared with NGT (161.3±92.0). After adjustment for age, sex, and BMI, isolated IFG (146.6±80.2) was also significantly associated with a decline in HOMA-%β relative to NGT (P=0.005). This study suggests that differences in the underlying metabolic defects leading to diabetes in Arab Americans with IFG and/or IGT exist and may require different strategies for the prevention of diabetes.

Assessment of the salt tolerance and environmental biosafety of Eucalyptus camaldulensis harboring a mangrin transgene.

PubMed

Yu, Xiang; Kikuchi, Akira; Shimazaki, Takayoshi; Yamada, Akiyo; Ozeki, Yoshihiro; Matsunaga, Etsuko; Ebinuma, Hiroyasu; Watanabe, Kazuo N

2013-01-01

Increasing soil salinization of arable land has a major impact on the global ecosystem. One approach to increase the usable global forest area is to develop transgenic trees with higher tolerance to conditions of salt stress. An allene oxide cyclase homolog, mangrin, contains a core protein domain that enhances the salt tolerance of its host. We utilized this feature to develop improved salt-tolerant eucalyptus trees, by using transgenic Eucalyptus camaldulensis carrying the mangrin gene as a model. Since the Japanese government requires an environmental biosafety assessment for the surrounding biosphere, we performed experiments on trees grown in a special netted-house. This study examined the transgenic E. camaldulensis carrying the mangrin gene to assess the feasibility of using these transformants, and assessed their salt tolerance and environmental biosafety. We found that seven of 36 transgenic genotypes had significantly higher salt tolerance than non-transformants, and more importantly, that these plants had no significant impact on environmental biosafety. These results suggest that introduction of the mangrin gene may be one approach to safely enhance salt tolerance in genetically modified Eucalyptus species, and that the transformants have no apparent risks in terms of environmental biosafety. Thus, this study provides valuable information regarding the use of transgenic trees in situ.

Enhancements and Extensions of Formal Models for Risk Assessment in Software Projects

DTIC Science & Technology

2002-09-01

the five defect categories. Cosmetic Defects. The name that corresponds to QSM®’s cosmetic defects. Cosmetic defects can be described as deferred...California. June 2002. (Fent00) Fenton , N. E. and Neil, M., Software Metrics: Roadmap. Proceedings of the Conference on the Future of Software

Resorption of Autogenous Bone Graft in Cranioplasty: Resorption and Reintegration Failure

PubMed Central

Lee, Si Hoon; Lee, Uhn; Park, Cheol Wan; Lee, Sang Gu; Kim, Woo Kyung

2014-01-01

Objective Re-implantation of autologous skull bone has been known to be difficult because of its propensity for resorption. Moreover, the structural characteristics of the area of the defect cannot tolerate physiologic loading, which is an important factor for graft healing. This paper describes our experiences and results with cranioplasty following decompressive craniectomy using autologous bone flaps. Methods In an institutional review, the authors identified 18 patients (11 male and 7 female) in whom autologous cranioplasty was performed after decompressive craniectomy from January 2008 to December 2011. We examined the age, reasons for craniectomy, size of the skull defect, presence of bony resorption, and postoperative complications. Results Postoperative bone resorption occurred in eight cases (44.4%). Among them, two experienced symptomatic breakdown of the autologous bone graft that required a second operation to reconstruct the skull contour using porous polyethylene implant (Medpor®). The incidence of bone resorption was more common in the pediatric group and in those with large cranial defects (>120 cm2). No significant correlation was found with sex, reasons for craniectomy, and cryopreservation period. Conclusion The use of autologous bone flap for reconstruction of a skull defect after decompressive craniectomy is a quick and cost-effective method. But, the resorption rate was greater in children and in patients with large skull defects. As a result, we suggest compressive force of the tightened scalp, young age, large skull defect, the gap between bone flap and bone edge and heat sterilization of autologous bone as risk factors for bone resorption. PMID:27169026

[Transthoracic and transesophageal echocardiography in the pre- and postoperative assessment of interatrial communication].

PubMed

San Román, J A; Vilacosta, I; Zamorano, J; Castillo, J A; Rollán, M J; Villanueva, M A; Almería, C; Sánchez-Harguindey, L

1993-12-01

Transthoracic echocardiography is the most useful noninvasive method to diagnose atrial septal defect. It is suggested by some authors that transesophageal echocardiography is more accurate than transthoracic echocardiography in this setting. Our aim was to compare the usefulness of both techniques in: 1) diagnosing atrial septal defect, 2) detecting associated anomalies and 3) postoperative assessment. Pre and postoperative transthoracic and transesophageal echocardiography were performed in 27 patients in whom diagnosis of atrial septal defect was confirmed at surgery. Transthoracic echocardiography demonstrated the defect in 20 patients (74%) (8 ostium primum, 10 ostium secundum and 2 sinus venosus). The 27 patients (100%) were correctly diagnosed by transesophageal echocardiography (8 ostium primum, 12 ostium secundum and 7 sinus venosus). Defect size determined by transthoracic echocardiography had a poor correlation with the surgical measurement (r = 0.34). A good correlation was obtained when transesophageal versus surgical defect size measurements were compared (r = 0.85; p < 0.05). Transesophageal echocardiography was superior in detecting associated anomalies (5 patients with anomalous partial pulmonary venous drainage, 3 persistence of left superior vena cava and 1 atrial septal aneurysm). Moreover, this technique better determined residual atrial septal defect, and detected a postsurgical inferior vena cava connection to the left atrium. Transesophageal echocardiography is superior to transthoracic echocardiography in diagnosing atrial septal defect sinus venosus type, detecting associated anomalies and postoperative assessment. Transthoracic echocardiography is diagnostic in the majority of patients with atrial septal defect ostium primum and ostium secundum types.

Fault Detection and Isolation for Hydraulic Control

NASA Technical Reports Server (NTRS)

1987-01-01

Pressure sensors and isolation valves act to shut down defective servochannel. Redundant hydraulic system indirectly senses failure in any of its electrical control channels and mechanically isolates hydraulic channel controlled by faulty electrical channel so flat it cannot participate in operating system. With failure-detection and isolation technique, system can sustains two failed channels and still functions at full performance levels. Scheme useful on aircraft or other systems with hydraulic servovalves where failure cannot be tolerated.

Statistical Process Control Techniques for the Telecommunications Systems Manager

DTIC Science & Technology

1992-03-01

products that are out of 59 tolerance and bad designs. The third type of defect, mistakes, are remedied by Poka - Yoke methods that are 1 introduced later...based on total production costs plus quality costs. Once production is underway, interventions are determined by their impact on the QLF. F. POKA - YOKE ...Mistakes require process improvements called Poka Yoke or mistake proofing. Shiego Shingo developed Poka Yoke methods to incorporate 100% inspection at

A comparative study of the mechanical and thermal properties of defective ZrC, TiC and SiC.

PubMed

Jiang, M; Zheng, J W; Xiao, H Y; Liu, Z J; Zu, X T

2017-08-24

ZrC and TiC have been proposed to be alternatives to SiC as fuel-cladding and structural materials in nuclear reactors due to their strong radiation tolerance and high thermal conductivity at high temperatures. To unravel how the presence of defects affects the thermo-physical properties under irradiation, first-principles calculations based on density function theory were carried out to investigate the mechanical and thermal properties of defective ZrC, TiC and SiC. As compared with the defective SiC, the ZrC and TiC always exhibit larger bulk modulus, smaller changes in the Young's and shear moduli, as well as better ductility. The total thermal conductivity of ZrC and TiC are much larger than that of SiC, implying that under radiation environment the ZrC and TiC will exhibit superior heat conduction ability than the SiC. One disadvantage for ZrC and TiC is that their Debye temperatures are generally lower than that of SiC. These results suggest that further improving the Debye temperature of ZrC and TiC will be more beneficial for their applications as fuel-cladding and structural materials in nuclear reactors.

Classification of Partial Discharge Measured under Different Levels of Noise Contamination.

PubMed

Jee Keen Raymond, Wong; Illias, Hazlee Azil; Abu Bakar, Ab Halim

2017-01-01

Cable joint insulation breakdown may cause a huge loss to power companies. Therefore, it is vital to diagnose the insulation quality to detect early signs of insulation failure. It is well known that there is a correlation between Partial discharge (PD) and the insulation quality. Although many works have been done on PD pattern recognition, it is usually performed in a noise free environment. Also, works on PD pattern recognition in actual cable joint are less likely to be found in literature. Therefore, in this work, classifications of actual cable joint defect types from partial discharge data contaminated by noise were performed. Five cross-linked polyethylene (XLPE) cable joints with artificially created defects were prepared based on the defects commonly encountered on site. Three different types of input feature were extracted from the PD pattern under artificially created noisy environment. These include statistical features, fractal features and principal component analysis (PCA) features. These input features were used to train the classifiers to classify each PD defect types. Classifications were performed using three different artificial intelligence classifiers, which include Artificial Neural Networks (ANN), Adaptive Neuro-Fuzzy Inference System (ANFIS) and Support Vector Machine (SVM). It was found that the classification accuracy decreases with higher noise level but PCA features used in SVM and ANN showed the strongest tolerance against noise contamination.

Bismuth and antimony-based oxyhalides and chalcohalides as potential optoelectronic materials

NASA Astrophysics Data System (ADS)

Ran, Zhao; Wang, Xinjiang; Li, Yuwei; Yang, Dongwen; Zhao, Xin-Gang; Biswas, Koushik; Singh, David J.; Zhang, Lijun

2018-03-01

In the last decade the ns2 cations (e.g., Pb2+ and Sn2+)-based halides have emerged as one of the most exciting new classes of optoelectronic materials, as exemplified by for instance hybrid perovskite solar absorbers. These materials not only exhibit unprecedented performance in some cases, but they also appear to break new ground with their unexpected properties, such as extreme tolerance to defects. However, because of the relatively recent emergence of this class of materials, there remain many yet to be fully explored compounds. Here, we assess a series of bismuth/antimony oxyhalides and chalcohalides using consistent first principles methods to ascertain their properties and obtain trends. Based on these calculations, we identify a subset consisting of three types of compounds that may be promising as solar absorbers, transparent conductors, and radiation detectors. Their electronic structure, connection to the crystal geometry, and impact on band-edge dispersion and carrier effective mass are discussed.

Bismuth and antimony-based oxyhalides and chalcohalides as potential optoelectronic materials

DOE PAGES

Ran, Zhao; Wang, Xinjiang; Li, Yuwei; ...

2018-03-22

In the last decade the ns 2 cations (e.g., Pb 2+ and Sn 2+)-based halides have emerged as one of the most exciting new classes of optoelectronic materials, as exemplified by for instance hybrid perovskite solar absorbers. These materials not only exhibit unprecedented performance in some cases, but they also appear to break new ground with their unexpected properties, such as extreme tolerance to defects. However, because of the relatively recent emergence of this class of materials, there remain many yet to be fully explored compounds. Here, we assess a series of bismuth/antimony oxyhalides and chalcohalides using consistent first principlesmore » methods to ascertain their properties and obtain trends. Based on these calculations, we identify a subset consisting of three types of compounds that may be promising as solar absorbers, transparent conductors, and radiation detectors. Their electronic structure, connection to the crystal geometry, and impact on band-edge dispersion and carrier effective mass are discussed.« less

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram

PubMed Central

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

Objective To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. Methods The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989–2002) and up to 5 years later (1989–2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery–Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. Results The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants’ relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Conclusions Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability. PMID:27123184

The Role of Heat Tolerance Testing in Recovery and Return to Duty

DTIC Science & Technology

2008-10-01

CV diseases Hyperthyroidism Pheochromocytoma Infectious diseases Diabetes mellitus Psychiatric illness Parkinsonism Congenital abnormalities: CF...environments. To assess the heat tolerance status of prior heat stroke patient. Heat tolerance test (HTT) “HTT was effective in evaluating the heat tolerance

Long-term efficacy of biomodeled polymethyl methacrylate implants for orbitofacial defects.

PubMed

Groth, Michael J; Bhatnagar, Aparna; Clearihue, William J; Goldberg, Robert A; Douglas, Raymond S

2006-01-01

To report the long-term efficacy of custom polymethyl methacrylate implants using high-resolution computed tomographic modeling in the reconstruction of complex orbitofacial defects secondary to trauma. Nine patients with complex orbitofacial bone defects after trauma were evaluated for this retrospective, nonrandomized, noncomparative study. All the patients underwent reconstruction using custom, heat-cured polymethyl methacrylate implants. Patients were followed up postoperatively and evaluated for complications. Nine consecutive patients (5 men and 4 women) aged 28 to 63 years who underwent surgical reconstruction using prefabricated, heat-cured polymethyl methacrylate implants were included in the study. The interval between injury and presentation ranged from 1 month to 40 years. There were no significant complications, including infection, extrusion, or displacement of the implant. In all of the patients, wound healing was uneventful, with antibiotic drugs administered perioperatively. Mean follow-up was 4.3 years from the first visit (range, 6 months to 10 years). Computed tomographic biomodeled, prefabricated, heat-cured polymethyl methacrylate implants are well tolerated in the long term. Their advantages include customized design, long-term biocompatibility, and excellent aesthetic results.

Detecting defective electrical components in heterogeneous infra-red images by spatial control charts

NASA Astrophysics Data System (ADS)

Jamshidieini, Bahman; Fazaee, Reza

2016-05-01

Distribution network components connect machines and other loads to electrical sources. If resistance or current of any component is more than specified range, its temperature may exceed the operational limit which can cause major problems. Therefore, these defects should be found and eliminated according to their severity. Although infra-red cameras have been used for inspection of electrical components, maintenance prioritization of distribution cubicles is mostly based on personal perception and lack of training data prevents engineers from developing image processing methods. New research on the spatial control chart encouraged us to use statistical approaches instead of the pattern recognition for the image processing. In the present study, a new scanning pattern which can tolerate heavy autocorrelation among adjacent pixels within infra-red image was developed and for the first time combination of kernel smoothing, spatial control charts and local robust regression were used for finding defects within heterogeneous infra-red images of old distribution cubicles. This method does not need training data and this advantage is crucially important when the training data is not available.

Lipid-Antigen Presentation by CD1d+ B Cells Is Essential for the Maintenance of Invariant Natural Killer T Cells

PubMed Central

Bosma, Anneleen; Abdel-Gadir, Azza; Isenberg, David A.; Jury, Elizabeth C.; Mauri, Claudia

2012-01-01

Summary B cells perform many immunological functions, including presenting lipid antigen to CD1d-restricted invariant natural killer T (iNKT) cells, known to contribute to maintaining tolerance in autoimmunity. Patients with systemic lupus erythematous (SLE) display dysregulated B cell responses and reduced peripheral iNKT cell frequencies. The significance of these defects and how they relate to SLE pathogenesis remain elusive. We report that B cells are essential for iNKT cell expansion and activation in healthy donors but fail to exert a similar effect in SLE patients. Defective B cell-mediated stimulation of iNKT cells in SLE patients was associated with altered CD1d recycling, a defect recapitulated in B cells from healthy donors after stimulation with interferon-α (IFN-α) and anti-immunoglobulin (Ig). iNKT cell number and function were restored in SLE patients responding to anti-CD20 treatment upon normalization of CD1d expression exclusively in repopulated immature B cells. We propose that healthy B cells are pivotal for iNKT cell homeostasis. PMID:22406267

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders: an evolving web of heritable autoimmune diseases.

PubMed

Verbsky, James W; Chatila, Talal A

2013-12-01

To summarize recent progress in our understanding of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders. A number of Mendelian disorders of immune dysregulation and autoimmunity have been noted to result from defects in T regulatory cell, development and function. The best characterized of these is IPEX, resulting from mutations affecting FOXP3. A number of other gene defects that affect T regulatory cell function also give rise to IPEX-related phenotypes, including loss-of-function mutations in CD25, STAT5b and ITCH. Recent progress includes the identification of gain-of-function mutations in STAT1 as a cause of an IPEX-like disease, emerging FOXP3 genotype/phenotype relationships in IPEX, and the elucidation of a role for the microbiota in the immune dysregulation associated with regulatory T cell deficiency. An expanding spectrum of genetic defects that compromise T regulatory cell function underlies human disorders of immune dysregulation and autoimmunity. Collectively, these disorders offer novel insights into pathways of peripheral tolerance and their disruption in autoimmunity.

Optical filters for linearly polarized light using sculptured nematic thin flim of TiO2

NASA Astrophysics Data System (ADS)

Muhammad, Zahir; Wali, Faiz; Rehman, Zia ur

2018-05-01

A study of optical filters using sculptured nematic thin films is presented in this article. A central 90◦ twist-defect between two sculptured nematic thin films (SNTFs) sections transmit light of same polarization state and reflect other in the spectral Bragg regime. The SNTFs reflect light of both linearly polarized states in the Bragg regime if the amplitude of modulation of vapor incident angle is increased. A twist-defect in a tilt-modulated sculptured nematic thin films as a result produces bandpass or ultra-narrow bandpass filter depending upon the thickness of the SNTFs. However, both the bandpass or/and ultra-narrow bandpass filters can make polarization-insensitive Bragg mirrors by the appropriate modulation of the tilted 2D nanostructures of a given sculptured nematic thin films. Moreover, it is also observed that the sculptured nematic thin films are very tolerant of the structural defects if the amplitude of modulating vapor incident angle of the structural nano-materials is sufficiently large. Similarly, we observed the affect of incident angles on Bragg filters.

Comparison between multislice and cone-beam computerized tomography in the volumetric assessment of cleft palate.

PubMed

Albuquerque, Marco Antonio; Gaia, Bruno Felipe; Cavalcanti, Marcelo Gusmão Paraíso

2011-08-01

The aim of this study was to determine the applicability of multislice and cone-beam computerized tomography (CT) in the assessment of bone defects in patients with oral clefts. Bone defects were produced in 9 dry skulls to mimic oral clefts. All defects were modeled with wax. The skulls were submitted to multislice and cone-beam CT. Subsequently, physical measurements were obtained by the Archimedes principle of water displacement of wax models. The results demonstrated that multislice and cone-beam CT showed a high efficiency rate and were considered to be effective for volumetric assessment of bone defects. It was also observed that both CT modalities showed excellent results with high reliability in the study of the volume of bone defects, with no difference in performance between them. The clinical applicability of our research has shown these CT modalities to be immediate and direct, and they is important for the diagnosis and therapeutic process of patients with oral cleft. Copyright © 2011 Mosby, Inc. All rights reserved.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

PubMed

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Modeling of defect-tolerant thin multi-junction solar cells for space application

NASA Astrophysics Data System (ADS)

Mehrotra, A.; Alemu, A.; Freundlich, A.

2012-02-01

Using drift-diffusion model and considering experimental III-V material parameters, AM0 efficiencies of lattice-matched multijunction solar cells have been calculated and the effects of dislocations and radiation damage have been analyzed. Ultrathin multi-junction devices perform better in presence of dislocations or/and radiation harsh environment compared to conventional thick multijunction devices. Our results show that device design optimization of Ga0.51In0.49P/GaAs multijunction devices leads to an improvement in EOL efficiency from 4.8%, for the conventional thick device design, to 12.7%, for the EOL optimized thin devices. In addition, an optimized defect free lattice matched Ga0.51In0.49P/GaAs solar cell under 1016cm-2 1Mev equivalent electron fluence is shown to give an EOL efficiency of 12.7%; while a Ga0.51In0.49P/GaAs solar cell with 108 cm-2 dislocation density under 1016cm-2 electron fluence gives an EOL efficiency of 12.3%. The results suggest that by optimizing the device design, we can obtain nearly the same EOL efficiencies for high dislocation metamorphic solar cells and defect filtered metamorphic multijunction solar cells. The findings relax the need for thick or graded buffer used for defect filtering in metamorphic devices. It is found that device design optimization allows highly dislocated devices to be nearly as efficient as defect free devices for space applications.

Modeling and optimal designs for dislocation and radiation tolerant single and multijunction solar cells

NASA Astrophysics Data System (ADS)

Mehrotra, A.; Alemu, A.; Freundlich, A.

2011-02-01

Crystalline defects (e.g. dislocations or grain boundaries) as well as electron and proton induced defects cause reduction of minority carrier diffusion length which in turn results in degradation of efficiency of solar cells. Hetro-epitaxial or metamorphic III-V devices with low dislocation density have high BOL efficiencies but electron-proton radiation causes degradation in EOL efficiencies. By optimizing the device design (emitter-base thickness, doping) we can obtain highly dislocated metamorphic devices that are radiation resistant. Here we have modeled III-V single and multi junction solar cells using drift and diffusion equations considering experimental III-V material parameters, dislocation density, 1 Mev equivalent electron radiation doses, thicknesses and doping concentration. Thinner device thickness leads to increment in EOL efficiency of high dislocation density solar cells. By optimizing device design we can obtain nearly same EOL efficiencies from high dislocation solar cells than from defect free III-V multijunction solar cells. As example defect free GaAs solar cell after optimization gives 11.2% EOL efficiency (under typical 5x1015cm-2 1 MeV electron fluence) while a GaAs solar cell with high dislocation density (108 cm-2) after optimization gives 10.6% EOL efficiency. The approach provides an additional degree of freedom in the design of high efficiency space cells and could in turn be used to relax the need for thick defect filtering buffer in metamorphic devices.

Concrete Condition Assessment Using Impact-Echo Method and Extreme Learning Machines

PubMed Central

Zhang, Jing-Kui; Yan, Weizhong; Cui, De-Mi

2016-01-01

The impact-echo (IE) method is a popular non-destructive testing (NDT) technique widely used for measuring the thickness of plate-like structures and for detecting certain defects inside concrete elements or structures. However, the IE method is not effective for full condition assessment (i.e., defect detection, defect diagnosis, defect sizing and location), because the simple frequency spectrum analysis involved in the existing IE method is not sufficient to capture the IE signal patterns associated with different conditions. In this paper, we attempt to enhance the IE technique and enable it for full condition assessment of concrete elements by introducing advanced machine learning techniques for performing comprehensive analysis and pattern recognition of IE signals. Specifically, we use wavelet decomposition for extracting signatures or features out of the raw IE signals and apply extreme learning machine, one of the recently developed machine learning techniques, as classification models for full condition assessment. To validate the capabilities of the proposed method, we build a number of specimens with various types, sizes, and locations of defects and perform IE testing on these specimens in a lab environment. Based on analysis of the collected IE signals using the proposed machine learning based IE method, we demonstrate that the proposed method is effective in performing full condition assessment of concrete elements or structures. PMID:27023563

Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers.

