Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity).

PubMed

Laron, Zvi; Ginsberg, Shira; Lilos, Pearl; Arbiv, Mira; Vaisman, Nahum

2006-07-01

To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. Lifelong congenital IGF-I deficiency leads to extreme adiposity.

Rayleigh matches in carriers of inherited color vision defects: the contribution from the third L/M photopigment.

PubMed

Sun, Yang; Shevell, Steven K

2008-01-01

The mother or daughter of a male with an X-chromosome-linked red/green color defect is an obligate carrier of the color deficient gene array. According to the Lyonization hypothesis, a female carrier's defective gene is expressed and thus carriers may have more than two types of pigments in the L/M photopigment range. An open question is how a carrier's third cone pigment in the L/M range affects the postreceptoral neural signals encoding color. Here, a model considered how the signal from the third pigment pools with signals from the normal's two pigments in the L/M range. Three alternative assumptions were considered for the signal from the third cone pigment: it pools with the signal from (1) L cones, (2) M cones, or (3) both types of cones. Spectral-sensitivity peak, optical density, and the relative number of each cone type were factors in the model. The model showed that differences in Rayleigh matches among carriers can be due to individual differences in the number of the third type of L/M cone, and the spectral sensitivity peak and optical density of the third L/M pigment; surprisingly, however, individual differences in the cone ratio of the other two cone types (one L and the other M) did not affect the match. The predicted matches were compared to Schmidt's (1934/1955) report of carriers' Rayleigh matches. For carriers of either protanomaly or deuteranomaly, these matches were not consistent with the signal from the third L/M pigment combining with only the signal from M cones. The matches could be accounted for by pooling the third-pigment's response with L-cone signals, either exclusively or randomly with M-cone responses as well.

Topological Transformation of Defects in Nematic Liquid Crystals

NASA Astrophysics Data System (ADS)

Pagel, Zachary; Atherton, Timothy; Guasto, Jeffrey; Cebe, Peggy

A topological transformation around silica microsphere inclusions in nematic liquid crystal cells (LCC) is experimentally studied. Silica microspheres are coated to induce homeotropic LC anchoring to the spheres. Parallel rub directions of the alignment polymer during LCC construction create a splay wall that traps the microspheres. Application of an out-of-plane electric field then permits a transformation of hedgehog defects, reversing the orientation of the defect around microspheres. The transformation controllably reverses the microsphere's direction of travel during AC electrophoresis due to defect-dependent velocity anisotropy. A similar transformation is studied on chains of microspheres with hedgehog defects, where the defect orientation is reversed on the entire chain. Polarized and confocal microscopies are used to study the defect structures. Results contribute to recent developments in microsphere electrokinetics in nematic LCs, as the transformation adds an additional degree of control in the electrophoretic motion of microspheres and chains of microspheres with dipolar defects. The author thanks NSF Grant DMR-1608126 for funding reseearch and Tufts University for funding travel.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.

PubMed

Seemann, Wiebke K; Wenzel, Daniela; Schrage, Ramona; Etscheid, Justine; Bödefeld, Theresa; Bartol, Anna; Warnken, Mareille; Sasse, Philipp; Klöckner, Jessica; Holzgrabe, Ulrike; DeAmici, Marco; Schlicker, Eberhard; Racké, Kurt; Kostenis, Evi; Meyer, Rainer; Fleischmann, Bernd K; Mohr, Klaus

2017-02-01

Drug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M 2 -receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side effect is one of the main reasons that limit clinical application of muscarinic agonists. Herein we show that dualsteric (orthosteric/allosteric) agonists induce less cardiac depression ex vivo and in vivo than conventional full agonists. Exploration of the underlying mechanism in living cells employing cellular dynamic mass redistribution identified context-sensitive agonism of these dualsteric agonists. They translate elevation of intracellular cAMP into a switch from full to partial agonism. Designed context-sensitive agonism opens an avenue toward postreceptor pharmacologic selectivity, which even works in target tissues operated by the same subtype of pharmacologic receptor. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Postreceptoral chromatic-adaptation mechanisms in the red-green and blue-yellow systems using simple reaction times

NASA Astrophysics Data System (ADS)

Medina, José M.; Díaz, José A.

2006-05-01

Simple visual-reaction times (VRT) were measured for a variety of stimuli selected along red-green (L-M axis) and blue-yellow [S-(L+M) axis] directions in the isoluminant plane under different adaptation stimuli. Data were plotted in terms of the RMS cone contrast in contrast-threshold units. For each opponent system, a modified Piéron function was fitted in each experimental configuration and on all adaptation stimuli. A single function did not account for all the data, confirming the existence of separate postreceptoral adaptation mechanisms in each opponent system under suprathreshold conditions. The analysis of the VRT-hazard functions suggested that both color-opponent mechanisms present a well-defined, transient-sustained structure at marked suprathreshold conditions. The influence of signal polarity and chromatic adaptation on each color axis proves the existence of asymmetries in the integrated hazard functions, suggesting separate detection mechanisms for each pole (red, green, blue, and yellow detectors).

Genotype-phenotype relationships in human red/green color-vision defects: molecular and psychophysical studies.

PubMed Central

Deeb, S S; Lindsey, D T; Hibiya, Y; Sanocki, E; Winderickx, J; Teller, D Y; Motulsky, A G

1992-01-01

The relationship between the molecular structure of the X-linked red and green visual pigment genes and color-vision phenotype as ascertained by anomaloscopy was studied in 64 color-defective males. The great majority of red-green defects were associated with either the deletion of the green-pigment gene or the formation of 5' red-green hybrid genes or 5' green-red hybrid genes. A rapid PCR-based method allowed detection of hybrid genes, including those undetectable by Southern blot analysis, as well as more precise localization of the fusion points in hybrid genes. Protan color-vision defects appeared always associated with 5' red-green hybrid genes. Carriers of single red-green hybrid genes with fusion in introns 1-4 were protanopes. However, carriers of hybrid genes with red-green fusions in introns 2, 3, or 4 in the presence of additional normal green genes manifested as either protanopes or protanomalous trichromats, with the majority being protanomalous. Deutan defects were associated with green-pigment gene deletions, with 5' green-red hybrid genes, or, rarely, with 5' green-red-green hybrid genes. Complete green-pigment gene deletions or green-red fusions in intron 1 were usually associated with deuteranopia, although we unexpectedly found three carriers of a single red-pigment gene without any green-pigment genes to be deuteranomalous trichromats. All but one of the other deuteranomalous subjects had green-red hybrid genes with intron 1, 2, 3, or 4 fusions, as well as several normal green-pigment genes. The one exception had a grossly normal gene array, presumably with a more subtle mutation. Amino acid differences in exon 5 largely determine whether a hybrid gene will be more redlike or more greenlike in phenotype. Various discrepancies as to severity (dichromacy or trichromacy) remain unexplained but may arise because of variability of expression, postreceptoral variation, or both. When phenotypic color-vision defects exist, the kind of defect (protan or deutan) can be predicted by molecular analysis. Red-green hybrid genes are probably always associated with protan color-vision defects, while the presence of green-red hybrid genes may not always manifest phenotypically with color-vision defects. Four subjects who were found to have 5' green-red hybrid genes in addition to normal red- and green-pigment genes had normal color vision as determined by anomaloscopy. These were discovered among a group of 129 Caucasian males who had been recruited as volunteers for a vision study.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 PMID:1415215

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: comparison with rest-redistribution thallium 201 imaging.

PubMed

Iskandrian, A S; Powers, J; Cave, V; Wasserleben, V; Cassell, D; Heo, J

1995-01-01

This study examined the ability of dynamic 123I-labeled iodophenylpentadecanoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease. Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi 123I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34% +/- 11%). The segmental uptake was compared with that of rest-redistribution 201Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11 +/- 5 vs 10 +/- 5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (kappa = 0.78 +/- 0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (kappa = 0.54 +/- 0.04). However, there were more reversible IPPA defects than reversible thallium defects (7 +/- 4 vs 3 +/- 4 segments/patient; p = 0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33% +/- 11% to 39% +/- 12% (p = 0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10 +/- 4 vs 5 +/- 4 segments/patient; p = 0.075). 123I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.

Reverse Dynamization: Influence of Fixator Stiffness on the Mode and Efficiency of Large-Bone-Defect Healing at Different Doses of rhBMP-2.

PubMed

Glatt, Vaida; Bartnikowski, Nicole; Quirk, Nicholas; Schuetz, Michael; Evans, Christopher

2016-04-20

Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions. Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing. In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification. These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully. Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Reverse Dynamization

PubMed Central

Glatt, Vaida; Bartnikowski, Nicole; Quirk, Nicholas; Schuetz, Michael; Evans, Christopher

2016-01-01

Background: Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions. Methods: Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing. Results: In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification. Conclusions: These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully. Clinical Relevance: Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation. PMID:27098327

Reverse shoulder arthroplasty due to glenoid bone defects.

PubMed

Díaz Miñarro, J C; Izquierdo Fernández, A; Muñoz Reyes, F; Carpintero Lluch, R; Uceda Carrascosa, P; Muñoz Luna, F; López Jordán, A; Carpintero Benítez, P

2016-01-01

Reverse shoulder arthroplasty is becoming a useful tool for many diseases of the shoulder. Any severe glenoid bone defect may affect the fixing of the glenoid component. The aim of this paper is to evaluate the medium-term outcomes of reverse shoulder arthroplasty associated with a glenoplasty. A retrospective study was conducted on 5 patients from our hospital, selected due to glenoid defects of different etiology. All of them where treated with reverse shoulder arthroplasty associated with glenoplasty with bone graft. The minimum follow-up was one year (mean 30.4 months). All grafts were radiologically integrated, with no signs of resorption or necrosis being observed. At 12 months, the Constant score was 66.75 and the mean EVA score was 1. Glenoplasty surgery is technically demanding for restoring original bone size in patients with glenoid structural defects, enabling a reverse shoulder arthroplasty to be implanted. Thus improving both the function and clinical outcomes in selected patients with glenohumeral pathology and providing them with a solution. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Design and analysis of forward and reverse models for predicting defect accumulation, defect energetics, and irradiation conditions

DOE PAGES

Stewart, James A.; Kohnert, Aaron A.; Capolungo, Laurent; ...

2018-03-06

The complexity of radiation effects in a material’s microstructure makes developing predictive models a difficult task. In principle, a complete list of all possible reactions between defect species being considered can be used to elucidate damage evolution mechanisms and its associated impact on microstructure evolution. However, a central limitation is that many models use a limited and incomplete catalog of defect energetics and associated reactions. Even for a given model, estimating its input parameters remains a challenge, especially for complex material systems. Here, we present a computational analysis to identify the extent to which defect accumulation, energetics, and irradiation conditionsmore » can be determined via forward and reverse regression models constructed and trained from large data sets produced by cluster dynamics simulations. A global sensitivity analysis, via Sobol’ indices, concisely characterizes parameter sensitivity and demonstrates how this can be connected to variability in defect evolution. Based on this analysis and depending on the definition of what constitutes the input and output spaces, forward and reverse regression models are constructed and allow for the direct calculation of defect accumulation, defect energetics, and irradiation conditions. Here, this computational analysis, exercised on a simplified cluster dynamics model, demonstrates the ability to design predictive surrogate and reduced-order models, and provides guidelines for improving model predictions within the context of forward and reverse engineering of mathematical models for radiation effects in a materials’ microstructure.« less

Design and analysis of forward and reverse models for predicting defect accumulation, defect energetics, and irradiation conditions

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

Stewart, James A.; Kohnert, Aaron A.; Capolungo, Laurent

The complexity of radiation effects in a material’s microstructure makes developing predictive models a difficult task. In principle, a complete list of all possible reactions between defect species being considered can be used to elucidate damage evolution mechanisms and its associated impact on microstructure evolution. However, a central limitation is that many models use a limited and incomplete catalog of defect energetics and associated reactions. Even for a given model, estimating its input parameters remains a challenge, especially for complex material systems. Here, we present a computational analysis to identify the extent to which defect accumulation, energetics, and irradiation conditionsmore » can be determined via forward and reverse regression models constructed and trained from large data sets produced by cluster dynamics simulations. A global sensitivity analysis, via Sobol’ indices, concisely characterizes parameter sensitivity and demonstrates how this can be connected to variability in defect evolution. Based on this analysis and depending on the definition of what constitutes the input and output spaces, forward and reverse regression models are constructed and allow for the direct calculation of defect accumulation, defect energetics, and irradiation conditions. Here, this computational analysis, exercised on a simplified cluster dynamics model, demonstrates the ability to design predictive surrogate and reduced-order models, and provides guidelines for improving model predictions within the context of forward and reverse engineering of mathematical models for radiation effects in a materials’ microstructure.« less

Reverse radial artery flap for soft tissue defects of hand in pediatric age group.

PubMed

Cheema, Saeed Ashraf; Talaat, Nabeela

2009-01-01

To highlight the usefulness of reverse radial artery flap in covering various soft tissue defects of hand in paediatric age group. A total of 16 reverse radial artery flaps were utilized in a period of three years to cover various soft tissue defects of hand for paediatric age group patients. The age ranged from 5-18 years. The two common causes of soft tissue defects in this series were mechanical trauma and fireworks trauma with five cases in each group. Three of the cases were burn victims and other two presented with earth quake injuries. One patient had wound because of road traffic accident. Soft tissue defects of palm were covered with this flap in eight cases while in three cases it was wrapped around the thumb. First web space defects were covered with this flap in two cases. Two cases required coverage of amputation stump at transmetacarpal level and yet another required a big flap to cover the soft tissue defects at palm, dorsum and thumb. Donor site was covered with split skin graft in all cases but one, which was closed primarily. We had partial loss of flap in one case. Grafted donor sites healed uneventfully and were quite acceptable to the patients in due course of time. Reverse radial artery flap has a quite long arc of rotation which brings it great ease to cover the soft tissue defects of various areas of hand like palm, dorsum, first web space and thumb.

Origin of reverse annealing in radiation-damaged silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.

1980-01-01

The paper employs relative defect concentrations, energy levels, capture cross sections, and minority carrier diffusion lengths in order to identify the defect responsible for the reverse annealing observed in a radiation damaged n(+)/p silicon solar cell. It is reported that the responsible defect, with the energy level at +0.30 eV, has been tentatively identified as boron-oxygen-vacancy complex. In conclusion, it is shown that removal of this defect could result in significant cell recovery when annealing at temperatures well below the currently required 400 C.

Pseudohypopituitary syndromes.

PubMed

Heinze, E; Holl, R W

1992-07-01

In a child with short stature, the finding of normal or elevated GH levels in the presence of low concentrations of IGF-I raises the following possibilities. (1) A modification of the GH molecule, which is still detected by RIA, but inactive biologically. Therefore, an RRA or bioassay for hGH should result in considerably lower GH measurements compared with RIA determinations in the same sample. As both bioassays as well as RRAs are not widely available and are hampered by several difficulties, few children with this presumptive diagnosis have been described. So far, it has not been possible to define a specific molecular defect in one of these patients. (2) Abnormalities of the GH receptor or postreceptor mechanisms lead to a GH insensitivity syndrome. Laron-type dwarfism is usually due to a deletion in the gene for hepatic GH receptors: the serum binding protein for GH is absent. In three additional populations, the Pygmies of Zaire, the little women of Loja in Ecuador and the Mountain Ok people in Papua New Guinea, alterations of GH receptor function have been described. Finally, some reports describe patients with normal or elevated serum levels of both growth hormone and IGF-I in whom resistance to IGF has been implied in the pathogenesis of small stature.

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome

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

Tsigos, C.; Arai, K.; Latronico, A.C.

1995-07-01

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 famlies with triple A syndrome. The proband with IGD was a homozygote for an A {r_arrow}G substitution, changing tyrosine 254 to cysteine in the third extracellular loopmore » of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome. 19 refs., 1 fig.« less

Copper amplification of prostaglandin E/sub 2/ stimulation of the release of luteinizing hormone-releasing hormone is a postreceptor event

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

Barnea, A.; Cho, G.

1987-01-01

The authors have shown that copper amplifies prostaglandin E/sub 2/ (PGE/sub 2/) stimulation of luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA) and that this process is calcium-dependent. Since a Ca-cAMP pathway has been implicated in PGE/sub 2/ action on the LH-RH neuron, in this study the authors wished to ascertain if copper exerts its effect on the PGE/sub 2/ receptor or on a postreceptor component involved in PGE/sub 2/ action. MEA of adult male rats were incubated for 5 min with 200 ..mu..M Cu/histidine and then incubated for 15 min either with 10 ..mu..M PGE/submore » 2/ (Cu/PGE/sub 2/), 100 ..mu..M forskolin (Cu/forskolin), or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (Cu/cAMP). Basal release of LH-RH was 4.6 +/- 0.45 pg/15 min per MEA determined by radioimmunoassay. Net stimulated release during the 15-min exposure to PGE/sub 2/, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate was 3.6 +/- 0.52, 3.1 +/- 0.39, and 1.6 +/- 0.42 pg/15 min per MEA, respectively. Net stimulated release after exposure to Cu/PGE/sub 2/, Cu/forskolin, or Cu/cAMP indicated that copper amplifies the action of PGE/sub 2/ and forskolin but not cAMP action. When MEA were exposed to a mixture of PGE/sub 2/ and forskolin for 15 min, the effects of these two secretagogues on LH-RH release were not additive. In contrast to PGE/sub 2/ and forskolin, copper did not amplify K/sup +/ stimulation of OH-RH release. These results are supportive of the proposition that PGE/sub 2/ stimulation of OH-RH release is mediated by the Ca-cAMP pathway and that copper amplification of PGE/sub 2/ action is a postreceptor event.« less

Correlation between morphological defects, electron beam-induced current imaging, and the electrical properties of 4H-SiC Schottky diodes

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

Wang, Y.; Ali, G.N.; Mikhov, M.K.

2005-01-01

Defects in SiC degrade the electrical properties and yield of devices made from this material. This article examines morphological defects in 4H-SiC and defects visible in electron beam-induced current (EBIC) images and their effects on the electrical characteristics of Schottky diodes. Optical Nomarski microscopy and atomic force microscopy were used to observe the morphological defects, which are classified into 26 types based on appearance alone. Forward and reverse current-voltage characteristics were used to extract barrier heights, ideality factors, and breakdown voltages. Barrier heights decrease about linearly with increasing ideality factor, which is explained by discrete patches of low barrier heightmore » within the main contact. Barrier height, ideality, and breakdown voltage all degrade with increasing device diameter, suggesting that discrete defects are responsible. Electroluminescence was observed under reverse bias from microplasmas associated with defects containing micropipes. EBIC measurements reveal several types of features corresponding to recombination centers. The density of dark spots observed by EBIC correlates strongly with ideality factor and barrier height. Most morphological defects do not affect the reverse characteristics when no micropipes are present, but lower the barrier height and worsen the ideality factor. However, certain multiple-tailed defects, irregularly shaped defects and triangular defects with 3C inclusions substantially degrade both breakdown voltage and barrier height, and account for most of the bad devices that do not contain micropipes. Micropipes in these wafers are also frequently found to be of Type II, which do not run parallel to the c axis.« less

Correlation Between Morphological Defects, Electron Beam Induced Current Imaging, and the Electrical Properties of 4H-SiC Schottky Diodes

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

Wang,Y.; Ali, G.; Mikhov, M.

2005-01-01

Defects in SiC degrade the electrical properties and yield of devices made from this material. This article examines morphological defects in 4H-SiC and defects visible in electron beam-induced current (EBIC) images and their effects on the electrical characteristics of Schottky diodes. Optical Nomarski microscopy and atomic force microscopy were used to observe the morphological defects, which are classified into 26 types based on appearance alone. Forward and reverse current-voltage characteristics were used to extract barrier heights, ideality factors, and breakdown voltages. Barrier heights decrease about linearly with increasing ideality factor, which is explained by discrete patches of low barrier heightmore » within the main contact. Barrier height, ideality, and breakdown voltage all degrade with increasing device diameter, suggesting that discrete defects are responsible. Electroluminescence was observed under reverse bias from microplasmas associated with defects containing micropipes. EBIC measurements reveal several types of features corresponding to recombination centers. The density of dark spots observed by EBIC correlates strongly with ideality factor and barrier height. Most morphological defects do not affect the reverse characteristics when no micropipes are present, but lower the barrier height and worsen the ideality factor. However, certain multiple-tailed defects, irregularly shaped defects and triangular defects with 3C inclusions substantially degrade both breakdown voltage and barrier height, and account for most of the bad devices that do not contain micropipes. Micropipes in these wafers are also frequently found to be of Type II, which do not run parallel to the c axis.« less

Microscale localization and isolation of light emitting imperfections in monocrystalline silicon solar cells

NASA Astrophysics Data System (ADS)

Gajdoš, Adam; Škvarenina, Lubomír.; Škarvada, Pavel; Macků, Robert

2017-12-01

An imperfections or defects may appear in fabricated monocrystalline solar cells. These microstructural imperfections could have impact on the parameters of whole solar cell. The research is divided into two parts, firstly, the detection and localization defects by using several techniques including current-voltage measurement, scanning probe microscopy (SPM), scanning electron microscope (SEM) and electroluminescence. Secondly, the defects isolation by a focused ion beam (FIB) milling and impact of a milling process on solar cells. The defect detection is realized by I-V measurement under reverse biased sample. For purpose of localization, advantage of the fact that defects or imperfections in silicon solar cells emit the visible and near infrared electroluminescence under reverse biased voltage is taken, and CCD camera measurement for macroscopic localization of these spots is applied. After rough macroscopic localization, microscopic localization by scanning probe microscopy combined with a photomultiplier (shadow mapping) is performed. Defect isolation is performed by a SEM equipped with the FIB instrument. FIB uses a beam of gallium ions which modifies crystal structure of a material and may affect parameters of solar cell. As a result, it is interesting that current in reverse biased sample with isolated defect is smaller approximately by 2 orders than current before isolation process.

Identification and Analysis of Partial Shading Breakdown Sites in CuIn xGa (1-x)Se 2 Modules

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

Palmiotti, Elizabeth; Johnston, Steven; Gerber, Andreas

In this paper, CuIn xGa (1-x) (CIGS) mini-modules are stressed under reverse bias, resembling partial shading conditions, to predict and characterize where failures occur. Partial shading can cause permanent damage in the form of 'wormlike' defects on thin-film modules due to thermal runaway. This results in module-scale power losses. We have used dark lock-in thermography (DLIT) to spatially observe localized heating when reverse-bias breakdown occurs on various CIGS mini-modules. For better understanding of how and where these defects originated and propagated, we have developed techniques where the current is limited during reverse-bias stressing. This allows for DLIT-based detection and detailedmore » studying of the region where breakdown is initiated before thermal runaway leads to permanent damage. Statistics of breakdown sites using current-limited conditions has allowed for reasonable identification of the as-grown defects where permanent breakdown will likely originate. Scanning electron microscope results and wormlike defect analysis show that breakdown originates in defects such as small pits, craters, or cracks in the CIGS layer, and the wormlike defects propagate near the top CIGS interface.« less

Identification and Analysis of Partial Shading Breakdown Sites in CuIn xGa (1-x)Se 2 Modules

DOE PAGES

Palmiotti, Elizabeth; Johnston, Steven; Gerber, Andreas; ...

2017-12-20

In this paper, CuIn xGa (1-x) (CIGS) mini-modules are stressed under reverse bias, resembling partial shading conditions, to predict and characterize where failures occur. Partial shading can cause permanent damage in the form of 'wormlike' defects on thin-film modules due to thermal runaway. This results in module-scale power losses. We have used dark lock-in thermography (DLIT) to spatially observe localized heating when reverse-bias breakdown occurs on various CIGS mini-modules. For better understanding of how and where these defects originated and propagated, we have developed techniques where the current is limited during reverse-bias stressing. This allows for DLIT-based detection and detailedmore » studying of the region where breakdown is initiated before thermal runaway leads to permanent damage. Statistics of breakdown sites using current-limited conditions has allowed for reasonable identification of the as-grown defects where permanent breakdown will likely originate. Scanning electron microscope results and wormlike defect analysis show that breakdown originates in defects such as small pits, craters, or cracks in the CIGS layer, and the wormlike defects propagate near the top CIGS interface.« less

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging: Preprint

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

Prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia: study by 99mTc-sestamibi radionuclide scintigraphy.

PubMed

Ismail, Ahmed M; Rayan, Mona; Adel, Amr; Demerdash, Salah; Atef, Mohamed; Abdallah, Mohamed; Nammas, Wail

2014-02-01

We explored the prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia (CAE), as demonstrated by (99m)Tc-sestamibi scintigraphy. Prospectively, we enrolled 35 patients with angiographically documented CAE and no significant coronary obstruction, who underwent elective coronary angiography. Patients underwent Stress-rest (99m)Tc-sestamibi scintigraphy within 4 days of coronary angiography. They were divided into 2 groups: group I: with normal perfusion scan; and group II: with reversible perfusion defects. The mean age was 49.6 ± 6.9 years; 34 (97.1 %) were males. Seventy-nine (75.2 %) arteries were affected by CAE. Among 79 arteries affected by CAE, affection was diffuse in 37 (46.8 %). Thirteen (37.1 %) patients had normal perfusion scan (group I), whereas 22 (62.9 %) had reversible perfusion defects (group II). Among 22 patients with reversible perfusion defects, 20 (90.9 %) had mild and 2 (9.1 %) had moderate ischemia. Among 49 myocardial segments with reversible perfusion defects, 22 (44.9 %) were basal, 18 (36.7 %) mid-, and 9 (18.4 %) apical segments. Diffuse CAE was significantly more prevalent in group II versus group I, in all 3 major coronary arteries (p < 0.05 for all). In patients with isolated CAE who underwent elective coronary angiography, reversible perfusion defects demonstrated by (99m)Tc-sestamibi scintigraphy were rather prevalent, mostly mild, more likely to affect the basal and mid-segments of the myocardium, and more frequently associated with diffuse ectasia.

[Repairing of soft tissue defect in leg by free vascularized thoracoumbilical flap with reversed flow].

PubMed

Xu, Y Q; Li, Z Y; Li, J

2000-11-01

To investigate the clinical effect of free vascularized thoracoumbilical flap with reversal flow in repairing the soft tissue defect in leg with tibia exposure. Forty-four casting mould specimens of leg arteries were studied firstly. Then 25 cases with soft tissue defect and tibia exposure in the proximal-middle segment of leg were adopted in this study. Among them, 18 cases had long distance thrombosis of the anterior tibial vessels or posterior tibial vessels due to traumatic lesion. The maximal size of defect was 28 cm x 11 cm and the minimal size of defect was 11 cm x 9 cm. In operation, the thoracoumbilical flap which was based on the inferior epigastric vessels was anastomosed to the distal end of the anterior tibial vessels or posterior tibial vessels. Anterior tibial artery, posterior tibial artery and fibular artery had rich communication branches in foot and ankle. All the flaps survived, the color and cosmetic result of them were good. The free vascularized thoracoumbilical flap with reversed flow is practical in repairing the soft tissue defect of leg with tibia exposure. Either the anterior tibial vessels or the posterior tibial vessels is normal, and the distal end of injured blood vessels is available, this technique can be adopted.

Evidence for Alterations in Stimulatory G proteins and Oxytocin Levels in Children with Autism

PubMed Central

Jacobson, Jill D.; Ellerbeck, Kathryn A.; Kelly, Kelsie A.; Fleming, Kandace K.; Jamison, T. Rene; Coffey, Charles W.; Smith, Catherine M.; Reese, R. Matthew; Sands, Scott A.

2014-01-01

The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin’s post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways. PMID:24485488

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

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

Tellier, P.; Paycha, F.; Antony, I.

1988-08-01

In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on themore » size and severity of myocardial thallium-201 defects. Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.« less

Purinergic modulation of frog electroretinographic responses: The role of the ionotropic receptor P2X7.

PubMed

Kupenova, Petia; Popova, Elka; Vitanova, Liliya

2017-01-01

The contribution of the purinergic receptors P2X7 (P2X7Rs) to the electroretinographic (ERG) responses was studied by testing the effects of the selective P2X7R antagonist A438079 and the selective P2X7R agonist Bz-ATP on the electroretinograms obtained in perfused frog (Rana ridibunda) eyecup preparations under a variety of stimulation conditions. The P2X7R blockade by 200 µM A438079 diminished the amplitude of the photoreceptor components: the a-wave and the pharmacologically isolated mass receptor potential. In the pure rod-driven and pure cone-driven responses, the amplitude of the postreceptoral ON (b-wave) and OFF (d-wave) components was also diminished. The OFF responses were affected to a greater extent compared to the ON responses. In the mixed rod- and cone-driven responses, obtained in the mesopic intensity range, the b-wave amplitude was increased, while the d-wave amplitude was decreased. The amplitude of the oscillatory potentials was diminished. The relative amplitude changes produced by the P2X7R blockade were greater in the dark-adapted compared to the light-adapted eyes. The application of 100 µM Bz-ATP produced small effects opposite to those of the antagonist, while a prolonged (>20 min) treatment with 1 mM Bz-ATP resulted in a significant amplitude reduction or even abolishment of b- and d-waves. Our results show that endogenous ATP through its P2X7Rs exerts significant, mostly potentiating effects on the ERG photoreceptor and postreceptoral responses. There is a clear ON/OFF asymmetry of the effects on the ERG postreceptoral responses favoring OFF responses: they are always strongly potentiated, while the ON responses are either less potentiated (in the rod-driven and most of the cone-driven responses) or even inhibited (in the mixed rod- and cone-driven responses). The overstimulation of P2X7Rs can produce acute pathological changes, that is, a decrease or abolishment of the ERG responses.

Reverse-flow retroauricular island flap in facial reconstruction.

PubMed

Benlier, Erol; Top, Husamettin; Cinar, Can; Yazar, Sukru; Aygit, A Cemal; Cetinkale, Oguz

2007-12-01

Reconstruction of facial skin defects requires good-quality skin cover to satisfy aesthetic expectations of patient, especially when the skin defect is on the uncovered area of the face. Limitations in the available local tissue and donor-site morbidity restrict the options. In an effort to solve these problems, we have begun to use a subcutaneous pedicled retroauricular reverse-flow flap. Between January 1997 and December 2005, reverse-flow subcutaneous pedicled retroauricular island flap was used to cover facial defects in 12 patients who underwent surgical excision of skin tumor. The patients ranged in age from 44 to 81 years with a mean age of 58 years. Only one case experienced a superficial necrosis in the distal one-quarter part of the flap. The functional and aesthetic results were satisfactory for both patients and surgeons, and no tumor recurrence was observed during the 12 to 28 months (mean, 18.8 months) follow-up period. This flap can be used reliably for the reconstruction of facial skin defects of small and medium size. The preference of frontal branch pedicled flap enables more distal facial area defects to be covered, such as dorsal nasal, nasolabial, and upper lip, than flaps based on parietal branch.

Monocyte function in infectious mononucleosis: evidence for a reversible cellular defect.

PubMed

Britton, S

1976-10-01

Migration of blood monocytes from patients with acute infectious mononucleosis and from normal controls was measured against chemotactic factors in serum. Moncytes from patients with acute infectious mononucleosis showed decreased migration as compared with that of control monocytes. However, serum from patients with infectious mononucleosis contained normal or above normal amounts of chemotaxins for monocytes. The migratory defect of monocytes from patients with infectious mononucleosis was reversible within three months after the onset of diesease. The cause of this monocyte migration defect in infectious mononucleosis is though to be an in vivo blockade of receptors on monocytes for chemotaxins, and it is speculated that this defect can partially explain the explain the ablated delayed-hypersensitivity skin reactions in this disease.

Achieving fixation in glenoids with superior wear using reverse shoulder arthroplasty.

PubMed

Roche, Christopher P; Stroud, Nicholas J; Martin, Brian L; Steiler, Cindy A; Flurin, Pierre-Henri; Wright, Thomas W; Zuckerman, Joseph D; Dipaola, Matthew J

2013-12-01

Superior glenoid wear is a common challenge with reverse shoulder arthroplasty and, if left uncorrected, can result in superior glenoid tilt, which increases the risk of aseptic glenoid loosening. This study evaluates the impact of an E2 superior defect on reverse shoulder glenoid fixation in composite scapulae after correction of glenoid tilt by use of 2 different glenoid reaming techniques: eccentric reaming and off-axis reaming. A superior glenoid defect was created in 14 composite scapulae. The superior defect was corrected by 2 different glenoid reaming techniques: (1) eccentric reaming with implantation of a standard glenoid baseplate and (2) off-axis reaming with implantation of a superior-augment glenoid baseplate. Each corrected superior-defect scapula was then cyclically loaded (along with a control group consisting of 7 non-worn scapulae) for 10,000 cycles at 750 N; glenoid baseplate displacement was measured for each group to quantify fixation before and after cyclic loading. Regardless of the glenoid reaming technique or the glenoid baseplate type, each standard and superior-augment glenoid baseplate remained well fixed in this superior-defect model scenario after cyclic loading. No differences in baseplate displacement were observed either before or after cyclic loading between groups. Our results suggest that either glenoid reaming technique may be used to achieve fixation in the clinically challenging situation of superior wear with reverse shoulder arthroplasty. Basic science, biomechanical study. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

The reverse sural artery fasciomusculocutaneous flap for small lower-limb defects: the use of the gastrocnemius muscle cuff as a plug for small bony defects following debridement of infected/necrotic bone.

PubMed

Al-Qattan, M M

2007-09-01

The reverse sural artery fasciomusculocutaneous flap is a modification of the original fasciocutaneous flap in which a midline gastrocnemius muscle cuff around the buried sural pedicle is included in the flap. This modification was done to improve the blood supply of the distal part of the flap, which is harvested from the upper leg. The aim of this paper is to demonstrate that there is another important advantage of the modified flap: the use of the muscle cuff as a "plug" for small lower limb defects following debridement of infected/necrotic bone. A total of 10 male adult patients with small complex lower-limb defects with underlying bone pathology were treated with the modified flap using the muscle component to fill up the small bony defects. The bony pathology included necrotic exposed bone without evidence of osteomyelitis or wound infection (n = 1), an underlying neglected tibial fracture with wound infection (n = 4), and a sinus at the heel with underlying calcaneal osteomyelitis (n = 5). Primary wound healing of the flap into the defect was noted in all patients. No recurrence of calcaneal osteomyelitis was seen and all tibial fractures united following appropriate orthopedic fixation. It was concluded that the reverse sural artery fasciomusculocutaneous flap is well suited for small complex lower-limb defects with underlying bone pathology.

Transformation between divacancy defects induced by an energy pulse in graphene.

PubMed

Xia, Jun; Liu, XiaoYi; Zhou, Wei; Wang, FengChao; Wu, HengAn

2016-07-08

The mutual transformations among the four typical divacancy defects induced by a high-energy pulse were studied via molecular dynamics simulation. Our study revealed all six possible mutual transformations and found that defects transformed by absorbing energy to overcome the energy barrier with bonding, debonding, and bond rotations. The reversibility of defect transformations was also investigated by potential energy analysis. The energy difference was found to greatly influence the transformation reversibility. The direct transformation path was irreversible if the energy difference was too large. We also studied the correlation between the transformation probability and the input energy. It was found that the transformation probability had a local maxima at an optimal input energy. The introduction of defects and their structural evolutions are important for tailoring the exceptional properties and thereby performances of graphene-based devices, such as nanoporous membranes for the filtration and desalination of water.

Prevalence of ECG changes during adenosine stress and its association with perfusion defect on myocardial perfusion scintigraphy.

PubMed

Taywade, Sameer K; Ramaiah, Vijayaraghavan L; Basavaraja, Harish; Venkatasubramaniam, Parameswaran R; Selvakumar, Job

2017-04-01

Myocardial perfusion scintigraphy (MPS) is a valuable, noninvasive imaging modality in the evaluation of patients with coronary artery disease. Adenosine stress may occasionally be associated with ECG changes. This study evaluated the strength of association between adenosine stress-related ECG changes and perfusion defects on Tc-MPS. 117 (mean age: 61.25±9.27 years; sex: men 87, women 30) patients with known/suspected coronary artery disease underwent adenosine stress MPS. ECG was monitored continuously during adenosine stress for ST-depression. On the basis of the summed difference score, reversible perfusion defects were categorized as follows: normal: less than 4, mild: 4-8, moderate: 9-13, and severe: more than 13. ST-depression was observed in 27/117 (23.1%) and reversible perfusion defects were observed in 18/27 (66.66%) patients. 2/27, 6/27, and 10/27 patients had mild, moderate, and severe ischemia, respectively. 9/27 patients had normal perfusion. ECG changes and perfusion defects showed a moderate strength of association (correlation coefficient r=0.35, P=0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of ECG findings for prediction of ischemia were 35.29, 86.36, 67.67, and 63.33%, respectively. ECG changes during adenosine stress are not uncommon. It shows a moderate strength of association with reversible perfusion defects. ECG changes during adenosine merit critical evaluation of MPS findings.

Simultaneous chromatic and luminance human electroretinogram responses.

PubMed

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-07-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

Oxygen optical gas sensing by reversible fluorescence quenching in photo-oxidized poly(9,9-dioctylfluorene) thin films.

PubMed

Anni, M; Rella, R

2010-02-04

We investigated the fluorescence (FL) dependence on the environment oxygen content of poly(9,9-dioctylfluorene) (PF8) thin films. We show that the PF8 interactions with oxygen are not limited to the known irreversible photo-oxidation, resulting in the formation of Keto defects, but also reversible FL quenching is observed. This effect, which is stronger for the Keto defects than for the PF8, has been exploited for the realization of a prototype oxygen sensor based on FL quenching. The sensing sensitivity of Keto defects is comparable with the state of the art organic oxygen sensors based on phosphorescence quenching.

Fluoropolymer Dynamics: Effects of Perfluoromethyl Branches

NASA Astrophysics Data System (ADS)

Eby, R. K.; Holt, D. B.; Farmer, B. L.; Adams, D. D.

1997-03-01

Previous simulations of polytetrafluoroethylene (PTFE) in the solid state showed that the interaction and movement of helix reversals plays an important role in the dynamic behavior of this important polymer. Copolymers of TFE and hexafluoropropylene (HFP), which can be viewed as PTFE with perfluoromethyl (PFM) group branch defects, is also widely used. Molecular mechanics and dynamics calculations have been performed with PTFE chain clusters containing PFM branches to investigate the effect of these defects on the local crystalline environment (and vice versa) and on the motions and interactions of helix reversals. Initial results indicate that helix reversals are attracted to sites of PFM branches in a chain. Such an interaction will impede the motions of helix reversals and have an impact on macroscopic mechanical properties such as resistance to plastic deformation under shear.

I2 basal stacking fault as a degradation mechanism in reverse gate-biased AlGaN/GaN HEMTs

NASA Astrophysics Data System (ADS)

Lang, A. C.; Hart, J. L.; Wen, J. G.; Miller, D. J.; Meyer, D. J.; Taheri, M. L.

2016-09-01

Here, we present the observation of a bias-induced, degradation-enhancing defect process in plasma-assisted molecular beam epitaxy grown reverse gate-biased AlGaN/GaN high electron mobility transistors (HEMTs), which is compatible with the current theoretical framework of HEMT degradation. Specifically, we utilize both conventional transmission electron microscopy and aberration-corrected transmission electron microscopy to analyze microstructural changes in not only high strained regions in degraded AlGaN/GaN HEMTs but also the extended gate-drain access region. We find a complex defect structure containing an I2 basal stacking fault and offer a potential mechanism for device degradation based on this defect structure. This work supports the reality of multiple failure mechanisms during device operation and identifies a defect potentially involved with device degradation.

Posterior shoulder dislocation with a reverse Hill-Sachs lesion treated with frozen femoral head bone allograft combined with osteochondral autograft transfer.

PubMed

Mastrokalos, Dimitrios S; Panagopoulos, Georgios N; Galanopoulos, Ioannis P; Papagelopoulos, Panayiotis J

2017-10-01

Management of a posterior shoulder dislocation with an associated reverse Hill-Sachs lesion is challenging, both diagnostically and therapeutically. Diagnosis is frequently delayed or missed, whereas the resulting humeral head defect is often larger and more difficult to salvage than in anterior shoulder dislocations. This report presents the case of a 29-year-old male with a recurrent posterior shoulder dislocation associated with a large reverse Hill-Sachs defect, treated with bone augmentation of the lesion with a combination of fresh femoral head allograft and a locally harvested humeral head autograft transfer, with a successful outcome. Level of evidence V.

Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

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

Spina, D.; Rigby, P.J.; Paterson, J.W.

1989-11-01

The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using (125I)iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissuemore » featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.« less

Insulin resistance in porphyria cutanea tarda.

PubMed

Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

1989-06-01

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

NASA Technical Reports Server (NTRS)

Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

2007-01-01

Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

Reverse pedicle-based greater saphenous neuro-veno-fasciocutaneous flap for reconstruction of lower leg and foot.

PubMed

Kansal, Sandeep; Goil, Pradeep; Agarwal, Vijay; Agarwal, Swarnima; Mishra, Shashank; Agarwal, Deepak; Singh, Pranay

2014-01-01

Paucity of soft tissue available locally for reconstruction of defects in leg and foot presents a challenge for reconstructive surgeon. The use of reverse pedicle-based greater saphenous neuro-veno-fasciocutaneous flap in reconstruction of lower leg and foot presents a viable alternative to free flap and cross-leg flap reconstruction. The vascular axis of the flap is formed by the vessels accompanying the saphenous nerve and the greater saphenous vein. We present here our experience with reverse saphenous neurocutaneous flap which provides a stable cover without the need to sacrifice any important vessel of leg. The study is conducted from March 2003 through Dec 2009 and included a total of 96 patients with defects in lower two-thirds of leg and foot. There are 74 males and 22 females. Distal pivot point was kept approximately 5-6 cm from tip of medial malleolus, thus preserving the distal most perforator, and the flap is turned and inserted into the defect. Donor site is covered with a split thickness skin graft. Postoperative follow-up period was 6 weeks to 6 months. The procedure is uneventful in 77 cases. Infection is observed in 14 cases. Partial flap necrosis occurs in 2 cases. Total flap necrosis is noted in 3 cases. Reverse pedicle saphenous flap can be used to reconstruct defects of lower one-third leg and foot with a reliable blood supply with a large arc of rotation while having minimal donor site morbidity.