PubMed

Zane, Lee T; Hughes, Matilda H; Shakib, Sepehr

2016-10-01

Inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis often present in sensitive and thin-skinned areas that are at higher risk for topical treatment-related skin irritation (e.g., burning, stinging). Our objective was to address the need for topical treatments that can be safely applied to these areas. We assessed the local tolerability of crisaborole topical ointment when applied to sensitive and thin-skinned areas of healthy volunteers. In this phase I, randomized, double-blind, vehicle-controlled, single-center study, 32 subjects were randomized 3:1 to twice-daily application of crisaborole topical ointment, 2 %, (n = 24) or vehicle ointment (n = 8) for 21 days to 13 anatomic skin areas, including the face/hairline, genitals, extensor, and intertriginous areas. The primary endpoint was assessment of the frequency and severity of local tolerability symptoms (burning/stinging, erythema, and pruritus) using the Local Tolerability Scale. Overall, 98.8 % of all tolerability assessments had a grade of 0 (no signs/symptoms of irritation) and 0.1 % had a grade >1 (mild); no differences were observed in the frequency of local tolerability scores between treatment groups. The total frequency of local tolerability assessments graded >0 (none) was lower across all application sites with crisaborole ointment (0.0-2.2 %) than with vehicle ointment (2.4-7.1 %). Local tolerability did not change over time, and was comparable between sensitive and nonsensitive skin areas. Crisaborole ointment application to sensitive skin areas was well tolerated in healthy volunteers, supporting its potential role as a topical treatment alternative for patients with AD or psoriasis.

Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

PubMed Central

Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

2009-01-01

Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

The Relationship between Population Structure and Aluminum Tolerance in Cultivated Sorghum

PubMed Central

Caniato, Fernanda F.; Guimarães, Claudia T.; Hamblin, Martha; Billot, Claire; Rami, Jean-François; Hufnagel, Barbara; Kochian, Leon V.; Liu, Jiping; Garcia, Antonio Augusto F.; Hash, C. Tom; Ramu, Punna; Mitchell, Sharon; Kresovich, Stephen; Oliveira, Antônio Carlos; de Avellar, Gisela; Borém, Aluízio; Glaszmann, Jean-Christophe; Schaffert, Robert E.; Magalhaes, Jurandir V.

2011-01-01

Background Acid soils comprise up to 50% of the world's arable lands and in these areas aluminum (Al) toxicity impairs root growth, strongly limiting crop yield. Food security is thereby compromised in many developing countries located in tropical and subtropical regions worldwide. In sorghum, SbMATE, an Al-activated citrate transporter, underlies the AltSB locus on chromosome 3 and confers Al tolerance via Al-activated root citrate release. Methodology Population structure was studied in 254 sorghum accessions representative of the diversity present in cultivated sorghums. Al tolerance was assessed as the degree of root growth inhibition in nutrient solution containing Al. A genetic analysis based on markers flanking AltSB and SbMATE expression was undertaken to assess a possible role for AltSB in Al tolerant accessions. In addition, the mode of gene action was estimated concerning the Al tolerance trait. Comparisons between models that include population structure were applied to assess the importance of each subpopulation to Al tolerance. Conclusion/Significance Six subpopulations were revealed featuring specific racial and geographic origins. Al tolerance was found to be rather rare and present primarily in guinea and to lesser extent in caudatum subpopulations. AltSB was found to play a role in Al tolerance in most of the Al tolerant accessions. A striking variation was observed in the mode of gene action for the Al tolerance trait, which ranged from almost complete recessivity to near complete dominance, with a higher frequency of partially recessive sources of Al tolerance. A possible interpretation of our results concerning the origin and evolution of Al tolerance in cultivated sorghum is discussed. This study demonstrates the importance of deeply exploring the crop diversity reservoir both for a comprehensive view of the dynamics underlying the distribution and function of Al tolerance genes and to design efficient molecular breeding strategies aimed at enhancing Al tolerance. PMID:21695088

Natural Variation at the FRD3 MATE Transporter Locus Reveals Cross-Talk between Fe Homeostasis and Zn Tolerance in Arabidopsis thaliana

PubMed Central

Pineau, Christophe; Loubet, Stéphanie; Lefoulon, Cécile; Chalies, Claude; Fizames, Cécile; Lacombe, Benoit; Ferrand, Marina; Loudet, Olivier; Berthomieu, Pierre; Richard, Odile

2012-01-01

Zinc (Zn) is essential for the optimal growth of plants but is toxic if present in excess, so Zn homeostasis needs to be finely tuned. Understanding Zn homeostasis mechanisms in plants will help in the development of innovative approaches for the phytoremediation of Zn-contaminated sites. In this study, Zn tolerance quantitative trait loci (QTL) were identified by analyzing differences in the Bay-0 and Shahdara accessions of Arabidopsis thaliana. Fine-scale mapping showed that a variant of the Fe homeostasis-related FERRIC REDUCTASE DEFECTIVE3 (FRD3) gene, which encodes a multidrug and toxin efflux (MATE) transporter, is responsible for reduced Zn tolerance in A. thaliana. Allelic variation in FRD3 revealed which amino acids are necessary for FRD3 function. In addition, the results of allele-specific expression assays in F1 individuals provide evidence for the existence of at least one putative metal-responsive cis-regulatory element. Our results suggest that FRD3 works as a multimer and is involved in loading Zn into xylem. Cross-homeostasis between Fe and Zn therefore appears to be important for Zn tolerance in A. thaliana with FRD3 acting as an essential regulator. PMID:23236296

Adaptive evolution of baker's yeast in a dough‐like environment enhances freeze and salinity tolerance

PubMed Central

Aguilera, Jaime; Andreu, Pasqual; Randez‐Gil, Francisca; Prieto, Jose Antonio

2010-01-01

Summary We used adaptive evolution to improve freeze tolerance of industrial baker's yeast. Our hypothesis was that adaptation to low temperature is accompanied by enhanced resistance of yeast to freezing. Based on this hypothesis, yeast was propagated in a flour‐free liquid dough model system, which contained sorbitol and NaCl, by successive batch refreshments maintained constantly at 12°C over at least 200 generations. Relative to the parental population, the maximal growth rate (µmax) under the restrictive conditions, increased gradually over the time course of the experiment. This increase was accompanied by enhanced freeze tolerance. However, these changes were not the consequence of genetic adaptation to low temperature, a fact that was confirmed by prolonged selection of yeast cells in YPD at 12°C. Instead, the experimental populations showed a progressive increase in NaCl tolerance. This phenotype was likely achieved at the expense of others traits, since evolved cells showed a ploidy reduction, a defect in the glucose derepression mechanism and a loss in their ability to utilize gluconeogenic carbon sources. We discuss the genetic flexibility of S. cerevisiae in terms of adaptation to the multiple constraints of the experimental design applied to drive adaptive evolution and the technologically advantageous phenotype of the evolved population. PMID:21255321

Beta-cell function in individuals carrying the mitochondrial tRNA leu (UUR) mutation.

PubMed

Salles, João Eduardo; Kasamatsu, Teresa S; Dib, Sérgio A; Moisés, Regina S

2007-01-01

To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response. Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response. Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. The first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones. We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. In addition, our data suggest that this could be a functional defect.

A defect in homologous recombination leads to increased translesion synthesis in E. coli

PubMed Central

Naiman, Karel; Pagès, Vincent; Fuchs, Robert P.

2016-01-01

DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. PMID:27257075

Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency

PubMed Central

Walter, Jolan E.; Rucci, Francesca; Patrizi, Laura; Recher, Mike; Regenass, Stephan; Paganini, Tiziana; Keszei, Marton; Pessach, Itai; Lang, Philipp A.; Poliani, Pietro Luigi; Giliani, Silvia; Al-Herz, Waleed; Cowan, Morton J.; Puck, Jennifer M.; Bleesing, Jack; Niehues, Tim; Schuetz, Catharina; Malech, Harry; DeRavin, Suk See; Facchetti, Fabio; Gennery, Andrew R.; Andersson, Emma; Kamani, Naynesh R.; Sekiguchi, JoAnn; Alenezi, Hamid M.; Chinen, Javier; Dbaibo, Ghassan; ElGhazali, Gehad; Fontana, Adriano; Pasic, Srdjan; Detre, Cynthia; Terhorst, Cox

2010-01-01

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations. PMID:20547827

Genome-wide transcriptomic analysis of BR-deficient Micro-Tom reveals correlations between drought stress tolerance and brassinosteroid signaling in tomato.

PubMed

Lee, Jinsu; Shim, Donghwan; Moon, Suyun; Kim, Hyemin; Bae, Wonsil; Kim, Kyunghwan; Kim, Yang-Hoon; Rhee, Sung-Keun; Hong, Chang Pyo; Hong, Suk-Young; Lee, Ye-Jin; Sung, Jwakyung; Ryu, Hojin

2018-06-01

Brassinosteroids (BRs) are plant steroid hormones that play crucial roles in a range of growth and developmental processes. Although BR signal transduction and biosynthetic pathways have been well characterized in model plants, their biological roles in an important crop, tomato (Solanum lycopersicum), remain unknown. Here, cultivated tomato (WT) and a BR synthesis mutant, Micro-Tom (MT), were compared using physiological and transcriptomic approaches. The cultivated tomato showed higher tolerance to drought and osmotic stresses than the MT tomato. However, BR-defective phenotypes of MT, including plant growth and stomatal closure defects, were completely recovered by application of exogenous BR or complementation with a SlDWARF gene. Using genome-wide transcriptome analysis, 619 significantly differentially expressed genes (DEGs) were identified between WT and MT plants. Several DEGs were linked to known signaling networks, including those related to biotic/abiotic stress responses, lignification, cell wall development, and hormone responses. Consistent with the higher susceptibility of MT to drought stress, several gene sets involved in responses to drought and osmotic stress were differentially regulated between the WT and MT tomato plants. Our data suggest that BR signaling pathways are involved in mediating the response to abiotic stress via fine-tuning of abiotic stress-related gene networks in tomato plants. Copyright © 2018. Published by Elsevier Masson SAS.

Reinterpreting recent thymic emigrant function: defective or adaptive?

PubMed

Cunningham, Cody A; Helm, Eric Y; Fink, Pamela J

2018-04-01

Recent thymic emigrants (RTEs) are those peripheral T cells that have most recently completed thymic development and egress. Over the past decade, significant advances have been made in understanding the cell-extrinsic and cell-intrinsic requirements for RTE maturation to mature naïve (MN) T cells and in detailing the functional differences that characterize these two T cell populations. Much of this work has suggested that RTEs are hypo-functional versions of more mature T cells. However, recent evidence has indicated that rather than being defective T cells, RTEs are exquisitely adapted to their cellular niche. In this review, we argue that RTEs are not flawed mature T cells but are adapted to fill an underpopulated T cell compartment, while maintaining self tolerance and possessing the capacity to mount robust immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fault tolerant control based on interval type-2 fuzzy sliding mode controller for coaxial trirotor aircraft.

PubMed

Zeghlache, Samir; Kara, Kamel; Saigaa, Djamel

2015-11-01

In this paper, a robust controller for a Six Degrees of Freedom (6 DOF) coaxial trirotor helicopter control is proposed in presence of defects in the system. A control strategy based on the coupling of the interval type-2 fuzzy logic control and sliding mode control technique are used to design a controller. The main purpose of this work is to eliminate the chattering phenomenon and guaranteeing the stability and the robustness of the system. In order to achieve this goal, interval type-2 fuzzy logic control has been used to generate the discontinuous control signal. The simulation results have shown that the proposed control strategy can greatly alleviate the chattering effect, and perform good reference tracking in presence of defects in the system. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

[Hormonal mechanisms of pathogenesis and cure of experimental gastroduodenal ulcer by the Okabe technique].

PubMed

Frolkov, V K; Polushina, N D; Shvarts, V Ia; Kozharskiĭ, V V; Zaporozhchenko, I G; Kartazaeva, V A

1992-01-01

The dynamics of hormonal secretion was studied in relation with the development of an ulcer defect in rats with acetate-induced gastroduodenal ulcer after Okabe. The formation of the ulcer was accompanied by increased gastrin, glucagon, cortisol, growth hormone, and histamine secretion and reduced glucose tolerance. The level of intragastric pH reduced, the activity of proteolytic enzymes in the gastrointestinal tract increased. Correlation analysis bore evidence for the contribution of gastroenteropancreatic hormones to the compensatory-adaptational responses, whereas with a higher blood cortisol level the surface of the ulcer defect was larger. Oral mineral water (Essentuki No. 17) promoted the secretion of gastrin, glucagon, and insulin and the experimental ulcers grew smaller in this case. The involvement of the hormonal factors in the mechanisms of the development of experimental acetate-induced ulcer is discussed.

Temperature stress and plant sexual reproduction: uncovering the weakest links.

PubMed

Zinn, Kelly E; Tunc-Ozdemir, Meral; Harper, Jeffrey F

2010-04-01

The reproductive (gametophytic) phase in flowering plants is often highly sensitive to hot or cold temperature stresses, with even a single hot day or cold night sometimes being fatal to reproductive success. This review describes studies of temperature stress on several crop plants, which suggest that pollen development and fertilization may often be the most sensitive reproductive stage. Transcriptome and proteomic studies on several plant species are beginning to identify stress response pathways that function during pollen development. An example is provided here of genotypic differences in the reproductive stress tolerance between two ecotypes of Arabidopsis thaliana Columbia (Col) and Hilversum (Hi-0), when reproducing under conditions of hot days and cold nights. Hi-0 exhibited a more severe reduction in seed set, correlated with a reduction in pollen tube growth potential and tropism defects. Hi-0 thus provides an Arabidopsis model to investigate strategies for improved stress tolerance in pollen. Understanding how different plants cope with stress during reproductive development offers the potential to identify genetic traits that could be manipulated to improve temperature tolerance in selected crop species being cultivated in marginal climates.

Fault-tolerant quantum computation with nondeterministic entangling gates

NASA Astrophysics Data System (ADS)

Auger, James M.; Anwar, Hussain; Gimeno-Segovia, Mercedes; Stace, Thomas M.; Browne, Dan E.

2018-03-01

Performing entangling gates between physical qubits is necessary for building a large-scale universal quantum computer, but in some physical implementations—for example, those that are based on linear optics or networks of ion traps—entangling gates can only be implemented probabilistically. In this work, we study the fault-tolerant performance of a topological cluster state scheme with local nondeterministic entanglement generation, where failed entangling gates (which correspond to bonds on the lattice representation of the cluster state) lead to a defective three-dimensional lattice with missing bonds. We present two approaches for dealing with missing bonds; the first is a nonadaptive scheme that requires no additional quantum processing, and the second is an adaptive scheme in which qubits can be measured in an alternative basis to effectively remove them from the lattice, hence eliminating their damaging effect and leading to better threshold performance. We find that a fault-tolerance threshold can still be observed with a bond-loss rate of 6.5% for the nonadaptive scheme, and a bond-loss rate as high as 14.5% for the adaptive scheme.

WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW.

PubMed

Moreira-Marconi, Eloá; Sá-Caputo, Danubia C; Dionello, Carla F; Guedes-Aguiar, Eliane O; Sousa-Gonçalves, Cintia R; Morel, Danielle S; Paineiras-Domingos, Laisa L; Souza, Patricia L; Kütter, Cristiane R; Costa-Cavalcanti, Rebeca G; Costa, Glenda; Paiva, Patricia C; Figueiredo, Claudia; Brandão-Sobrinho-Neto, Samuel; Stark, Christina; Unger, Marianne; Bernardo-Filho, Mario

2017-01-01

Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients. Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm. A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation. It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients.

EASApprox® skin-stretching system: A secure and effective method to achieve wound closure.

PubMed

Song, Mingzhi; Zhang, Zhen; Liu, Tao; Liu, Song; Li, Gang; Liu, Zhaochang; Huang, Jingyang; Chen, Song; Li, Linan; Guo, Li; Qiu, Yang; Wan, Jiajia; Liu, Yuejian; Wu, Tao; Wang, Xiaoyong; Lu, Ming; Wang, Shouyu

2017-07-01

Large skin defects are commonly observed in the clinic and have attracted much attention recently. Therefore, finding an effective solution for large skin defects is a global problem. The objective of the present study was to assess the effectiveness of the EASApprox ® skin-stretching system for closing large skin defects. Skin defects (5×5 cm) were created on the forearms of 9 Bama miniature pigs, which were randomly divided into the following three groups: Direct suture, the new EASApprox ® skin-stretching device and Kirschner wires. Microcirculation was assessed before surgery and after wound closure. Following the different treatments, the defects were sutured, and wound healing was assessed based on a clinical score. Furthermore, microscopic and ultramicroscopic structures were evaluated, including collagen, elastic fibers and the microvessel density. Significant differences in the clinical score and microvessel density were observed among the groups. Additionally, the mean length obtained for elastic fibers was larger than that obtained for the other two groups. Finally, the new EASApprox ® skin-stretching device resulted in successful wound management and with only minor side effects on skin histology and microcirculation. Therefore, this method has the potential to be used for healing large skin defects.

Characterization of Local Carrier Dynamics in AlN and AlGaN Films using High Spatial- and Time-resolution Cathodoluminescence Spectroscopy

DTIC Science & Technology

2012-10-12

21/2012 Abstract: In order to assess the impacts of structural and point defects on the local carrier (exciton) recombination dynamics in...quantitatively understood as functions of structural / point defect and impurity concentrations (crystal imperfections). However, only few papers [5...NOTES 14. ABSTRACT In order to assess the impacts of structural and point defects on the local carrier (exciton) recombination dynamics in wide bandgap

Quantifying tolerance indicator values for common stream fish species of the United States

USGS Publications Warehouse

Meador, M.R.; Carlisle, D.M.

2007-01-01

The classification of fish species tolerance to environmental disturbance is often used as a means to assess ecosystem conditions. Its use, however, may be problematic because the approach to tolerance classification is based on subjective judgment. We analyzed fish and physicochemical data from 773 stream sites collected as part of the U.S. Geological Survey's National Water-Quality Assessment Program to calculate tolerance indicator values for 10 physicochemical variables using weighted averaging. Tolerance indicator values (TIVs) for ammonia, chloride, dissolved oxygen, nitrite plus nitrate, pH, phosphorus, specific conductance, sulfate, suspended sediment, and water temperature were calculated for 105 common fish species of the United States. Tolerance indicator values for specific conductance and sulfate were correlated (rho = 0.87), and thus, fish species may be co-tolerant to these water-quality variables. We integrated TIVs for each species into an overall tolerance classification for comparisons with judgment-based tolerance classifications. Principal components analysis indicated that the distinction between tolerant and intolerant classifications was determined largely by tolerance to suspended sediment, specific conductance, chloride, and total phosphorus. Factors such as water temperature, dissolved oxygen, and pH may not be as important in distinguishing between tolerant and intolerant classifications, but may help to segregate species classified as moderate. Empirically derived tolerance classifications were 58.8% in agreement with judgment-derived tolerance classifications. Canonical discriminant analysis revealed that few TIVs, primarily chloride, could discriminate among judgment-derived tolerance classifications of tolerant, moderate, and intolerant. To our knowledge, this is the first empirically based understanding of fish species tolerance for stream fishes in the United States.

Guidelines for Sampling, Assessing, and Restoring Defective Grout in Prestressed Concrete Bridge Post-Tensioning Ducts

DOT National Transportation Integrated Search

2013-05-01

This document is a technical summary of the Federal Highway Administration report, "Guidelines for Sampling, Assessing, and Restoring Defective Grout in Prestressed Concrete Bridge Post-Tensioning Ducts" (FHWA-HRT-13-028). The objectives of this stud...

Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease

PubMed Central

Mochel, Fanny; Duteil, Sandrine; Marelli, Cécilia; Jauffret, Céline; Barles, Agnès; Holm, Janette; Sweetman, Lawrence; Benoist, Jean-François; Rabier, Daniel; Carlier, Pierre G; Durr, Alexandra

2010-01-01

We previously identified a systemic metabolic defect associated with early weight loss in patients with Huntington's disease (HD), suggesting a lack of substrates for the Krebs cycle. Dietary anaplerotic therapy with triheptanoin is used in clinical trials to promote energy production in patients with peripheral and brain Krebs cycle deficit, as its metabolites – C5 ketone bodies – cross the blood–brain barrier. We conducted a short-term clinical trial in six HD patients (UHDRS (Unified Huntington Disease Rating Scale)=33±13, 15–49) to monitor the tolerability of triheptanoin. We also assessed peripheral markers of short-term efficacy that were shown to be altered in the early stages of HD, that is, low serum IGF1 and 31P-NMR spectroscopy (NMRS) in muscle. At baseline, 31P-NMRS displayed two patients with end-exercise muscle acidosis despite a low work output. On day 2, the introduction of triheptanoin was well tolerated in all patients, and in particular, there was no evidence of mitochondrial overload from triheptanoin-derived metabolites. After 4 days of triheptanoin-enriched diet, muscle pH regulation was normalized in the two patients with pretreatment metabolic abnormalities. A significant increase in serum IGF1 was also observed in all patients (205±60 ng/ml versus 246±68 ng/ml, P=0.010). This study provides a rationale for extending our anaplerotic approach with triheptanoin in HD. PMID:20512158

The Mediator subunit SFR6/MED16 controls defence gene expression mediated by salicylic acid and jasmonate responsive pathways.

PubMed

Wathugala, Deepthi L; Hemsley, Piers A; Moffat, Caroline S; Cremelie, Pieter; Knight, Marc R; Knight, Heather

2012-07-01

• Arabidopsis SENSITIVE TO FREEZING6 (SFR6) controls cold- and drought-inducible gene expression and freezing- and osmotic-stress tolerance. Its identification as a component of the MEDIATOR transcriptional co-activator complex led us to address its involvement in other transcriptional responses. • Gene expression responses to Pseudomonas syringae, ultraviolet-C (UV-C) irradiation, salicylic acid (SA) and jasmonic acid (JA) were investigated in three sfr6 mutant alleles by quantitative real-time PCR and susceptibility to UV-C irradiation and Pseudomonas infection were assessed. • sfr6 mutants were more susceptible to both Pseudomonas syringae infection and UV-C irradiation. They exhibited correspondingly weaker PR (pathogenesis-related) gene expression than wild-type Arabidopsis following these treatments or after direct application of SA, involved in response to both UV-C and Pseudomonas infection. Other genes, however, were induced normally in the mutants by these treatments. sfr6 mutants were severely defective in expression of plant defensin genes in response to JA; ectopic expression of defensin genes was provoked in wild-type but not sfr6 by overexpression of ERF5. • SFR6/MED16 controls both SA- and JA-mediated defence gene expression and is necessary for tolerance of Pseudomonas syringae infection and UV-C irradiation. It is not, however, a universal regulator of stress gene transcription and is likely to mediate transcriptional activation of specific regulons only. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Ideal sinks are not always ideal. Radiation damage accumulation in nanocomposites

DOE PAGES

Uberuaga, Blas Pedro; Choudhury, Samrat; Caro, Alfredo

2014-11-27

Designing radiation tolerant materials is one of the primary challenges associated with advanced nuclear energy systems. One attractive route that has received much attention world-wide is to introduce a high density of sinks, often in the form of interfaces or secondary phases. Here, we develop a simple model of such nanocomposites and examine the ramifications of various factors on the overall radiation stability of the material. In particular, we determine how the distribution of secondary phases, the relative sink strength of those phases, and the irradiation temperature influence the radiation tolerance of the matrix. We find that the best scenariomore » is one in which the sinks have intermediate strength, transiently trapping defects before releasing them back into the matrix.This provides new insight into the optimal properties of nanocomposites for radiation damage environments.« less

Commensal microbiota influence systemic autoimmune responses

PubMed Central

Van Praet, Jens T; Donovan, Erin; Vanassche, Inge; Drennan, Michael B; Windels, Fien; Dendooven, Amélie; Allais, Liesbeth; Cuvelier, Claude A; van de Loo, Fons; Norris, Paula S; Kruglov, Andrey A; Nedospasov, Sergei A; Rabot, Sylvie; Tito, Raul; Raes, Jeroen; Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine; Van de Wiele, Tom; Eberl, Gérard; Ware, Carl F; Elewaut, Dirk

2015-01-01

Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life. PMID:25599993

FISH AND AMPHIBIAN TOLERANCE VALUES AND AN ASSEMBLAGE TOLERANCE INDEX FOR STEAMS AND RIVERS IN THE WESTERN USA

EPA Science Inventory

Aquatic species' tolerances to overall human disturbance are key components of biological assessments of aquatic ecosystems. These tolerance classifications enable development of metrics for use in multimetric indexes, such as the index of biotic integrity (IBI). Usually, species...

Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model.

PubMed

Dong, Zhiwei; Chen, Yajie; Peng, Yuan; Wang, Fan; Yang, Zichen; Huang, Guangtao; Chen, Yu; Yuan, Zhiqiang; Cao, Tongtong; Peng, Yizhi

2017-01-01

Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection. © 2017 The Author(s). Published by S. Karger AG, Basel.

cost and benefits optimization model for fault-tolerant aircraft electronic systems

NASA Technical Reports Server (NTRS)

1983-01-01

The factors involved in economic assessment of fault tolerant systems (FTS) and fault tolerant flight control systems (FTFCS) are discussed. Algorithms for optimization and economic analysis of FTFCS are documented.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

PubMed

Weyer, Peter J; Brender, Jean D; Romitti, Paul A; Kantamneni, Jiji R; Crawford, David; Sharkey, Joseph R; Shinde, Mayura; Horel, Scott A; Vuong, Ann M; Langlois, Peter H

2014-12-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects

PubMed Central

Weyer, Peter J.; Brender, Jean D.; Romitti, Paul A.; Kantamneni, Jiji R.; Crawford, David; Sharkey, Joseph R.; Shinde, Mayura; Horel, Scott A.; Vuong, Ann M.; Langlois, Peter H.

2016-01-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997–2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers’ overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS. PMID:25473985

Proposal to Develop Enhancements and Extensions of Formal Models for Risk Assessment In Software Projects

DTIC Science & Technology

2002-09-01

seconds per minute that the runtime environment was up and running. Defect Categories. The labels of the 5 defect categories. 78 Cosmetic Defects...The name that corresponds to QSM’s cosmetic defects. Cosmetic defects can be described as deferred, such as errors in format of displays or...2002. [Fent00] Fenton , N. E. and Neil, M. Software Metrics: Roadmap. Proceedings of the Conference on the Future of Software Engineering, 2000, pp

Enhancement of Radiation Tolerance by Interfaces in Nanostructured Metallic Materials

DTIC Science & Technology

2013-06-05

MeV Ar+ ions, respectively [14],[15]. Chimi et al. measured the electrical resistivity of irradiated nc gold and found that enlarged defect...2011.10.052 07/28/2011 1.00 Nan Li, M. S. Martin, O. Anderoglu, A. Misra, L. Shao, H. Wang, X. Zhang. He ion irradiation damage in Al? Nb ...climb at interfaces in nanolayered Al/ Nb composites, Scripta Materialia, (08 2010): 363. doi: 10.1016/j.scriptamat.2010.04.005 07/28/2011 5.00 E.G. Fu

Effect of Surface and Defect Chemistry on the Photocatalytic Properties of Intentionally Defect-Rich ZnO Nanorod Arrays.

PubMed

Kegel, Jan; Zubialevich, Vitaly Z; Schmidt, Michael; Povey, Ian M; Pemble, Martyn E

2018-05-30

Due to the abundance of intrinsic defects in zinc oxide (ZnO), the material properties are often governed by same. Knowledge of the defect chemistry has proven to be highly important, especially in terms of the photocatalytic degradation of pollutants. Given the fact that defect-free materials or structures exhibiting only one type of defect are extremely difficult to produce, it is necessary to evaluate what influence various defects may have when present together in the material. In this study, intentionally defect-rich ZnO nanorod (NR) arrays are grown using a simple low-temperature solution-based growth technique. Upon changing the defect chemistry using rapid thermal annealing (RTA) the material properties are carefully assessed and correlated to the resulting photocatalytic properties. Special focus is put on the investigation of these properties for samples showing strong orange photoluminescence (PL). It is shown that intense orange emitting NR arrays exhibit improved dye-degradation rates under UV-light irradiation. Furthermore, strong dye-adsorption has been observed for some samples. This behavior is found to stem from a graphitic surface structure (e.g., shell) formed during RTA in vacuum. Since orange-luminescent samples also exhibit an enhancement of the dye adsorption a possible interplay and synergy of these two defects is elucidated. Additionally, evidence is presented suggesting that in annealed ZnO NRs structural defects may be responsible for the often observed PL emission at 3.31 eV. However, a clear correlation with the photocatalytic properties could not be established for these defects. Building on the specific findings presented here, this study also presents some more general guidelines which, it is suggested, should be employed when assessing the photocatalytic properties of defect-rich ZnO.

Mutational Evidence for the Critical Role of CBF Transcription Factors in Cold Acclimation in Arabidopsis1

PubMed Central

Zhang, Zhengjing; Li, Yuanya

2016-01-01

The three tandemly arranged CBF genes, CBF1, CBF2, and CBF3, are involved in cold acclimation. Due to the lack of stable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants deficient in all three CBF genes, it is still unclear whether the CBF genes are essential for freezing tolerance and whether they may have other functions besides cold acclimation. In this study, we used the CRISPR/Cas9 system to generate cbf single, double, and triple mutants. Compared to the wild type, the cbf triple mutants are extremely sensitive to freezing after cold acclimation, demonstrating that the three CBF genes are essential for cold acclimation. Our results show that the three CBF genes also contribute to basal freezing tolerance. Unexpectedly, we found that the cbf triple mutants are defective in seedling development and salt stress tolerance. Transcript profiling revealed that the CBF genes regulate 414 cold-responsive (COR) genes, of which 346 are CBF-activated genes and 68 are CBF-repressed genes. The analysis suggested that CBF proteins are extensively involved in the regulation of carbohydrate and lipid metabolism, cell wall modification, and gene transcription. Interestingly, like the triple mutants, cbf2 cbf3 double mutants are more sensitive to freezing after cold acclimation compared to the wild type, but cbf1 cbf3 double mutants are more resistant, suggesting that CBF2 is more important than CBF1 and CBF3 in cold acclimation-dependent freezing tolerance. Our results not only demonstrate that the three CBF genes together are required for cold acclimation and freezing tolerance, but also reveal that they are important for salt tolerance and seedling development. PMID:27252305

Evaluation of selected speech parameters after prosthesis supply in patients with maxillary or mandibular defects.

PubMed

Müller, Rainer; Höhlein, Andreas; Wolf, Annette; Markwardt, Jutta; Schulz, Matthias C; Range, Ursula; Reitemeier, Bernd

2013-01-01

Ablative surgery of oropharyngeal tumors frequently leads to defects in the speech organs, resulting in impairment of speech up to the point of unintelligibility. The aim of the present study was the assessment of selected parameters of speech with and without resection prostheses. The speech sounds of 22 patients suffering from maxillary and mandibular defects were recorded using a digital audio tape (DAT) recorder with and without resection prostheses. Evaluation of the resonance and the production of the sounds /s/, /sch/, and /ch/ was performed by 2 experienced speech therapists. Additionally, the patients completed a non-standardized questionnaire containing a linguistic self-assessment. After prosthesis supply, the number of patients with rhinophonia aperta decreased from 7 to 2 while the number of patients with intelligible speech increased from 2 to 20. Correct production of the sounds /s/, /sch/, and /ch/ increased from 2 to 13 patients. A significant improvement of the evaluated parameters could be observed only in patients with maxillary defects. The linguistic self-assessment showed a higher satisfaction in patients with maxillary defects. In patients with maxillary defects due to ablative tumor surgery, an increase in speech performance and intelligibility is possible by supplying resection prostheses. © 2013 S. Karger GmbH, Freiburg.

Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU.

PubMed

van Spronsen, F J; van Rijn, M; Dorgelo, B; Hoeksma, M; Bosch, A M; Mulder, M F; de Klerk, J B C; de Koning, T; Rubio-Gozalbo, M Estela; de Vries, M; Verkerk, P H

2009-02-01

The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.

Drought tolerance in potato (S. tuberosum L.): Can we learn from drought tolerance research in cereals?

PubMed

Monneveux, Philippe; Ramírez, David A; Pino, María-Teresa

2013-05-01

Drought tolerance is a complex trait of increasing importance in potato. Our knowledge is summarized concerning drought tolerance and water use efficiency in this crop. We describe the effects of water restriction on physiological characteristics, examine the main traits involved, report the attempts to improve drought tolerance through in vitro screening and marker assisted selection, list the main genes involved and analyze the potential interest of native and wild potatoes to improve drought tolerance. Drought tolerance has received more attention in cereals than in potato. The review compares these crops for indirect selection methods available for assessment of drought tolerance related traits, use of genetic resources, progress in genomics, application of water saving techniques and availability of models to anticipate the effects of climate change on yield. It is concluded that drought tolerance improvement in potato could greatly benefit from the transfer of research achievements in cereals. Several promising research directions are presented, such as the use of fluorescence, reflectance, color and thermal imaging and stable isotope techniques to assess drought tolerance related traits, the application of the partial root-zone drying technique to improve efficiency of water supply and the exploitation of stressful memory to enhance hardiness. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Ceramic Defects in Metal-Ceramic Fixed Dental Prostheses Made from Co-Cr and Au-Pt Alloys: A Retrospective Study.

PubMed

Mikeli, Aikaterini; Boening, Klaus W; Lißke, Benjamin

2015-01-01

Ceramic defects in porcelain-fused-to-metal (PFM) restorations may depend on framework alloy type. This study assessed ceramic defects on cobalt-chromium- (Co-Cr-) and gold-platinum- (Au-Pt-) based PFM restorations. In this study, 147 Co-Cr-based and 168 Au-Pt-based PFM restorations inserted between 1998 and 2010 (139 patients) were examined for ceramic defects. Detected defects were assigned to three groups according to clinical defect relevance. Ceramic defect rates (Co-Cr-based: 12.9%; Au-Pt-based: 7.2%) revealed no significant difference but a strong statistical trend (U test, P = .082). Most defects were of little clinical relevance. Co-Cr PFM restorations may be at higher risk for ceramic defects compared to Au-Pt-based restorations.

Damage evolution of ion irradiated defected-fluorite La 2 Zr 2 O 7 epitaxial thin films

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

Kaspar, Tiffany C.; Gigax, Jonathan G.; Shao, Lin

2017-05-01

Pyrochlore-structure oxides, A2B2O7, may exhibit remarkable radiation tolerance due to the ease with which they can accommodate disorder by transitioning to a defected fluorite structure. The mechanism of defect formation was explored by evaluating the radiation damage behavior of high quality epitaxial La2Zr2O7 thin films with the defected fluorite structure, irradiated with 1 MeV Zr+ at doses up to 10 displacements per atom (dpa). The level of film damage was evaluated as a function of dose by Rutherford backscattering spectrometry in the channeling geometry (RBS/c) and scanning transmission electron microscopy (STEM). At lower doses, the surface of the La2Zr2O7 filmmore » amorphized, and the amorphous fraction as a function of dose fit well to a stimulated amorphization model. As the dose increased, the surface amorphization slowed, and amorphization appeared at the interface. Even at a dose of 10 dpa, the core of the film remained crystalline, despite the prediction of amorphization from the model. To inform future ab initio simulations of La2Zr2O7, the bandgap of a thick La2Zr2O7 film was measured to be indirect at 4.96 eV, with a direct transition at 5.60 eV.« less

Classification of Partial Discharge Measured under Different Levels of Noise Contamination

PubMed Central

2017-01-01

Cable joint insulation breakdown may cause a huge loss to power companies. Therefore, it is vital to diagnose the insulation quality to detect early signs of insulation failure. It is well known that there is a correlation between Partial discharge (PD) and the insulation quality. Although many works have been done on PD pattern recognition, it is usually performed in a noise free environment. Also, works on PD pattern recognition in actual cable joint are less likely to be found in literature. Therefore, in this work, classifications of actual cable joint defect types from partial discharge data contaminated by noise were performed. Five cross-linked polyethylene (XLPE) cable joints with artificially created defects were prepared based on the defects commonly encountered on site. Three different types of input feature were extracted from the PD pattern under artificially created noisy environment. These include statistical features, fractal features and principal component analysis (PCA) features. These input features were used to train the classifiers to classify each PD defect types. Classifications were performed using three different artificial intelligence classifiers, which include Artificial Neural Networks (ANN), Adaptive Neuro-Fuzzy Inference System (ANFIS) and Support Vector Machine (SVM). It was found that the classification accuracy decreases with higher noise level but PCA features used in SVM and ANN showed the strongest tolerance against noise contamination. PMID:28085953

Damage evolution of ion irradiated defected-fluorite La 2 Zr 2 O 7 epitaxial thin films

DOE PAGES

Kaspar, Tiffany C.; Gigax, Jonathan G.; Shao, Lin; ...

2017-05-01

Pyrochlore-structure oxides, A 2B 2O 7, may exhibit remarkable radiation tolerance due to the ease with which they can accommodate disorder by transitioning to a defected fluorite structure. In this paper, the mechanism of defect formation was explored by evaluating the radiation damage behavior of high quality epitaxial La 2Zr 2O 7 thin films with the defected fluorite structure, irradiated with 1 MeV Zr + at doses up to 10 displacements per atom (dpa). The level of film damage was evaluated as a function of dose by Rutherford backscattering spectrometry in the channeling geometry (RBS/c) and scanning transmission electron microscopymore » (STEM). At lower doses, the surface of the La 2Zr 2O 7 film amorphized, and the amorphous fraction as a function of dose fit well to a stimulated amorphization model. As the dose increased, the surface amorphization slowed, and amorphization appeared at the interface. Even at a dose of 10 dpa, the core of the film remained crystalline, despite the prediction of amorphization from the model. To inform future ab initio simulations of La 2Zr 2O 7, the bandgap of a thick La 2Zr 2O 7 film was measured to be indirect at 4.96 eV, with a direct transition at 5.60 eV.« less

Current deflection NDE for pipeline inspection and monitoring

NASA Astrophysics Data System (ADS)

Jarvis, Rollo; Cawley, Peter; Nagy, Peter B.

2016-02-01

Failure of oil and gas pipelines can often be catastrophic, therefore routine inspection for time dependent degradation is essential. In-line inspection is the most common method used; however, this requires the insertion and retrieval of an inspection tool that is propelled by the fluid in the pipe and risks becoming stuck, so alternative methods must often be employed. This work investigates the applicability of a non-destructive evaluation technique for both the detection and growth monitoring of defects, particularly corrosion under insulation. This relies on injecting an electric current along the pipe and indirectly measuring the deflection of current around defects from perturbations in the orthogonal components of the induced magnetic flux density. An array of three orthogonally oriented anisotropic magnetoresistive sensors has been used to measure the magnetic flux density surrounding a 6'' schedule-40 steel pipe carrying 2 A quasi-DC axial current. A finite element model has been developed that predicts the perturbations in magnetic flux density caused by current deflection which has been validated by experimental results. Measurements of the magnetic flux density at 50 mm lift-off from the pipe surface are stable and repeatable to the order of 100 pT which suggests that defect detection or monitoring growth of corrosion-type defects may be possible with a feasible magnitude of injected current. Magnetic signals are additionally incurred by changes in the wall thickness of the pipe due to manufacturing tolerances, and material property variations. If a monitoring scheme using baseline subtraction is employed then the sensitivity to defects can be improved while avoiding false calls.

Prolapse of inverted ileal loops through a patent vitellointestinal duct

PubMed Central

Pathak, Ashish; Agarwal, Nitin; Singh, Poonam; Dhaneria, Mamta

2015-01-01

We report a case of a prolapsed patent vitellointestinal duct (PVID) in a 2-month-old girl child who presented with sudden increase in size of a polypoidal lesion into a large, ‘Y’-shaped reddish, prolapsing lesion, discharging gaseous and faecal matter at her umbilicus. The lesion was diagnosed as a prolapse of inverted ileal loops through the PVID. The child had no associated congenital anomalies. A transumbilical exploration was performed, followed by wedge resection and anastomosis. The child tolerated the procedure well and the postoperative course was uneventful. If the omphalomesenteric duct fails to obliterate a range of congenital defects related to the umbilicus, it can become clinically apparent. Meckel's diverticulum is the commonest of these defects but is most often asymptomatic. PVID is the most common symptomatic anomaly of the patent omphalomesenteric duct and requires prompt surgical correction to avoid complications. PMID:26494719

Prolapse of inverted ileal loops through a patent vitellointestinal duct.

PubMed

Pathak, Ashish; Agarwal, Nitin; Singh, Poonam; Dhaneria, Mamta

2015-10-22

We report a case of a prolapsed patent vitellointestinal duct (PVID) in a 2-month-old girl child who presented with sudden increase in size of a polypoidal lesion into a large, 'Y'-shaped reddish, prolapsing lesion, discharging gaseous and faecal matter at her umbilicus. The lesion was diagnosed as a prolapse of inverted ileal loops through the PVID. The child had no associated congenital anomalies. A transumbilical exploration was performed, followed by wedge resection and anastomosis. The child tolerated the procedure well and the postoperative course was uneventful. If the omphalomesenteric duct fails to obliterate a range of congenital defects related to the umbilicus, it can become clinically apparent. Meckel's diverticulum is the commonest of these defects but is most often asymptomatic. PVID is the most common symptomatic anomaly of the patent omphalomesenteric duct and requires prompt surgical correction to avoid complications. 2015 BMJ Publishing Group Ltd.

Electronic Properties, Screening, and Efficient Carrier Transport in NaSbS 2

DOE PAGES

Sun, Jifeng; Singh, David J.

2017-02-13

NaSbS 2 is a semiconductor that was recently shown to have remarkable efficacy as a solar absorber indicating efficient charge collection even in material containing defects. We report first-principles calculations of properties that show (1) an indirect gap only slightly smaller than the direct gap, which may impede the recombination of photoexcited carriers, (2) highly anisotropic electronic and optical properties reflecting a layered crystal structure, (3) a pushed-up valence-band maximum due to repulsion from the Sb 5s states, and (4) cross-gap hybridization between the S p—derived valence bands and the Sb 5p states. This latter feature leads to enhanced Bornmore » effective charges that can provide local screening and, therefore, defect tolerance. Finally, these features are discussed in relation to the performance of the compound as a semiconductor with efficient charge collection.« less

Validation diagnostics for defective thermocouple circuits

NASA Astrophysics Data System (ADS)

Reed, R. P.

Thermocouples, properly used under favorable conditions, can measure temperature with an accepted tolerance. However, when improperly applied or exposed to hostile mechanical, chemical, thermal, or radiation environments, they often fail without the error being evident in the temperature record. Conversely, features that appear to be unreasonable in temperature records can be authentic. When hidden failure occurs during measurement, deliberate recording of supplementary information is necessary to distinguish valid from faulty data. Loop resistance change, circuit isolation, isolated noise potential, and other measures can reveal symptoms of developing defects. Monitored continually along with temperature, they can reveal the occurrence, location, and natures of damage incurred during measurement. Special multiterminal branched thermocouple circuits and combinatorial multiplex switching allow detection of dc measurement noise and decalibration. Symptoms of insidious failure, often consequential, are illustrated by examples from field experience in measuring temperature of a propagating retorting front in underground coal gasification.

Softening due to Grain Boundary Cavity Formation and its Competition with Hardening in Helium Implanted Nanocrystalline Tungsten

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

Cunningham, W. Streit; Gentile, Jonathan M.; El-Atwani, Osman

The unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity viamore » grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten.« less

Softening due to Grain Boundary Cavity Formation and its Competition with Hardening in Helium Implanted Nanocrystalline Tungsten

DOE PAGES

Cunningham, W. Streit; Gentile, Jonathan M.; El-Atwani, Osman; ...

2018-02-13

The unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity viamore » grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten.« less

Three point-advancement closure for skin defects.

PubMed

Tamir, G; Birkby, C S; Berg, D

1999-10-01

Circular skin defects are common following Mohs' surgery. Traditional closure (primary, flap, or graft) may involve extensive surgery. Multidirectional advancement closures such as the purse-string closure have been advocated as another useful tool in such cases. To describe a variation on purse-string closure that, in certain cases, is an excellent alternative to other reconstructions, and will provide good cosmetic and functional outcome. A three-point anchoring suture is placed after undermining to advance the surrounding tissue toward the centre, creating a "Mercedes Benz" or tripod closure following removal of "dog-ears." Circular wounds in designated areas can be more easily closed, creating well-tolerated, favourable scars. Large wounds may be closed with the advantage of avoidance of larger flaps, of decreased wound healing compared to second intention, and of minimizing removal of healthy tissue. An initial trial of closure with this method does not limit subsequent use of other repairs should it be less than satisfactory.

Effects of Lean Six Sigma application in healthcare services: a literature review.

PubMed

Ahmed, Selim; Manaf, Noor H A; Islam, Rafikul

2013-01-01

The healthcare organization is the place where defects and mistakes cannot be tolerated. A simple mistake can cost a human life so defects or mistakes must be eliminated in healthcare service processes. A Lean Six Sigma (LSS) approach is the best option in a healthcare environment for dealing with a critical patient. The LSS methodology optimizes the average reduction of a desired process. The expected results can be reductions in several aspects of healthcare such as patient waiting time in emergency departments, lost charges for billing in patient financial services, delinquent medical records, diagnostic result turnaround times, accounts receivable days, patients' length of stay, or medication errors. This paper mainly discusses the effects of the LSS approach in different hospitals around the world according to the literature review. This review also discusses the relationship between LSS as well as their impacts on healthcare services based on literature review.

Analysis of the Effects of Residual Strains and Defects on Skin/Stiffener Debonding using Decohesion Elements

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Camanho, Pedro P.

2003-01-01

Delamination is one of the predominant forms of failure in laminated composites especially when there is no reinforcement in the thickness direction. To develop composite structures that are more damage tolerant, it is necessary to understand how delamination develops and how it can affect the residual performance. A number of factors such as residual thermal strains, matrix curing shrinkage, and manufacturing defects affect how damage will grow in a composite structure. It is important to develop analysis methods that are computationally efficient that can account for all such factors. The objective of the current work is to apply a newly developed decohesion element to investigate the debond strength of skin/stiffener composite specimens. The process of initiation of delaminations and the propagation of delamination fronts is investigated. The numerical predictions are compared with published experimental results.