Simultaneous chromatic and luminance human electroretinogram responses

PubMed Central

Parry, Neil R A; Murray, Ian J; Panorgias, Athanasios; McKeefry, Declan J; Lee, Barry B; Kremers, Jan

2012-01-01

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats’ ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing. PMID:22586211

Case Report Reconstruction of Exposed Ilium With Reverse Turnover Latissimus Dorsi Muscle Flap

PubMed Central

Hayashida, Kenji; Endo, Yoshie; Kamebuchi, Katsuhiko

2011-01-01

Objective: It is difficult to cover a large skin and soft tissue defect with exposure of the ilium. We therefore performed a new reconstruction technique, using a reverse latissimus dorsi muscle flap fed by perforating branches of only the 10th intercostal artery. Methods: A 45-year-old man had a large traumatic defect located on the hip with exposure of the iliac crest. After confirming and preserving perforating branches of the 10th intercostal artery, the latissimus dorsi muscle flap was turned over just proximal to the perforating branch, and a split-thickness skin graft was performed over the flap. Results: The skin graft took place well and there were no circulation problems. Conclusions: This flap covered a larger area on the hip than the musculocutaneous flap. Furthermore, this is easier to perform and is less invasive than a vascularized free flap. Skin and soft tissue defects that expose bones of the lumbar or hip region can be reconstructed with a local flap; however, the deficit is small for this coverage and usually there is little skin and soft tissue to cover the wound defect in the surrounding area. Thus, it is often difficult to deal with large defects. We performed a reconstruction, using a reverse latissimus dorsi flap fed by perforating branches of the 10th intercostal artery for a large skin and soft tissue defect of the hip with exposure of the iliac crest, resulting in a good outcome. This technique is thought to be useful for reconstruction when the ilium is exposed, and we report the case and surgical procedure. PMID:21559059

Time Reversal Method for Pipe Inspection with Guided Wave

NASA Astrophysics Data System (ADS)

Deng, Fei; He, Cunfu; Wu, Bin

2008-02-01

The temporal-spatial focusing effect of the time reversal method on the guided wave inspection in pipes is investigated. A steel pipe model with outer diameter of 70 mm and wall thickness of 3.5 mm is numerically built to analyse the reflection coefficient of L(0,2) mode when the time reversal method is applied in the model. According to the calculated results, it is shown that a synthetic time reversal array method is effective to improve the signal-to-noise ratio of a guided wave inspection system. As an intercepting window is widened, more energy can be included in a re-emitted signal, which leads to a large reflection coefficient of L(0,2) mode. It is also shown that when a time reversed signal is reapplied in the pipe model, by analysing the motion of the time reversed wave propagating along the pipe model, a defect can be identified. Therefore, it is demonstrated that the time reversal method can be used to locate the circumferential position of a defect in a pipe. Finally, through an experiment corresponding with the pipe model, the experimental result shows that the above-mentioned method can be valid in the inspection of a pipe.

Hybrid algorithms for fuzzy reverse supply chain network design.

PubMed

Che, Z H; Chiang, Tzu-An; Kuo, Y C; Cui, Zhihua

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods.

Hybrid Algorithms for Fuzzy Reverse Supply Chain Network Design

PubMed Central

Che, Z. H.; Chiang, Tzu-An; Kuo, Y. C.

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods. PMID:24892057

Effects of gamma-irradiation on cotyledon cell separation and pectin solubilisation in hard-to-cook cowpeas.

PubMed

Jombo, Talknice Z; Minnaar, Amanda; Taylor, John Rn

2018-03-01

Cowpeas stored under high temperature and humidity develop the hard-to-cook defect (HTC). This defect greatly increases cooking times and energy costs. To better understand the mechanisms involved in the HTC defect development, the effects of gamma-irradiation on cotyledon cellular structure and pectin solubility in two cowpea cultivars with different susceptibility to HTC defect were investigated. Gamma-irradiation decreased cotyledon cell wall thickness, increased cell size, and intercellular spaces in both cowpea cultivars and reduced cooking time of the less HTC susceptible cultivar. However, it did not reverse the HTC defect in the susceptible cultivar. Gamma-irradiation also increased the levels of cold water- and hot water-soluble pectin. The irradiation effects were thus mainly due to hydrolysis of pectin fractions in the cell walls. However, chelator-soluble pectin (CSP) solubility was not affected. As the cell wall changes brought about by gamma-irradiation were associated with pectin solubilisation, this supports the phytate-phytase-pectin theory as a major cause of the HTC defect. However, the non-reversal of the defect in HTC susceptible cowpeas and the absence of an effect on CSP indicate that other mechanisms are involved in HTC defect development in cowpeas, possibly the formation of alkali-soluble, ester bonded pectins. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

PubMed

Clancy, R L; Gleeson, M; Cox, A; Callister, R; Dorrington, M; D'Este, C; Pang, G; Pyne, D; Fricker, P; Henriksson, A

2006-04-01

Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Impairment of Human Immunodeficiency Virus Type-1 Integrase SUMOylation Correlates with an Early Replication Defect*

PubMed Central

Zamborlini, Alessia; Coiffic, Audrey; Beauclair, Guillaume; Delelis, Olivier; Paris, Joris; Koh, Yashuiro; Magne, Fabian; Giron, Marie-Lou; Tobaly-Tapiero, Joelle; Deprez, Eric; Emiliani, Stephane; Engelman, Alan; de Thé, Hugues; Saïb, Ali

2011-01-01

HIV-1 integrase (IN) orchestrates the integration of the reverse transcribed viral cDNA into the host cell genome and participates also in other steps of HIV-1 replication. Cellular and viral factors assist IN in performing its multiple functions, and post-translational modifications contribute to modulate its activities. Here, we show that HIV-1 IN is modified by SUMO proteins and that phylogenetically conserved SUMOylation consensus motifs represent major SUMO acceptor sites. Viruses harboring SUMOylation site IN mutants displayed a replication defect that was mapped during the early stages of infection, before integration but after reverse transcription. Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication. PMID:21454548

Is there any advantage to the acquisition of 24-hour thallium images, in the presence of persistent perfusion defects at 4 h after reinjection?

PubMed

Bobba, K; Botvinick, E H; Sciammarella, M G; Starsken, N F; Zhu, Y Y; Lapidus, A; Dae, M W

1998-05-01

We determined the incidence of delayed 24-h reversibility post thallium-201 reinjection and imaging at 4 h, as well as the prognostic and significance of such delayed reversibility. We studied 46 consecutive patients with persistent thallium-201 perfusion or incompletely reversible single-photon emission tomography (SPET) perfusion defects acquired within 10 min after reinjection performed 4 h after stress. In 38 of 46 patients (82%) 24-h images showed no further reversibility beyond the post-reinjection 4-h study (group A). Eight of 46 patients (17%) demonstrated reversibility on 24-h imaging (group B). Of these eight, three patients showed no improvement compared with the post-stress images, with a mean perfusion score of the abnormal segments of 1. 25+/-0.50 on the 4-h images, and of 3.00 on the 24-h images, where normal is 4. Four patients presented with nine mixed regions. Four of these regions showed an improvement in the mean perfusion score of 2.50+/-0.58 on 4- and 24-h images. Two of them, with moderate/severe defects, demonstrated complete reversibility at 4-h post-reinjection imaging. In addition, five other regions presented no improvement at 4-h imaging, but showed an improvement in the mean perfusion score from 0.80+/-0.84 at 4-h to 3.30+/-0.89 at 24-h imaging. Two of these regions in one patient showed a severe perfusion score of 0 at 4 h, and complete reversibility at 24 hours, with a mean score improvement of 4. Another patient had three severe perfusion defects; two of them redistributed partially at 4 h and completely at 24 h. The remaining segment with a perfusion score of 0 at 4 h, presented complete reversibility with a score of 4 at 24 h. Two (4%) patients revealed significant reversibility at 24 h in a region that was severely underperfused after post-reinjection imaging at 4 h. Among group B patients, 75% (6/8) had recent acute ischemic syndrome, compared with only 13% (5/38) in group A (P = 0. 001). Among 11 patients with unstable angina, six (55%) had evidence of delayed 24-h reversibility, compared with 2 of 35 (6%) patients without clinically acute ischemia (P = 0.001). On follow-up, there were seven (17%) cardiac deaths among the 38 group A patients but three (38%) among the eight group B patients (P = 0.3). These findings suggest that although the presence of delayed 24-h 201Tl, post-reinjection reversibility is infrequent, it has potential clinical importance. Thus, delayed 24-h imaging should be considered in the context of unstable angina or other acute coronary syndromes.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2015-10-01

IFM ) through the separated bone cortices (fracture gap). In research funded by a CDMRP Idea Development Award, we used a rat segmental defect...491, 2011. [3] V. Glatt, M . Miller, a Ivkovic, F. Liu, N. Parry, D. Griffin, M . Vrahas, and C. Evans, “Improved healing of large segmental defects...2012. [4] M . Mehta, S . Checa, J. Lienau, D. Hutmacher, and G. N. Duda, “In vivo tracking of segmental bone defect healing reveals that callus

Effect of threading defects on InGaN /GaN multiple quantum well light emitting diodes

NASA Astrophysics Data System (ADS)

Ferdous, M. S.; Wang, X.; Fairchild, M. N.; Hersee, S. D.

2007-12-01

Photoelectrochemical etching was used to measure the threading defect (TD) density in InGaN multiple quantum well light-emitting diodes (LEDs) fabricated from commercial quality epitaxial wafers. The TD density was measured in the LED active region and then correlated with the previously measured characteristics of these LEDs. It was found that the reverse leakage current increased exponentially with TD density. The temperature dependence of this dislocation-related leakage current was consistent with a hopping mechanism at low reverse-bias voltage and Poole-Frenkel emission at higher reverse-bias voltage. The peak intensity and spectral width of the LED electroluminescence were found to be only weakly dependent on TD density for the measured TD range of 1×107-2×108cm-2.

Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

PubMed

Johnson, Jennifer A; Hemnes, Anna R; Perrien, Daniel S; Schuster, Manfred; Robinson, Linda J; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R; Tada, Yuji; Harral, Julie W; Talati, Megha; Lane, Kirk B; Fagan, Karen A; West, James

2012-03-01

The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

PubMed

Schiffmann, D A; White, J H; Cooper, A; Nutley, M A; Harding, S E; Jumel, K; Solari, R; Ray, K P; Gay, N J

1999-09-07

In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

Structural analysis of retinal photoreceptor ellipsoid zone and postreceptor retinal layer associated with visual acuity in patients with retinitis pigmentosa by ganglion cell analysis combined with OCT imaging

PubMed Central

Liu, Guodong; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang

2016-01-01

Abstract The aim of this study was to examine changes in photoreceptor ellipsoid zone (EZ) and postreceptor retinal layer in retinitis pigmentosa (RP) patients by ganglion cell analysis (GCA) combined with optical coherence tomography (OCT) imaging to evaluate the structure–function relationships between retinal layer changes and best corrected visual acuity (BCVA). Sixty-eight eyes of 35 patients with RP and 65 eyes of 35 normal controls were analyzed in the study. The average length of EZ was 911.1 ± 208.8 μm in RP patients, which was shortened with the progression of the disease on the OCT images. The average ganglion cell–inner plexiform layer thickness (GCIPLT) was 54.7 ± 18.9 μm in RP patients, while in normal controls it was 85.6 ± 6.8 μm. The GCIPLT in all quarters became significantly thinner along with outer retinal thinning. There was a significantly positive correlation between BCVA and EZ (r = −0.7622, P < 0.001) and GCIPLT (r = −0.452, P < 0.001). Therefore, we assess the retinal layer changes from a new perspective in RP patients, which suggests that EZ and GCIPLT obtained by GCA combined with OCT imaging are the direct and valid indicators to diagnosis and predict the pathological process of RP. PMID:28033301

Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

PubMed

Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

2008-01-01

Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

Dystrophin Is Required for Proper Functioning of Luminance and Red-Green Cone Opponent Mechanisms in the Human Retina.

PubMed

Barboni, Mirella Telles Salgueiro; Martins, Cristiane Maria Gomes; Nagy, Balázs Vince; Tsai, Tina; Damico, Francisco Max; da Costa, Marcelo Fernandes; de Cassia, Rita; Pavanello, M; Lourenço, Naila Cristina Vilaça; de Cerqueira, Antonia Maria Pereira; Zatz, Mayana; Kremers, Jan; Ventura, Dora Fix

2016-07-01

Visual information is processed in parallel pathways in the visual system. Parallel processing begins at the synapse between the photoreceptors and their postreceptoral neurons in the human retina. The integrity of this first neural connection is vital for normal visual processing downstream. Of the numerous elements necessary for proper functioning of this synaptic contact, dystrophin proteins in the eye play an important role. Deficiency of muscle dystrophin causes Duchenne muscular dystrophy (DMD), an X-linked disease that affects muscle function and leads to decreased life expectancy. In DMD patients, postreceptoral retinal mechanisms underlying scotopic and photopic vision and ON- and OFF-pathway responses are also altered. In this study, we recorded the electroretinogram (ERG) while preferentially activating the (red-green) opponent or the luminance pathway, and compared data from healthy participants (n = 16) with those of DMD patients (n = 10). The stimuli were heterochromatic sinusoidal modulations at a mean luminance of 200 cd/m2. The recordings allowed us also to analyze ON and OFF cone-driven retinal responses. We found significant differences in 12-Hz response amplitudes and phases between controls and DMD patients, with conditions with large luminance content resulting in larger response amplitudes in DMD patients compared to controls, whereas responses of DMD patients were smaller when pure chromatic modulation was given. The results suggest that dystrophin is required for the proper function of luminance and red-green cone opponent mechanisms in the human retina.

Characterization of a Case of Pigmentary Retinopathy in Sanfilippo Syndrome Type IIIA Associated with Compound Heterozygous Mutations in the SGSH Gene.

PubMed

Wilkin, Justin; Kerr, Natalie C; Byrd, Kathryn W; Ward, Jewell C; Iannaccone, Alessandro

2016-06-01

To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel. Heparan-N-sulfatidase enzyme function testing in skin fibroblasts and white blood cells and SGSH gene sequencing were obtained. Clinical office examinations, examinations under anesthesia, electroretinogram, spectral domain optical coherence tomography (SD-OCT), and fundus photography were performed over a 5-year period. Fundus examination revealed a progressive breadcrumb-like pigmentary retinopathy with perifoveal pigmentary involvement. SD-OCT showed loss of normal neuroretinal lamination and cystic macular changes responsive to treatment with carbonic anhydrase inhibitors. Electroretinography exhibited complex characteristics indicative of a generalized retinal rod > cone dysfunction with significant ON > OFF postreceptoral response compromise. Sequencing revealed compound heterozygous mutations in the SGSH gene, the novel c.88G > C (p.A30P) change and a second, previously reported one (c.734G > A, p.R245H). We have identified ocular features of a patient with Sanfilippo syndrome type IIIA harboring a novel SGHS mutation that were not previously known to occur in this disease - namely, a progressive retinopathy with distinctive features, cystic macular changes responsive to carbonic anhydrase inhibitors, and complex electroretinographic abnormalities consistent with postreceptoral dysfunction. SD-OCT imaging revealed retinal lamination changes consistent with previously reported histologic studies. Both the SD-OCT and the electroretinogram changes appear attributable to intraretinal deposition of heparan sulfate.

Implication of Proteins Containing Tetratricopeptide Repeats in Conditional Virulence Phenotypes of Legionella pneumophila

PubMed Central

Bandyopadhyay, Purnima; Sumer, Eren U.; Jayakumar, Deepak; Liu, Shuqing; Xiao, Huifang

2012-01-01

Legionella pneumophila, the causative agent of Legionnaires' disease, is a ubiquitous freshwater bacterium whose virulence phenotypes require a type IV secretion system (T4SS). L. pneumophila strain JR32 contains two virulence-associated T4SSs, the Dot/Icm and Lvh T4SSs. Defective entry and phagosome acidification phenotypes of dot/icm mutants are conditional and reversed by incubating broth-grown stationary-phase cultures in water (WS treatment) prior to infection, as a mimic of the aquatic environment of Legionella. Reversal of dot/icm virulence defects requires the Lvh T4SS and is associated with a >10-fold induction of LpnE, a tetratricopeptide repeat (TPR)-containing protein. In the current study, we demonstrated that defective entry and phagosome acidification phenotypes of mutants with changes in LpnE and EnhC, another TPR-containing protein, were similarly reversed by WS treatment. In contrast to dot/icm mutants for which the Lvh T4SS was required, reversal for the ΔlpnE or the ΔenhC mutant required that the other TPR-containing protein be present. The single and double ΔlpnE and ΔenhC mutants showed a hypersensitivity to sodium ion, a phenotype associated with dysfunction of the Dot/Icm T4SS. The ΔlpnE single and the ΔlpnE ΔenhC double mutant showed 3- to 9-fold increases in translocation of Dot/Icm T4SS substrates, LegS2/SplY and LepB. Taken together, these data identify TPR-containing proteins in a second mechanism by which the WS mimic of a Legionella environmental niche can reverse virulence defects of broth-grown cultures and implicate LpnE and EnhC directly or indirectly in translocation of Dot/Icm T4SS protein substrates. PMID:22563053

Propeller Flap for Complex Distal Leg Reconstruction: A Versatile Alternative when Reverse Sural Artery Flap is Not Feasible.

PubMed

Ademola, Samuel A; Michael, Afieharo I; Oladeji, Femi J; Mbaya, Kefas M; Oyewole, O

2015-01-01

Reverse sural artery fasciocutaneous flap has become a workhorse for the reconstruction of distal leg soft tissue defects. When its use is not feasible, perforator-based propeller flap offers a better, easier, faster, and cheaper alternative to free flap. We present our experience with two men both aged 34 years who sustained Gustilo 3B injuries from gunshot. The donor area for reversed sural artery flap was involved in the injuries. They had early debridement, external fixation, and wound coverage with perforator-based propeller flaps. The donor sites were covered with skin graft. All flaps survived. There were minor wound edge ulcers due to the pressure of positioning that did not affect flap survival and the ulcers healed with conservative management. Perforator-based propeller flap is a versatile armamentarium for reconstruction of soft tissue defects of the distal leg in resource-constrained settings, especially when the donor area for a reverse flow sural flap artery is involved in the injury.

Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1.

PubMed

Roper, James A; Williamson, Rosalind C; Bally, Blandine; Cowell, Christopher A M; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D

2015-11-01

Chronic skin-healing defects are one of the leading challenges to lifelong well-being, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed, and driving wound contraction. We discover that mechanical stimulation of the skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples. By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in the skin, we identify future opportunities for management of chronic wounds.

Imaging Study of Multi-Crystalline Silicon Wafers Throughout the Manufacturing Process: Preprint

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

Johnston, S.; Yan, F.; Zaunbracher, K.

2011-07-01

Imaging techniques are applied to multi-crystalline silicon bricks, wafers at various process steps, and finished solar cells. Photoluminescence (PL) imaging is used to characterize defects and material quality on bricks and wafers. Defect regions within the wafers are influenced by brick position within an ingot and height within the brick. The defect areas in as-cut wafers are compared to imaging results from reverse-bias electroluminescence and dark lock-in thermography and cell parameters of near-neighbor finished cells. Defect areas are also characterized by defect band emissions. The defect areas measured by these techniques on as-cut wafers are shown to correlate to finishedmore » cell performance.« less

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

PubMed Central

Kopera, Huira C.; Moldovan, John B.; Morrish, Tammy A.; Moran, John V.

2011-01-01

Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that contain activities required for conventional retrotransposition by a mechanism termed target-site primed reverse transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic subunit-deficient CHO cell lines, which are defective for the nonhomologous end-joining DNA repair pathway, revealed an alternative endonuclease-independent (ENi) pathway for L1 retrotransposition. Interestingly, some ENi retrotransposition events in DNA protein kinase catalytic subunit-deficient cells are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease-defective L1 ribonucleoprotein particles can use oligonucleotide adapters that mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA. Importantly, these ribonucleoprotein particles also contain a nuclease activity that can process the oligonucleotide adapters before the initiation of reverse transcription. Finally, we demonstrate that ORF1p is not strictly required for ENi retrotransposition at dysfunctional telomeres. Thus, these data further highlight similarities between the mechanism of ENi L1 retrotransposition and telomerase. PMID:21940498

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase.

PubMed

Kopera, Huira C; Moldovan, John B; Morrish, Tammy A; Garcia-Perez, Jose Luis; Moran, John V

2011-12-20

Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that contain activities required for conventional retrotransposition by a mechanism termed target-site primed reverse transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic subunit-deficient CHO cell lines, which are defective for the nonhomologous end-joining DNA repair pathway, revealed an alternative endonuclease-independent (ENi) pathway for L1 retrotransposition. Interestingly, some ENi retrotransposition events in DNA protein kinase catalytic subunit-deficient cells are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease-defective L1 ribonucleoprotein particles can use oligonucleotide adapters that mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA. Importantly, these ribonucleoprotein particles also contain a nuclease activity that can process the oligonucleotide adapters before the initiation of reverse transcription. Finally, we demonstrate that ORF1p is not strictly required for ENi retrotransposition at dysfunctional telomeres. Thus, these data further highlight similarities between the mechanism of ENi L1 retrotransposition and telomerase.

Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in APPNL-F/NL-F knock-in mice.

PubMed

Shah, Disha; Latif-Hernandez, Amira; De Strooper, Bart; Saito, Takashi; Saido, Takaomi; Verhoye, Marleen; D'Hooge, Rudi; Van der Linden, Annemie

2018-04-19

Amyloid pathology occurs early in Alzheimer's disease (AD), and has therefore been the focus of numerous studies. Transgenic mouse models have been instrumental to study amyloidosis, but observations might have been confounded by APP-overexpression artifacts. The current study investigated early functional defects in an APP knock-in mouse model, which allows assessing the effects of pathological amyloid-beta (Aβ) without interference of APP-artifacts. Female APP NL/NL knock-in mice of 3 and 7 months old were compared to age-matched APP NL-F/NL-F mice with increased Aβ42/40 ratio and initial Aβ-plaque deposition around 6 months of age. Spatial learning was examined using a Morris water maze protocol consisting of acquisition and reversal trials interleaved with reference memory tests. Functional connectivity (FC) of brain networks was assessed using resting-state functional MRI (rsfMRI). The Morris water maze data revealed that 3 months old APP NL-F/NL-F mice were unable to reach the same reference memory proficiency as APP NL/NL mice after reversal training. This cognitive defect in 3-month-old APP NL-F/NL-F mice coincided with hypersynchronous FC of the hippocampal, cingulate, caudate-putamen, and default-mode-like networks. The occurrence of these defects in APP NL-F/NL-F mice demonstrates that cognitive flexibility and synchronicity of telencephalic activity are specifically altered by early Aβ pathology without changes in APP neurochemistry.

Formation of a physiological reverse shoulder joint.