Damage tolerance assessment handbook. Volume 2 : airframe damage tolerance evaluation

DOT National Transportation Integrated Search

1999-02-01

The handbook is presented in two volumes. Volume I introduces the damage tolerance concept with an historical perspective followed by the fundamentals of fracture mechanics and fatigue crack propagation. Various fracture criteria and crack growth rul...

Damage Tolerance of Composites

NASA Technical Reports Server (NTRS)

Hodge, Andy

2007-01-01

Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

78 FR 32146 - Triforine; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... America Holding Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act... triforine residues to be imported into the United States. III. Aggregate Risk Assessment and Determination... determination on aggregate exposure for triforine including exposure resulting from the tolerances established...

Initial stages of ion beam-induced phase transformations in Gd2O3 and Lu2O3

NASA Astrophysics Data System (ADS)

Chen, Chien-Hung; Tracy, Cameron L.; Wang, Chenxu; Lang, Maik; Ewing, Rodney C.

2018-02-01

The atomic-scale evolution of lanthanide sesquioxides Gd2O3 and Lu2O3 irradiated with 1 MeV Kr ions at room temperature and 120 K, up to fluences of 1 × 1016 ions/cm2 (˜20 dpa), has been characterized by in situ transmission electron microscopy. At room temperature, both oxides exhibited high radiation tolerance. Irradiation did not cause any observable structural change in either material, likely due to the mobility of irradiation-induced point defects, causing efficient defect annihilation. For Gd2O3, having the larger cation ionic radius of the two materials, an irradiation-induced stacking fault structure appeared at low fluences in the low temperature irradiation. As compared with the cubic-to-monoclinic phase transformations known to result from higher energy (˜GeV) ion irradiation, Kr ions of lower energies (˜MeV) yield much lower rates of damage accumulation and thus less extensive structural modification. At a fluence of 2.5 × 1015 ions/cm2, only the initial stages of the cubic-to-monoclinic (C to B) phase transformation process, consisting of the formation and aggregation of defects, have been observed.

Effects of crystallization interfaces on irradiated ferroelectric thin films

NASA Astrophysics Data System (ADS)

Brewer, S. J.; Williams, S. C.; Cress, C. D.; Bassiri-Gharb, N.

2017-11-01

This work investigates the role of crystallization interfaces and chemical heterogeneity in the radiation tolerance of chemical solution-deposited lead zirconate titanate (PZT) thin films. Two sets of PZT thin films were fabricated with crystallization performed at (i) every deposited layer or (ii) every three layers. The films were exposed to a range of 60Co gamma radiation doses, between 0.2 and 20 Mrad, and their functional response was compared before and after irradiation. The observed trends indicate enhancements of dielectric, ferroelectric, and piezoelectric responses at low radiation doses and degradation of the same at higher doses. Response enhancements are expected to result from low-dose (≤2 Mrad), ionizing radiation-induced charging of internal interfaces—an effect that results in neutralization of pre-existing internal bias in the samples. At higher radiation doses (>2 Mrad), accumulation and self-ordering of radiation-modified, mobile, oxygen vacancy-related defects contribute to degradation of dielectric, ferroelectric, and piezoelectric properties, exacerbated in the samples with more crystallization layers, potentially due to increased defect accumulation at these internal interfaces. These results suggest that the interaction between radiation and crystallization interfaces is multifaceted—the effects of ionization, domain wall motion, point defect mobility, and microstructure are considered.

[PHACES syndrome].

PubMed

Morcillo Azcárate, J; Bernabeu-Wittel, J; Fernández-Pineda, I; Conejo-Mir, M D; Tuduri Limousin, I; Aspiazu Salinas, D A; de Agustín Asensio, J C

2010-04-01

PHACES syndrome associates a segmental facial hemangioma with cerebral malformations, aortic branches/cranial arteries anomalies, cardiac defects, eye anomalies or ventral wall defects. The aim of this study is to analyze our experience with this syndrome. Retrospective study of the cases seen at our unit in the last year. We treat 4 cases; 3 girls and 1 child. Besides the segmental hemangioma they presented: 3 vascular cerebral malformations; 2 structural cardiopathies; 2 cerebral malformations, 1 microftalmia. We did not find ventral wall defects. A case received treatment with two cycles of metilprednisolone i.v. and oral prednisone, with favourable course; two cases received initial treatment with oral prednisone continued of oral propanolol in rising pattern up to 2 mg/kg/day, Obtaining both the detention of the tumour growth and regression of the lesion, with very good tolerance. A 7-year-old patient has been treated with colouring pulse laser for her residual lesions. When we see a segmental facial hemangioma we must perform a wide diagnostic study in order to discard a PHACES syndrome. Multidisciplinar approach to the patient by a wide expert's group gets an earlier diagnose and improves the outcome. Propranolol is a promising therapeutic alternative.

Semi-dwarfism and lodging tolerance in tef (Eragrostis tef) is linked to a mutation in the α-Tubulin 1 gene

PubMed Central

Jöst, Moritz; Esfeld, Korinna; Burian, Agata; Cannarozzi, Gina; Chanyalew, Solomon; Kuhlemeier, Cris; Assefa, Kebebew; Tadele, Zerihun

2015-01-01

Genetic improvement of native crops is a new and promising strategy to combat hunger in the developing world. Tef is the major staple food crop for approximately 50 million people in Ethiopia. As an indigenous cereal, it is well adapted to diverse climatic and soil conditions; however, its productivity is extremely low mainly due to susceptibility to lodging. Tef has a tall and weak stem, liable to lodge (or fall over), which is aggravated by wind, rain, or application of nitrogen fertilizer. To circumvent this problem, the first semi-dwarf lodging-tolerant tef line, called kegne, was developed from an ethyl methanesulphonate (EMS)-mutagenized population. The response of kegne to microtubule-depolymerizing and -stabilizing drugs, as well as subsequent gene sequencing and segregation analysis, suggests that a defect in the α-Tubulin gene is functionally and genetically tightly linked to the kegne phenotype. In diploid species such as rice, homozygous mutations in α-Tubulin genes result in extreme dwarfism and weak stems. In the allotetraploid tef, only one homeologue is mutated, and the presence of the second intact α-Tubulin gene copy confers the agriculturally beneficial semi-dwarf and lodging-tolerant phenotype. Introgression of kegne into locally adapted and popular tef cultivars in Ethiopia will increase the lodging tolerance in the tef germplasm and, as a result, will improve the productivity of this valuable crop. PMID:25399019

Software dependability in the Tandem GUARDIAN system

NASA Technical Reports Server (NTRS)

Lee, Inhwan; Iyer, Ravishankar K.

1995-01-01

Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.

Protective role of anthocyanins in plants under low nitrogen stress.

PubMed

Liang, Jian; He, Junxian

2018-04-15

Nitrogen (N) is a major nutrient of plants but often a limiting factor for plant growth and crop yield. To adapt to N deficiency, plants have evolved adaptive responses including accumulation of anthocyanins. However, it is still unclear whether the accumulated anthocyanins are part of the components of plant tolerance under low N stress. Here, we demonstrate that low N-induced anthocyanins contribute substantially to the low N tolerance of Arabidopsis thaliana. pap1-1, a mutant defective in MYB75 (PAP1), a MYB-type transcription factor that positively regulates anthocyanin biosynthesis in Arabidopsis, was found to have significantly decreased survival rate to low N stress compared to its wild-type plants. Similarly, tt3, a mutant with severe deficiency in dihydroflavonol 4-reductase (DFR), a key enzyme in anthocyanin biosynthesis, also showed much lower survival rate under low N stress. These results indicate that anthocyanins are substantial contributors of plant tolerance to low N stress. Furthermore, a metabolomics analysis using LC-MS revealed changes in flavonoid profile in the pap1-1 and tt3 plants, which established a causal relationship between plant adaptation to low N stress and these compounds including anthocyanins. Our results showed an important role of anthocyanins rather than flavonols in conferring plant tolerance to low N stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Maternal Use of Weight Loss Products and the Risk of Neural Tube Defects in Offspring: A Systematic Literature Review.

PubMed

Hoang, Thanh T; Agopian, A J; Mitchell, Laura E

2018-01-15

Several studies have assessed potential associations between use of weight loss products in the periconceptional period and neural tube defects (NTDs). However, the individual studies are inconclusive and there has not been a systematic review of this literature. We conducted a systematic search, using Ovid MEDLINE and PubMed, to identify studies that evaluated the association between products used for weight loss and the risk of NTDs. Because many studies of birth defects only evaluate a composite birth defect outcome, we evaluated studies that defined the outcome as "any major birth defect" or as NTDs. We abstracted data on study design, exposure definition, outcome definition, covariates and effect size estimates from each article that met our inclusion criteria. For studies that evaluated a composite birth defect outcome, we also abstracted the number of NTD cases included in the composite outcome. We used a modified version of the Newcastle-Ottawa Scale to assess the quality of each article. We screened 865 citations and identified nine articles that met our inclusion criteria. The majority of studies reported positive associations between maternal use of weight loss products and birth defects (overall and NTDs). However, there were few significant associations and there was considerable heterogeneity in the specific exposures assessed across the nine studies. Our systematic review of weight loss products and NTDs indicates that the literature on this topic is sparse. Because several studies reported modest, positive associations between risk and use of weight loss products, additional studies are warranted. Birth Defects Research 110:48-55, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Germline incorporation of a replication-defective adenoviral vector in mice does not alter immune responses to adenoviral vectors.

PubMed

Camargo, F D; Huey-Louie, D A; Finn, A V; Sassani, A B; Cozen, A E; Moriwaki, H; Schneider, D B; Agah, R; Dichek, D A

2000-11-01

The utility of adenoviral vectors is limited by immune responses to adenoviral antigens. We sought to develop immune-competent mice in which the immune response to adenoviral antigens was selectively absent. To do so, we generated mice that were transgenic for a replication-defective vector. Adenoviral antigens might be seen as self-antigens by these mice, and the mice could exhibit immunologic tolerance after postnatal exposure to adenoviral vectors. In addition, characterization of these mice could reveal potential consequences of germline transmission of an adenoviral vector, as might occur in a gene therapy trial. Injection of a "null" (not containing a transgene) E1, E3-deleted vector genome into mouse zygotes yielded five founders that were capable of transmitting the vector genome. Among offspring of these mice, transgenic pups were significantly underrepresented: 108 of 255 pups (42%) were transgenic (P<0.02 versus expected frequency of 50%). Postnatal transgenic mice, however, had no apparent abnormalities. Persistence of an adenoviral vector after intravenous injection was equivalent in livers of transgenic mice and their nontransgenic littermates. Transgenic and nontransgenic mice also had equivalent humoral and cellular immune responses to adenoviral vector injection. Mice that are transgenic for an E1, E3-deleted adenoviral genome can be easily generated; however, they are not tolerant of adenovirus. Moreover, germline transmission of an adenoviral vector genome does not prevent generation of a robust immune response after exposure to adenoviral antigens.

Phytohormones and Beneficial Microbes: Essential Components for Plants to Balance Stress and Fitness

PubMed Central

Egamberdieva, Dilfuza; Wirth, Stephan J.; Alqarawi, Abdulaziz A.; Abd_Allah, Elsayed F.; Hashem, Abeer

2017-01-01

Plants are subjected to various abiotic stresses, such as drought, extreme temperature, salinity, and heavy metals. Abiotic stresses have negative impact on the physiology and morphology of plants through defects in the genetic regulation of cellular pathways. Plants employ several tolerance mechanisms and pathways to avert the effects of stresses that are triggered whenever alterations in metabolism are encountered. Phytohormones are among the most important growth regulators; they are known for having a prominent impact on plant metabolism, and additionally, they play a vital role in the stimulation of plant defense response mechanisms against stresses. Exogenous phytohormone supplementation has been adopted to improve growth and metabolism under stress conditions. Recent investigations have shown that phytohormones produced by root-associated microbes may prove to be important metabolic engineering targets for inducing host tolerance to abiotic stresses. Phytohormone biosynthetic pathways have been identified using several genetic and biochemical methods, and numerous reviews are currently available on this topic. Here, we review current knowledge on the function of phytohormones involved in the improvement of abiotic stress tolerance and defense response in plants exposed to different stressors. We focus on recent successes in identifying the roles of microbial phytohormones that induce stress tolerance, especially in crop plants. In doing so, this review highlights important plant morpho-physiological traits that can be exploited to identify the positive effects of phytohormones on stress tolerance. This review will therefore be helpful to plant physiologists and agricultural microbiologists in designing strategies and tools for the development of broad spectrum microbial inoculants supporting sustainable crop production under hostile environments. PMID:29163398

Recurrent neural tube defects, risk factors and vitamins.

PubMed Central

Wild, J; Read, A P; Sheppard, S; Seller, M J; Smithells, R W; Nevin, N C; Schorah, C J; Fielding, D W; Walker, S; Harris, R

1986-01-01

Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect. Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects, area of residence, immediately prior miscarriage, and interpregnancy interval. None of these factors, however, contributed any significant differential risk between supplemented and unsupplemented mothers. Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation. PMID:3521496

Mercury toxicity in the aquatic oligochaete Sparganophilus pearsei. II: Autotomy as a novel form of protection.

PubMed

Vidal, D E; Horne, A J

2003-11-01

Aquatic oligochaetes are commonly used for toxicity testing and for assessment of sediment impairment; some species can be relatively tolerant of sediment contaminants. However, there have been few studies of tolerance mechanisms; most work has focused on behavioral changes. The aquatic oligochaete worm, Sparganophilus pearsei, can be extremely tolerant to mercury in sediments depending on its prior history of exposure. Three S. pearsei populations, differing in their history of mercury exposure and in their tolerance to mercury, were assessed to determine tolerance mechanisms. In mercury-contaminated sediments, tolerant worms accumulated this contaminant in their caudal segments (i.e., their tails), which were then jettisoned via the process of autotomy, thus providing a mechanism of detoxification. This detoxification process appears to require a certain level of tolerance and may represent a novel exposure route for other organisms via feeding on discarded tails or release of accumulated contaminants as the tails decompose. Measurements of tissue mercury concentrations as contaminant body residues for this species (CBRs) are compared to other aquatic invertebrates.

Assessing variation in tolerance in 23 Muslim-majority and Western countries.

PubMed

Milligan, Scott; Andersen, Robert; Brym, Robert

2014-08-01

Scholars disagree over whether Islam hinders the development of liberal democracy in Muslim-majority countries. We contribute to this debate by assessing the influence of Islam at the individual and national levels on ethnic, racial, and religious tolerance in 23 countries. Our analyses are based on a set of multilevel models fitted to World Values Survey data and national-level contextual information from various sources. Our findings suggest that people living in Muslim-majority countries tend to be less tolerant than are those living in Western countries. Although a significant part of this difference is attributable to variation in level of economic development and income inequality, Muslim countries remain less tolerant even after controlling for these factors. On the other hand, controlling for other individual-level factors, nonpracticing Muslims in Western countries are more tolerant than are all others in both Muslim-majority and Western countries. This finding challenges common claims about the effects of Islam as a religion on tolerance, suggesting that it is Islamic political regimes--not Islam itself--that pose problems for social tolerance.

Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

PubMed

Trott, C M; Ouyang, J; El Fakhri, G

2010-11-21

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW

PubMed Central

Moreira-Marconi, Eloá; Sá-Caputo, Danubia C; Dionello, Carla F; Guedes-Aguiar, Eliane O; Sousa-Gonçalves, Cintia R; Morel, Danielle S; Paineiras-Domingos, Laisa L; Souza, Patricia L; Kütter, Cristiane R; Costa-Cavalcanti, Rebeca G; Costa, Glenda; Paiva, Patricia C; Figueiredo, Claudia; Brandão-Sobrinho-Neto, Samuel; Stark, Christina; Unger, Marianne; Bernardo-Filho, Mario

2017-01-01

Background: Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients. Materials and Methods: Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm. Results: A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation: Conclusion: It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients. PMID:28740938

Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.

PubMed

Timón-Gómez, Alba; Proft, Markus; Pascual-Ahuir, Amparo

2013-01-01

Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

Ketamine for chronic pain: risks and benefits

PubMed Central

Niesters, Marieke; Martini, Christian; Dahan, Albert

2014-01-01

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

Investigations of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates using CRT colors.

PubMed

Wang, Zhehong; Xu, Haisong

2008-12-01

In order to investigate the performance of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates, a psychophysical experiment was carried out by the method of constant stimuli using CRT colors. Five hue circles at three lightness (L*=30, 50, and 70) and chroma (C*ab=10, 20, and 30) levels were selected to ensure that the color-difference tolerances did not exceed the color gamut of the CRT display. Twelve color centers distributed evenly every 30 degrees along each hue circle were assessed by a panel of eight observers, and the corresponding color-difference tolerances were obtained. The hue circle with L*=50 and C*ab=20 was assessed with three different visual scales (DeltaV=3.06, 5.92, and 8.87 CIELAB units), which ranged from small to large visual scales, while the remaining hue circles were observed only with the small visual scale. The lightness tolerances had no significant correlation with the hue angles, while chroma and hue tolerances showed considerable hue angle dependences. The color-difference tolerances were linearly proportional to the visual scales but with different slopes. The lightness tolerances with different lightness levels but the same chroma showed the crispening effect to some extent, while the chroma and hue tolerances decreased with the increment of the lightness. For the color-difference tolerances with different chroma levels but the same lightness, there was no correlation between the lightness tolerances and the chroma levels, while the chroma and hue tolerances were nearly linearly proportional to the chroma levels.

Using field data to assess the tolerance of freshwater fish to elevated ionic concentrations

EPA Science Inventory

We used field data of fish occurrences and specific conductivity to assess the tolerance of freshwater fish to elevated ions. The concentration at which a species was expected to no longer be observed [the extirpation concentration (XC95)] was identified from the 95th percentile ...

Critical temperature: A quantitative method of assessing cold tolerance

Treesearch

D.H. DeHayes; M.W., Jr. Williams

1989-01-01

Critical temperature (Tc), defined as the highest temperature at which freezing injury to plant tissues can be detected, provides a biologically meaningful and statistically defined assessment of the relative cold tolerance of plant tissues. A method is described for calculating critical temperatures in laboratory freezing studies that use...

Tolerability of a Skin Care Regimen Formulated for Acne-Prone Skin in Children.

PubMed

Hensley, David; Meckfessel, Matthew H

2015-01-01

The epidemiology and demographic profile of acne vulgaris has evolved over the past several decades, with a noted earlier onset occurring in patients as young as 7 years of age. The combination of a foaming facial wash and a facial moisturizer with a sun protection factor (SPF) of 30 is an over-the-counter cleansing and moisturizing regimen for acne-prone skin that has been shown to be safe and tolerable in subjects 12 years of age and older. To assess the tolerability of this skin care regimen in children ages 7 to 11 years with acne-prone skin. This was an open-label, single-center study that investigated the safety and tolerability of these products in subjects 7 to 11 years of age (ClinicalTrials.gov, NCT01909713). Subjects used the foaming wash twice daily and the SPF 30 moisturizer once daily. Subjects were assessed for cutaneous tolerability, and satisfaction at baseline and weeks 1 and 3. Thirty-five subjects enrolled and completed the study. The cutaneous tolerability score of most subjects was none when assessed by the investigator and subject or legally authorized representative at weeks 1 and 3. The products were well tolerated and a positive impression for cosmetic acceptability was reported for both products by the study population on the questionnaire. This study supports the use of a skin care regimen comprising a wash and a moisturizer in acne-prone patients as young as 7 years old since these products were safe, well tolerated, and liked by subjects. © 2015 Wiley Periodicals, Inc.

Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

PubMed Central

Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

2014-01-01

Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor substrate-1, and AS160 phosphorylation and impaired glucose transporter type 4 translocation. PMID:24797633

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

PubMed

Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin

2017-12-01

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Energy and redox metabolism of glucose-6-phosphate-dehydrogenase-deficient erythrocytes.

PubMed

Schuster, R; Jacobasch, G; Holzhütter, H G

1989-07-01

The effects of various forms of glucose-6-phosphate dehydrogenase deficiency on erythrocyte metabolism have been studied on the basis of a complex mathematical model which comprises the main pathways of this cell: glycolysis, pentose pathway, reactions of the glutathione and adenine nucleotide metabolism. The calculated flux rates through the oxidative pentose pathway with and without methylene blue are in good accord with experimental results. The degree of deficiency as predicted by the model on the basis of calculated upper oxidative load boundaries, as well as of maximal methylene blue stimulation, correlates with the individual clinical manifestation of the metabolic disease. Therefore, the model allows one to judge the degree of metabolic disorder in the presence of glucose-6-phosphate dehydrogenase enzymopathies if the kinetic properties of the defect enzyme are known. Experimentally accessible parameters for an assessment of the oxidative load capacity of cells in vivo are proposed. It is pointed out that the threshold of tolerance as to energetic load is drastically reduced in the case of severe glucose-6-phosphate dehydrogenase deficiency.

Abdominal {gamma}-Radiation Induces an Accumulation of Function-Impaired Regulatory T Cells in the Small Intestine

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

Billiard, Fabienne; Buard, Valerie; Benderitter, Marc

Purpose: To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4{sup +}FoxP3{sup +} regulatory T cells (Tregs) in a mouse model of abdominal irradiation. Methods and Materials: Mice were exposed to a single abdominal dose of {gamma}-radiation (10 Gy). We evaluated small intestine Treg infiltration by Foxp3 immunostaining and the functional suppressive activity of Tregs isolated from mesenteric lymph nodes. Results: Foxp3 immunostaining showed that radiation induced a long-term infiltration of the intestine by Tregs (levels 5.5 times greater than in controls). Co-culture of Tregs from mesenteric lymph nodes with CD4{sup +} effectormore » cells showed that the Tregs had lost their suppressive function. This loss was associated with a significant decrease in the levels of Foxp3, TGF-{beta}, and CTLA-4 mRNA, all required for optimal Treg function. At Day 90 after irradiation, Tregs regained their suppressive activity as forkhead box P3 (Foxp3), transforming growth factor beta (TGF-{beta}), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression returned to normal. Analysis of the secretory function of mesenteric lymph node Tregs, activated in vitro with anti-CD3/anti-CD28 Abs, showed that this dysfunction was independent of a defect in interleukin-10 secretion. Conclusion: Radiation caused a long-term accumulation of function-impaired Foxp3{sup +}CD4{sup +} Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.« less

Toward understanding dynamic annealing processes in irradiated ceramics

NASA Astrophysics Data System (ADS)

Myers, Michael Thomas

High energy particle irradiation inevitably generates defects in solids in the form of collision cascades. The ballistic formation and thermalization of cascades occur rapidly and are believed to be reasonably well understood. However, knowledge of the evolution of defects after damage cascade thermalization, referred to as dynamic annealing, is quite limited. Unraveling the mechanisms associated with dynamic an- nealing is crucial since such processes play an important role in the formation of stable post-irradiation disorder in ion-beam-processed semiconductors and determines the "radiation tolerance" of many nuclear materials. The purpose of this dissertation is to further our understanding of the processes involved in dynamic annealing. In order to achieve this, two main tasks are undertaken. First, the effects of dynamic annealing are investigated in ZnO, a technologically relevant material that exhibits very high dynamic defect annealing at room temper- ature. Such high dynamic annealing leads to unusual defect accumulation in heavy ion bombarded ZnO. Through this work, the puzzling features that were observed more than a decade ago in ion-channeling spectra have finally been explained. We show that the presence of a polar surface substantially alters damage accumulation. Non-polar surface terminations of ZnO are shown to exhibit enhanced dynamic an- nealing compared to polar surface terminated ZnO. Additionally, we demonstrate one method to reduce radiation damage in polar surface terminated ZnO by means of a surface modification. These results advance our efforts in the long-sought-after goal of understanding complex radiation damage processes in ceramics. Second, a pulsed-ion-beam method is developed and demonstrated in the case of Si as a prototypical non-metallic target. Such a method is shown to be a novel experimental technique for direct extraction of dynamic annealing parameters. The relaxation times and effective diffusion lengths of mobile defects during the dynamic annealing process play a vital role in damage accumulation. We demonstrate that these parameters dominate the formation of stable post-irradiation disorder. In Si, a defect lifetime of ˜ 6 ms and a characteristic defect diffusion length of ˜ 30 nm are measured. These results should nucleate future pulsed-beam studies of dynamic defect interaction processes in technologically relevant materials. In particular, un- derstanding length- and time-scales of defect interactions are essential for extending laboratory findings to nuclear material lifetimes and to the time-scales of geological storage of nuclear waste.

What we don't know can hurt us: Nonresponse bias assessment in birth defects research.

PubMed

Strassle, Paula D; Cassell, Cynthia H; Shapira, Stuart K; Tinker, Sarah C; Meyer, Robert E; Grosse, Scott D

2015-07-01

Nonresponse bias assessment is an important and underutilized tool in survey research to assess potential bias due to incomplete participation. This study illustrates a nonresponse bias sensitivity assessment using a survey on perceived barriers to care for children with orofacial clefts in North Carolina. Children born in North Carolina between 2001 and 2004 with an orofacial cleft were eligible for inclusion. Vital statistics data, including maternal and child characteristics, were available on all eligible subjects. Missing 'responses' from nonparticipants were imputed using assumptions based on the distribution of responses, survey method (mail or phone), and participant maternal demographics. Overall, 245 of 475 subjects (51.6%) responded to either a mail or phone survey. Cost as a barrier to care was reported by 25.0% of participants. When stratified by survey type, 28.3% of mail respondents and 17.2% of phone respondents reported cost as a barrier. Under various assumptions, the bias-adjusted estimated prevalence of cost as barrier to care ranged from 16.1% to 30.0%. Maternal age, education, race, and marital status at time of birth were not associated with subjects reporting cost as a barrier. As survey response rates continue to decline, the importance of assessing the potential impact of nonresponse bias has become more critical. Birth defects research is particularly conducive to nonresponse bias analysis, especially when birth defect registries and birth certificate records are used. Future birth defect studies which use population-based surveillance data and have incomplete participation could benefit from this type of nonresponse bias assessment. Birth Defects Research (Part A) 103:603-609, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, Indonesia

PubMed Central

Duboscq, Julie; Micheletta, Jérôme; Agil, Muhammad; Hodges, Keith; Thierry, Bernard; Engelhardt, Antje

2013-01-01

In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared-teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared-teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the relevance of the social style concept in the assessment of the degree of tolerance/despotism in social systems. Am. J. Primatol. 75:361-375, 2013. © 2013 Wiley Periodicals, Inc. PMID:23307343

A constructive nonlinear array (CNA) method for barely visible impact detection in composite materials

NASA Astrophysics Data System (ADS)

Malfense Fierro, Gian Piero; Meo, Michele

2017-04-01

Currently there are numerous phased array techniques such as Full Matrix Capture (FMC) and Total Focusing Method (TFM) that provide good damage assessment for composite materials. Although, linear methods struggle to evaluate and assess low levels of damage, while nonlinear methods have shown great promise in early damage detection. A sweep and subtraction evaluation method coupled with a constructive nonlinear array method (CNA) is proposed in order to assess damage specific nonlinearities, address issues with frequency selection when using nonlinear ultrasound imaging techniques and reduce equipment generated nonlinearities. These methods were evaluated using multiple excitation locations on an impacted composite panel with a complex damage (barely visible impact damage). According to various recent works, damage excitation can be accentuated by exciting at local defect resonance (LDR) frequencies; although these frequencies are not always easily determinable. The sweep methodology uses broadband excitation to determine both local defect and material resonances, by assessing local defect generated nonlinearities using a laser vibrometer it is possible to assess which frequencies excite the complex geometry of the crack. The dual effect of accurately determining local defect resonances, the use of an image subtraction method and the reduction of equipment based nonlinearities using CNA result in greater repeatability and clearer nonlinear imaging (NIM).

Diagnostic Accuracy and Clinical Implications of Translabial Ultrasound for the Assessment of Levator Ani Defects and Levator Ani Biometry in Women With Pelvic Organ Prolapse: A Systematic Review.

PubMed

Notten, Kim J B; Vergeldt, Tineke F M; van Kuijk, Sander M J; Weemhoff, Mirjam; Roovers, Jan-Paul W R

The aim of this study was to assess the diagnostic accuracy and clinical implications of translabial 3-dimensional (3D) ultrasound for the assessment of levator ani defects and biometry in women with pelvic organ prolapse (POP). We performed a systematic literature search through computerized databases including MEDLINE (via PubMed), EMBASE (via OvidSP), and the Cochrane Library using both medical subject headings and text terms from January 1, 2003, to December 25, 2015.We included articles that reported on POP status and diagnostic accuracy measurements with translabial 3D ultrasound or transperineal ultrasound for the detection of levator ani defects or for measuring pelvic floor biometry, that is, levator ani hiatus, or reported on the clinical relevance of using translabial 3D ultrasound for levator ani defects or measuring pelvic floor biometry in women with POP. Thirty-one articles were selected in accordance with parts of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that can be applied to studies of diagnostic accuracy. Twenty-two articles (71%) are coauthored by 1 expert in this field. Detecting levator ani defects with translabial 3D ultrasound compared with magnetic resonance imaging showed a moderate to good agreement, whereas measuring hiatal biometry on translabial 3D ultrasound compared with magnetic resonance imaging showed a moderate to very good agreement.The interobserver agreement for diagnosing levator ani defects and measuring the levator hiatal area showed a moderate to very good agreement. Furthermore, levator ani defects increase the risk of cystocele and uterine prolapse, and levator ani defects are associated with recurrent POP.Finally, a larger hiatus was associated with POP and recurrent POP. Translabial 3D ultrasound is reproducible for diagnosing levator ani defects and ballooning hiatus. Both levator ani defects and a larger hiatal area are, in a selected population of patients with pelvic floor dysfunction, associated with POP and recurrent POP. More research is needed concerning external validation because most data in this article are coauthored by 1 expert in this field.

Comparison of Multidetector Computed Tomography and Flat-Panel Computed Tomography Regarding Visualization of Cortical Fractures, Cortical Defects, and Orthopedic Screws: A Phantom Study.

PubMed

Neubauer, Jakob; Benndorf, Matthias; Lang, Hannah; Lampert, Florian; Kemna, Lars; Konstantinidis, Lukas; Neubauer, Claudia; Reising, Kilian; Zajonc, Horst; Kotter, Elmar; Langer, Mathias; Goerke, Sebastian M

2015-08-01

To compare the visualization of cortical fractures, cortical defects, and orthopedic screws in a dedicated extremity flat-panel computed tomography (FPCT) scanner and a multidetector computed tomography (MDCT) scanner.We used feet of European roe deer as phantoms for cortical fractures, cortical defects, and implanted orthopedic screws. FPCT and MDCT scans were performed with equivalent dose settings. Six observers rated the scans according to number of fragments, size of defects, size of defects opposite orthopedic screws, and the length of different screws. The image quality regarding depiction of the cortical bone was assessed. The gold standard (real number of fragments) was evaluated by autopsy.The correlation of reader assessment of fragments, cortical defects, and screws with the gold standard was similar for FPCT and MDCT. Three readers rated the subjective image quality of the MDCT to be higher, whereas the others showed no preferences.Although the image quality was rated higher in the MDCT than in the FPCT by 3 out of 6 observers, both modalities proved to be comparable regarding the visualization of cortical fractures, cortical defects, and orthopedic screws and of use to musculoskeletal radiology regarding fracture detection and postsurgical evaluation in our experimental setting.

8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae.

PubMed

Hernández, Agustín; Serrano-Bueno, Gloria; Perez-Castiñeira, José Román; Serrano, Aurelio

2015-11-01

8-Dehydrosterols are present in a wide range of biologically relevant situations, from human rare diseases to amine fungicide-treated fungi and crops. However, the molecular bases of their toxicity are still obscure. We show here that 8-dehydrosterols, but not other sterols, affect yeast vacuole acidification through V-ATPases. Moreover, erg2Δ cells display reductions in proton pumping rates consistent with ion-transport uncoupling in vitro. Concomitantly, subunit Vph1p shows conformational changes in the presence of 8-dehydrosterols. Expression of a plant vacuolar H(+)-pumping pyrophosphatase as an alternative H(+)-pump relieves Vma(-)-like phenotypes in erg2Δ-derived mutant cells. As a consequence of these acidification defects, endo- and exo-cytic traffic deficiencies that can be alleviated with a H(+)-pumping pyrophosphatase are also observed. Despite their effect on membrane traffic, 8-dehydrosterols do not induce endoplasmic reticulum stress or assembly defects on the V-ATPase. Autophagy is a V-ATPase dependent process and erg2Δ mutants accumulate autophagic bodies under nitrogen starvation similar to Vma(-) mutants. In contrast to classical Atg(-) mutants, this defect is not accompanied by impairment of traffic through the CVT pathway, processing of Pho8Δ60p, GFP-Atg8p localisation or difficulties to survive under nitrogen starvation conditions, but it is concomitant to reduced vacuolar protease activity. All in all, erg2Δ cells are autophagy mutants albeit some of their phenotypic features differ from classical Atg(-) defective cells. These results may pave the way to understand the aetiology of sterol-related diseases, the cytotoxic effect of amine fungicides, and may explain the tolerance to these compounds observed in plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Defect-rich Ni-Ti layered double hydroxide as a highly efficient support for Au nanoparticles in base-free and solvent-free selective oxidation of benzyl alcohol.

PubMed

Liu, Mengran; Fan, Guoli; Yu, Jiaying; Yang, Lan; Li, Feng

2018-04-17

Tuning the surface properties of supported metal catalysts is of vital importance for governing their catalytic performances in nanocatalysis. Here, we report highly dispersed nanometric gold nanoparticles (NPs) supported on Ni-Ti layered double hydroxides (NiTi-LDHs), which were employed in solvent-free and base-free selective oxidation of benzyl alcohol. A series of characterization techniques demonstrated that defect-rich NiTi-LDHs could efficiently stabilize Au NPs and decrease surface electron density of Au NPs. The as-formed Au/NiTi-LDH catalyst with a Ni/Ti molar ratio of 3 : 1 and an Au loading of 0.71 wt% yielded the highest turnover frequency value of ∼4981 h-1 at 120 °C among tested Au/NiTi-LDH catalysts with different Ni/Ti molar ratios, along with a high benzaldehyde selectivity of 98%. High catalytic efficiency of the catalyst was mainly correlated with surface cooperation between unique defects (i.e. defective Ti3+ species and oxygen vacancies) and abundant hydroxyl groups on the brucite-like layers of the NiTi-LDH support, which could lead to the preferential adsorption and activation of an alcohol hydroxyl moiety in benzyl alcohol and oxygen molecule, as well as the formation of more electron-deficient Ni3+ and Au0 species on the catalyst surface. Furthermore, the present Au/NiTi-LDH catalyst tolerated the oxidation of a wide variety of substrate structures into the corresponding aldehydes, acids or ketones. Our primary results illustrate that defect-rich NiTi-LDHs are promising supports which can efficiently modify surface structure and electronic properties of supported metal catalysts and consequently improve their catalytic performances.

Precision cast vs. wrought superalloys

NASA Technical Reports Server (NTRS)

Tien, J. K.; Borofka, J. C.; Casey, M. E.

1986-01-01

While cast polycrystalline superalloys recommend themselves in virtue of better 'buy-to-fly' ratios and higher strengthening gamma-prime volume fractions than those of wrought superalloys, the expansion of their use into such critical superalloy applications as gas turbine hot section components has been slowed by insufficient casting process opportunities for microstructural control. Attention is presently drawn, however, to casting process developments facilitating the production of defect-tolerant superalloy castings having improved fracture reliability. Integrally bladed turbine wheel and thin-walled turbine exhaust case near-net-shape castings have been produced by these means.

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

El-Atwani, Osman; Nathaniel II, James E.; Leff, Asher C.

Nanocrystalline materials are radiation-tolerant materials’ candidates due to their high defect sink density. Here, nanocrystalline iron films were irradiated with 10 keV helium ions in situ in a transmission electron microscope at elevated temperatures. Grain-size-dependent bubble density changes and denuded zone occurrence were observed at 700 K, but not at 573 K. This transition, attributed to increased helium–vacancy migration at elevated temperatures, suggests that nanocrystalline microstructures are more resistant to swelling at 700 K due to decreased bubble density. Finally, denuded zone formation had no correlation with grain size and misorientation angle under the conditions studied.

Progressive Damage and Fracture of Unstiffened and Stiffened Composite Pressure Vessels

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Gotsis, Pascal K.; Chamis, Christos C.

1997-01-01

Structural durability and damage tolerance characteristics of pressurized graphite/epoxy laminated thin composite cylinders are investigated via computational simulation. Both unstiffened and integral hoop stiffened cylinders are considered. A computer code is utilized for the simulation of composite structural degradation under loading. Damage initiation, growth, accumulation, and propagation to structural fracture are included in the simulation. The increase of burst pressure due to hoop stiffening is quantified. Results demonstrate the significance of the type and size of local defects on the structural durability of pressurized composite cylindrical shells.

Development of a fish assemblage tolerance index for the National Rivers and Streams Assessment

EPA Science Inventory

Whittier et al (Trans. Amer. Fish. Soc. 136:254-271) developed an assemblage tolerance index (ATI) for stream fishes in the western US based on quantitative tolerance values developed for individual fish and amphibian species. The ATI is conceptually similar to the Hilsenhoff Bi...

Tolerance to exercise intensity modulates pleasure when exercising in music: The upsides of acoustic energy for High Tolerant individuals.

PubMed

Carlier, Mauraine; Delevoye-Turrell, Yvonne

2017-01-01

Moderate physical activity can be experienced by some as pleasurable and by others as discouraging. This may be why many people lack sufficient motivation to participate in the recommended 150 minutes of moderately intense exercise per week. In the present study, we assessed how pleasure and enjoyment were modulated differently by one's tolerance to self-paced physical activity. Sixty-three healthy individuals were allocated to three independent experimental conditions: a resting condition (watching TV), a cycling in silence condition, and a cycling in music condition. The tolerance threshold was assessed using the PRETIE-Questionnaire. Physical activity consisted in cycling during 30 minutes, at an intensity perceived as "somewhat difficult" on the Ratings of Perceived Exertion Scale. While controlling for self-reported physical activity level, results revealed that for the same perception of exertion and a similar level of enjoyment, the High Tolerance group produced more power output than the Low Tolerance group. There was a positive effect of music for High Tolerant individuals only, with music inducing greater power output and more pleasure. There was an effect of music on heart rate frequency in the Low Tolerant individuals without benefits in power output or pleasure. Our results suggest that for Low Tolerant individuals, energizing environments can interfere with the promised (positive) distracting effects of music. Hence, tolerance to physical effort must be taken into account to conceive training sessions that seek to use distracting methods as means to sustain pleasurable exercising over time.

Graded Aerobic Treadmill Testing in Adolescent Traumatic Brain Injury Patients.

PubMed

Cordingley, Dean M; Girardin, Richard; Morissette, Marc P; Reimer, Karen; Leiter, Jeff; Russell, Kelly; Ellis, Michael J

2017-11-01

To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.

Risk reduction using DDP (Defect Detection and Prevention): Software support and software applications

NASA Technical Reports Server (NTRS)

Feather, M. S.

2001-01-01

Risk assessment and mitigation is the focus of the Defect Detection and Prevention (DDP) process, which has been applied to spacecraft technology assessments and planning, both hardware and software. DDP's major elements and their relevance to core requirement engineering concerns are summarized. The accompanying research demonstration illustrates DDP's tool support, and further customizations for application to software.

Healing assessment of tile sets for error tolerance in DNA self-assembly.

PubMed

Hashempour, M; Mashreghian Arani, Z; Lombardi, F

2008-12-01

An assessment of the effectiveness of healing for error tolerance in DNA self-assembly tile sets for algorithmic/nano-manufacturing applications is presented. Initially, the conditions for correct binding of a tile to an existing aggregate are analysed using a Markovian approach; based on this analysis, it is proved that correct aggregation (as identified with a so-called ideal tile set) is not always met for the existing tile sets for nano-manufacturing. A metric for assessing tile sets for healing by utilising punctures is proposed. Tile sets are investigated and assessed with respect to features such as error (mismatched tile) movement, punctured area and bond types. Subsequently, it is shown that the proposed metric can comprehensively assess the healing effectiveness of a puncture type for a tile set and its capability to attain error tolerance for the desired pattern. Extensive simulation results are provided.

Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs.

PubMed

Löscher, Wolfgang; Schmidt, Dieter

2006-08-01

Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists.

77 FR 41367 - Dow AgroSciences LLC; Availability of Petition, Plant Pest Risk Assessment, and Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... Assessment for Determination of Nonregulated Status of Soybean Genetically Engineered for Herbicide Tolerance... been genetically engineered for tolerance to broadleaf herbicides in the phenoxy auxin group (such as the herbicide 2,4-D) and the herbicide glufosinate. The petition has been submitted in accordance with...

Assessing Your Board's Risk Tolerance

ERIC Educational Resources Information Center

Griswold, John S.; Jarvis, William F.

2014-01-01

In the wake of the financial crisis, trustees of many endowed nonprofit institutions realized that their portfolio was riskier than they thought and their own ability to tolerate loss wasn't as strong as they imagined. What can board and investment committee members do to improve their ability to assess their--and their institution's--capacity for…

77 FR 53144 - Nitric Acid; Exemption From the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

... Cosmetic Act (FFDCA), requesting establishment of an exemption from the requirement of a tolerance. This... ingredients. IV. Aggregate Risk Assessment and Determination of Safety Section 408(c)(2)(A)(i) of FFDCA allows... to assess the hazards of and to make a determination on aggregate exposure for nitric acid including...

Effect of manipulated state aggression on pain tolerance.

PubMed

Stephens, Richard; Allsop, Claire

2012-08-01

Swearing produces a pain lessening (hypoalgesic) effect for many people; an emotional response may be the underlying mechanism. In this paper, the role of manipulated state aggression on pain tolerance and pain perception is assessed. In a repeated-measures design, pain outcomes were assessed in participants asked to play for 10 minutes a first-person shooter video game vs a golf video game. Sex differences were explored. After playing the first-person shooter video game, aggressive cognitions, aggressive affect, heart rate, and cold pressor latency were increased, and pain perception was decreased. These data indicate that people become more pain tolerant with raised state aggression and support our theory that raised pain tolerance from swearing occurs via an emotional response.

Assessment of water pipes durability under pressure surge

NASA Astrophysics Data System (ADS)

Pham Ha, Hai; Minh, Lanh Pham Thi; Tang Van, Lam; Bulgakov, Boris; Bazhenova, Soafia

2017-10-01

Surge phenomenon occurs on the pipeline by the closing valve or pump suddenly lost power. Due to the complexity of the water hammer simulation, previous researches have only considered water hammer on the single pipe or calculation of some positions on water pipe network, it have not been analysis for all of pipe on the water distribution systems. Simulation of water hammer due to closing valve on water distribution system and the influence level of pressure surge is evaluated at the defects on pipe. Water hammer on water supply pipe network are simulated by Water HAMMER software academic version and the capacity of defects are calculated by SINTAP. SINTAP developed from Brite-Euram projects in Brussels-Belgium with the aim to develop a process for assessing the integrity of the structure for the European industry. Based on the principle of mechanical fault, indicating the size of defects in materials affect the load capacity of the product in the course of work, the process has proposed setting up the diagram to fatigue assessment defect (FAD). The methods are applied for water pipe networks of Lien Chieu district, Da Nang city, Viet Nam, the results show the affected area of wave pressure by closing the valve and thereby assess the greatest pressure surge effect to corroded pipe. The SINTAP standard and finite element mesh analysis at the defect during the occurrence of pressure surge which will accurately assess the bearing capacity of the old pipes. This is one of the bases to predict the leakage locations on the water distribution systems. Amount of water hammer when identified on the water supply networks are decreasing due to local losses at the nodes as well as the friction with pipe wall, so this paper adequately simulate water hammer phenomena applying for actual water distribution systems. The research verified that pipe wall with defect is damaged under the pressure surge value.

Scene and human face recognition in the central vision of patients with glaucoma

PubMed Central

Aptel, Florent; Attye, Arnaud; Guyader, Nathalie; Boucart, Muriel; Chiquet, Christophe; Peyrin, Carole

2018-01-01

Primary open-angle glaucoma (POAG) firstly mainly affects peripheral vision. Current behavioral studies support the idea that visual defects of patients with POAG extend into parts of the central visual field classified as normal by static automated perimetry analysis. This is particularly true for visual tasks involving processes of a higher level than mere detection. The purpose of this study was to assess visual abilities of POAG patients in central vision. Patients were assigned to two groups following a visual field examination (Humphrey 24–2 SITA-Standard test). Patients with both peripheral and central defects and patients with peripheral but no central defect, as well as age-matched controls, participated in the experiment. All participants had to perform two visual tasks where low-contrast stimuli were presented in the central 6° of the visual field. A categorization task of scene images and human face images assessed high-level visual recognition abilities. In contrast, a detection task using the same stimuli assessed low-level visual function. The difference in performance between detection and categorization revealed the cost of high-level visual processing. Compared to controls, patients with a central visual defect showed a deficit in both detection and categorization of all low-contrast images. This is consistent with the abnormal retinal sensitivity as assessed by perimetry. However, the deficit was greater for categorization than detection. Patients without a central defect showed similar performances to the controls concerning the detection and categorization of faces. However, while the detection of scene images was well-maintained, these patients showed a deficit in their categorization. This suggests that the simple loss of peripheral vision could be detrimental to scene recognition, even when the information is displayed in central vision. This study revealed subtle defects in the central visual field of POAG patients that cannot be predicted by static automated perimetry assessment using Humphrey 24–2 SITA-Standard test. PMID:29481572

Comparison of genome-wide selection strategies to identify furfural tolerance genes in Escherichia coli.