PubMed

Lerner, Markus; Turkmen, Ismail; Bernd, Ludger

2016-01-20

Congenital shoulder deformities are rarely seen in orthopaedic practice. Proximal humeral defects and glenoid hypoplasia have been reported separately in the literature. We present a case involving a 31-year-old woman having a cosmetic problem with her upper arm who was diagnosed with reverse shoulder joint deformity. This article presents the clinical, radiological and biomechanical findings of a physiological reverse shoulder joint. This is the first such reported case. 2016 BMJ Publishing Group Ltd.

A Novel Approach for Reconstruction of Finger Neurocutaneous Defect: A Sensory Reverse Dorsal Digital Artery Flap from the Neighboring Digit.

PubMed

Feng, Shi-Ming; Sun, Qing-Qing; Cheng, Jian; Wang, Ai-Guo

2017-11-01

Providing soft tissue coverage for finger neurocutaneous defects presents aesthetic and sensory challenges. A common source for reconstruction of soft tissue defects of the fingers is the same finger. However, when the donor areas are damaged by concomitant injuries, this option is not available. The present study aims to reconstruct finger neurocutaneous defects using a sensory reverse dorsal digital artery flap from the neighboring digit and to evaluate the efficacy of this technique. The study included 16 patients, with an average age of 34.9 years (range, 20-53 years) at the time of surgery, from May 2010 to June 2013. The sensory reverse dorsal digital artery flap was used in all 16 patients, who had a combination of soft tissue and digital nerve defects. The mean size of the soft tissue defects was 3.1 cm × 2.0 cm, and the mean flap size was 3.3 cm × 2.2 cm. The length of the nerve defects ranged from 1.3 to 2.5 cm (mean, 2.0 cm), which were reconstructed with dorsal branches of the proper digital nerve transfer. The active motion of the fingers (injured and donor) and the flap sensibility (static two-point discrimination) were measured. The appearance and functional recovery of the injured finger and the donor site were assessed using the Michigan Hand Outcomes Questionnaire. All flaps survived completely. No complications were reported, and no further flap debulking procedure was required. At the mean follow-up period of 24 months (range, 18-30 months), the mean static two-point discrimination was 6.5 mm (range, 5-10 mm) of the reconstructed area; the mean ranges of motions of the injured finger and the opposite finger at the proximal interphalangeal and distal interphalangeal joints were 102.2° and 103.5°, and 70.3° and 76.5°, respectively. The average ranges of motions of the metacarpophalangeal and proximal interphalangeal joints of the donor fingers were 90° and 103.4°, respectively. Based on the Michigan Hand Outcomes Questionnaire, 10 patients were strongly satisfied and 6 were satisfied with the functional recovery of the injured finger; however, 13 patients were strongly satisfied and 3 were satisfied with the appearance of the injured finger. The sensory reverse dorsal digital artery flap from the neighboring digit, based on the dorsal branch of the digital artery, is an effective and additional option for finger neurocutaneous defect reconstruction when use of the local and regional flaps is not feasible. © 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Observation of zone folding induced acoustic topological insulators and the role of spin-mixing defects

NASA Astrophysics Data System (ADS)

Deng, Yuanchen; Ge, Hao; Tian, Yuan; Lu, Minghui; Jing, Yun

2017-11-01

This article reports on the experimental realization of a flow-free, pseudospin-based acoustic topological insulator designed using the strategy of zone folding. Robust sound one-way propagation is demonstrated with the presence of non-spin-mixing defects. On the other hand, it is shown that spin-mixing defects, which break the geometric symmetry and therefore the pseudo-time-reversal symmetry, can open up nontrivial band gaps within the edge state frequency band, and their width can be tailored by the extent of the defect. This provides a possible route for realizing tunable acoustic topological insulators.

Vigabatrin can enhance electroretinographic responses in pigmented and albino rats.

PubMed

Akula, James D; Noonan, Emily R; Di Nardo, Alessia; Favazza, Tara L; Zhang, Nan; Sahin, Mustafa; Hansen, Ronald M; Fulton, Anne B

2015-08-01

To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats. Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55 injections of 250 mg·kg(-1)·day(-1) VGB or 25-26 injections of 500 mg·kg(-1)·day(-1) VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ(cone), Vm(cone)). The oscillatory potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50 Hz) were studied in the time and frequency domains. A subset of rats' eyes was harvested for Western blotting or histology. Of the parameters derived from dark-adapted ERG responses, in both pigmented and albino rats, VGB repeatedly and reliably enhanced electroretinographic parameters; no significant ERG deficits were noted. No significant alterations were observed in ER/oxidative stress or in the Akt cell death/survival pathway. There were migrations of photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into the outer nuclear layer in VGB-treated rats; these were never observed in sham-treated animals. Although VGB is associated with retinal dysfunction in patients and VGB toxicity has been demonstrated by other laboratories in the albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was observed.

Chiral filtration-induced spin/valley polarization in silicene line defects

NASA Astrophysics Data System (ADS)

Ren, Chongdan; Zhou, Benhu; Sun, Minglei; Wang, Sake; Li, Yunfang; Tian, Hongyu; Lu, Weitao

2018-06-01

The spin/valley polarization in silicene with extended line defects is investigated according to the chiral filtration mechanism. It is shown that the inner-built quantum Hall pseudo-edge states with identical chirality can serve as a chiral filter with a weak magnetic field and that the transmission process is restrained/strengthened for chiral states with reversed/identical chirality. With two parallel line defects, which act as natural chiral filtration, the filter effect is greatly enhanced, and 100% spin/valley polarization can be achieved.

Influence of columnar defects on the thermodynamic properties of BSCCO

NASA Astrophysics Data System (ADS)

van der Beek, C. J.; Indenbom, M. V.; Berseth, V.; Konczykowski, M.; Li, T. W.; Kes, P. H.; Benoit, W.

1996-03-01

Amorphous columnar defects strongly affect the reversible magnetization of Bi2Sr2CaCu2O8+δ single crystals both in the vortex solid, where the change reflects the change in vortex energy due to pinning, and in the vortex liquid, where the randomly positioned columns disrupt the interaction between superconducting fluctuations.

HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.

PubMed

Sorin, Masha; Yung, Eric; Wu, Xuhong; Kalpana, Ganjam V

2006-08-31

INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that presence of INI1 or some other host factor in virions and reverse transcription complexes may be important for early events of HIV-1 replication.

Large effect of columnar defects on the thermodynamic properties of Bi2Sr2CaCu2O8 single crystals

NASA Astrophysics Data System (ADS)

van der Beek, C. J.; Konczykowski, M.; Li, T. W.; Kes, P. H.; Benoit, W.

1996-07-01

The introduction of columnar defects by irradiation with 5.8-GeV Pb ions is shown to affect significantly the reversible magnetic properties of Bi2Sr2CaCu2O8+δ single crystals. Notably, the suppression of superconducting fluctuations on length scales greater than the separation between columns leads to the disappearance of the ``crossing point'' in the critical fluctuation regime. At lower temperatures, the strong modification of the vortex energy due to pinning leads to an important change of the reversible magnetization. The analysis of the latter permits the direct determination of the pinning energy.

A complex structure in the mRNA of Tf1 is recognized and cleaved to generate the primer of reverse transcription.

PubMed

Lin, J H; Levin, H L

1997-01-15

All retroviruses and LTR-containing retrotransposons are thought to require specific tRNA molecules to serve as primers of reverse transcription. An exception is the LTR-containing retrotransposon Tf1, isolated from Schizosaccharomyces pombe. Instead of requiring a tRNA, the reverse transcriptase of Tf1 uses the first 11 bases of the Tf1 transcript as the primer for reverse transcription. The primer is generated by a cleavage that occurs between bases 11 and 12 of the Tf1 mRNA. Sequence analysis of the 5' untranslated region of the Tf1 mRNA resulted in the identification of a region with the potential to form an RNA structure of 89 bases that included the primer binding site and the first 11 bases of the Tf1 mRNA. Systematic mutagenesis of this region revealed 34 single-point mutants in the structure that resulted in reduced transposition activity. The defects in transposition correlated with reduced level of Tf1 reverse transcripts as determined by DNA blot analysis. Evidence that the RNA structure did form in vivo included the result that strains with second site mutations that restored complementarity resulted in increased levels of reverse transcripts and Tf1 transposition. The majority of the mutants defective for reverse transcription were unable to cleave the Tf1 mRNA between bases 11 and 12. These data indicate that formation of an extensive RNA structure was required for the cleavage reaction that generated the primer for Tf1 reverse transcription.

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

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

Hosenpud, J.D.; Montanaro, A.; Hart, M.V.

1984-08-01

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment,more » major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.« less

Radiation damage annealing mechanisms and possible low temperature annealing in silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.

1980-01-01

Deep level transient spectroscopy and the Shockley-Read-Hall recombination theory are used to identify the defect responsible for reverse annealing in 2 ohm-cm n+/p silicon solar cells. This defect, with energy level at Ev + 0.30 eV, has been tentatively identified as a boron-oxygen-vacancy complex. It has been also determined by calculation that the removal of this defect could result in significant annealing at temperatures as low as 200 C for 2 ohm-cm and lower resistivity cells.

Molecules with enhanced electronic polarizabilities based on defect-like states in conjugated polymers

NASA Technical Reports Server (NTRS)

Beratan, David N. (Inventor)

1991-01-01

Highly conjugated organic polymers typically have large non-resonant electronic susceptibilities, which give the molecules unusual optical properties. To enhance these properties, defects are introduced into the polymer chain. Examples include light doping of the conjugated polymer and synthesis, conjugated polymers which incorporate either electron donating or accepting groups, and conjugated polymers which contain a photoexcitable species capable of reversibly transferring its electron to an acceptor. Such defects in the chain permit enhancement of the second hyperpolarizability by at least an order of magnitude.

Stress-induced reversible and irreversible ferroelectric domain switching

NASA Astrophysics Data System (ADS)

Chen, Zibin; Huang, Qianwei; Wang, Feifei; Ringer, Simon P.; Luo, Haosu; Liao, Xiaozhou

2018-04-01

Ferroelectric materials have been extensively explored for applications in electronic devices because of their ferroelectric/ferroelastic domain switching behaviour under electric bias or mechanical stress. Recent findings on applying mechanical loading to manipulate reversible logical signals in non-volatile ferroelectric memory devices make ferroelectric materials more attractive to scientists and engineers. However, the dynamical microscopic structural behaviour of ferroelectric domains under stress is not well understood, which limits the applications of ferroelectric/ferroelastic switching in memory devices. Here, the kinetics of reversible and irreversible ferroelectric domain switching induced by mechanical stress in relaxor-based ferroelectrics was explored. In-situ transmission electron microscopy investigation revealed that 90° ferroelastic and 180° ferroelectric domain switching can be induced by low and high mechanical stresses. The nucleation and growth of nanoscale domains overwhelm the defect-induced pinning effect on the stable micro-domain walls. This study provides deep insights for exploring the mechanical kinetics for ferroelectric/ferroelastic domains and a clear pathway to overcome the domain pinning effect of defects in ferroelectrics.

Non-magnetic impurity effects in LiFeAs studied by STM/STS

NASA Astrophysics Data System (ADS)

Hanaguri, T.; Khim, Seung Hyun; Lee, Bumsung; Kim, Kee Hoon; Kitagawa, K.; Matsubayashi, K.; Mazaki, Y.; Uwatoko, Y.; Takigawa, M.; Takagi, H.

2012-02-01

Detecting the possible sign reversal of the superconducting gap in iron-based superconductors is highly non-trivial. Here we use non-magnetic impurity as a sign indicator. If the sign of the superconducting gap is positive everywhere in momentum space, in-gap bound state should not be observed near the impurity site unless it is magnetic. On the other hand, if there is a sign-reversal in the gap, even non-magnetic impurity may create in-gap bound state [1]. We performed STM/STS experiments on self-flux and Sn-flux grown LiFeAs crystals and examined the effects of Sn impurity. In STM images of Sn-flux grown samples, we found a ring-like object which may represent Sn. Tunneling spectrum taken at this defect site exhibits in-gap bound state. Together with flat-bottom superconducting gap observed far from the defects, sign-reversing s-wave gap is the most plausible gap structure in LiFeAs. [1] T. Kariyado and M. Ogata, JPSJ 79, 083704 (2010).

Application of time-reversal guided waves to field bridge testing for baseline-free damage diagnosis

NASA Astrophysics Data System (ADS)

Kim, S. B.; Sohn, H.

2006-03-01

There is ongoing research at Carnegie Mellon University to develop a "baseline-free" nondestructive evaluation technique. The uniqueness of this baseline-free diagnosis lies in that certain types of damage can be identified without direct comparison of test signals with previously stored baseline signals. By relaxing dependency on the past baseline data, false positive indications of damage, which might take place due to varying operational and environmental conditions of in-service structures, can be minimized. This baseline-free diagnosis technique is developed based on the concept of a time reversal process (TRP). According to the TRP, an input signal at an original excitation location can be reconstructed if a response signal obtained from another point is emitted back to the original point after being reversed in a time domain. Damage diagnosis lies in the premise that the time reversibility breaks down when a certain type of defect such as nonlinear damage exists along the wave propagation path. Then, the defect can be sensed by examining a reconstructed signal after the TRP. In this paper, the feasibility of the proposed NDT technique is investigated using actual test data obtained from the Buffalo Creek Bridge in Pennsylvania.

Compensation for red-green contrast loss in anomalous trichromats

PubMed Central

Boehm, A. E.; MacLeod, D. I. A.; Bosten, J. M.

2014-01-01

For anomalous trichromats, threshold contrasts for color differences captured by the L and M cones and their anomalous analogs are much higher than for normal trichromats. The greater spectral overlap of the cone sensitivities reduces chromatic contrast both at and above threshold. But above threshold, adaptively nonlinear processing might compensate for the chromatically impoverished photoreceptor inputs. Ratios of sensitivity for threshold variations and for color appearance along the two cardinal axes of MacLeod-Boynton chromaticity space were calculated for three groups: normals (N = 15), deuteranomals (N = 9), and protanomals (N = 5). Using a four-alternative forced choice (4AFC) task, threshold sensitivity was measured in four color-directions along the two cardinal axes. For the same participants, we reconstructed perceptual color spaces for the positions of 25 hues using multidimensional scaling (MDS). From the reconstructed color spaces we extracted “color difference ratios,” defined as ratios for the size of perceived color differences along the L/(L + M) axis relative to those along the S/(L + M) axis, analogous to “sensitivity ratios” extracted from the 4AFC task. In the 4AFC task, sensitivity ratios were 38% of normal for deuteranomals and 19% of normal for protanomals. Yet, in the MDS results, color difference ratios were 86% of normal for deuteranomals and 67% of normal for protanomals. Thus, the contraction along the L/(L + M) axis shown in the perceptual color spaces of anomalous trichromats is far smaller than predicted by their reduced sensitivity, suggesting that an adaptive adjustment of postreceptoral gain may magnify the cone signals of anomalous trichromats to exploit the range of available postreceptoral neural signals. PMID:25413625

Reverse Saphenous Conduit Flap in 19 Dogs and 1 Cat.

PubMed

Cavalcanti, Jacqueline V J; Barry, Sabrina L; Lanz, Otto I; Barnes, Katherine; Coutin, Julia V

2018-05-14

The purpose of this retrospective study was to report the outcomes of 19 dogs and 1 cat undergoing reverse saphenous conduit flap between 1999 and 2016. Reverse saphenous conduit flap was used to treat traumatic wounds and wounds resulting from tumor excision in the hind limb; the majority of cases had medial shearing injuries. All animals had complete flap survival. In five animals (20%), minor donor site dehiscence occurred, which did not require surgery. Other postoperative complications included signs of severe venous congestion in one dog. Reverse saphenous conduit flap is a useful technique to repair skin defects of the distal hind limb.

Spectroscopic Study of Deep Level Emissions from Acceptor Defects in ZnO Thin Films with Oxygen Rich Stoichiometry

NASA Astrophysics Data System (ADS)

Ilyas, Usman; Rawat, R. S.; Tan, T. L.

2013-10-01

This paper reports the tailoring of acceptor defects in oxygen rich ZnO thin films at different post-deposition annealing temperatures (500-800°C) and Mn doping concentrations. The XRD spectra exhibited the nanocrystalline nature of ZnO thin films along with inconsistent variation in lattice parameters suggesting the temperature-dependent activation of structural defects. Photoluminescence emission spectra revealed the temperature dependent variation in deep level emissions (DLE) with the presence of acceptors as dominating defects. The concentration of native defects was estimated to be increased with temperature while a reverse trend was observed for those with increasing doping concentration. A consistent decrease in DLE spectra, with increasing Mn content, revealed the quenching of structural defects in the optical band gap of ZnO favorable for good quality thin films with enhanced optical transparency.

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione.

PubMed

Nguyen, Dan; Samson, Susan L; Reddy, Vasumathi T; Gonzalez, Erica V; Sekhar, Rajagopal V

2013-06-01

Aging is associated with impaired fasted oxidation of nonesterified fatty acids (NEFA) suggesting a mitochondrial defect. Aging is also associated with deficiency of glutathione (GSH), an important mitochondrial antioxidant, and with insulin resistance. This study tested whether GSH deficiency in aging contributes to impaired mitochondrial NEFA oxidation and insulin resistance, and whether GSH restoration reverses these defects. Three studies were conducted: (i) in 82-week-old C57BL/6 mice, the effect of naturally occurring GSH deficiency and its restoration on mitochondrial (13) C1 -palmitate oxidation and glucose metabolism was compared with 22-week-old C57BL/6 mice; (ii) in 20-week C57BL/6 mice, the effect of GSH depletion on mitochondrial oxidation of (13) C1 -palmitate and glucose metabolism was studied; (iii) the effect of GSH deficiency and its restoration on fasted NEFA oxidation and insulin resistance was studied in GSH-deficient elderly humans, and compared with GSH-replete young humans. Chronic GSH deficiency in old mice and elderly humans was associated with decreased fasted mitochondrial NEFA oxidation and insulin resistance, and these defects were reversed with GSH restoration. Acute depletion of GSH in young mice resulted in lower mitochondrial NEFA oxidation, but did not alter glucose metabolism. These data suggest that GSH is a novel regulator of mitochondrial NEFA oxidation and insulin resistance in aging. Chronic GSH deficiency promotes impaired NEFA oxidation and insulin resistance, and GSH restoration reverses these defects. Supplementing diets of elderly humans with cysteine and glycine to correct GSH deficiency could provide significant metabolic benefits. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

Application of reverse engineering in the medical industry.

NASA Astrophysics Data System (ADS)

Kaleev, A. A.; Kashapov, L. N.; Kashapov, N. F.; Kashapov, R. N.

2017-09-01

The purpose of this research is to develop on the basis of existing analogs new design of ophthalmologic microsurgical tweezers by using reverse engineering techniques. Virtual model was obtained by using a three-dimensional scanning system Solutionix Rexcan 450 MP. Geomagic Studio program was used to remove defects and inaccuracies of the obtained parametric model. A prototype of the finished model was made on the installation of laser stereolithography Projet 6000. Total time of the creation was 16 hours from the reverse engineering procedure to 3D-printing of the prototype.

Defect Characteristics of Reverse Hill-Sachs Lesions.

PubMed

Moroder, Philipp; Tauber, Mark; Scheibel, Markus; Habermeyer, Peter; Imhoff, Andreas B; Liem, Dennis; Lill, Helmut; Buchmann, Stefan; Wolke, Julia; Guevara-Alvarez, Alberto; Salmoukas, Katharina; Resch, Herbert

2016-03-01

Little scientific evidence regarding reverse Hill-Sachs lesions (RHSLs) in posterior shoulder instability exists. Recently, standardized measurement methods of the size and localization were introduced, and the biomechanical effect of the extent and position of the defects on the risk of re-engagement was determined. To analyze the characteristics and patterns of RHSLs in a large case series using standardized measurements and to interpret the results based on the newly available biomechanical findings. Case series; Level of evidence, 4. In this multicenter study, 102 cases of RHSLs in 99 patients were collected from 7 different shoulder centers between 2004 and 2013. Patient- as well as injury-specific information was gathered, and defect characteristics in terms of the size, localization, and depth index were determined on computed tomography or magnetic resonance imaging scans by means of standardized measurements. Additionally, the position (gamma angle) of the posterior defect margin as a predictor of re-engagement was analyzed. Three types of an RHSL were distinguished based on the pathogenesis and chronicity of the lesion: dislocation (D), locked dislocation (LD), and chronic locked dislocation (CLD). While the localization of the defects did not vary significantly between the subgroups (P = .072), their mean size differed signficantly (D: 32.6° ± 11.7°, LD: 49.4° ± 17.2°, CLD: 64.1° ± 20.7°; P < .001). The mean gamma angle as a predictor of re-engagement was similarly significantly different between groups (D: 83.8° ± 14.5°, LD: 96.5° ± 17.9°, CLD: 108.7° ± 18.4°; P < .001). The orientation of the posterior defect margin was consistently quite parallel to the humeral shaft axis, with a mean difference of 0.3° ± 8.1°. The distinction between the 3 different RHSL types based on the pathogenesis and chronicity of the defect helps identify defects prone to re-engagement. The gamma angle as a measurement of the position of the posterior defect margin and therefore a predictor of re-engagement varies significantly between the defect types. © 2016 The Author(s).

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2016-10-01

characterization of a novel external fixator for dynamizing ovine osseous defects. Poster No. 2185. Orthopedic Research Society Annual Meeting, Orlando...REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT...SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S

Reverse leakage current characteristics of InGaN/GaN multiple quantum well ultraviolet/blue/green light-emitting diodes

NASA Astrophysics Data System (ADS)

Zhou, Shengjun; Lv, Jiajiang; Wu, Yini; Zhang, Yuan; Zheng, Chenju; Liu, Sheng

2018-05-01

We investigated the reverse leakage current characteristics of InGaN/GaN multiple quantum well (MQW) near-ultraviolet (NUV)/blue/green light-emitting diodes (LEDs). Experimental results showed that the NUV LED has the smallest reverse leakage current whereas the green LED has the largest. The reason is that the number of defects increases with increasing nominal indium content in InGaN/GaN MQWs. The mechanism of the reverse leakage current was analyzed by temperature-dependent current–voltage measurement and capacitance–voltage measurement. The reverse leakage currents of NUV/blue/green LEDs show similar conduction mechanisms: at low temperatures, the reverse leakage current of these LEDs is attributed to variable-range hopping (VRH) conduction; at high temperatures, the reverse leakage current of these LEDs is attributed to nearest-neighbor hopping (NNH) conduction, which is enhanced by the Poole–Frenkel effect.

Paradoxical roles of hydrogen in electrochemical performance of graphene: High rate capacity and atomistic origins

DOE PAGES

Ye, Jianchao C.; Ong, Mitchell T.; Heo, Tae Wook; ...

2015-11-05

Atomic hydrogen exists ubiquitously in graphene materials made by chemical methods. Yet determining the effect of hydrogen on the electrochemical performance of graphene remains a significant challenge. Here we report the experimental observations of high rate capacity in hydrogen-treated 3-dimensional (3D) graphene nanofoam electrodes for lithium ion batteries. Structural and electronic characterization suggests that defect sites and hydrogen play synergistic roles in disrupting sp 2 graphene to facilitate fast lithium transport and reversible surface binding, as evidenced by the fast charge-transfer kinetics and increased capacitive contribution in hydrogen-treated 3D graphene. In concert with experiments, multiscale calculations reveal that defect complexesmore » in graphene are prerequisite for low-temperature hydrogenation, and that the hydrogenation of defective or functionalized sites at strained domain boundaries plays a beneficial role in improving rate capacity by opening gaps to facilitate easier Li penetration. Additional reversible capacity is provided by enhanced lithium binding near hydrogen-terminated edge sites. Furthermore, these findings provide qualitative insights in helping the design of graphene-based materials for high-power electrodes.« less

Universal roles of hydrogen in electrochemical performance of graphene: high rate capacity and atomistic origins

PubMed Central

Ye, Jianchao; Ong, Mitchell T.; Heo, Tae Wook; Campbell, Patrick G.; Worsley, Marcus A.; Liu, Yuanyue; Shin, Swanee J.; Charnvanichborikarn, Supakit; Matthews, Manyalibo J.; Bagge-Hansen, Michael; Lee, Jonathan R.I.; Wood, Brandon C.; Wang, Y. Morris

2015-01-01

Atomic hydrogen exists ubiquitously in graphene materials made by chemical methods. Yet determining the effect of hydrogen on the electrochemical performance of graphene remains a significant challenge. Here we report the experimental observations of high rate capacity in hydrogen-treated 3-dimensional (3D) graphene nanofoam electrodes for lithium ion batteries. Structural and electronic characterization suggests that defect sites and hydrogen play synergistic roles in disrupting sp2 graphene to facilitate fast lithium transport and reversible surface binding, as evidenced by the fast charge-transfer kinetics and increased capacitive contribution in hydrogen-treated 3D graphene. In concert with experiments, multiscale calculations reveal that defect complexes in graphene are prerequisite for low-temperature hydrogenation, and that the hydrogenation of defective or functionalized sites at strained domain boundaries plays a beneficial role in improving rate capacity by opening gaps to facilitate easier Li penetration. Additional reversible capacity is provided by enhanced lithium binding near hydrogen-terminated edge sites. These findings provide qualitative insights in helping the design of graphene-based materials for high-power electrodes. PMID:26536830

Facile synthesis and electrochemical properties of continuous porous spheres assembled from defect-rich, interlayer-expanded, and few-layered MoS2/C nanosheets for reversible lithium storage

NASA Astrophysics Data System (ADS)

Chen, Biao; Lu, Huihui; Zhao, Naiqin; Shi, Chunsheng; Liu, Enzuo; He, Chunnian; Ma, Liying

2018-05-01

Hollow or continuous porous hierarchical MoS2/C structures with large Li-ion and electron transport kinetics, and high structural stability are urgent needs for their application in lithium ion batteries. In this regard, a novel continuous porous micro-sphere constructed from defect-rich, interlayer-expanded, and few-layered MoS2/C nanosheets is successfully synthesized through a facile one-pot hydrothermal method. The polyvinyl pyrrolidone surfactant serves as carbon source and supporter, while the CS2 works as soft template and sulfur source during hydrothermal process. The morphologies, structures, and electrochemical properties are systematically characterized. Importantly, it should be noted that the unique porous micro-spheres with merits of rich-defect, expanded-interlayer, few-layer (<5 layers), abundant pores and integrating carbon are favorable for lithium ion batteries application. When the uniform composites are used as lithium ion batteries anode materials, they deliver a high reversible capacity, excellent cycling performance (average capacity fading of 0.037% per cycle at 0.2 A g-1), and good rate capability.

Detection of small surface defects using DCT based enhancement approach in machine vision systems

NASA Astrophysics Data System (ADS)

He, Fuqiang; Wang, Wen; Chen, Zichen

2005-12-01

Utilizing DCT based enhancement approach, an improved small defect detection algorithm for real-time leather surface inspection was developed. A two-stage decomposition procedure was proposed to extract an odd-odd frequency matrix after a digital image has been transformed to DCT domain. Then, the reverse cumulative sum algorithm was proposed to detect the transition points of the gentle curves plotted from the odd-odd frequency matrix. The best radius of the cutting sector was computed in terms of the transition points and the high-pass filtering operation was implemented. The filtered image was then inversed and transformed back to the spatial domain. Finally, the restored image was segmented by an entropy method and some defect features are calculated. Experimental results show the proposed small defect detection method can reach the small defect detection rate by 94%.

Transgenic expression of Map3k4 rescues T-associated sex reversal (Tas) in mice

PubMed Central

Warr, Nick; Siggers, Pam; Carré, Gwenn-Aël; Bogani, Debora; Brixey, Rachel; Akiyoshi, Mika; Tachibana, Makoto; Teboul, Lydia; Wells, Sara; Sanderson, Jeremy; Greenfield, Andy

2014-01-01

Disorders of sex development in the human population range in severity from mild genital defects to gonadal sex reversal. XY female development has been associated with heterozygous mutations in several genes, including SOX9, WT1 and MAP3K1. In contrast, XY sex reversal in mice usually requires complete absence of testis-determining gene products. One exception to this involves T-associated sex reversal (Tas), a phenomenon characterized by the formation of ovotestes or ovaries in XY mice hemizygous for the hairpin-tail (Thp) or T-Orleans (TOrl) deletions on proximal mouse chromosome 17. We recently reported that mice heterozygous for a null allele of Map3k4, which resides in the Thp deletion, exhibit XY ovotestis development and occasional gonadal sex reversal on the sensitized C57BL/6J-YAKR (B6-YAKR) genetic background, reminiscent of the Tas phenotype. However, these experiments did not exclude the possibility that loss of other loci in the Thp deletion, or other effects of the deletion itself, might contribute to Tas. Here, we show that disruption to Sry expression underlies XY gonadal defects in B6-YAKR embryos harbouring the Thp deletion and that a functional Map3k4 bacterial artificial chromosome rescues these abnormalities by re-establishing a normal Sry expression profile. These data demonstrate that Map3k4 haploinsufficiency is the cause of T-associated sex reversal and that levels of this signalling molecule are a major determinant of the expression profile of Sry. PMID:24452333

Comparison of Photoluminescence Imaging on Starting Multi-Crystalline Silicon Wafers to Finished Cell Performance: Preprint

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

Johnston, S.; Yan, F.; Dorn, D.

2012-06-01

Photoluminescence (PL) imaging techniques can be applied to multicrystalline silicon wafers throughout the manufacturing process. Both band-to-band PL and defect-band emissions, which are longer-wavelength emissions from sub-bandgap transitions, are used to characterize wafer quality and defect content on starting multicrystalline silicon wafers and neighboring wafers processed at each step through completion of finished cells. Both PL imaging techniques spatially highlight defect regions that represent dislocations and defect clusters. The relative intensities of these imaged defect regions change with processing. Band-to-band PL on wafers in the later steps of processing shows good correlation to cell quality and performance. The defect bandmore » images show regions that change relative intensity through processing, and better correlation to cell efficiency and reverse-bias breakdown is more evident at the starting wafer stage as opposed to later process steps. We show that thermal processing in the 200 degrees - 400 degrees C range causes impurities to diffuse to different defect regions, changing their relative defect band emissions.« less

Pattern-reversal electroretinograms in unilateral glaucoma.

PubMed

Wanger, P; Persson, H E

1983-06-01

Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded from 11 patients with unilateral glaucoma. All glaucomatous eyes had reduced amplitudes both compared to the opposite eye in the same patient and to reference values. In 10 of the 11 cases this reduction was below the level of normal variation. The difference in pattern-reversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant. No differences were observed in flash ERGs or OPs. The histopathologic correlate to the visual field defects in glaucoma is retinal ganglion cell degeneration. The present electrophysiologic findings support the view, based on results from animal experiments, that the pattern-reversal ERG reflects ganglion cell activity.

Feline leukemia virus infection requires a post-receptor binding envelope-dependent cellular component.

PubMed

Hussain, Naveen; Thickett, Kelly R; Na, Hong; Leung, Cherry; Tailor, Chetankumar S

2011-12-01

Gammaretrovirus receptors have been suggested to contain the necessary determinants to mediate virus binding and entry. Here, we show that murine NIH 3T3 and baby hamster kidney (BHK) cells overexpressing receptors for subgroup A, B, and C feline leukemia viruses (FeLVs) are weakly susceptible (10(1) to 10(2) CFU/ml) to FeLV pseudotype viruses containing murine leukemia virus (MLV) core (Gag-Pol) proteins, whereas FeLV receptor-expressing murine Mus dunni tail fibroblast (MDTF) cells are highly susceptible (10(4) to 10(6) CFU/ml). However, NIH 3T3 cells expressing the FeLV subgroup B receptor PiT1 are highly susceptible to gibbon ape leukemia virus pseudotype virus, which differs from the FeLV pseudotype viruses only in the envelope protein. FeLV resistance is not caused by a defect in envelope binding, low receptor expression levels, or N-linked glycosylation. Resistance is not alleviated by substitution of the MLV core in the FeLV pseudotype virus with FeLV core proteins. Interestingly, FeLV resistance is alleviated by fusion of receptor-expressing NIH 3T3 and BHK cells with MDTF or human TE671 cells, suggesting the absence of an additional cellular component in NIH 3T3 and BHK cells that is required for FeLV infection. The putative FeLV-specific cellular component is not a secreted factor, as MDTF conditioned medium does not alleviate the block to FeLV infection. Together, our findings suggest that FeLV infection requires an additional envelope-dependent cellular component that is absent in NIH 3T3 and BHK cells but that is present in MDTF and TE671 cells.

High rectifying behavior in Al/Si nanocrystal-embedded SiOxNy/p-Si heterojunctions

NASA Astrophysics Data System (ADS)

Jacques, E.; Pichon, L.; Debieu, O.; Gourbilleau, F.; Coulon, N.

2011-05-01

We examine the electrical properties of MIS devices made of Al/Si nanocrystal-SiOxNy/p-Si. The J-V characteristics of the devices present a high rectifying behavior. Temperature measurements show that the forward current is thermally activated following the thermal diffusion model of carriers. At low reverse bias, the current is governed by thermal emission amplified by the Poole-Frenkel effect of carriers from defects located at the silicon nanocrystals/SiOxNy interfaces, whereas tunnel conduction in silicon oxynitride matrix dominates at high reverse bias. The devices exhibit a rectification ratio >104 for the current measured at V = ± 1 V. Study reveals that thermal annealing in forming gas (H2/N2) improves the electrical properties of the devices due to the passivation of defects.

Assessment of long-term donor-site morbidity after harvesting the latissimus dorsi flap for neonatal myelomeningocele repair.

PubMed

Osinga, R; Mazzone, L; Meuli, M; Meuli-Simmen, C; von Campe, A

2014-08-01

The latissimus dorsi flap (LDF) has been employed very successfully over decades to cover large soft-tissue defects. Its donor-site morbidity has been extensively investigated in adults - but not in children - and is considered to be nonrestrictive. The aim of this long-term study was to assess donor-site morbidity with the modified Constant score more than 8 years after coverage of large myelomeningocele (MMC) defects with a reverse latissimus dorsi flap. Within the first days after birth, the reverse latissimus dorsi muscle flap was used uni- or bilaterally in three neonates to cover a large MMC defect. Bilateral shoulder function was tested more than 8 years postoperatively according to the modified Constant score. The mean age at follow-up was 11.7 years. None of the patients experienced any pain or shoulder restrictions during normal daily activities. They all managed to position both of their arms comfortably above the head. Forward flexion was normal in all patients as was abduction and external rotation. Dorsal extension was minimally reduced on the operated side. Internal rotation was symmetric in all patients; the extent of active movement varied from excellent to poor. Our long-term data suggest that there is no specific and significant impairment of shoulder function after using the distally pedicled reverse LDF for neonatal MMC repair. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Comparison of preparation techniques for CoFeNb/CNTs catalyst

NASA Astrophysics Data System (ADS)

Hamid, Hami Haslinda; Zabidi, Noor Asmawati Mohd; Gholami, Zahra; Shaharun, Maizatul Shima

2016-11-01

CoFe-based catalysts were prepared using reverse-microemulsion and co-impregnation method. Effect of different preparation techniques on morphology and physiochemical properties of the FTS catalyst CoFeNb/CNTs was investigated. TEM analyses show that the morphological properties of catalysts were affected by preparation techniques. Reverse-micremulsion and co-impregnation method resulted in average particle size of 5.61 nm and 6.20 nm respectively. CoFe-impregnation catalyst is reducible at lower temperature compared to that of reverse-microemulsion catalyst. Acid and thermal treatment of CNTs created defects onto CNTs-support.

Acoustically driven degradation in single crystalline silicon solar cell

NASA Astrophysics Data System (ADS)

Olikh, O. Ya.

2018-05-01

The influence of ultrasound on current-voltage characteristics of crystalline silicon solar sell was investigated experimentally. The transverse and longitudinal acoustic waves were used over a temperature range of 290-340 K. It was found that the ultrasound loading leads to the reversible decrease in the photogenerated current, open-circuit voltage, fill factor, carrier lifetime, and shunt resistance as well as the increase in the ideality factor. The experimental results were described by using the models of coupled defect level recombination, Shockley-Read-Hall recombination, and dislocation-induced impedance. The contribution of the boron-oxygen related defects, iron-boron pairs, and oxide precipitates to both the carrier recombination and acousto-defect interaction was discussed. The experimentally observed phenomena are associated with the increase in the distance between coupled defects as well as the extension of the carrier capture coefficient of complex point defects and dislocations.

Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase.

PubMed

Vergis, Nikhil; Khamri, Wafa; Beale, Kylie; Sadiq, Fouzia; Aletrari, Mina O; Moore, Celia; Atkinson, Stephen R; Bernsmeier, Christine; Possamai, Lucia A; Petts, Gemma; Ryan, Jennifer M; Abeles, Robin D; James, Sarah; Foxton, Matthew; Hogan, Brian; Foster, Graham R; O'Brien, Alastair J; Ma, Yun; Shawcross, Debbie L; Wendon, Julia A; Antoniades, Charalambos G; Thursz, Mark R

2017-03-01

In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-γ (IFN-γ) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91 phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-γ stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2017-12-01

reverse dynamization. This was supplemented by finite element analysis and the use of a strain gauge. This aim was successfully completed, with the...testing deformation results for model validation. Development of a Finite Element (FE) model was conducted through ANSYS 16 to help characterize...Fixators were characterized through mechanical testing by sawbone and ovine cadaver tibiae samples, and data was used to validate a finite element

Reliability of III-V electronic devices -- the defects that cause the trouble

NASA Astrophysics Data System (ADS)

Pantelides, Sokrates T.

2012-02-01

Degradation of electronic devices by hot electrons is universally attributed to the generation of defects, but the mechanisms for defect generation and the specific nature of the pertinent defects are not known for most systems. Here we describe three recent case studies [1] in III-V high-electron-mobility transistors that illustrate the power of combining density functional calculations and experimental data to identify the pertinent defects and associated degradation mechanisms. In all cases, benign pre-existing defects are either depassivated (irreversible degradation) or transformed to a metastable state (reversible degradation). This work was done in collaboration with R.D. Schrimpf, D.M. Fleetwood, Y. Puzyrev, X. Shen, T. Roy, S. DasGupta, and B.R. Tuttle. Devices were provided by D.F. Brown, J. Speck and U. Mishra, and by J. Bergman and B. Brar. [4pt] [1] Y. S. Puzyrev et al., Appl. Phys. Lett. 96, 053505 (2010); T. Roy et al., Appl. Phys. Lett. 96, 133503 (2010); X. Shen et al., J. Appl. Phys. 108, 114505 (2010).

Reverse total shoulder glenoid baseplate stability with superior glenoid bone loss.

PubMed

Martin, Elise J; Duquin, Thomas R; Ehrensberger, Mark T

2017-10-01

Superior wear of the glenoid bone is common in patients with rotator cuff arthropathy. This can become a treatment challenge for patients who require shoulder arthroplasty. In reverse shoulder arthroplasty (RSA), glenoid bone loss may affect the stability of baseplate fixation. The primary purpose of this biomechanical laboratory study was to assess the initial fixation stability of RSA glenosphere baseplates in the presence of variable amounts of superior glenoid bone loss. High-density solid rigid polyurethane foam (30 pounds/cubic foot) was machined to model the glenoid with variable superior defects that provided different levels of support (100%, 90%, 75%, and 50%) for the glenosphere baseplate. The samples were cyclically loaded (0-750 N at 1 Hz for 5000 cycles) at a 60° glenohumeral angle. The micromotion and migration of the baseplate were calculated from displacement data captured during the loading tests with an array of 3 linear variable differential transformers mounted around the baseplate. Micromotion was significantly greater in samples with 50% defects compared with those with smaller defects. Migration was significantly greater after testing for all defect sizes. Initial fixation of RSA glenosphere baseplates was significantly reduced in models with 50% bone loss on the superior edge compared with models with less bone loss in this high-density bone foam model. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Microstructure evolution characteristics induced by oxygen vacancy generation in anatase TiO2 based resistive switching devices

NASA Astrophysics Data System (ADS)

Liu, Chen; Gao, Bin; Huang, Peng; Kang, Jinfeng

2017-03-01

In this work, first principle calculations are employed to study the microstructure characteristics of the anatase TiO2 resistive switching material associated with the generation of oxygen vacancy (V o) based nanofilaments during the switching process. The calculations indicate that both the magnéli phase Ti4O7 and V o-defect phase of anatase TiO2 may be formed with the generation of oxygen vacancies during the forming and SET processes. Based on the calculations, a new physical insight is proposed to clarify the microstructure evolution characteristics of the anatase TiO2 resistive switching material and the correlation with resistive switching behaviors. During the forming or SET process, the anatase TiO2 is first excited to a transition state with the generation of oxygen vacancies, then fully relaxes to a stable V o-defect state. This V o-defect state may either recover to the original state with the recombination of the oxygen vacancies, which causes the reversible resistive switching behavior, or further transform to a much more stable state—the magnéli phase Ti4O7, through a phase transition process with the generation of many more oxygen vacancies. The phase transition from V o- defective anatase phase to magnéli phase Ti4O7 causes the failure of the resistive switching due to the significantly reduced possibility of the reversible phase transition from the magnéli phase to the anatase phase, compared with the possibility of the recombination from the V o-defective anatase.

Light-induced defects in hybrid lead halide perovskite

NASA Astrophysics Data System (ADS)

Sharia, Onise; Schneider, William

One of the main challenges facing organohalide perovskites for solar application is stability. Solar cells must last decades to be economically viable alternatives to traditional energy sources. While some causes of instability can be avoided through engineering, light-induced defects can be fundamentally limiting factor for practical application of the material. Light creates large numbers of electron and hole pairs that can contribute to degradation processes. Using ab initio theoretical methods, we systematically explore first steps of light induced defect formation in methyl ammonium lead iodide, MAPbI3. In particular, we study charged and neutral Frenkel pair formation involving Pb and I atoms. We find that most of the defects, except negatively charged Pb Frenkel pairs, are reversible, and thus most do not lead to degradation. Negative Pb defects create a mid-gap state and localize the conduction band electron. A minimum energy path study shows that, once the first defect is created, Pb atoms migrate relatively fast. The defects have two detrimental effects on the material. First, they create charge traps below the conduction band. Second, they can lead to degradation of the material by forming Pb clusters.

Sensitivity of thermal transport in thorium dioxide to defects

NASA Astrophysics Data System (ADS)

Park, Jungkyu; Farfán, Eduardo B.; Mitchell, Katherine; Resnick, Alex; Enriquez, Christian; Yee, Tien

2018-06-01

In this research, the reverse non-equilibrium molecular dynamics is employed to investigate the effect of vacancy and substitutional defects on the thermal transport in thorium dioxide (ThO2). Vacancy defects are shown to severely alter the thermal conductivity of ThO2. The thermal conductivity of ThO2 decreases significantly with increasing the defect concentration of oxygen vacancy; the thermal conductivity of ThO2 decreases by 20% when 0.1% oxygen vacancy defects are introduced in the 100 unit cells of ThO2. The effect of thorium vacancy defect on the thermal transport in ThO2 is even more detrimental; ThO2 with 0.1% thorium vacancy defect concentration exhibits a 38.2% reduction in its thermal conductivity and the thermal conductivity becomes only 8.2% of that of the pristine sample when the thorium vacancy defect concentration is increased to 5%. In addition, neutron activation of thorium produces uranium and this uranium substitutional defects in ThO2 are observed to affect the thermal transport in ThO2 marginally when compared to vacancy defects. This indicates that in the thorium fuel cycle, fissile products such as 233U is not likely to alter the thermal transport in ThO2 fuel.