PubMed

Glebes, Tirzah Y; Sandoval, Nicholas R; Gillis, Jacob H; Gill, Ryan T

2015-01-01

Engineering both feedstock and product tolerance is important for transitioning towards next-generation biofuels derived from renewable sources. Tolerance to chemical inhibitors typically results in complex phenotypes, for which multiple genetic changes must often be made to confer tolerance. Here, we performed a genome-wide search for furfural-tolerant alleles using the TRackable Multiplex Recombineering (TRMR) method (Warner et al. (2010), Nature Biotechnology), which uses chromosomally integrated mutations directed towards increased or decreased expression of virtually every gene in Escherichia coli. We employed various growth selection strategies to assess the role of selection design towards growth enrichments. We also compared genes with increased fitness from our TRMR selection to those from a previously reported genome-wide identification study of furfural tolerance genes using a plasmid-based genomic library approach (Glebes et al. (2014) PLOS ONE). In several cases, growth improvements were observed for the chromosomally integrated promoter/RBS mutations but not for the plasmid-based overexpression constructs. Through this assessment, four novel tolerance genes, ahpC, yhjH, rna, and dicA, were identified and confirmed for their effect on improving growth in the presence of furfural. © 2014 Wiley Periodicals, Inc.

Pattern of congenital heart diseases in Rwandan children with genetic defects

PubMed Central

Teteli, Raissa; Uwineza, Annette; Butera, Yvan; Hitayezu, Janvier; Murorunkwere, Seraphine; Umurerwa, Lamberte; Ndinkabandi, Janvier; Hellin, Anne-Cécile; Jamar, Mauricette; Caberg, Jean-Hubert; Muganga, Narcisse; Mucumbitsi, Joseph; Rusingiza, Emmanuel Kamanzi; Mutesa, Leon

2014-01-01

Introduction Congenital heart diseases (CHD) are commonly associated with genetic defects. Our study aimed at determining the occurrence and pattern of CHD association with genetic defects among pediatric patients in Rwanda. Methods A total of 125 patients with clinical features suggestive of genetic defects were recruited. Echocardiography and standard karyotype studies were performed in all patients. Results CHDs were detected in the majority of patients with genetic defects. The commonest isolated CHD was ventricular septal defect found in many cases of Down syndrome. In total, chromosomal abnormalities represented the majority of cases in our cohort and were associated with various types of CHDs. Conclusion Our findings showed that CHDs are common in Rwandan pediatric patients with genetic defects. These results suggest that a routine echocardiography assessment combined with systematic genetic investigations including standard karyotype should be mandatory in patients presenting characteristic clinical features in whom CHD is suspected to be associated with genetic defect. PMID:25722758

Clinical and radiographical evaluation of a bioresorbable collagen membrane of fish origin in the treatment of periodontal intrabony defects: A preliminary study.

PubMed

Santosh Kumar, B B; Aruna, D R; Gowda, Vinayak S; Galagali, Sushama R; Prashanthy, R; Navaneetha, H

2013-09-01

Recently, there has been interest in non-mammalian collagen sources such as fish collagen in periodontal regeneration. In the present study, collagen barrier membrane of fish origin was assessed in the treatment of periodontal intrabony defects. Ten systemically healthy chronic periodontitis patients having a paired osseous defect in the mandibular posterior teeth were selected and randomly assigned to receive a collagen membrane (test) or open flap debridement (control) in a split mouth design. Clinical parameters such as Plaque index, Gingival bleeding index, Probing pocket depth, Relative attachment level, and Recession were recorded at baseline, 3, 6, and at 9 months, while radiographic evaluation was done to assess alveolar crestal bone level and percentage of defect fill at 6 and 9 months using autoCAD 2007 software. Student's t test (two-tailed, dependent) was used to find the significance of study parameters on continuous scale. Significance was set at 5% level of significance. Wilcoxon signed rank test was used to find the significance of percentage change of defect fill. The comparison between the two groups did not show any statistically significant differences in the parameters assessed (P > 0.05) but, within each group, clinical parameters showed statistically significant differences from baseline to 9 months (P < 0.05). Within the limits of the study, it can be inferred that no significant differences were found either by using collagen membrane of fish origin or open flap debridement in the treatment of periodontal intrabony defects.

Infrared machine vision system for the automatic detection of olive fruit quality.

PubMed

Guzmán, Elena; Baeten, Vincent; Pierna, Juan Antonio Fernández; García-Mesa, José A

2013-11-15

External quality is an important factor in the extraction of olive oil and the marketing of olive fruits. The appearance and presence of external damage are factors that influence the quality of the oil extracted and the perception of consumers, determining the level of acceptance prior to purchase in the case of table olives. The aim of this paper is to report on artificial vision techniques developed for the online estimation of olive quality and to assess the effectiveness of these techniques in evaluating quality based on detecting external defects. This method of classifying olives according to the presence of defects is based on an infrared (IR) vision system. Images of defects were acquired using a digital monochrome camera with band-pass filters on near-infrared (NIR). The original images were processed using segmentation algorithms, edge detection and pixel value intensity to classify the whole fruit. The detection of the defect involved a pixel classification procedure based on nonparametric models of the healthy and defective areas of olives. Classification tests were performed on olives to assess the effectiveness of the proposed method. This research showed that the IR vision system is a useful technology for the automatic assessment of olives that has the potential for use in offline inspection and for online sorting for defects and the presence of surface damage, easily distinguishing those that do not meet minimum quality requirements. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature.

PubMed

Morad, Golnaz; Kheiri, Lida; Khojasteh, Arash

2013-12-01

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration. An electronic search of English-language papers was conducted on PubMed database. Studies that assessed the use of DPSCs in bone regeneration in vivo were included and experiments evaluating regeneration of hard tissues other than bone were excluded. The retrieved articles were thoroughly reviewed according to the source of stem cell, cell carrier, the in vivo experimental model, defect type, method of evaluating bone regeneration, and the obtained results. Further assessment of the results was conducted by classifying the studies based on the defect type. Seventeen papers formed the basis of this systematic review. Sixteen out of 17 experiments were performed on animal models with mouse and rat being the most frequently used animal models. Seven out of 17 animal studies, contained subcutaneous pockets on back of the animal for stem cell implantation. In only one study hard tissue formation was not observed. Other types of defects used in the retrieved studies, included cranial defects and mandibular bone defects, in all of which bone formation was reported. When applied in actual bone defects, DPSCs were capable of regenerating bone. Nevertheless, a precise conclusion regarding the efficiency of DPSCs for bone regeneration is yet to be made, considering the limited number of the in vivo experiments and the heterogeneity within their methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

Importance of transcatheter closure test for giant ventricular septal defect associated with pulmonary hypertension: a case with successful surgical repair of the defect.

PubMed

Shang, Xiaoke; Lu, Rong; Dong, Nianguo

2018-06-20

This is the first attempt to use a temporary occluder to close a giant perimembranous ventricular septal defect (32 mm), which obtains clinical evidence of good haemodynamics in patients with severe pulmonary hypertension. This may provide an alternative assessment to guide cardiac surgeons in determining a definitive treatment.

Retrospective review of congenital heart disease in 976 dogs.

PubMed

Oliveira, P; Domenech, O; Silva, J; Vannini, S; Bussadori, R; Bussadori, C

2011-01-01

Knowledge of epidemiology is important for recognition of cardiovascular malformations. Review the incidence of congenital heart defects in dogs in Italy and assess breed and sex predispositions. Nine hundred and seventy-six dogs diagnosed with congenital heart disease (CHD) of 4,480 dogs presented to Clinica Veterinaria Gran Sasso for cardiovascular examination from 1997 to 2010. A retrospective analysis of medical records regarding signalment, history, clinical examination, radiography, electrocardiography, echocardiography, angiography, and postmortem examination was performed. Breed and sex predisposition were assessed with the odds ratio test. CHD was observed in 21.7% of cases. A total of 1,132 defects were observed with single defects in 832 cases (85%), 2 concurrent defects in 132 cases (14%), and 3 concurrent defects in 12 cases (1%). The most common defects were pulmonic stenosis (PS; 32.1%), subaortic stenosis (SAS; 21.3%), and patent ductus arteriosus (20.9%), followed by ventricular septal defect (VSD; 7.5%), valvular aortic stenosis (AS; 5.7%), and tricuspid dysplasia (3.1%). SAS, PS, and VSD frequently were associated with other defects. Several breed and sex predispositions were identified. The results of this study are in accordance with previous studies, with slight differences. The breed and sex predilections identified may be of value for the diagnosis and screening of CHD in dogs. Additionally, the relatively high percentage of concurrent heart defects emphasizes the importance of accurate and complete examinations for identification. Because these data are from a cardiology referral center, a bias may exist. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

PubMed

Kreuz, Peter Cornelius; Kalkreuth, Richard Horst; Niemeyer, Philipp; Uhl, Markus; Erggelet, Christoph

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Assessment of digital panoramic radiography's diagnostic value in angular bony lesions with 5 mm or deeper pocket depth in mandibular molars.

PubMed

Saberi, Bardia Vadiati; Nemati, Somayeh; Malekzadeh, Meisam; Javanmard, Afrooz

2017-01-01

Assessment of alveolar bone level in periodontitis is very important in determining prognosis and treatment plan. Panoramic radiography is a diagnostic tool used to screen patients. The aim of the present study was to assess the diagnostic value of digital panoramic radiography in angular bony defects with 5 mm or deeper pocket depth in mandibular molars. In this cross-sectional study, ninety angular bony defects in mandibular molars teeth with 5 mm or deeper pocket depth were selected in sixty patients with the diagnosis of chronic periodontitis. Before surgery, bone probing was performed. During the surgery, the vertical distance from cementoenamel junction to the most apical part of bony defect was measured using a Williams probe and this measurements were employed as gold standard. This distance was measured on the panoramic radiographs by a Digital Calliper and Digital Ruler. All data were compare dusing independent samples t -test and Pearson's correlation coefficient. No significant difference was found between the results of bone probing and intra-surgical measurements ( P = 0.377). The mean defect depth determined by Digital Caliper and Digital Ruler on panoramic radiographs was significantly less than surgical measurements ( P < 0.001). The correlation between bone probing and surgical measurements in determining the defect depth was strong ( r = 0.98, P < 0.001). Radiographic measurements made by Digital Ruler ( r = 0.86), comparing to Digital Caliper ( r = 0.79), showed a higher degree of correlation with surgical measurements. Based on this study, bone probing is a reliable method in vertical alveolar bone defect measurements. While the information obtained from digital panoramic radiographs should be used with caution and the ability of digital panoramic radiography in the determination of defect depth is limited.

Masticatory function and oral health-related quality of life in patients after partial maxillectomies with closed or open defects.

PubMed

Said, Mohamed M; Otomaru, Takafumi; Yeerken, Yesiboli; Taniguchi, Hisashi

2017-07-01

The healing pattern after surgical resection of tumors of the oral cavity involving the maxilla may vary from one patient to another. The result may be open communication between the oral and nasal cavities (open defect) or complete oronasal separation after healing of the defect area (closed defect). The purpose of this clinical study was to compare masticatory function and oral health-related quality of life (OHRQoL) between patients with closed and open defects who had undergone a partial maxillectomy and were wearing dentomaxillary prostheses. Thirty-eight participants who had undergone a partial maxillectomy and who were wearing dentomaxillary prostheses were enrolled between September 2014 and April 2016. Participants were assigned to 2 groups according to the type of defect after healing: 19 participants had a closed defect, and 19 participants had an open defect. Masticatory function was evaluated objectively and subjectively. The objective measurement was food-mixing ability, which was assessed using color-changeable chewing gum. The subjective measurement was perceived mastication ability, rated as a masticatory score based on the patient's responses to a 35-item food intake questionnaire. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). The GOHAI questionnaire consists of 12 items reflecting 3 hypothesized domains of the impact of oral disease: physical function, psychosocial function, and pain or discomfort. Differences in the scores obtained by the 3 measurements were compared between the 2 groups, using the Wilcoxon rank-sum test (α=.05). No significant differences were seen between the 2 groups in objective mixing ability, subjective masticatory score, or GOHAI (P>.05). Regarding the GOHAI physical function domain, only the swallowing item was significantly lower (P=.025) in participants with an open defect than in participants with a closed defect. Regarding the GOHAI psychological function domain, the item related to patients' psychological worries or concerns about their teeth, gingival tissue, or dentures was significantly lower (P=.045) in patients with an open defect than in those with a closed defect. Other items related to physical function, psychological function, and pain or discomfort were not significantly different (P>.05) between the 2 groups. The closed or open defect in patients who had undergone a partial maxillectomy may not influence patients' masticatory function and overall OHRQoL if they have adequate prosthetic rehabilitation. However, special consideration should be given to patients with an open defect with regard to swallowing function and psychological concerns in order to improve their OHRQoL. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

SOS2 Promotes Salt Tolerance in Part by Interacting with the Vacuolar H+-ATPase and Upregulating Its Transport Activity▿

PubMed Central

Batelli, Giorgia; Verslues, Paul E.; Agius, Fernanda; Qiu, Quansheng; Fujii, Hiroaki; Pan, Songqin; Schumaker, Karen S.; Grillo, Stefania; Zhu, Jian-Kang

2007-01-01

The salt overly sensitive (SOS) pathway is critical for plant salt stress tolerance and has a key role in regulating ion transport under salt stress. To further investigate salt tolerance factors regulated by the SOS pathway, we expressed an N-terminal fusion of the improved tandem affinity purification tag to SOS2 (NTAP-SOS2) in sos2-2 mutant plants. Expression of NTAP-SOS2 rescued the salt tolerance defect of sos2-2 plants, indicating that the fusion protein was functional in vivo. Tandem affinity purification of NTAP-SOS2-containing protein complexes and subsequent liquid chromatography-tandem mass spectrometry analysis indicated that subunits A, B, C, E, and G of the peripheral cytoplasmic domain of the vacuolar H+-ATPase (V-ATPase) were present in a SOS2-containing protein complex. Parallel purification of samples from control and salt-stressed NTAP-SOS2/sos2-2 plants demonstrated that each of these V-ATPase subunits was more abundant in NTAP-SOS2 complexes isolated from salt-stressed plants, suggesting that the interaction may be enhanced by salt stress. Yeast two-hybrid analysis showed that SOS2 interacted directly with V-ATPase regulatory subunits B1 and B2. The importance of the SOS2 interaction with the V-ATPase was shown at the cellular level by reduced H+ transport activity of tonoplast vesicles isolated from sos2-2 cells relative to vesicles from wild-type cells. In addition, seedlings of the det3 mutant, which has reduced V-ATPase activity, were found to be severely salt sensitive. Our results suggest that regulation of V-ATPase activity is an additional key function of SOS2 in coordinating changes in ion transport during salt stress and in promoting salt tolerance. PMID:17875927

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

PubMed

Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

2012-05-10

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

PubMed

Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K; Nyirjesy, Sarah C; Peleckis, Amy J; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C; Kelly, Andrea; Rickels, Michael R

2017-01-01

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. © 2017 by the American Diabetes Association.

Immunological Tolerance to Muscle Autoantigens Involves Peripheral Deletion of Autoreactive CD8+ T Cells

PubMed Central

Franck, Emilie; Bonneau, Carole; Jean, Laetitia; Henry, Jean-Paul; Lacoume, Yann; Salvetti, Anna; Boyer, Olivier; Adriouch, Sahil

2012-01-01

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4+ T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8+ T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8+ tolerance in SM-Ova mice. We show herein that Ova-specific CD8+ T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8+ T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells. PMID:22570714

Antigen-Specific Immune Modulation Targets mTORC1 Function To Drive Chemokine Receptor-Mediated T Cell Tolerance.

PubMed

Chen, Weirong; Wan, Xiaoxiao; Ukah, Tobechukwu K; Miller, Mindy M; Barik, Subhasis; Cattin-Roy, Alexis N; Zaghouani, Habib

2016-11-01

To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Indeed, Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell-dependent manner. In return, programmed death-ligand 1 interacts with the constitutively expressed programmed death-1 on the target T cells and stimulates docking of Src homology 2 domain-containing tyrosine phosphatase 2 phosphatase to the cytoplasmic tail of programmed death-1. Active Src homology 2 domain-containing tyrosine phosphatase 2 impairs the signaling function of the PI3K/protein kinase B (AKT) pathway, leading to functional defect of mTORC1, downregulation of CXCR3 expression, and suppression of T1D. Thus, mTORC1 component of the metabolic pathway serves as a target for chemokine receptor-mediated T cell tolerance and suppression of T1D. Copyright © 2016 by The American Association of Immunologists, Inc.

Calculation of weighted averages approach for the estimation of ping tolerance values

USGS Publications Warehouse

Silalom, S.; Carter, J.L.; Chantaramongkol, P.

2010-01-01

A biotic index was created and proposed as a tool to assess water quality in the Upper Mae Ping sub-watersheds. The Ping biotic index was calculated by utilizing Ping tolerance values. This paper presents the calculation of Ping tolerance values of the collected macroinvertebrates. Ping tolerance values were estimated by a weighted averages approach based on the abundance of macroinvertebrates and six chemical constituents that include conductivity, dissolved oxygen, biochemical oxygen demand, ammonia nitrogen, nitrate nitrogen and orthophosphate. Ping tolerance values range from 0 to 10. Macroinvertebrates assigned a 0 are very sensitive to organic pollution while macroinvertebrates assigned 10 are highly tolerant to pollution.

Assessment of five cold chilling tolerance traits and GWAS mapping in rice using the USDA mini-core collection

USDA-ARS?s Scientific Manuscript database

Rice (Oryza sativa L.) is often exposed to cool or cold temperatures during spring planting in a temperate climate. A better understanding of the genetic pathways regulating this chilling tolerance will enable breeders to develop varieties with improved tolerance during the germination and young see...

Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

PubMed

Goebel, Emily A; Stegmaier, Melissa; Gorassini, Donald R; Kubica, Matthew; Parfitt, Jeremy R; Driman, David K

2018-06-01

Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective. This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens. Raters included surgeons, pathologists, pathology residents, pathologists' assistants, and pathologists' assistant trainees. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters postfixation. Four parameters were evaluated: mesorectal bulk, surface regularity, defects, and coning. Interrater agreement was measured using ordinal α-values. The study was conducted at a single academic center. The primary outcome was agreement between individuals when grading total mesorectal excision specimens. A total of 37 total mesorectal excision specimens were assessed. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning, and overall grade were 0.85, 0.85, 0.92, 0.84, and 0.91. When compared with all raters, pathologists and residents had higher agreement and pathologists and surgeons had lower agreement. Ordinal α-values comparing pathologist and pathologist's assistant agreement for overall grade were similar pre- and postfixation (0.78 vs 0.80), but agreement for assessing defects decreased postfixation. Among pathologists' assistants, agreement was higher when grading specimens postfixation than when grading fresh specimens. Assessment bias may have occurred because of the greater number of pathologists' assistants participating than the number of residents and pathologists. The results indicate good interrater agreement for the assessment of overall grade, with defects showing the best interrater agreement in fresh specimens. Although total mesorectal excision specimens may be consistently graded postfixation, the assessment of defects postfixation may be less reliable. This study highlights the need for additional knowledge-transfer activities to ensure consistency and accurate grading of total mesorectal excision specimens. See Video Abstract at http://links.lww.com/DCR/A497.

Radiological Assessment of Bioengineered Bone in a Muscle Flap for the Reconstruction of Critical-Size Mandibular Defect

PubMed Central

Al-Fotawei, Randa; Ayoub, Ashraf F.; Heath, Neil; Naudi, Kurt B.; Tanner, K. Elizabeth; Dalby, Matthew J.; McMahon, Jeremy

2014-01-01

This study presents a comprehensive radiographic evaluation of bone regeneration within a pedicled muscle flap for the reconstruction of critical size mandibular defect. The surgical defect (20 mm×15 mm) was created in the mandible of ten experimental rabbits. The masseter muscle was adapted to fill the surgical defect, a combination of calcium sulphate/hydroxyapatite cement (CERAMENT™ |SPINE SUPPORT), BMP-7 and rabbit mesenchymal stromal cells (rMSCs) was injected inside the muscle tissue. Radiographic assessment was carried out on the day of surgery and at 4, 8, and 12 weeks postoperatively. At 12 weeks, the animals were sacrificed and cone beam computerized tomography (CBCT) scanning and micro-computed tomography (µ-CT) were carried out. Clinically, a clear layer of bone tissue was identified closely adherent to the border of the surgical defect. Sporadic radio-opaque areas within the surgical defect were detected radiographically. In comparison with the opposite non operated control side, the estimated quantitative scoring of the radio-opacity was 46.6% ±15, the mean volume of the radio-opaque areas was 63.4% ±20. Areas of a bone density higher than that of the mandibular bone (+35% ±25%) were detected at the borders of the surgical defect. The micro-CT analysis revealed thinner trabeculae of the regenerated bone with a more condensed trabecular pattern than the surrounding native bone. These findings suggest a rapid deposition rate of the mineralised tissue and an active remodelling process of the newly regenerated bone within the muscle flap. The novel surgical model of this study has potential clinical application; the assessment of bone regeneration using the presented radiolographic protocol is descriptive and comprehensive. The findings of this research confirm the remarkable potential of local muscle flaps as local bioreactors to induce bone formation for reconstruction of maxillofacial bony defects. PMID:25226170

Field test comparison of two dermal tolerance assessment methods of hand hygiene products.

PubMed

Girard, R; Carré, E; Pires-Cronenberger, S; Bertin-Mandy, M; Favier-Bulit, M C; Coyault, C; Coudrais, S; Billard, M; Regard, A; Kerhoas, A; Valdeyron, M L; Cracco, B; Misslin, P

2008-06-01

This study aimed to compare the sensitivity and workload requirement of two dermal tolerance assessment methods of hand hygiene products, in order to select a suitable pilot testing method for field tests. An observer-rating method and a self-assessment method were compared in 12 voluntary hospital departments (autumn/winter of 2005-2006). Three test-periods of three weeks were separated by two-week intervals during which the routine products were reintroduced. The observer rating method scored dryness and irritation on four-point scales. In the self-assessment method, the user rated appearance, intactness, moisture content, and sensation on a visual analogue scale which was converted into a 10-point numerical scale. Eleven products (soaps) were tested (223/250 complete reports for observer rating, 131/251 for self-assessment). Two products were significantly less well tolerated than the routine product according to the observers, four products according to the self-assessments. There was no significant difference between the two methods when products were classified according to tolerance (Fisher's test: P=0.491). For the symptom common to both assessment methods (dryness), there is a good correlation between the two methods (Spearman's Rho: P=0.032). The workload was higher for observer rating method (288 h of observer time plus 122 h of prevention team and pharmacist time compared with 15 h of prevention team and pharmacist time for self-assessment). In conclusion, the self-assessment method was considered more suitable for pilot testing, although further time should be allocated for educational measures as the return rate of complete self-assessment forms was poor.

In-situ TEM observation of the response of ultrafine- and nanocrystalline-grained tungsten to extreme irradiation environments

PubMed Central

El-Atwani, O.; Hinks, J. A.; Greaves, G.; Gonderman, S.; Qiu, T.; Efe, M.; Allain, J. P.

2014-01-01

The accumulation of defects, and in particular He bubbles, can have significant implications for the performance of materials exposed to the plasma in magnetic-confinement nuclear fusion reactors. Some of the most promising candidates for deployment into such environments are nanocrystalline materials as the engineering of grain boundary density offers the possibility of tailoring their radiation resistance properties. In order to investigate the microstructural evolution of ultrafine- and nanocrystalline-grained tungsten under conditions similar to those in a reactor, a transmission electron microscopy study with in situ 2 keV He+ ion irradiation at 950°C has been completed. A dynamic and complex evolution in the microstructure was observed including the formation of defect clusters, dislocations and bubbles. Nanocrystalline grains with dimensions less than around 60 nm demonstrated lower bubble density and greater bubble size than larger nanocrystalline (60–100 nm) and ultrafine (100–500 nm) grains. In grains over 100 nm, uniform distributions of bubbles and defects were formed. At higher fluences, large faceted bubbles were observed on the grain boundaries, especially on those of nanocrystalline grains, indicating the important role grain boundaries can play in trapping He and thus in giving rise to the enhanced radiation tolerance of nanocrystalline materials. PMID:24796578

A chemically induced new pea (Pisum sativum) mutant SGECdt with increased tolerance to, and accumulation of, cadmium.

PubMed

Tsyganov, Viktor E; Belimov, Andrei A; Borisov, Alexey Y; Safronova, Vera I; Georgi, Manfred; Dietz, Karl-Josef; Tikhonovich, Igor A

2007-02-01

To date, there are no crop mutants described in the literature that display both Cd accumulation and tolerance. In the present study a unique pea (Pisum sativum) mutant SGECd(t) with increased Cd tolerance and accumulation was isolated and characterized. Ethylmethane sulfonate mutagenesis of the pea line SGE was used to obtain the mutant. Screening for Cd-tolerant seedlings in the M2 generation was performed using hydroponics in the presence of 6 microm CdCl2. Hybridological analysis was used to identify the inheritance of the mutant phenotype. Several physiological and biochemical characteristics of SGECd(t) were studied in hydroponic experiments in the presence of 3 microm CdCl2, and elemental analysis was conducted. The mutant SGECd(t) was characterized as having a monogenic inheritance and a recessive phenotype. It showed increased Cd concentrations in roots and shoots but no obvious morphological defects, demonstrating its capability to cope well with increased Cd levels in its tissues. The enhanced Cd accumulation in the mutant was accompanied by maintenance of homeostasis of shoot Ca, Mg, Zn and Mn contents, and root Ca and Mg contents. Through the application of La(+3) and the exclusion of Ca from the nutrient solution, maintenance of nutrient homeostasis in Cd-stressed SGECd(t) was shown to contribute to the increased Cd tolerance. Control plants of the mutant (i.e. no Cd treatment) had elevated concentrations of glutathione (GSH) in the roots. Through measurements of chitinase and guaiacol-dependent peroxidase activities, as well as proline and non-protein thiol (NPT) levels, it was shown that there were lower levels of Cd stress both in roots and shoots of SGECd(t). Accumulation of phytochelatins [(PCcalculated) = (NPT)-(GSH)] could be excluded as a cause of the increased Cd tolerance in the mutant. The SGECd(t) mutant represents a novel and unique model to study adaptation of plants to toxic heavy metal concentrations.

Reactivity to negative affect in smokers: the role of implicit associations and distress tolerance in smoking cessation.

PubMed

Cameron, Amy; Reed, Kathleen Palm; Ninnemann, Andrew

2013-12-01

Avoidance of negative affect is one motivational factor that explains smoking cessation relapse during cessation attempts. This negative reinforcement model of smoking cessation and relapse has demonstrated the importance of one's ability to tolerate nicotine withdrawal symptoms, particularly negative affect states, in remaining abstinent from smoking. Distress tolerance and implicit associations are two individual constructs that may influence the strength of this relationship. In this pilot study the authors examined implicit associations related to avoidance and negative affect using a modified Implicit Association Test (IAT), a measure designed to examine implicit associations related to negative affect and avoidance, and the relationship of these associations to distress tolerance and smoking relapse. In total, 40 participants were recruited through community flyers as part of a larger smoking cessation study. Participants completed a brief smoking history, behavioral distress tolerance assessments, and the modified IAT. Smoking status was assessed via phone 3days and 6days post-quit date. Results from a Cox proportional hazard model revealed that implicit associations between avoidance and negative affect were significantly negatively correlated with time to relapse after a smoking cessation attempt, whereas the behavioral distress tolerance assessments did not predict time to relapse. This study provides novel information about the cognitive associations that may underlie avoidant behavior in smokers, and may be important for understanding smoking relapse when negative affect states are particularly difficult to tolerate. Authors discuss the importance of implicit associations in understanding smoking relapse and how they can be targeted in treatment. © 2013.

Global variation in thermal tolerances and vulnerability of endotherms to climate change

PubMed Central

Khaliq, Imran; Hof, Christian; Prinzinger, Roland; Böhning-Gaese, Katrin; Pfenninger, Markus

2014-01-01

The relationships among species' physiological capacities and the geographical variation of ambient climate are of key importance to understanding the distribution of life on the Earth. Furthermore, predictions of how species will respond to climate change will profit from the explicit consideration of their physiological tolerances. The climatic variability hypothesis, which predicts that climatic tolerances are broader in more variable climates, provides an analytical framework for studying these relationships between physiology and biogeography. However, direct empirical support for the hypothesis is mostly lacking for endotherms, and few studies have tried to integrate physiological data into assessments of species' climatic vulnerability at the global scale. Here, we test the climatic variability hypothesis for endotherms, with a comprehensive dataset on thermal tolerances derived from physiological experiments, and use these data to assess the vulnerability of species to projected climate change. We find the expected relationship between thermal tolerance and ambient climatic variability in birds, but not in mammals—a contrast possibly resulting from different adaptation strategies to ambient climate via behaviour, morphology or physiology. We show that currently most of the species are experiencing ambient temperatures well within their tolerance limits and that in the future many species may be able to tolerate projected temperature increases across significant proportions of their distributions. However, our findings also underline the high vulnerability of tropical regions to changes in temperature and other threats of anthropogenic global changes. Our study demonstrates that a better understanding of the interplay among species' physiology and the geography of climate change will advance assessments of species' vulnerability to climate change. PMID:25009066

Dissecting the assays to assess microbial tolerance to toxic chemicals in bioprocessing.

PubMed

Zingaro, Kyle A; Nicolaou, Sergios A; Papoutsakis, Eleftherios T

2013-11-01

Microbial strains are increasingly used for the industrial production of chemicals and biofuels, but the toxicity of components in the feedstock and product streams limits process outputs. Selected or engineered microbes that thrive in the presence of toxic chemicals can be assessed using tolerance assays. Such assays must reasonably represent the conditions the cells will experience during the intended process and measure the appropriate physiological trait for the desired application. We review currently used tolerance assays, and examine the many parameters that affect assay outcomes. We identify and suggest the use of the best-suited assays for each industrial bioreactor operating condition, discuss next-generation assays, and propose a standardized approach for using assays to examine tolerance to toxic chemicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tolerance of negative emotion moderates the amplification of mental contamination following an evoking task: A randomized experimental study.

PubMed

Fergus, Thomas A

2018-06-01

Contamination is a near universal feeling, with mental contamination representing a contamination feeling in the absence of direct physical contact with a source. Extant research indicates that tolerance of negative emotion is important for understanding emotional reactions to images, thoughts, and memories, all of which are common sources of mental contamination. Extending research linking distress tolerance to mental contamination, this study examined if individual differences in the tolerance of negative emotion moderates the amplification of mental contamination following an evoking task. Unselected participants completed a self-report measure of tolerance of negative emotion during an online session. They later attended an in-person session and were randomized to an experimental scenario group: betrayal (n = 49) or control (n = 49). Participants imagined themselves in a scenario, with the betrayal scenario designed to evoke mental contamination. Mental contamination was assessed by self-report before and after the scenario. The betrayal, but not control, scenario caused an increase in mental contamination. Tolerance for negative emotion moderated the effect of group on mental contamination. Group differences in mental contamination evidenced at low, but not high, distress tolerance. A novel experimental manipulation and an unselected sample were used. Future research could assess tolerance of negative emotion using a behavioral task. These results indicate that tolerance of negative emotion may be important for understanding when individuals experience mental contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design Parameters for Subwavelength Transparent Conductive Nanolattices

DOE PAGES

Diaz Leon, Juan J.; Feigenbaum, Eyal; Kobayashi, Nobuhiko P.; ...

2017-09-29

Recent advancements with the directed assembly of block copolymers have enabled the fabrication over cm 2 areas of highly ordered metal nanowire meshes, or nanolattices, which are of significant interest as transparent electrodes. Compared to randomly dispersed metal nanowire networks that have long been considered the most promising next-generation transparent electrode material, such ordered nanolattices represent a new design paradigm that is yet to be optimized. Here in this paper, through optical and electrical simulations, we explore the potential design parameters for such nanolattices as transparent conductive electrodes, elucidating relationships between the nanowire dimensions, defects, and the nanolattices’ conductivity andmore » transmissivity. We find that having an ordered nanowire network significantly decreases the length of nanowires required to attain both high transmissivity and high conductivity, and we quantify the network’s tolerance to defects in relation to other design constraints. Furthermore, we explore how both optical and electrical anisotropy can be introduced to such nanolattices, opening an even broader materials design space and possible set of applications.« less

Emitter Choice for Epitaxial CdTe Solar Cells

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

Song, Tao; Kanevce, Ana; Sites, James R.

2016-11-21

High-quality epitaxial CdTe layers with low defect density and high carrier concentration have been demonstrated by several research groups. Nevertheless, one primary challenge for high-performance epitaxial CdTe solar cells is how to choose a suitable emitter partner for the junction formation. The numerical simulations show that a type I heterojunction with small conduction band offset (0.1 eV = ..delta..Ec = 0.3 eV) is necessary to maintain a good cell efficiency even with large interface recombination. Otherwise, a small 'cliff' can assist interface recombination causing smaller Voc, and a large 'spike' (..delta..Ec = 0.4 eV) can impede the photo current andmore » lead to a reduction of JSC and FF. Among the three possible emitters, CdS, CdMgTe, and MgZnO, CdMgTe (with ~30% Mg) and MgZnO (with ~ 20% Mg) are likely to be a better choice since their type-I junction can tolerate a larger density of interface defects.« less

Effects of polymethylmethacrylate-transfer residues on the growth of organic semiconductor molecules on chemical vapor deposited graphene

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

Kratzer, Markus, E-mail: markus.kratzer@unileoben.ac.at; Teichert, Christian; Bayer, Bernhard C.

Scalably grown and transferred graphene is a highly promising material for organic electronic applications, but controlled interfacing of graphene thereby remains a key challenge. Here, we study the growth characteristics of the important organic semiconductor molecule para-hexaphenyl (6P) on chemical vapor deposited graphene that has been transferred with polymethylmethacrylate (PMMA) onto oxidized Si wafer supports. A particular focus is on the influence of PMMA residual contamination, which we systematically reduce by H{sub 2} annealing prior to 6P deposition. We find that 6P grows in a flat-lying needle-type morphology, surprisingly independent of the level of PMMA residue and of graphene defects.more » Wrinkles in the graphene typically act as preferential nucleation centers. Residual PMMA does however limit the length of the resulting 6P needles by restricting molecular diffusion/attachment. We discuss the implications for organic device fabrication, with particular regard to contamination and defect tolerance.« less

Design Parameters for Subwavelength Transparent Conductive Nanolattices

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

Diaz Leon, Juan J.; Feigenbaum, Eyal; Kobayashi, Nobuhiko P.

Recent advancements with the directed assembly of block copolymers have enabled the fabrication over cm 2 areas of highly ordered metal nanowire meshes, or nanolattices, which are of significant interest as transparent electrodes. Compared to randomly dispersed metal nanowire networks that have long been considered the most promising next-generation transparent electrode material, such ordered nanolattices represent a new design paradigm that is yet to be optimized. Here in this paper, through optical and electrical simulations, we explore the potential design parameters for such nanolattices as transparent conductive electrodes, elucidating relationships between the nanowire dimensions, defects, and the nanolattices’ conductivity andmore » transmissivity. We find that having an ordered nanowire network significantly decreases the length of nanowires required to attain both high transmissivity and high conductivity, and we quantify the network’s tolerance to defects in relation to other design constraints. Furthermore, we explore how both optical and electrical anisotropy can be introduced to such nanolattices, opening an even broader materials design space and possible set of applications.« less

Laser-ultrasonic inspection of hybrid laser-arc welded HSLA-65 steel

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

Lévesque, D.; Rousseau, G.; Monchalin, J.-P.

2014-02-18

The hybrid laser-arc welding (HLAW) process is a relatively low heat input joining technology that combines the synergistic qualities of both the high energy density laser beam for deep penetration and the arc for wide fit-up gap tolerance. This process is especially suitable for the shipbuilding industry where thick-gauge section, long steel plates have been widely used in a butt joint configuration. In this study, preliminary exploration was carried out to detect and visualize the welding defects using laser ultrasonics combined with the synthetic aperture focusing technique (SAFT). Results obtained on 9.3 mm thick butt-welded HSLA-65 steel plates indicated thatmore » the laser-ultrasonic SAFT inspection technique can successfully detect and visualize the presence of porosity, lack of fusion and internal crack defects. This was further confirmed by X-ray digital radiography and metallography. The results obtained clearly show the potential of using the laser-ultrasonic technology for the automated inspection of hybrid laser-arc welds.« less

Laser-ultrasonic inspection of hybrid laser-arc welded HSLA-65 steel

NASA Astrophysics Data System (ADS)

Lévesque, D.; Rousseau, G.; Wanjara, P.; Cao, X.; Monchalin, J.-P.

2014-02-01

The hybrid laser-arc welding (HLAW) process is a relatively low heat input joining technology that combines the synergistic qualities of both the high energy density laser beam for deep penetration and the arc for wide fit-up gap tolerance. This process is especially suitable for the shipbuilding industry where thick-gauge section, long steel plates have been widely used in a butt joint configuration. In this study, preliminary exploration was carried out to detect and visualize the welding defects using laser ultrasonics combined with the synthetic aperture focusing technique (SAFT). Results obtained on 9.3 mm thick butt-welded HSLA-65 steel plates indicated that the laser-ultrasonic SAFT inspection technique can successfully detect and visualize the presence of porosity, lack of fusion and internal crack defects. This was further confirmed by X-ray digital radiography and metallography. The results obtained clearly show the potential of using the laser-ultrasonic technology for the automated inspection of hybrid laser-arc welds.

Large Area Nano-transfer Printing of Sub-50-nm Metal Nanostructures Using Low-cost Semi-flexible Hybrid Templates

NASA Astrophysics Data System (ADS)

Nagel, Robin D.; Haeberle, Tobias; Schmidt, Morten; Lugli, Paolo; Scarpa, Giuseppe

2016-03-01

In this work, we present a method for printing metal micro- and nanopatterns down to sub-50-nm feature sizes using replicated, defect-tolerant stamps made out of OrmoStamp®; material. The relevant parameters for a successful transfer over large areas were investigated and yields above 99 % have been achieved. Comparing our results to conventional nano-transfer printing using PDMS stamps, we find that the more rigid hybrid polymer used here prevents unintended transfer from interspaces between structures of large distance due to roof collapse and deformation of nano-sized structures due to lateral collapse. Yet, our stamps are flexible enough to ensure intimate contact with the underlying substrate over large areas even in the presence of defect particles. Additionally, the presented patterning technique is resist-, solvent-, and chemical-free and is therefore ideally suited for applications in organic nanoelectronics where standard nanostructuring methods can harm or destroy the organic material.

The roles of specific xanthophylls in photoprotection

PubMed Central

Niyogi, Krishna K.; Björkman, Olle; Grossman, Arthur R.

1997-01-01

Xanthophyll pigments have critical structural and functional roles in the photosynthetic light-harvesting complexes of algae and vascular plants. Genetic dissection of xanthophyll metabolism in the green alga Chlamydomonas reinhardtii revealed functions for specific xanthophylls in the nonradiative dissipation of excess absorbed light energy, measured as nonphotochemical quenching of chlorophyll fluorescence. Mutants with a defect in either the α- or β-branch of carotenoid biosynthesis exhibited less nonphotochemical quenching but were still able to tolerate high light. In contrast, a double mutant that was defective in the synthesis of lutein, loroxanthin (α-carotene branch), zeaxanthin, and antheraxanthin (β-carotene branch) had almost no nonphotochemical quenching and was extremely sensitive to high light. These results strongly suggest that in addition to the xanthophyll cycle pigments (zeaxanthin and antheraxanthin), α-carotene-derived xanthophylls such as lutein, which are structural components of the subunits of the light-harvesting complexes, contribute to the dissipation of excess absorbed light energy and the protection of plants from photo-oxidative damage. PMID:9391170

Dislocation loop formation in model FeCrAl alloys after neutron irradiation below 1 dpa

DOE PAGES

Field, Kevin G.; Briggs, Samuel A.; Sridharan, Kumar; ...

2017-08-01

FeCrAl alloys with varying compositions and microstructures are under consideration for accident-tolerant fuel cladding, but limited details exist on dislocation loop formation and growth for this class of alloys under neutron irradiation. Four model FeCrAl alloys with chromium contents ranging from 10.01 to 17.51 wt % and alunimum contents of 4.78 to 2.93 wt % were neutron irradiated to doses of 0.3–0.8 displacements per atom (dpa) at temperatures of 335–355°C. On-zone STEM imaging revealed a mixed population of black dots and larger dislocation loops with either a/2< 111 > or a< 100 > Burgers vectors. Weak composition dependencies were observedmore » and varied depending on whether the defect size, number density, or ratio of defect types was of interest. Here, the results were found to mirror those of previous studies on FeCrAl and FeCr alloys irradiated under similar conditions, although distinct differences exist.« less

Dislocation loop formation in model FeCrAl alloys after neutron irradiation below 1 dpa

NASA Astrophysics Data System (ADS)

Field, Kevin G.; Briggs, Samuel A.; Sridharan, Kumar; Yamamoto, Yukinori; Howard, Richard H.

2017-11-01

FeCrAl alloys with varying compositions and microstructures are under consideration for accident-tolerant fuel cladding, but limited details exist on dislocation loop formation and growth for this class of alloys under neutron irradiation. Four model FeCrAl alloys with chromium contents ranging from 10.01 to 17.51 wt % and aluminum contents of 4.78 to 2.93 wt % were neutron irradiated to doses of 0.3-0.8 displacements per atom (dpa) at temperatures of 335-355 °C. On-zone STEM imaging revealed a mixed population of black dots and larger dislocation loops with either a / 2 〈 111 〉 or a 〈 100 〉 Burgers vectors. Weak composition dependencies were observed and varied depending on whether the defect size, number density, or ratio of defect types was of interest. Results were found to mirror those of previous studies on FeCrAl and FeCr alloys irradiated under similar conditions, although distinct differences exist.

ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

NASA Astrophysics Data System (ADS)

Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

2016-05-01

At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts printability of defects at wafer level and automates the process of defect dispositioning from images captured using high resolution inspection machine. It first eliminates false defects due to registration, focus errors, image capture errors and random noise caused during inspection. For the remaining real defects, actual mask-like contours are generated using the Calibre® ILT solution [1][2], which is enhanced to predict the actual mask contours from high resolution defect images. It enables accurate prediction of defect contours, which is not possible from images captured using inspection machine because some information is already lost due to optical effects. Calibre's simulation engine is used to generate images at wafer level using scanner optical conditions and mask-like contours as input. The tool then analyses simulated images and predicts defect printability. It automatically calculates maximum CD variation and decides which defects are severe to affect patterns on wafer. In this paper, we assess the printability of defects for the mask of advanced technology nodes. In particular, we will compare the recovered mask contours with contours extracted from SEM image of the mask and compare simulation results with AIMSTM for a variety of defects and patterns. The results of printability assessment and the accuracy of comparison are presented in this paper. We also suggest how this method can be extended to predict printability of defects identified on EUV photomasks.

The Tolerability Profile of Clindamycin 1%/Benzoyl Peroxide 5% Gel vs. Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel for Facial Acne

PubMed Central

Cirigliano, Marcela; Gwazdauskas, Jennifer A; Gonzalez, Pablo

2012-01-01

Objective: To compare the first two weeks of tolerability of clindamycin/benzoyl peroxide gel versus adapalene/benzoyl peroxide gel followed by six weeks of open-label clindamycin/benzoyl peroxide gel therapy in subjects with mild-to-moderate acne who participated in two eight-week, identically designed, clinical studies. Methods: Using a split-face method, patients received both clindamycin/benzoyl peroxide gel and adapalene/benzoyl peroxide gel once daily for two weeks (allocation to the right or left side of the face was randomized) in an investigator-blinded fashion. Patients then went on to receive a further six weeks of open-label, full-face clindamycin/benzoyl peroxide gel. The primary outcome was to compare signs and symptoms of tolerability during the first two weeks of treatment using an investigator-assessed 4-point rating scale. Secondary endpoints included assessment of acne severity (Investigator Static Global Assessment and lesion counts), quality of life, product acceptability/preference, and patient assessments of tolerability and safety. Results: Of the 76 subjects enrolled in the two studies, 72 completed them. Overall both products were well tolerated, but mean scores for erythema, dryness, and peeling were significantly higher with adapalene/benzoyl peroxide gel than with clindamycin/benzoyl peroxide gel at both Weeks 1 and 2 (p<0.03). Patients also rated clindamycin/benzoyl peroxide gel significantly more tolerable than adapalene/benzoyl peroxide gel for redness, dryness, burning, itching, and scaling at Weeks 1 and 2 (p 0.0073). Mean Investigator Static Global Assessment score improved with both products during the first two weeks of treatment and continued to show significant improvement versus baseline when treatment with clindamycin/benzoyl peroxide gel was continued for a further six weeks (p<0.001 at Week 8). Lesion counts improved throughout the study with significant reductions from baseline occurring at Weeks 5 and 8 (p<0.0001 for both time points for total lesion counts). Clindamycin/benzoyl peroxide gel and adapalene/benzoyl peroxide gel were well tolerated, with most adverse events of mild-to-moderate severity. Conclusion: Clindamycin/benzoyl peroxide gel had better tolerability with regard to erythema, dryness, and peeling than adapalene/benzoyl peroxide gel during the first two weeks of treatment. PMID:22808305

Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells

NASA Astrophysics Data System (ADS)

Rich, Devra P.; Anderson, Matthew P.; Gregory, Richard J.; Cheng, Seng H.; Paul, Sucharita; Jefferson, Douglas M.; McCann, John D.; Klinger, Katherine W.; Smith, Alan E.; Welsh, Michael J.

1990-09-01

The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (ΔF508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.

Nutrient enrichment and fish nutrient tolerance: Assessing biologically relevant nutrient criteria

USGS Publications Warehouse

Meador, Michael R.