Effect of insulin-like factors on glucose transport activity in unweighted rat skeletal muscle

NASA Technical Reports Server (NTRS)

Henriksen, Erik J.; Ritter, Leslie S.

1993-01-01

The effect of 3 or 6 days of unweighting on glucose transport activity, as assessed by 2-deoxyglucose uptake, in soleus strips stimulated by maximally effective concentrations of insulin, IGF-I, vanadate, or phospholipase C (PLC) is examined. Progressively increased responses to maximally effective doses of insulin or insulin-like growth factor were observed after 3 and 6 days of unweighting compared with weight matched control strips. Enhanced maximal responses to vanadate (6 days only) and PLC (3 and 6 days) were also observed. The data provide support for the existance of postreceptor binding mechanisms for the increased action of insulin on the glucose transport system in unweighted rat skeletal muscle.

Theory of chromatic noise masking applied to testing linearity of S-cone detection mechanisms.

PubMed

Giulianini, Franco; Eskew, Rhea T

2007-09-01

A method for testing the linearity of cone combination of chromatic detection mechanisms is applied to S-cone detection. This approach uses the concept of mechanism noise, the noise as seen by a postreceptoral neural mechanism, to represent the effects of superposing chromatic noise components in elevating thresholds and leads to a parameter-free prediction for a linear mechanism. The method also provides a test for the presence of multiple linear detectors and off-axis looking. No evidence for multiple linear mechanisms was found when using either S-cone increment or decrement tests. The results for both S-cone test polarities demonstrate that these mechanisms combine their cone inputs nonlinearly.

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

PubMed Central

Kleinridders, André; Ferris, Heather A.; Cai, Weikang

2014-01-01

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

Effects of Voltage-Bias Annealing on Metastable Defect Populations in CIGS and CZTSe Solar Cells

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

Harvey, Steven P.; Johnston, Steve; Teeter, Glenn

2016-11-21

We report on voltage-bias annealing (VBA) experiments performed on CIGS and CZTSe solar cells. In these experiments, completed devices were annealed at moderate temperatures and subsequently quenched with continuously applied voltage bias. These treatments resulted in substantial reversible changes in device characteristics. Photovoltaic (PV) conversion efficiency of the CIGS device varied from below 3% to above 15%, with corresponding changes in CIGS hole density from ~1014 cm-3 to ~1017 cm-3. In the CZTSe device, open-circuit voltage varied from 289 meV to 446 meV, caused by an approximately factor of fifty change in the CZTSe hole density. We interpret these findingsmore » in terms of reversible changes to the metastable point-defect populations that control key properties in these materials. Implications for optimization of PV materials and connections to long-term stability of PV devices are discussed.« less

Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy

PubMed Central

Watkins, Crystal C.; Sawa, Akira; Jaffrey, Samie; Blackshaw, Seth; Barrow, Roxanne K.; Snyder, Solomon H.; Ferris, Christopher D.

2000-01-01

Gastrointestinal dysfunction is common in diabetic patients. In genetic (nonobese diabetic) and toxin-elicited (streptozotocin) models of diabetes in mice, we demonstrate defects in gastric emptying and nonadrenergic, noncholinergic relaxation of pyloric muscle, which resemble defects in mice harboring a deletion of the neuronal nitric oxide synthase gene (nNOS). The diabetic mice manifest pronounced reduction in pyloric nNOS protein and mRNA. The decline of nNOS in diabetic mice does not result from loss of myenteric neurons. nNOS expression and pyloric function are restored to normal levels by insulin treatment. Thus diabetic gastropathy in mice reflects an insulin-sensitive reversible loss of nNOS. In diabetic animals, delayed gastric emptying can be reversed with a phosphodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy. PMID:10930440

Probing topological protection using a designer surface plasmon structure

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

Gao, Fei; Gao, Zhen; Shi, Xihang

Topological photonic states, inspired by robust chiral edge states in topological insulators, have recently been demonstrated in a few photonic systems, including an array of coupled on-chip ring resonators at communication wavelengths. However, the intrinsic difference between electrons and photons determines that the 'topological protection' in time-reversal-invariant photonic systems does not share the same robustness as its counterpart in electronic topological insulators. Here in a designer surface plasmon platform consisting of tunable metallic sub-wavelength structures, we construct photonic topological edge states and probe their robustness against a variety of defect classes, including some common time-reversal-invariant photonic defects that can breakmore » the topological protection, but do not exist in electronic topological insulators. Furthermore, this is also an experimental realization of anomalous Floquet topological edge states, whose topological phase cannot be predicted by the usual Chern number topological invariants.« less

Probing topological protection using a designer surface plasmon structure

DOE PAGES

Gao, Fei; Gao, Zhen; Shi, Xihang; ...

2016-05-20

Topological photonic states, inspired by robust chiral edge states in topological insulators, have recently been demonstrated in a few photonic systems, including an array of coupled on-chip ring resonators at communication wavelengths. However, the intrinsic difference between electrons and photons determines that the 'topological protection' in time-reversal-invariant photonic systems does not share the same robustness as its counterpart in electronic topological insulators. Here in a designer surface plasmon platform consisting of tunable metallic sub-wavelength structures, we construct photonic topological edge states and probe their robustness against a variety of defect classes, including some common time-reversal-invariant photonic defects that can breakmore » the topological protection, but do not exist in electronic topological insulators. Furthermore, this is also an experimental realization of anomalous Floquet topological edge states, whose topological phase cannot be predicted by the usual Chern number topological invariants.« less

Water-sensitive positron trapping modes in nanoporous magnesium aluminate ceramics

NASA Astrophysics Data System (ADS)

Filipecki, J.; Ingram, A.; Klym, H.; Shpotyuk, O.; Vakiv, M.

2007-08-01

The water-sensitive positron trapping modes in nanoporous MgAl2O4 ceramics with a spinel structure are studied. It is shown that water-sorption processes in magnesium aluminate ceramics leads to corresponding increase in positron trapping rates of extended defects located near intergranual boundaries. This catalytic affect has reversible nature, being strongly dependent on sorption water fluxes in ceramics. The fixation of all water-dependent positron trapping inputs allow to refine the most significant changes in positron trapping rate of extended defects.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2014-10-01

initiated. One such fixator has been tested on a cadaveric sheep tibia. In the unlocked, loose position, the axial stiffness of the tibia and fixator...suggested by our previous studies using rats. This aspect of the project is the present focus of attention, and additional cadaver legs will be tested...characterize external fixators). A 3 mm tibial defect was created in the leg of a cadaveric sheep, and stabilized with an experimental external

Implication of the VirD4 coupling protein of the Lvh type 4 secretion system in virulence phenotypes of Legionella pneumophila.

PubMed

Bandyopadhyay, Purnima; Lang, Elza A S; Rasaputra, Komal S; Steinman, Howard M

2013-08-01

The genome of the Philadelphia-1 strain of Legionella pneumophila, the causative organism of Legionnaires' disease, encodes two virulence-associated type 4 secretion systems (T4SSs), the Dot/Icm type 4B (T4BSS) and the Lvh type 4A (T4ASS). Broth stationary-phase cultures of most dot/icm mutants are defective in entry and evasion of phagosome acidification. However, those virulence defects can be reversed by incubating broth cultures of dot/icm mutants in water, termed water stress (WS). WS reversal requires the lvh T4ASS locus, suggesting an interaction between the two T4SSs in producing Legionella virulence phenotypes. In the current work, the loss of WS reversal in a dotA Δlvh mutant of strain JR32 was shown to be attributable to loss of the lvh virD4 gene, encoding the putative coupling protein of the T4ASS. Transformation of a dotA Δlvh mutant with virD4 also reversed entry and phagosome acidification defects in broth cultures. In addition, broth cultures of Δlvh and ΔvirD4 mutants, which were dot/icm(+), showed 5-fold and >6-fold increases in translocation of the Dot/Icm translocation substrates, proteins RalF and SidD, respectively. These data demonstrate that the Lvh T4ASS functions in both broth stationary-phase cultures conventionally used for infection and cultures exposed to WS treatment. Our studies in a dotA Δlvh mutant and in a dot/icm(+) background establish that VirD4 and the Lvh T4ASS contribute to virulence phenotypes and are consistent with independent functioning of Dot/Icm and Lvh T4SSs or functional substitution of the Lvh VirD4 protein for a component(s) of the Dot/Icm T4BSS.

Implication of the VirD4 Coupling Protein of the Lvh Type 4 Secretion System in Virulence Phenotypes of Legionella pneumophila

PubMed Central

Bandyopadhyay, Purnima; Lang, Elza A. S.; Rasaputra, Komal S.

2013-01-01

The genome of the Philadelphia-1 strain of Legionella pneumophila, the causative organism of Legionnaires' disease, encodes two virulence-associated type 4 secretion systems (T4SSs), the Dot/Icm type 4B (T4BSS) and the Lvh type 4A (T4ASS). Broth stationary-phase cultures of most dot/icm mutants are defective in entry and evasion of phagosome acidification. However, those virulence defects can be reversed by incubating broth cultures of dot/icm mutants in water, termed water stress (WS). WS reversal requires the lvh T4ASS locus, suggesting an interaction between the two T4SSs in producing Legionella virulence phenotypes. In the current work, the loss of WS reversal in a dotA Δlvh mutant of strain JR32 was shown to be attributable to loss of the lvh virD4 gene, encoding the putative coupling protein of the T4ASS. Transformation of a dotA Δlvh mutant with virD4 also reversed entry and phagosome acidification defects in broth cultures. In addition, broth cultures of Δlvh and ΔvirD4 mutants, which were dot/icm+, showed 5-fold and >6-fold increases in translocation of the Dot/Icm translocation substrates, proteins RalF and SidD, respectively. These data demonstrate that the Lvh T4ASS functions in both broth stationary-phase cultures conventionally used for infection and cultures exposed to WS treatment. Our studies in a dotA Δlvh mutant and in a dot/icm+ background establish that VirD4 and the Lvh T4ASS contribute to virulence phenotypes and are consistent with independent functioning of Dot/Icm and Lvh T4SSs or functional substitution of the Lvh VirD4 protein for a component(s) of the Dot/Icm T4BSS. PMID:23729650

Creation and annealing of metastable defect states in CH3NH3PbI3 at low temperatures

NASA Astrophysics Data System (ADS)

Lang, F.; Shargaieva, O.; Brus, V. V.; Rappich, J.; Nickel, N. H.

2018-02-01

Methylammonium lead iodide (CH3NH3PbI3), an organic-inorganic perovskite widely used for optoelectronic applications, is known to dissociate under illumination with light at photon energies around 2.7 eV and higher. Here, we show that photo-induced dissociation is not limited to ambient temperatures but can be observed even at 5 K. The photo-induced dissociation of N-H bonds results in the formation of metastable states. Photoluminescence (PL) measurements reveal the formation of defect states that are located 100 meV within the bandgap. This is accompanied by a quenching of the band-to-band PL by one order of magnitude. Defect generation is reversible and annealing at 30 K recovers the band-to-band PL, while the light-induced defect states disappear concurrently.

Multi-crack imaging using nonclassical nonlinear acoustic method

NASA Astrophysics Data System (ADS)

Zhang, Lue; Zhang, Ying; Liu, Xiao-Zhou; Gong, Xiu-Fen

2014-10-01

Solid materials with cracks exhibit the nonclassical nonlinear acoustical behavior. The micro-defects in solid materials can be detected by nonlinear elastic wave spectroscopy (NEWS) method with a time-reversal (TR) mirror. While defects lie in viscoelastic solid material with different distances from one another, the nonlinear and hysteretic stress—strain relation is established with Preisach—Mayergoyz (PM) model in crack zone. Pulse inversion (PI) and TR methods are used in numerical simulation and defect locations can be determined from images obtained by the maximum value. Since false-positive defects might appear and degrade the imaging when the defects are located quite closely, the maximum value imaging with a time window is introduced to analyze how defects affect each other and how the fake one occurs. Furthermore, NEWS-TR-NEWS method is put forward to improve NEWS-TR scheme, with another forward propagation (NEWS) added to the existing phases (NEWS and TR). In the added phase, scanner locations are determined by locations of all defects imaged in previous phases, so that whether an imaged defect is real can be deduced. NEWS-TR-NEWS method is proved to be effective to distinguish real defects from the false-positive ones. Moreover, it is also helpful to detect the crack that is weaker than others during imaging procedure.

TAC1 Gene Products Regulate Pituitary Hormone Secretion and Gene Expression in Prepubertal Grass Carp Pituitary Cells.

PubMed

Hu, Guangfu; He, Mulan; Ko, Wendy K W; Wong, Anderson O L

2017-06-01

Tachykinin-1 (TAC1) is known to have diverse functions in mammals, but similar information is scarce in fish species. Using grass carp as a model, the pituitary actions, receptor specificity and postreceptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. TAC1 encoding SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in the carp pituitary. The newly cloned receptors were shown to be functional with properties similar to mammalian counterparts. In carp pituitary cells, SP and NKA could trigger luteinizing hormone (LH), prolactin (PRL), and somatolactin α (SLα) secretion, with parallel rises in PRL and SLα transcripts. Short-term SP treatment (3 hours) induced LH release, whereas prolonged induction (24 hours) could attenuate LHβ messenger RNA (mRNA) expression. At pituitary cell level, LH, PRL, and SLα regulation by TAC1 gene products were mediated by NK1R, NK2R, and NK3R, respectively. Apparently, SP- and NKA-induced LH and SLα secretion and transcript expression were mediated by adenylyl cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholiphase C (PLC)/inositol 1,4,5-triphosphate/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/CaM-dependent protein kinase-II pathways. The signal transduction for PRL responses was similar, except for the absence of a PKC component. Regarding SP inhibition of LHβ mRNA expression, the cAMP/PKA- and PLC/PKC-dependent (but not Ca2+/CaM-dependent) cascades were involved. These results, as a whole, suggest that TAC1 gene products play a role in LH, PRL, and SLα regulation via overlapping postreceptor signaling coupled to different subtypes of tachykinin receptor expressed in the carp pituitary. Copyright © 2017 Endocrine Society.

The neurovascular relation in oxygen-induced retinopathy.

PubMed

Akula, James D; Mocko, Julie A; Benador, Ilan Y; Hansen, Ronald M; Favazza, Tara L; Vyhovsky, Tanya C; Fulton, Anne B

2008-01-01

Longitudinal studies in rat models of retinopathy of prematurity (ROP) have demonstrated that abnormalities of retinal vasculature and function change hand-in-hand. In the developing retina, vascular and neural structures are under cooperative molecular control. In this study of rats with oxygen-induced retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were examined during the course of retinopathy to evaluate their roles in the observed neurovascular congruency. Oxygen exposures designed to induce retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also studied. Sensitivities of the rod photoreceptors (S(rod)) and the postreceptor cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar tortuosity, T(A), was derived from digital fundus images using Retinal Image multi-Scale Analysis (RISA) image analysis software. mRNA expression of VEGF(164), semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT-PCR of retinal extracts. Tests were performed at P15-P16, P18-P19, and P25-P26. Relations among ERG, RISA, and PCR parameters were evaluated using linear regression on log transformed data. Sm was low and T(A) was high at young ages, then both resolved by P25-P26. VEGF(164) and Sema3A mRNA expression were also elevated early and decreased with age. Low Sm was significantly associated with high VEGF(164) and Sema3A expression. Low S(rod) was also significantly associated with high VEGF(164). S(rod) and Sm were both correlated with T(A). NRP-1 expression was little affected by OIR. The postreceptor retina appears to mediate the vascular abnormalities that characterize OIR. Because of the relationships revealed by these data, early treatment that targets the neural retina may mitigate the effects of ROP.

The neurovascular relation in oxygen-induced retinopathy

PubMed Central

Akula, James D.; Mocko, Julie A.; Benador, Ilan Y.; Hansen, Ronald M.; Favazza, Tara L.; Vyhovsky, Tanya C.

2008-01-01

Purpose Longitudinal studies in rat models of retinopathy of prematurity (ROP) have demonstrated that abnormalities of retinal vasculature and function change hand-in-hand. In the developing retina, vascular and neural structures are under cooperative molecular control. In this study of rats with oxygen-induced retinopathy (OIR) models of ROP, mRNA expression of vascular endothelial growth factor (VEGF), semaphorin (Sema), and their neuropilin receptor (NRP) were examined during the course of retinopathy to evaluate their roles in the observed neurovascular congruency. Methods Oxygen exposures designed to induce retinopathy were delivered to Sprague-Dawley rat pups (n=36) from postnatal day (P) 0 to P14 or from P7 to P14. Room-air-reared controls (n=18) were also studied. Sensitivities of the rod photoreceptors (Srod) and the postreceptor cells (Sm) were derived from electroretinographic (ERG) records. Arteriolar tortuosity, TA, was derived from digital fundus images using Retinal Image multi-Scale Analysis (RISA) image analysis software. mRNA expression of VEGF164, semaphorin IIIA (Sema3A), and neuropilin-1 (NRP-1) was evaluated by RT–PCR of retinal extracts. Tests were performed at P15–P16, P18–P19, and P25–P26. Relations among ERG, RISA, and PCR parameters were evaluated using linear regression on log transformed data. Results Sm was low and TA was high at young ages, then both resolved by P25–P26. VEGF164 and Sema3A mRNA expression were also elevated early and decreased with age. Low Sm was significantly associated with high VEGF164 and Sema3A expression. Low Srod was also significantly associated with high VEGF164. Srod and Sm were both correlated with TA. NRP-1 expression was little affected by OIR. Conclusions The postreceptor retina appears to mediate the vascular abnormalities that characterize OIR. Because of the relationships revealed by these data, early treatment that targets the neural retina may mitigate the effects of ROP. PMID:19112532

Unsurmountable antagonism of brain 5-hydroxytryptamine2 receptors by (+)-lysergic acid diethylamide and bromo-lysergic acid diethylamide.

PubMed

Burris, K D; Sanders-Bush, E

1992-11-01

Lysergic acid diethylamide (LSD) and its structural analogue 2-bromo-lysergic acid diethylamide (BOL) act as unsurmountable antagonists of serotonin-elicited contractions in smooth muscle preparations. Two different models, allosteric and kinetic, have been invoked to explain these findings. The present studies investigate the mechanism of antagonism of brain 5-hydroxytryptamine (5HT)2 receptors, utilizing cells transfected with 5HT2 receptor cDNA cloned from rat brain. A proximal cellular response, phosphoinositide hydrolysis, was examined in order to minimize possible postreceptor effects. Even though LSD behaved as a partial agonist and BOL as a pure antagonist, both drugs blocked the effect of serotonin in an unsurmountable manner, i.e., increasing concentrations of serotonin could not overcome the blocking effect of LSD or BOL. Radioligand binding studies showed that preincubation of membranes with either LSD or BOL reduced the density of [3H]ketanserin binding sites, suggesting that the drugs bind tightly to the 5HT2 receptor and are not displaced during the binding assay. Two additional experiments supported this hypothesis. First, the off-rate of [3H] LSD was slow (20 min), relative to that of [3H]ketanserin (approximately 4 min). Second, when the length of incubation with [3H]ketanserin was increased to 60 min, the LSD-induced decrease in Bmax was essentially eliminated. The possibility that LSD and BOL decrease [3H]ketanserin binding by interacting with an allosteric site was rejected, because neither drug altered the rate of dissociation of [3H]ketanserin. The most parsimonious interpretation of these results is that unsurmountable antagonism reflects prolonged occupancy of the receptor by slowly reversible antagonists.

Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

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

Burroughs, S.F.; Johnson, G.J.

beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of (14C)-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; butmore » no irreversible inhibition of alpha 2 adrenergic receptors, measured with (3H)-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist (3H)-U46619 and antagonist (3H)-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ((Ca2+)i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in (Ca2+)i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.« less

Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions Using Homologous Osteochondral Allograft.

PubMed

Alkaduhimi, Hassanin; van den Bekerom, Michel P J; van Deurzen, Derek F P

2017-06-01

Posterior shoulder dislocations are accompanied by high forces and can result in an anteromedial humeral head impression fracture called a reverse Hill-Sachs lesion. This reverse Hill-Sachs lesion can result in serious complications including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis, persistent joint stiffness, and loss of shoulder function. Treatment is challenging and depends on the amount of bone loss. Several techniques have been reported to describe the surgical treatment of lesions larger than 20%. However, there is still limited evidence with regard to the optimal procedure. Favorable results have been reported by performing segmental reconstruction of the reverse Hill-Sachs lesion with bone allograft. Although the procedure of segmental reconstruction has been used in several studies, its technique has not yet been well described in detail. In this report we propose a step-by-step description of the technique how to perform a segmental reconstruction of a reverse Hill-Sachs defect.

Trap-assisted tunneling in Si-InAs nanowire heterojunction tunnel diodes.

PubMed

Bessire, Cedric D; Björk, Mikael T; Schmid, Heinz; Schenk, Andreas; Reuter, Kathleen B; Riel, Heike

2011-10-12

We report on the electrical characterization of one-sided p(+)-si/n-InAs nanowire heterojunction tunnel diodes to provide insight into the tunnel process occurring in this highly lattice mismatched material system. The lattice mismatch gives rise to dislocations at the interface as confirmed by electron microscopy. Despite this, a negative differential resistance with peak-to-valley current ratios of up to 2.4 at room temperature and with large current densities is observed, attesting to the very abrupt and high-quality interface. The presence of dislocations and other defects that increase the excess current is evident in the first and second derivative of the I-V characteristics as distinct peaks arising from trap-and phonon-assisted tunneling via the corresponding defect levels. We observe this assisted tunneling mainly in the forward direction and at low reverse bias but not at higher reverse biases because the band-to-band generation rates are peaked in the InAs, which is also confirmed by modeling. This indicates that most of the peaks are due to dislocations and defects in the immediate vicinity of the interface. Finally, we also demonstrate that these devices are very sensitive to electrical stress, in particular at room temperature, because of the extremely high electrical fields obtained at the abrupt junction even at low bias. The electrical stress induces additional defect levels in the band gap, which reduce the peak-to-valley current ratios.