2013-01-01

Relationships between nutrient concentrations and fish nutrient tolerance were assessed relative to established nutrient criteria. Fish community, nitrate plus nitrite (nitrate), and total phosphorus (TP) data were collected during summer low-flow periods in 2003 and 2004 at stream sites along a nutrient-enrichment gradient in an agricultural basin in Indiana and Ohio and an urban basin in the Atlanta, Georgia, area. Tolerance indicator values for nitrate and TP were assigned for each species and averaged separately for fish communities at each site (TIVo). Models were used to predict fish species expected to occur at a site under minimally disturbed conditions and average tolerance indicator values were determined for nitrate and TP separately for expected communities (TIVe). In both areas, tolerance scores (TIVo/TIVe) for nitrate increased significantly with increased nitrate concentrations whereas no significant relationships were detected between TP tolerance scores and TP concentrations. A 0% increase in the tolerance score (TIVo/TIVe = 1) for nitrate corresponded to a nitrate concentration of 0.19 mg/l (compared with a USEPA summer nitrate criterion of 0.17 mg/l) in the urban area and 0.31 mg/l (compared with a USEPA summer nitrate criterion of 0.86 mg/l) in the agricultural area. Fish nutrient tolerance values offer the ability to evaluate nutrient enrichment based on a quantitative approach that can provide insights into biologically relevant nutrient criteria.

Effects and safety of periconceptional folate supplementation for preventing birth defects

PubMed Central

Maria De-Regil, Luz; Fernández-Gaxiola, Ana C; Dowswell, Therese; Peña-Rosas, Juan Pablo

2014-01-01

Background It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. Objectives This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies. Selection criteria We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. Data collection and analysis We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy. Main results Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term. We found no evidence of short-term side effects. Authors’ conclusions Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects. PMID:20927767

Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

PubMed

Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

2015-01-01

The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

Radiation tolerance of neutron-irradiated model Fe-Cr-Al alloys

DOE PAGES

Field, Kevin G.; Hu, Xunxiang; Littrell, Kenneth C.; ...

2015-07-14

The Fe Cr Al alloy system has the potential to form an important class of enhanced accident-tolerant cladding materials in the nuclear power industry owing to the alloy system's higher oxidation resistance in high-temperature steam environments compared with traditional zirconium-based alloys. However, radiation tolerance of Fe Cr Al alloys has not been fully established. In this study, a series of Fe Cr Al alloys with 10 18 wt % Cr and 2.9 4.9 wt % Al were neutron irradiated at 382 C to 1.8 dpa to investigate the irradiation-induced microstructural and mechanical property evolution as a function of alloy composition.more » Dislocation loops with Burgers vector of a/2 111 and a 100 were detected and quantified. Results indicate precipitation of Cr-rich is primarily dependent on the bulk chromium composition. Mechanical testing of sub-size-irradiated tensile specimens indicates the hardening response seen after irradiation is dependent on the bulk chromium composition. Furthermore, a structure property relationship was developed; it indicated that the change in yield strength after irradiation is caused by the formation of these radiation-induced defects and is dominated by the large number density of Cr-rich α' precipitates at sufficiently high chromium contents after irradiation.« less

SHIP1 intrinsically regulates NK cell signaling and education, resulting in tolerance of an MHC class I-mismatched bone marrow graft in mice.

PubMed

Gumbleton, Matthew; Vivier, Eric; Kerr, William G

2015-03-15

NK cells are an important component of host immune defense against malignancy and infection. NK cells are educated by MHC class I ligands to ensure self-tolerance while also promoting lytic competency against altered self and damaged self targets. However, the intracellular molecular events that culminate in tolerance and functional competency of educated NK cells remain undefined. Mice with germline deficiency in SHIP1 were shown to have a defective NK cell compartment. However, SHIP1 is expressed in all hematopoietic lineages, and consequently several hematolymphoid phenotypes have already been identified in certain cell types that are the result of SHIP1 deficiency in cells in separate and distinct lineages, that is, cell-extrinsic phenotypes. Thus, it was previously impossible to determine the NK cell-intrinsic role of SHIP1. In the present study, through the creation of an NK cell-specific deletion mouse model of SHIP1, we show that SHIP1 plays a profound NK lineage-intrinsic role in NK cell homeostasis, development, education, and cytokine production. Moreover, we show SHIP1 expression by NK cells is required for in vivo-mismatched bone marrow allograft rejection as well as for NK memory responses to hapten. Copyright © 2015 by The American Association of Immunologists, Inc.

Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

PubMed Central

Manco, Melania; Castagneto-Gissey, Lidia; Arrighi, Eugenio; Carnicelli, Annamaria; Brufani, Claudia; Luciano, Rosa; Mingrone, Geltrude

2014-01-01

Background Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. Research Design and Methods Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method). Results Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons). Conclusion Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls. PMID:24705280

ABF2, an ABRE-binding bZIP factor, is an essential component of glucose signaling and its overexpression affects multiple stress tolerance.

PubMed

Kim, Sunmi; Kang, Jung-Youn; Cho, Dong-Im; Park, Ji Hye; Kim, Soo Young

2004-10-01

Phytohormone abscisic acid (ABA) regulates stress-responsive gene expression during vegetative growth, which is mediated largely by cis-elements sharing the ACGTGGC consensus. Although many transcription factors are known to bind the elements in vitro, only a few have been demonstrated to have in vivo functions and their specific roles in ABA/stress responses are mostly unknown. Here, we report that ABF2, an ABF subfamily member of bZIP proteins interacting with the ABA-responsive elements, is involved in ABA/stress responses. Its overexpression altered ABA sensitivity, dehydration tolerance, and the expression levels of ABA/stress-regulated genes. Furthermore, ABF2 overexpression promoted glucose-induced inhibition of seedling development, whereas its mutation impaired glucose response. The reduced sugar sensitivity was not observed with mutants of two other ABF family members, ABF3 and ABF4. Instead, these mutants displayed defects in ABA, salt, and dehydration responses, which were not observed with the abf2 mutant. Our data indicate distinct roles of ABF family members: whereas ABF3 and ABF4 play essential roles in ABA/stress responses, ABF2 is required for normal glucose response. We also show that ABF2 overexpression affects multiple stress tolerance.

Mechanical tolerances study through simulations and experimental characterization for a 1000X micro-concentrator CPV module

NASA Astrophysics Data System (ADS)

Ritou, Arnaud; Voarino, Philippe; Goubault, Baptiste; David, Nadine; Bernardis, Sarah; Raccurt, Olivier; Baudrit, Mathieu

2017-09-01

Existing CPV technology markets are not compliant with a standard configuration. Concentrations vary from several suns to more than 1000 suns and the optical technology used could be very different. Nowadays, the market trends are moving toward more and more compact optical systems in order to exploit the Light Emitting Diode (LED) like approach. The aim is to increase the optical efficiency by using an ultra-short focal distance and to improve thermal management. Moreover the efficiency to weight ratio is increasing and the solar cell size becomes sub-millimetric. With these conditions, more stringent mechanical tolerances are essential to ensure an optimum optical alignment between cells and optics. A new process of micro-concentrator manufacturing is developed in this work. This process enables manufacturing and auto-alignment of Primary Optical Elements (POE) with Secondary Optical Elements (SOE) and solar cells with respect to certain mechanical tolerances. A 1000X micro-concentrator is manufactured with 0.6 x 0.6 mm² triple-junction cells and molded silicone optics. Mechanical alignment defects are studied by ray-tracing simulations and a prototype is characterized with respect to its mechanical behavior. An efficiency of 33.4% is measured with a Cell-to-Module ratio of 77.8%.

Role of the mRNA export factor Sus1 in oxidative stress tolerance in Candida albicans.

PubMed

Xiao, Chenpeng; Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Dan; Li, Mingchun

2018-02-05

In eukaryotes, the nuclear export of mRNAs is essential for gene expression. However, little is known about the role of mRNA nuclear export in the important fungal pathogen, Candida albicans. In this study, we identified C. albicans Sus1, a nucleus-localized protein that is required for mRNA export. Interestingly, the sus1Δ/Δ displayed hyper-sensitivity to extracellular oxidative stress, enhanced ROS accumulation and severe oxidative stress-related cell death. More strikingly, although the mutant exhibited normal activation of the expression of oxidative stress response (OSR) genes, it had attenuated activity of ROS scavenging system, which may be attributed to the defect in OSR mRNA export in this mutant. In addition, the virulence of the sus1Δ/Δ was seriously attenuated. Taken together, our findings provide evidence that the mRNA export factor Sus1 plays an important role in oxidative stress tolerance and pathogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Bandgap engineering in semiconductor alloy nanomaterials with widely tunable compositions

NASA Astrophysics Data System (ADS)

Ning, Cun-Zheng; Dou, Letian; Yang, Peidong

2017-12-01

Over the past decade, tremendous progress has been achieved in the development of nanoscale semiconductor materials with a wide range of bandgaps by alloying different individual semiconductors. These materials include traditional II-VI and III-V semiconductors and their alloys, inorganic and hybrid perovskites, and the newly emerging 2D materials. One important common feature of these materials is that their nanoscale dimensions result in a large tolerance to lattice mismatches within a monolithic structure of varying composition or between the substrate and target material, which enables us to achieve almost arbitrary control of the variation of the alloy composition. As a result, the bandgaps of these alloys can be widely tuned without the detrimental defects that are often unavoidable in bulk materials, which have a much more limited tolerance to lattice mismatches. This class of nanomaterials could have a far-reaching impact on a wide range of photonic applications, including tunable lasers, solid-state lighting, artificial photosynthesis and new solar cells.

SGD1, a key enzyme in tocopherol biosynthesis, is essential for plant development and cold tolerance in rice.

PubMed

Wang, Di; Wang, Yunlong; Long, Wuhua; Niu, Mei; Zhao, Zhigang; Teng, Xuan; Zhu, Xiaopin; Zhu, Jianping; Hao, Yuanyuan; Wang, Yongfei; Liu, Yi; Jiang, Ling; Wang, Yihua; Wan, Jianmin

2017-07-01

Tocopherols, a group of Vitamin E compounds, are essential components of the human diet. In contrast to well documented roles in animals, the functions of tocopherols in plants are less understood. In this study, we characterized two allelic rice dwarf mutant lines designated sgd1-1 and sgd1-2 (small grain and dwarf1). Histological observations showed that the dwarf phenotypes were mainly due to cell elongation defects. A map-based cloning strategy and subsequent complementation test showed that SGD1 encodes homogentisate phytyltransferase (HPT), a key enzyme in tocopherol biosynthesis. Mutation of SGD1 resulted in tocopherol deficiency in both sgd1mutants. No oxidant damage was detected in the sgd1 mutants. Further analysis showed that sgd1-2 was hypersensitive to cold stress. Our results indicate that SGD1 is essential for plant development and cold tolerance in rice. Copyright © 2017 Elsevier B.V. All rights reserved.

Feasibility and safety of a new generation of gore septal occluder device in children.

PubMed

Lombardi, Maristella; Tagliente, Maria R; Pirolo, Teodoro; Massari, Elena; Milella, Leonardo; Vairo, Ugo

2016-12-01

Transcatheter closure of an ostium secundum atrial septal defect (ASD) is now considered the standard care for most of children with the appropriate anatomy, and is a relatively well-tolerated procedure to reduce the clinical sequelae of ASD, with a low complication rate. The present case reports describe our clinical experience of the percutaneous closure of a secundum ASD in 10 children between December 2011 and November 2012, by means of a new generation of device, the GORE Septal Occluder device. The implantation was successful in all except two cases, the device being properly placed and deployed without malposition or embolization in the catheterization laboratory. No complications were related to the procedure. The successful implant was confirmed and no major adverse events were documented in the following 3-12 months. The new GORE Septal Occluder device appears to be a feasible, well-tolerated and successful tool for the closure of an ASD of 15 mm or less in childhood.

Quantum computing with Majorana fermion codes

NASA Astrophysics Data System (ADS)

Litinski, Daniel; von Oppen, Felix

2018-05-01

We establish a unified framework for Majorana-based fault-tolerant quantum computation with Majorana surface codes and Majorana color codes. All logical Clifford gates are implemented with zero-time overhead. This is done by introducing a protocol for Pauli product measurements with tetrons and hexons which only requires local 4-Majorana parity measurements. An analogous protocol is used in the fault-tolerant setting, where tetrons and hexons are replaced by Majorana surface code patches, and parity measurements are replaced by lattice surgery, still only requiring local few-Majorana parity measurements. To this end, we discuss twist defects in Majorana fermion surface codes and adapt the technique of twist-based lattice surgery to fermionic codes. Moreover, we propose a family of codes that we refer to as Majorana color codes, which are obtained by concatenating Majorana surface codes with small Majorana fermion codes. Majorana surface and color codes can be used to decrease the space overhead and stabilizer weight compared to their bosonic counterparts.

77 FR 59558 - Sulfentrazone; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... hay; wheat grain; wheat straw; and cowpea, succulent. The human health risk assessment used to support... Tolerances in/on: Rhubarb, Turnip Roots and Tops, Sunflower Subgroup 20B, Succulent Cowpea, Succulent Lima...

Do internal anal sphincter defects decrease the success rate of anal sphincter repair?

PubMed

Oberwalder, M; Dinnewitzer, A; Baig, M K; Nogueras, J J; Weiss, E G; Efron, J; Vernava, A M; Wexner, S D

2006-07-01

Anatomic anal sphincter defects can involve the internal anal sphincter (IAS), the external anal sphincter (EAS), or both muscles. Surgical repair of anteriorly located EAS defects consists of overlapping suture of the EAS or EAS imbrication; IAS imbrication can be added regardless of whether there is IAS injury. The aim of this study was to assess the functional outcome of anal sphincter repair in patients intraoperatively diagnosed with combined EAS/IAS defects compared to patients with isolated EAS defects. The medical records of patients who underwent anal sphincter repair between 1988 and 2000 and had follow-up of at least 3 months were retrospectively assessed. Fecal incontinence was assessed using the Cleveland Clinic Florida incontinence score wherein 0 equals perfect continence and 20 is associated with complete incontinence. Postoperative scores of 0-10 were interpreted as success whereas scores of 11-20 indicated failure. A total of 131 women were included in this study, including 38 with combined EAS/IAS defects (Group I) and 93 with isolated EAS defects (Group II). Thirty-three patients (87%) in Group I had imbrication of a deficient IAS, compared to 83 patients (89%) in Group II. All patients had either overlapping EAS repair (n=121) or EAS imbrication (n=10). Mean follow-up was 30.9 months (range, 3-131 months). There were no statistically significant differences between the two groups relative to age (48.3 vs. 53.0 years; p=0.14), preoperative incontinence score (16.1 vs. 16.7; p=0.38), extent of pudendal nerve terminal motor latency pathology (left, 11.1% vs. 8%; p=0.58; right, 8.6% vs. 15.1%; p=0.84), extent of pathology at electromyography (54.8% vs. 60.1%; p=0.43), and length of follow-up (26.9 vs. 32.5 months; p=0.31). The success rates of sphincter repair were 68.4% for Group I versus 55.9% for Group II (p=NS). Both groups were well matched for incidence of IAS imbrication as well as age, follow-up interval, and physiologic parameters. The success rates of anal sphincter repair were not statistically significant between the two groups. A pre-existing IAS defect does not preclude successful sphincteroplasty as compared to repair of an isolated EAS defect. Thus, patients with combined anal sphincter defects should not be considered as poor candidates for sphincter repair.

Efficacy and Tolerability of an Acne Treatment Regimen with Antiaging Benefits in Adult Women

PubMed Central

Jiang, Lily I.; Hino, Peter D.; Parker, Lydia; Stephens, Thomas J.; Mccook, John

2018-01-01

Objective: The objective of this study was to assess clinical safety and efficacy of a novel acne treatment regimen in adult women. Methods: Participants in the study included an ethnically diverse group of adult women (n=24) with mild-to-moderate acne who were treated twice daily with a topical regimen (cleanser, acne cream, and rebalancing gel) for eight weeks. Following baseline assessments, subjects returned to clinic at Weeks 2, 4, and 8 for clinical assessments and self-assessment questionnaires. Results: Twenty-one of the 24 enrolled women completed the eight-week clinical trial. Statistically significant clinical improvements were seen in both acne and aging parameters over time. The product regimen was well tolerated without adverse reactions commonly seen with topical acne products. Conclusion: The regimen demonstrated efficacy and tolerability in adult women with acne and signs of skin aging. PMID:29942425

Periodontal repair in dogs: examiner reproducibility in the supraalveolar periodontal defect model.

PubMed

Koo, Ki-Tae; Polimeni, Giuseppe; Albandar, Jasim M; Wikesjö, Ulf M E

2004-06-01

Histometric assessments are routinely used to evaluate biologic events ascertained in histologic sections acquired from animal and human studies. The objective of this study was to evaluate the intra- and inter-examiner reproducibility of histometric assessments in the supraalveolar periodontal defect model. Histometric analysis using incandescent and polarized light microscopy, an attached digital camera system, and a PC-based image analysis system including a custom program for the supraalveolar periodontal defect model was performed on histologic sections acquired from one jaw quadrant in each of 12 dogs. The animals had received an experimental protocol including implantation of a coral biomaterial and guided tissue regeneration (GTR) barrier devices, and were evaluated following a 4-week healing interval. Histometric parameters were recorded and repeated within a 3-month interval by two examiners following brief training. Intra- and inter-examiner reproducibility was assessed using the intra-class correlation coefficient (ICC). Most parameters showed high intra-examiner ICCs. Parameters including defect height, connective tissue repair, bone regeneration (height/area), formation of a junctional epithelium, positioning of the GTR device, ankylosis, root resorption, and defect area yielded an ICC> or 0..9. The ICCs for bone density and biomaterial density were somewhat lower (0.8 and 0.7, respectively). The inter-examiner reproducibility was somewhat lower compared to the intra-examiner reproducibility. Nevertheless, the ICCs were generally high (ICC range: 0.6-0.9). Histometric evaluations in the supraalveolar periodontal defect model yield highly reproducible results, in particular when a single examiner performs the histometric measurements, even when the examiner was exposed to limited training.

Influences on cocaine tolerance assessed under a multiple conjunctive schedule of reinforcement.

PubMed

Yoon, Jin Ho; Branch, Marc N

2009-11-01

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key-pecking responses of White Carneau pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose-effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.

Ecological and physiological thermal niches to understand distribution of Chagas disease vectors in Latin America.

PubMed

DE LA Vega, G J; Schilman, P E

2018-03-01

In order to assess how triatomines (Hemiptera, Reduviidae), Chagas disease vectors, are distributed through Latin America, we analysed the relationship between the ecological niche and the limits of the physiological thermal niche in seven species of triatomines. We combined two methodological approaches: species distribution models, and physiological tolerances. First, we modelled the ecological niche and identified the most important abiotic factor for their distribution. Then, thermal tolerance limits were analysed by measuring maximum and minimum critical temperatures, upper lethal temperature, and 'chill-coma recovery time'. Finally, we used phylogenetic independent contrasts to analyse the link between limiting factors and the thermal tolerance range for the assessment of ecological hypotheses that provide a different outlook for the geo-epidemiology of Chagas disease. In triatomines, thermo-tolerance range increases with increasing latitude mainly due to better cold tolerances, suggesting an effect of thermal selection. In turn, physiological analyses show that species reaching southernmost areas have a higher thermo-tolerance than those with tropical distributions, denoting that thermo-tolerance is limiting the southern distribution. Understanding the latitudinal range along its physiological limits of disease vectors may prove useful to test ecological hypotheses and improve strategies and efficiency of vector control at the local and regional levels. © 2017 The Royal Entomological Society.

A Computational Framework for Automation of Point Defect Calculations

NASA Astrophysics Data System (ADS)

Goyal, Anuj; Gorai, Prashun; Peng, Haowei; Lany, Stephan; Stevanovic, Vladan; National Renewable Energy Laboratory, Golden, Colorado 80401 Collaboration

A complete and rigorously validated open-source Python framework to automate point defect calculations using density functional theory has been developed. The framework provides an effective and efficient method for defect structure generation, and creation of simple yet customizable workflows to analyze defect calculations. The package provides the capability to compute widely accepted correction schemes to overcome finite-size effects, including (1) potential alignment, (2) image-charge correction, and (3) band filling correction to shallow defects. Using Si, ZnO and In2O3as test examples, we demonstrate the package capabilities and validate the methodology. We believe that a robust automated tool like this will enable the materials by design community to assess the impact of point defects on materials performance. National Renewable Energy Laboratory, Golden, Colorado 80401.

Genetic variation in tolerance of Douglas-fir to Swiss needle cast as assessed by symptom expression.

Treesearch

G.R. Jonhson

2002-01-01

The incidence of Swiss needle cast on Douglas-fir has increased significantly in recent years on the Oregon coast. Genetic variation in symptoms of disease infection, as measured by foliage traits, was assessed in two series of progeny trials to determine whether these "crown health" indicators were under genetic control and correlated with tolerance;...

Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity

PubMed Central

Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

2013-01-01

For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of “neuroendocrine self-peptides” has been proposed, together with the definition of “neuroendocrine self.” Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic or acquired, for example during an enteroviral infection. This novel knowledge of normal and pathologic functions of the thymus constitutes a solid basis for the development of a novel type of tolerogenic/negative self-vaccination against type 1 diabetes (T1D). PMID:24137108

Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity.

PubMed

Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

2013-10-16

For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of "neuroendocrine self-peptides" has been proposed, together with the definition of "neuroendocrine self." Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic or acquired, for example during an enteroviral infection. This novel knowledge of normal and pathologic functions of the thymus constitutes a solid basis for the development of a novel type of tolerogenic/negative self-vaccination against type 1 diabetes (T1D).

Ketamine for chronic pain: risks and benefits.

PubMed

Niesters, Marieke; Martini, Christian; Dahan, Albert

2014-02-01

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

PubMed

Pot, Michiel W; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; van Kuppevelt, Toin H; de Vries, Rob B M; Daamen, Willeke F

2016-01-01

Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly improved cartilage regeneration by 15.6% compared to non-treated empty defect controls. The addition of biologics to biomaterials significantly improved cartilage regeneration by 7.6% compared to control biomaterials. No significant differences were found between biomaterials from natural or synthetic origin or between scaffolds, hydrogels and blends. No noticeable differences were found in outcome between animal models. The risk of bias assessment indicated poor reporting for the majority of studies, impeding an assessment of the actual risk of bias. In conclusion, implantation of biomaterials in osteochondral defects improves cartilage regeneration compared to natural healing, which is further improved by the incorporation of biologics.

Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

PubMed Central

Pot, Michiel W.; Gonzales, Veronica K.; Buma, Pieter; IntHout, Joanna

2016-01-01

Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0–100% scale. Implantation of acellular biomaterials significantly improved cartilage regeneration by 15.6% compared to non-treated empty defect controls. The addition of biologics to biomaterials significantly improved cartilage regeneration by 7.6% compared to control biomaterials. No significant differences were found between biomaterials from natural or synthetic origin or between scaffolds, hydrogels and blends. No noticeable differences were found in outcome between animal models. The risk of bias assessment indicated poor reporting for the majority of studies, impeding an assessment of the actual risk of bias. In conclusion, implantation of biomaterials in osteochondral defects improves cartilage regeneration compared to natural healing, which is further improved by the incorporation of biologics. PMID:27651981