Detection of microstructural defects in chalcopyrite Cu(In,Ga)Se2 solar cells by spectrally-filtered electroluminescence

NASA Astrophysics Data System (ADS)

Skvarenina, L.; Gajdos, A.; Macku, R.; Skarvada, P.

2017-12-01

The aim of this research is to detect and localize microstructural defects by using an electrically excited light emission from a forward/reverse-bias stressed pn-junction in thin-film Cu(In; Ga)Se2 solar cells with metal wrap through architecture. A different origin of the local light emission from intrinsic/extrinsic imperfections in these chalcopyrite-based solar cells can be distinguished by a spectrally-filtered electroluminescence mapping. After a light emission mapping and localization of the defects in a macro scale is performed a micro scale exploration of the solar cell surface by a scanning electron microscope which follows the particular defects obtained by an electroluminescence. In particular, these macroscopic/microscopic examinations are performed independently, then the searching of the corresponding defects in the micro scale is rather difficult due to a diffused light emission obtained from the macro scale localization. Some of the defects accompanied by a highly intense light emission very often lead to a strong local overheating. Therefore, the lock-in infrared thermography is also performed along with an electroluminescence mapping.

Defect-Mediated Molecular Interaction and Charge Transfer in Graphene Mesh-Glucose Sensors.

PubMed

Kwon, Sun Sang; Shin, Jae Hyeok; Choi, Jonghyun; Nam, SungWoo; Park, Won Il

2017-04-26

We report the role of defects in enzymatic graphene field-effect transistor sensors by introducing engineered defects in graphene channels. Compared with conventional graphene sensors (Gr sensors), graphene mesh sensors (GM sensors), with an array of circular holes, initially exhibited a higher irreversible response to glucose, involving strong chemisorption to edge defects. However, after immobilization of glucose oxidase, the irreversibility of the responses was substantially diminished, without any reduction in the sensitivity of the GM sensors (i.e., -0.53 mV/mM for the GM sensor vs -0.37 mV/mM for Gr sensor). Furthermore, multiple cycle operation led to rapid sensing and improved the reversibility of GM sensors. In addition, control tests with sensors containing a linker showed that sensitivity was increased in Gr sensors but decreased in GM sensors. Our findings indicate that edge defects can be used to replace linkers for immobilization of glucose oxidase and improve charge transfer across glucose oxidase-graphene interfaces.

Topological defects in liquid crystals and molecular self-assembly (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abbott, Nicholas L.

2017-02-01

Topological defects in liquid crystals (LCs) have been widely used to organize colloidal dispersions and template polymerizations, leading to a range of elastomers and gels with complex mechanical and optical properties. However, little is understood about molecular-level assembly processes within defects. This presentation will describe an experimental study that reveals that nanoscopic environments defined by LC topological defects can selectively trigger processes of molecular self-assembly. By using fluorescence microscopy, cryogenic transmission electron microscopy and super-resolution optical microscopy, key signatures of molecular self-assembly of amphiphilic molecules in topological defects are observed - including cooperativity, reversibility, and controlled growth of the molecular assemblies. By using polymerizable amphiphiles, we also demonstrate preservation of molecular assemblies templated by defects, including nanoscopic "o-rings" synthesized from "Saturn-ring" disclinations. Our results reveal that topological defects in LCs are a versatile class of three-dimensional, dynamic and reconfigurable templates that can direct processes of molecular self-assembly in a manner that is strongly analogous to other classes of macromolecular templates (e.g., polymer—surfactant complexes). Opportunities for the design of exquisitely responsive soft materials will be discussed using bacterial endotoxin as an example.

Ultrasonic Time Reversal Mirrors

NASA Astrophysics Data System (ADS)

Fink, Mathias; Montaldo, Gabriel; Tanter, Mickael

2004-11-01

For more than ten years, time reversal techniques have been developed in many different fields of applications including detection of defects in solids, underwater acoustics, room acoustics and also ultrasound medical imaging and therapy. The essential property that makes time reversed acoustics possible is that the underlying physical process of wave propagation would be unchanged if time were reversed. In a non dissipative medium, the equations governing the waves guarantee that for every burst of sound that diverges from a source there exists in theory a set of waves that would precisely retrace the path of the sound back to the source. If the source is pointlike, this allows focusing back on the source whatever the medium complexity. For this reason, time reversal represents a very powerful adaptive focusing technique for complex media. The generation of this reconverging wave can be achieved by using Time Reversal Mirrors (TRM). It is made of arrays of ultrasonic reversible piezoelectric transducers that can record the wavefield coming from the sources and send back its time-reversed version in the medium. It relies on the use of fully programmable multi-channel electronics. In this paper we present some applications of iterative time reversal mirrors to target detection in medical applications.

Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation

PubMed Central

Nishimoto, Satoko; Kucharska, Anna; Newbury-Ecob, Ruth; Logan, Malcolm P. O.

2016-01-01

The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients. In Tbx hypomorphic mutants maintained on an INV mutant background, with situs inversus, the laterality of defects is reversed. Our data demonstrate an early, inherent asymmetry in the left and right limb-forming regions and that threshold levels of Tbx5 are required to overcome this asymmetry to ensure symmetric forelimb formation. PMID:27992425

Radiation damage annealing mechanisms and possible low temperature annealing in silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.

1980-01-01

The defect responsible for reverse annealing in 2 ohm/cm n(+)/p silicon solar cells was identified. This defect, with energy level at e sub v + 0.30 eV was tentatively identified as a boron oxygen-vacancy complex. Results indicate that its removal could result in significant annealing for 2 ohm/cm and lower resistivity cells at temperatures as low as 200 C. These results were obtained by use of an expression derived from the Shockley-Read-Hall recombination theory which relates measured diffusion length ratios to relative defect concentrations and electron capture cross sections. The relative defect concentrations and one of the required capture cross sections are obtained from Deep Level Transient Spectroscopy. Four additional capture cross sections are obtained using diffusion length data and data from temperature dependent lifetime studied. These calculated results are in reasonable agreement with experimental data.

Role of the charge state of interface defects in electronic inhomogeneity evolution with gate voltage in graphene

NASA Astrophysics Data System (ADS)

Singh, Anil Kumar; Gupta, Anjan K.

2018-05-01

Evolution of electronic inhomogeneities with back-gate voltage in graphene on SiO2 was studied using room temperature scanning tunneling microscopy and spectroscopy. Reversal of contrast in some places in the conductance maps and sharp changes in cross correlations between topographic and conductance maps, when graphene Fermi energy approaches its Dirac point, are attributed to the change in charge state of interface defects. The spatial correlations in the conductance maps, described by two length scales, and their growth during approach to Dirac point, show a qualitative agreement with the predictions of the screening theory of graphene. Thus a sharp change in the two length scales close to the Dirac point, seen in our experiments, is interpreted in terms of the change in charge state of some of the interface defects. A systematic understanding and control of the charge state of defects can help in memory applications of graphene.

Microgravity and Signaling Molecules in Rat Osteoblasts: Downstream of Receptor Tyrosine Kinase, G-Protein-Coupled Receptor, and Small GTP-Binding Proteins

NASA Technical Reports Server (NTRS)

Kumel, Yasuhiro; Shimokawa, Hitoyata; Morita, Sadao; Katano, Hisako; Akiyama, Hideo; Hirano, Masahiko; Ohya, Keiichi; Sams, Clarence F.; Whitson, Peggy A.

2005-01-01

Rat osteoblasts were cultured for 4 and 5 days aboard Space Shuttle and solubilized on board. The mRNA levels of the post-receptor signaling molecules were analyzed by quantitative RT-PCR. The G-protein alpha subunit G(alpha)q mRNA levels were elevated 3-fold by microgravity. G(alpha)q stimulates PLC(beta), and then PKC. PKC(delta) and PKC(theta) mRNA levels were increased 2- to 5-fold by microgravity The mRNA levels of SOS and Ras GRF were increased 4 to 5-fold by microgravity, while Ras GAP was not altered. Spaceflight-induced bone loss might be attributed to microgravity modulation of the signaling pathway in osteoblasts.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

PubMed

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Symposium overview: alterations in cytokine receptors by xenobiotics.

PubMed

Cohen, M D; Schook, L B; Oppenheim, J J; Freed, B M; Rodgers, K E

1999-04-01

A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

Functional thiols as repair and doping agents of defective MoS2 monolayers

NASA Astrophysics Data System (ADS)

Förster, Anja; Gemming, Sibylle; Seifert, Gotthard

2018-06-01

Recent experimental and theoretical studies indicate that thiols (R-SH) can be used to repair sulfur vacancy defects in MoS2 monolayers (MLs). This density functional theory study investigates how the thiol repair mechanism process can be used to dope MoS2 MLs. Fluorinated thiols as well as amine-containing ones are used to p- and n-dope the MoS2 ML, respectively. It is shown that functional groups are only physisorbed on the repaired MoS2 surface. This explains the reversible doping with fluorinated thiols.

Minority carrier diffusion and defects in InGaAsN grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Kurtz, Steven R.; Klem, J. F.; Allerman, A. A.; Sieg, R. M.; Seager, C. H.; Jones, E. D.

2002-02-01

To gain insight into the nitrogen-related defects of InGaAsN, nitrogen vibrational mode spectra, Hall mobilities, and minority carrier diffusion lengths are examined for InGaAsN (1.1 eV band gap) grown by molecular beam epitaxy (MBE). Annealing promotes the formation of In-N bonding, and lateral carrier transport is limited by large scale (≫mean free path) material inhomogeneities. Comparing solar cell quantum efficiencies with our earlier results for devices grown by metalorganic chemical vapor deposition (MOCVD), we find significant electron diffusion in the MBE material (reversed from the hole diffusion in MOCVD material), and minority carrier diffusion in InGaAsN cannot be explained by a "universal," nitrogen-related defect.

[Research and application of computer-aided technology in restoration of maxillary defect].

PubMed

Cheng, Xiaosheng; Liao, Wenhe; Hu, Qingang; Wang, Qian; Dai, Ning

2008-08-01

This paper presents a new method of designing restoration model of maxillectomy defect through Computer aided technology. Firstly, 3D maxillectomy triangle mesh model is constructed from Helical CT data. Secondly, the triangle mesh model is transformed into initial computer-aided design (CAD) model of maxillectomy through reverse engineering software. Thirdly, the 3D virtual restoration model of maxillary defect is obtained after designing and adjusting the initial CAD model through CAD software according to the patient's practical condition. Therefore, the 3D virtual restoration can be fitted very well with the broken part of maxilla. The exported design data can be manufactured using rapid prototyping technology and foundry technology. Finally, the result proved that this method is effective and feasible.

Disorder induced semiconductor to metal transition and modifications of grain boundaries in nanocrystalline zinc oxide thin film

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

Singh, Fouran; Kumar, Vinod; Chaudhary, Babloo

2012-10-01

This paper report on the disorder induced semiconductor to metal transition (SMT) and modifications of grain boundaries in nanocrystalline zinc oxide thin film. Disorder is induced using energetic ion irradiation. It eliminates the possibility of impurities induced transition. However, it is revealed that some critical concentration of defects is needed for inducing such kind of SMT at certain critical temperature. Above room temperature, the current-voltage characteristics in reverse bias attributes some interesting phenomenon, such as electric field induced charge transfer, charge trapping, and diffusion of defects. The transition is explained by the defects induced disorder and strain in ZnO crystallitesmore » created by high density of electronic excitations.« less

Volumetric Analysis of Alveolar Bone Defect Using Three-Dimensional-Printed Models Versus Computer-Aided Engineering.

PubMed

Du, Fengzhou; Li, Binghang; Yin, Ningbei; Cao, Yilin; Wang, Yongqian

2017-03-01

Knowing the volume of a graft is essential in repairing alveolar bone defects. This study investigates the 2 advanced preoperative volume measurement methods: three-dimensional (3D) printing and computer-aided engineering (CAE). Ten unilateral alveolar cleft patients were enrolled in this study. Their computed tomographic data were sent to 3D printing and CAE software. A simulated graft was used on the 3D-printed model, and the graft volume was measured by water displacement. The volume calculated by CAE software used mirror-reverses technique. The authors compared the actual volumes of the simulated grafts with the CAE software-derived volumes. The average volume of the simulated bone grafts by 3D-printed models was 1.52 mL, higher than the mean volume of 1.47 calculated by CAE software. The difference between the 2 volumes was from -0.18 to 0.42 mL. The paired Student t test showed no statistically significant difference between the volumes derived from the 2 methods. This study demonstrated that the mirror-reversed technique by CAE software is as accurate as the simulated operation on 3D-printed models in unilateral alveolar cleft patients. These findings further validate the use of 3D printing and CAE technique in alveolar defect repairing.

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

2014-01-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

2015-03-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Reverse saphenous conduit flap in small animals: Clinical applications and outcomes.

PubMed

Elliott, Ross C

2014-08-20

Due to the lack of skin elasticity defects of the distal hind limb can be a challenge to close. This article assesses a well-described, but completely under-used technique for closure of wounds on the distal tarsus. The technique was used with good success in six cases presenting to the Bryanston Veterinary Hospital with a wide range of underlying pathology ranging from trauma to neoplastic disease of the tarsus. All six cases were treated with a reverse saphenous conduit flap and two of them underwent radiation therapy with no adverse side effects. All cases showed excellent results with a very low degree of flap necrosis that never exceeded 15% of the total flap area. This skin flap provides an excellent treatment method that is reliable in closure of defects of the distal tarsus with few adverse effects. To the author's knowledge there has been only one previously published report on the clinical use of this type of skin flap, even though the flap is well described in most texts.

Fine golden rings: Tunable surface plasmon resonance from assembled nanorods in topological defects of liquid crystals

DOE PAGES

Lee, Elaine; Xia, Yu; Ferrier, Jr., Robert C.; ...

2016-02-08

Unprecedented, reversible, and dynamic control over an assembly of gold nanorods dispersed in liquid crystals (LC) is demonstrated. The LC director field is dynamically tuned at the nanoscale using microscale ring confinement through the interplay of elastic energy at different temperatures, thus fine-tuning its core replacement energy to reversibly sequester nanoscale inclusions at the microscale. As a result, this leads to shifts of 100 nm or more in the surface plasmon resonance peak, an order of magnitude greater than any previous work with AuNR composites.

A trombosis story and PRES

PubMed Central

Kartal, Vural; Zara, Zeynep; Yilmaz, Sema; Ayhan, Aylin; Yoruk, Asim; Timur, Cetin

2014-01-01

Trombosis is seen in children with acute lymphoblastic leukemia during or after L-asparaginase treatment. Posterior reversible encephalopathy syndrome (PRES) is a complex syndrome characterized with sudden hypertension, headache, nausea, vomiting, alteration in the state of consciousness, vision defect and seizures. The cases related to this syndrome have been reportedly seen after eclampsia, organ transplantation, immunsuppressive treatments, autoimmune diseases and chemotherapy. Vasogenic edema occuring in the brain parencyhma constitues the basic pathophysiology. We present a case who developed seizures during treatment for B-cell acute lymphoblastic leukemia and diagnosed as posterior reversible encephalopathy. PMID:28058302

A trombosis story and PRES.

PubMed

Kartal, Vural; Zara, Zeynep; Yilmaz, Sema; Ayhan, Aylin; Yoruk, Asim; Timur, Cetin

2014-01-01

Trombosis is seen in children with acute lymphoblastic leukemia during or after L-asparaginase treatment. Posterior reversible encephalopathy syndrome (PRES) is a complex syndrome characterized with sudden hypertension, headache, nausea, vomiting, alteration in the state of consciousness, vision defect and seizures. The cases related to this syndrome have been reportedly seen after eclampsia, organ transplantation, immunsuppressive treatments, autoimmune diseases and chemotherapy. Vasogenic edema occuring in the brain parencyhma constitues the basic pathophysiology. We present a case who developed seizures during treatment for B-cell acute lymphoblastic leukemia and diagnosed as posterior reversible encephalopathy.

Dictyostelium discoideum mutants with conditional defects in phagocytosis

PubMed Central

1994-01-01

We have isolated and characterized Dictyostelium discoideum mutants with conditional defects in phagocytosis. Under suspension conditions, the mutants exhibited dramatic reductions in the uptake of bacteria and polystyrene latex beads. The initial binding of these ligands was unaffected, however, indicating that the defect was not in a plasma membrane receptor: Because of the phagocytosis defect, the mutants were unable to grow when cultured in suspensions of heat-killed bacteria. The mutants exhibited normal capacities for fluid phase endocytosis and grew as rapidly as parental (AX4) cells in axenic medium. Both the defects in phagocytosis and growth on bacteria were corrected when the mutant Dictyostelium cells were cultured on solid substrates. Reversion and genetic complementation analysis suggested that the mutant phenotypes were caused by single gene defects. While the precise site of action of the mutations was not established, the mutations are likely to affect an early signaling event because the binding of bacteria to mutant cells in suspension was unable to trigger the localized polymerization of actin filaments required for ingestion; other aspects of actin function appeared normal. This class of conditional phagocytosis mutant should prove to be useful for the expression cloning of the affected gene(s). PMID:7519624

Do NiTi instruments show defects before separation? Defects caused by torsional fatigue in hand and rotary nickel-titanium (NiTi) instruments which lead to failure during clinical use.

PubMed

Chakka, N V Murali Krishna; Ratnakar, P; Das, Sanjib; Bagchi, Anandamy; Sudhir, Sudhir; Anumula, Lavanya

2012-11-01

Visual and microscopic evaluation of defects caused by torsional fatigue in hand and rotary nickel titanium (NiTi) instruments. Ninety-six NiTi greater taper instruments which were routinely used for root canal treatment only in anterior teeth were selected for the study. The files taken include ProTaper for hand use, ProTaper Rotary files and Endowave rotary files. After every use, the files were observed visually and microscopically (Stereomicroscope at 10×) to evaluate the defects caused by torsional fatigue. Scoring was given according to a new classification formulated which gives an indication of the severity of the defect or damage. Data was statistically analyzed using KruskallWallis and Mann-Whitney U test. Number of files showing defects were more under stereomicroscope than visual examination. But, the difference in the evaluation methods was not statistically significant. The different types of defects observed were bent instrument, straightening/stretching of twist contour and partial reverse twisting. Endowave files showed maximum number of defects followed by ProTaper for hand use and least in ProTaper Rotary. Visible defects due to torsional fatigue do occur in NiTi instruments after clinical use. Both visual and microscopic examinations were efficient in detecting defects caused due to torsional fatigue. This study emphasizes that all files should be observed for any visible defects before and after every instrumentation cycle to minimize the risk of instrument separation and failure of endodontic therapy.

Reversible control of doping in graphene-on-SiO2 by cooling under gate-voltage

NASA Astrophysics Data System (ADS)

Singh, Anil Kumar; Gupta, Anjan Kumar

2017-11-01

The electronic properties of graphene can be modulated by various doping techniques other than back-gate, but most such methods are not easily reversible and also lead to mobility reduction. Here, we report on the reversible control of doping in graphene by cooling under back-gate-voltage. The observed variation in hysteresis in our devices with the temperature and interface preparation method is attributed to the variation in the density of redox species, namely, H2O and O2, at the graphene/SiO2 interface, and their diffusion. With careful interface preparation, we have been able to make devices with negligible hysteresis at room temperature and by exploiting hysteresis at high temperatures, we get a wide, but reversible tunability of interface charge density and graphene doping, by cooling to room temperature under gate-voltage. Such reversible control of graphene doping by manipulating the interface defect charge density can help in making new data storage devices using graphene.

Bias-polarity-dependent UV/visible transferable electroluminescence from ZnO nanorod array LED with graphene oxide electrode supporting layer

NASA Astrophysics Data System (ADS)

Liu, Weizhen; Wang, Wei; Xu, Haiyang; Li, Xinghua; Yang, Liu; Ma, Jiangang; Liu, Yichun

2015-09-01

A simple top electrode preparation process, employing continuous graphene oxide films as electrode supporting layers, was adopted to fabricate a ZnO nanorod array/p-GaN heterojunction LED. The achieved LED demonstrated different electroluminescence behaviors under forward and reverse biases: a yellow-red emission band was observed under forward bias, whereas a blue-UV emission peak was obtained under reverse bias. Electroluminescence spectra under different currents and temperatures, as well as heterojunction energy-band alignments, reveal that the yellow-red emission under forward bias originates from recombinations related to heterointerface defects, whereas the blue-UV electroluminescence under reverse bias is ascribed to transitions from near-band-edge and Mg-acceptor levels in p-GaN.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

PubMed

D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe

2017-10-01

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.

Measuring the proton selectivity of graphene membranes

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

Walker, Michael I.; Keyser, Ulrich F., E-mail: ufk20@cam.ac.uk; Braeuninger-Weimer, Philipp

2015-11-23

By systematically studying the proton selectivity of free-standing graphene membranes in aqueous solutions, we demonstrate that protons are transported by passing through defects. We study the current-voltage characteristics of single-layer graphene grown by chemical vapour deposition (CVD) when a concentration gradient of HCl exists across it. Our measurements can unambiguously determine that H{sup +} ions are responsible for the selective part of the ionic current. By comparing the observed reversal potentials with positive and negative controls, we demonstrate that the as-grown graphene is only weakly selective for protons. We use atomic layer deposition to block most of the defects inmore » our CVD graphene. Our results show that a reduction in defect size decreases the ionic current but increases proton selectivity.« less

Investigations on the structure of Pb-Ge-Se glasses

NASA Astrophysics Data System (ADS)

Kalra, G.; Upadhyay, M.; Sharma, Y.; Abhaya, S.; Murugavel, S.; Amarendra, G.

2016-05-01

Chalcogenide glasses have attracted much attention because of their potential application in various solid state devices. In the present work, we report here the detailed thermal, structural, microstructural studies on PbxGe42-xSe58 with (0 ≤ x ≤ 20) glasses. The influence of Pb content on the glass transition temperature, specific heat, and non-reversing enthalphy is observed and discussed qualitatively The Raman spectroscopic studies on the all the glass compositions are carried out and deconvoluted into different structural units. The positron annihilation life-time spectroscopy (PALS) studies helped to understand the nature of defect states present in the glassy system and its variation with Pb content. The concentration of charged defect centers is found to increase, whereas the open volume defect concentration decreases with Pb content in these glasses.

Carrier dynamics and the role of surface defects: Designing a photocatalyst for gas-phase CO 2 reduction

DOE PAGES

Hoch, Laura B.; Szymanski, Paul; Ghuman, Kulbir Kaur; ...

2016-11-28

In 2O 3-x(OH) y nanoparticles have been shown to function as an effective gas-phase photocatalyst for the reduction of CO 2 to CO via the reverse water–gas shift reaction. Their photocatalytic activity is strongly correlated to the number of oxygen vacancy and hydroxide defects present in the system. To better understand how such defects interact with photogenerated electrons and holes in these materials, we have studied the relaxation dynamics of In 2O 3-x(OH) y nanoparticles with varying concentration of defects using two different excitation energies corresponding to above-band-gap (318-nm) and near-band-gap (405-nm) excitations. Our results demonstrate that defects play amore » significant role in the excited-state, charge relaxation pathways. Higher defect concentrations result in longer excited-state lifetimes, which are attributed to improved charge separation. This correlates well with the observed trends in the photocatalytic activity. These results are further supported by density-functional theory calculations, which confirm the positions of oxygen vacancy and hydroxide defect states within the optical band gap of indium oxide. This enhanced understanding of the role these defects play in determining the optoelectronic properties and charge carrier dynamics can provide valuable insight toward the rational development of more efficient photocatalytic materials for CO 2 reduction.« less

Carrier dynamics and the role of surface defects: Designing a photocatalyst for gas-phase CO 2 reduction

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

Hoch, Laura B.; Szymanski, Paul; Ghuman, Kulbir Kaur

In 2O 3-x(OH) y nanoparticles have been shown to function as an effective gas-phase photocatalyst for the reduction of CO 2 to CO via the reverse water–gas shift reaction. Their photocatalytic activity is strongly correlated to the number of oxygen vacancy and hydroxide defects present in the system. To better understand how such defects interact with photogenerated electrons and holes in these materials, we have studied the relaxation dynamics of In 2O 3-x(OH) y nanoparticles with varying concentration of defects using two different excitation energies corresponding to above-band-gap (318-nm) and near-band-gap (405-nm) excitations. Our results demonstrate that defects play amore » significant role in the excited-state, charge relaxation pathways. Higher defect concentrations result in longer excited-state lifetimes, which are attributed to improved charge separation. This correlates well with the observed trends in the photocatalytic activity. These results are further supported by density-functional theory calculations, which confirm the positions of oxygen vacancy and hydroxide defect states within the optical band gap of indium oxide. This enhanced understanding of the role these defects play in determining the optoelectronic properties and charge carrier dynamics can provide valuable insight toward the rational development of more efficient photocatalytic materials for CO 2 reduction.« less

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

Familial hypothyroidism results from both thyroidal and extrathyroidal dysfunction. Specific intrathyroidal abnormalities in thyroid hormone synthesis causing goitrous hypothyroidism are iodide trap defect, organification defect, "coupling" defect, iodoprotein defect, and dehalogenase defect. The diagnostic studies for each are outlined utilizing radioiodine(131I) studies. Other causes of cretinism include failure of the thyroid gland to respond to TSH and lack of pituitary TSH (or hypothalamic TRH). The syndrome of peripheral resistance to thyroid hormone is discussed. The diagnosis of inherited hypothyrodism rests on an adequate family history and measurement of both T4 and TSH levels which can be determined in cord blood or peripheral blood from the infant. The importance of early treatment of hypothyroidism in the neonatal period to prevent brain damage is emphasized. The rec:nt discovery of the importance of reverse T3 (RT3) in fetal thyroid metabolism is described, and the possibility of amniocentesis as an aid in prenatal diagnosis is considered. The place of intrauterine administration of thyroid hormone to the fetus at risk from hypothyroidism is uncertain at this time and requires carefully controlled studies and long-term follow-up.

The effect of alpha-particle and proton irradiation on the electrical and defect properties of n-GaAs

NASA Astrophysics Data System (ADS)

Goodman, S. A.; Auret, F. D.; Meyer, W. E.

1994-05-01

Radiation damage effects were studied in n-GaAs grown by organo-metallic vapour phase epitaxy (OMVPE) for a wide range of alpha-particle (2.0 MeV and 5.4 MeV) and proton (2.0 MeV) particle fluences, using an americium-241 (Am-241) radio-nuclide and a linear Van de Graaff accelerator as the particle sources. The samples were irradiated at 300 K, after fabricating palladium Schottky barrier diodes (SBDs) on the 1.2 × 10 16 cm 3 Si-doped epitaxial layers. The irradiation-induced defects are characterized using conventional deep level transient spectroscopy (DLTS). A correlation is made between the change in SBD characteristics and the quantity and type of defects introduced during irradiation. It is shown that the two parameters most susceptible to this irradiation are the reverse leakage current of the SBDs and the free carrier density of the epilayer. The introduction rate and the "signatures" of the alpha-particle and proton irradiation-induced defects are calculated and compared to those of similar defects introduced during electron irradiation.

Efficient Defect Engineering for Solution Combustion Processed In-Zn-O thin films for high performance transistors

NASA Astrophysics Data System (ADS)

Liang, Xiaoci; Wang, Chengcai; Liang, Jun; Liu, Chuan; Pei, Yanli

2017-09-01

The oxygen related defects in the solution combustion-processed InZnO vitally affect the field-effect mobility and on-off characteristics in thin film transistors (TFTs). We use photoelectron spectroscopy to reveal that these defects can be well controlled by adjusting the atmosphere and flow rate during the combustion reaction, but are hardly affected by further post-annealing after the reaction. In device performance, the threshold voltage of the InZnO-TFTs was regulated in a wide range from 3.5 V to 11.0 V. To compromise the high field-effect mobility and good subthreshold properties, we fabricate the TFTs with double active layers of InZnO to achieve vertical gradience in defect distribution. The resulting TFT exhibits much higher field-effect mobility as 17.5 cm2 · V-1 · s-1, a low reversed sub-threshold slope as 0.35 V/decade, and a high on-off ratio as 107. The presented understandings and methods on defect engineering are efficient in improving the device performance of TFTs made from the combustion reaction process.

Bflinks: Reliable Bugfix Links via Bidirectional References and Tuned Heuristics

PubMed Central

2014-01-01

Background. Data from software version archives and defect databases can be used for defect insertion circumstance analysis and defect prediction. The first step in such analyses is identifying defect-correcting changes in the version archive (bugfix commits) and enriching them with additional metadata by establishing bugfix links to corresponding entries in the defect database. Candidate bugfix commits are typically identified via heuristic string matching on the commit message. Research Questions. Which filters could be used to obtain a set of bugfix links? How to tune their parameters? What accuracy is achieved? Method. We analyze a modular set of seven independent filters, including new ones that make use of reverse links, and evaluate visual heuristics for setting cutoff parameters. For a commercial repository, a product expert manually verifies over 2500 links to validate the results with unprecedented accuracy. Results. The heuristics pick a very good parameter value for five filters and a reasonably good one for the sixth. The combined filtering, called bflinks, provides 93% precision and only 7% results loss. Conclusion. Bflinks can provide high-quality results and adapts to repositories with different properties. PMID:27433506

Hysteresis in single and polycrystalline iron thin films: Major and minor loops, first order reversal curves, and Preisach modeling

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

Cao, Yue; Xu, Ke; Jiang, Weilin

Hysteretic behavior was studied in a series of Fe thin films, grown by molecular beam epitaxy, having different grain sizes and grown on different substrates. Major and minor loops and first order reversal curves (FORCs) were collected to investigate magnetization mechanisms and domain behavior under different magnetic histories. The minor loop coefficient and major loop coercivity increase with decreasing grain size due to higher defect concentration resisting domain wall movement. First order reversal curves allowed estimation of the contribution of irreversible and reversible susceptibilities and switching field distribution. The differences in shape of the major loops and first order reversalmore » curves are described using a classical Preisach model with distributions of hysterons of different switching fields, providing a powerful visualization tool to help understand the magnetization switching behavior of Fe films as manifested in various experimental magnetization measurements.« less

Hysteresis in single and polycrystalline iron thin films: Major and minor loops, first order reversal curves, and Preisach modeling

DOE PAGES

Cao, Yue; Xu, Ke; Jiang, Weilin; ...

2015-07-03

Hysteretic behavior was studied in a series of Fe thin films, grown by molecular beam epitaxy, having different grain sizes and grown on different substrates. Major and minor loops and first order reversal curves (FORCs) were collected to investigate magnetization mechanisms and domain behavior under different magnetic histories. The minor loop coefficient and major loop coercivity increase with decreasing grain size due to higher defect concentration resisting domain wall movement. First order reversal curves allowed estimation of the contribution of irreversible and reversible susceptibilities and switching field distribution. The differences in shape of the major loops and first order reversalmore » curves are described using a classical Preisach model with distributions of hysterons of different switching fields, providing a powerful visualization tool to help understand the magnetization switching behavior of Fe films as manifested in various experimental magnetization measurements.« less

Breakdown voltage mapping through voltage dependent ReBEL intensity imaging of multi-crystalline Si solar cells

NASA Astrophysics Data System (ADS)

Dix-Peek, RM.; van Dyk, EE.; Vorster, FJ.; Pretorius, CJ.

2018-04-01

Device material quality affects both the efficiency and the longevity of photovoltaic (PV) cells. Therefore, identifying these defects can be beneficial in the development of more efficient and longer lasting PV cells. In this study, a combination of spatially-resolved, electroluminescence (EL), and light beam induced current (LBIC) measurements, were used to identify specific defects and features of a multi-crystalline Si PV cells. In this study, a novel approach is used to map the breakdown voltage of a PV cell through voltage dependent Reverse Bias EL (ReBEL) intensity imaging.

Theoretical evidence for unexpected O-rich phases at corners of MgO surfaces

NASA Astrophysics Data System (ADS)

Bhattacharya, Saswata; Berger, Daniel; Reuter, Karsten; Ghiringhelli, Luca M.; Levchenko, Sergey V.

2017-12-01

Realistic oxide materials are often semiconductors, in particular at elevated temperatures, and their surfaces contain undercoordinated atoms at structural defects such as steps and corners. Using hybrid density-functional theory and ab initio atomistic thermodynamics, we investigate the interplay of bond-making, bond-breaking, and charge-carrier trapping at the corner defects at the (100) surface of a p -doped MgO in thermodynamic equilibrium with an O2 atmosphere. We show that by manipulating the coordination of surface atoms, one can drastically change and even reverse the order of stability of reduced versus oxidized surface sites.

The first defective extended chromium atom chain complex with amine ligand containing naphthyridine and pyrazine

NASA Astrophysics Data System (ADS)

Wang, Wen-Zhen; Geng, Shu-Bo; Liu, Shuang; Zhao, Dan; Jia, Xin-Gang; Wei, Hai-Long; Ismayilov, Rayyat H.; Yeh, Chen-Yu; Lee, Gene-Hsiang; Peng, Shie-Ming

2017-06-01

Through a pyrazine and naphthyridine-containing diamino ligand, N2,N7-di(pyrazin-2-yl)-1,8-naphthyridine-2,7-diamine (H2dpznda), defective extended metal atom chain complexes with one chromium(II) metal absent in centre, [Cr5(μ5-dpznda)4Cl2] (1) and [Cr5(μ5-dpznda)4(NCS)2] (2) were obtained. An electrochemistry research showed that the pentachromium(II) complexes were quite resistant to reduction although accessible to oxidation, with two reversible redox couples at E1/2 = +0.59 and +0.30 V.

Current-voltage characteristics and increase in the quantum efficiency of three-terminal gate and avalanche-based silicon LEDs.

PubMed

Xu, Kaikai

2013-09-20

In this paper, the emission of visible light by a monolithically integrated silicon p-n junction under reverse-bias is discussed. The modulation of light intensity is achieved using an insulated-gate terminal on the surface of the p-n junction. By varying the gate voltage, the breakdown voltage of the p-n junction will be adjustable so that the reverse current I(sub) flowing through the p-n junction at a fixed reverse-bias voltage is changed. It is observed that the light, which is emitted from the defects located at the p-n junction, depends closely on the reverse current I(sub). In regard to the phenomenon of electroluminescence, the relationship between the optical emission power and the reverse current I(sub) is linear. On the other hand, it is observed that both the quantum efficiency and the power conversion efficiency are able to have obvious enhancement, although the reverse-bias of the p-n junction is reduced and the corresponding reverse-current is much lower. Moreover, the successful fabrication on monolithic silicon light source on the bulk silicon by means of standard silicon complementary metal-oxide-semiconductor process technology is presented.

Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection

PubMed Central

Cubas, Rafael; van Grevenynghe, Julien; Wills, Saintedym; Kardava, Lela; Santich, Brian H.; Buckner, Clarisa M.; Muir, Roshell; Tardif, Virginie; Nichols, Carmen; Procopio, Francesco; He, Zhong; Metcalf, Talibah; Ghneim, Khader; Locci, Michela; Ancuta, Petronella; Routy, Jean-Pierre; Trautmann, Lydie; Li, Yuxing; McDermott, Adrian B.; Koup, Rick A.; Petrovas, Constantinos; Migueles, Steven A.; Connors, Mark; Tomaras, Georgia D.; Moir, Susan; Crotty, Shane

2015-01-01

Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2–responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART. PMID:26546609

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2014 CFR

2014-07-01

... work fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2012 CFR

2012-07-01

... fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2013 CFR

2013-07-01

... fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

Reverse-Time Imaging Based on Full-Waveform Inverted Velocity Model for Nondestructive Testing of Heterogeneous Engineered Structures

NASA Astrophysics Data System (ADS)

Nguyen, L. T.; Modrak, R. T.; Saenger, E. H.; Tromp, J.

2017-12-01

Reverse-time migration (RTM) can reconstruct reflectors and scatterers by cross-correlating the source wavefield and the receiver wavefield given a known velocity model of the background. In nondestructive testing, however, the engineered structure under inspection is often composed of layers of various materials and the background material has been degraded non-uniformly because of environmental or operational effects. On the other hand, ultrasonic waveform tomography based on the principles of full-waveform inversion (FWI) has succeeded in detecting anomalous features in engineered structures. But the building of the wave velocity model of the comprehensive small-size and high-contrast defect(s) is difficult because it requires computationally expensive high-frequency numerical wave simulations and an accurate understanding of large-scale background variations of the engineered structure.To reduce computational cost and improve detection of small defects, a useful approach is to divide the waveform tomography procedure into two steps: first, a low-frequency model-building step aimed at recovering background structure using FWI, and second, a high-frequency imaging step targeting defects using RTM. Through synthetic test cases, we show that the two-step procedure appears more promising in most cases than a single-step inversion. In particular, we find that the new workflow succeeds in the challenging scenario where the defect lies along preexisting layer interface in a composite bridge deck and in related experiments involving noisy data or inaccurate source parameters. The results reveal the potential of the new wavefield imaging method and encourage further developments in data processing, enhancing computation power, and optimizing the imaging workflow itself so that the procedure can efficiently be applied to geometrically complex 3D solids and waveguides. Lastly, owing to the scale invariance of the elastic wave equation, this imaging procedure can be transferred to applications in regional scales as well.

Arrhythmias after transcatheter closure of perimembranous ventricular septal defects with a modified double-disk occluder: early and long-term results.

PubMed

Li, Pan; Zhao, Xian-xian; Zheng, Xing; Qin, Yong-wen

2012-07-01

With the development of interventional techniques and devices, transcatheter closure of perimembranous ventricular septal defect has been widely performed. However, there has been a lack of long-term follow-up results about postoperative ECG changes of PmVSD patients. We report our experience of early and late arrhythmias after transcatheter closure of PmVSD with a modified double-disk occluder (MDVO). We performed a retrospective review of 79 patients (47 males, 32 females) between September 2002 and May 2007 who underwent transcatheter closure of perimembranous ventricular septal defect. Symmetric and asymmetric PmVSD occluders were used. The diameter of the evaluated defects ranged from 3 to 12 mm, as measured by TTE and 3 to 15 mm by left ventriculography. Most cases of PmVSD were treated successfully with a single procedure, resulting in a successful closure rate of 97% (77/79 patients). There was no death in any of the patients. After the operation, 79 patients were followed-up for a range of 10-76 months (35.3 ± 17.4 months). In this series, 11 cases of incomplete right bundle branch block and five cases of complete right bundle branch block occurred during the early period after operation. During long-term follow-up, these issues declined in prevalence to five and four cases, respectively. Moreover, reversible third-degree AVB occurred during closure or after the procedure, and two of the three patients with reversible AVB received a temporary heart pacemaker implantation. These patients recovered 1 h, 6 days, and 9 days later, respectively. During 10-76 months of follow-up, no complications occurred in any of the patients, including residual shunt, severe aortic valve, or tricuspid valve regurgitation. Device closure of perimembranous ventricular septal defects with a modified double-disk occluder (MDVO) resulted in excellent closure rates and acceptably low arrhythmia rates.

Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

PubMed

Arrighi, James A; Burg, Matthew; Cohen, Ira S; Soufer, Robert

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS. These data indicate the feasibility of simultaneous assessment of perfusion and function responses during MS. Flow and function responses to MS are frequently not concordant. These data suggest that MS-induced changes in perfusion may represent a different phenomenon than MS-induced changes in left ventricular function (either globally or regionally).

First interactions between hydrogen and stress-induced reverse transformation of Ni-Ti superelastic alloy

NASA Astrophysics Data System (ADS)

Yokoyama, Ken'ichi; Hashimoto, Tatsuki; Sakai, Jun'ichi

2017-11-01

The first dynamic interactions between hydrogen and the stress-induced reverse transformation have been investigated by performing an unloading test on a Ni-Ti superelastic alloy subjected to hydrogen charging under a constant applied strain in the elastic deformation region of the martensite phase. Upon unloading the specimen, charged with a small amount of hydrogen, no change in the behaviour of the stress-induced reverse transformation is observed in the stress-strain curve, although the behaviour of the stress-induced martensite transformation changes. With increasing amount of hydrogen charging, the critical stress for the reverse transformation markedly decreases. Eventually, for a larger amount of hydrogen charging, the reverse transformation does not occur, i.e. there is no recovery of the superelastic strain. The residual martensite phase on the side surface of the unloaded specimen is confirmed by X-ray diffraction. Upon training before the unloading test, the properties of the reverse transformation slightly recover after ageing in air at room temperature. The present study indicates that to change the behaviour of the reverse transformation a larger amount of hydrogen than that for the martensite transformation is necessary. In addition, it is likely that a substantial amount of hydrogen in solid solution more strongly suppresses the reverse transformation than hydrogen trapped at defects, thereby stabilising the martensite phase.

The self-healing of defects induced by the hydriding phase transformation in palladium nanoparticles

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

Ulvestad, A.; Yau, A.

Nanosizing can dramatically alter material properties by enhancing surface thermodynamic contributions, shortening diffusion lengths, and increasing the number of catalytically active sites per unit volume. These mechanisms have been used to explain the improved properties of catalysts, battery materials, plasmonic materials, etc. Here we show that Pd nanoparticles also have the ability to self-heal defects in their crystal structures. Using Bragg coherent diffractive imaging, we image dislocations nucleated deep in a Pd nanoparticle during the forward hydriding phase transformation that heal during the reverse transformation, despite the region surrounding the dislocations remaining in the hydrogen-poor phase. We show that defectivemore » Pd nanoparticles exhibit sloped isotherms, indicating that defects act as additional barriers to the phase transformation. Our results resolve the formation and healing of structural defects during phase transformations at the single nanoparticle level and offer an additional perspective as to how and why nanoparticles differ from their bulk counterparts.« less

Electric-dipole effect of defects on the energy band alignment of rutile and anatase TiO₂.

PubMed

Zhang, Daoyu; Yang, Minnan; Dong, Shuai

2015-11-21

Titanium dioxide materials have been studied intensively and extensively for photocatalytic applications. A long-standing open question is the energy band alignment of rutile and anatase TiO2 phases, which can affect the photocatalytic process in the composite system. There are basically two contradictory viewpoints about the alignment of these two TiO2 phases supported by the respective experiments: (1) straddling type and (2) staggered type. In this work, our DFT plus U calculations show that the perfect rutile(110) and anatase(101) surfaces have the straddling type band alignment, whereas the surfaces with defects can turn the band alignment into the staggered type. The electric dipoles induced by defects are responsible for the reversal of band alignment. Thus the defects introduced during the preparation and post-treatment processes of materials are probably the answer to the above open question regarding the band alignment, which can be considered in real practice to tune the photocatalytic activity of materials.

Global Formation of Topological Defects in the Multiferroic Hexagonal Manganites

DOE PAGES

Meier, Q. N.; Lilienblum, M.; Griffin, S. M.; ...

2017-10-20

The spontaneous transformations associated with symmetry-breaking phase transitions generate domain structures and defects that may be topological in nature. The formation of these defects can be described according to the Kibble-Zurek mechanism, which provides a generic relation that applies from cosmological to interatomic length scales. Its verification is challenging, however, in particular at the cosmological scale where experiments are impractical. While it has been demonstrated for selected condensed-matter systems, major questions remain regarding, e.g., its degree of universality. Here, we develop a global Kibble-Zurek picture from the condensed-matter level. We show theoretically that a transition between two fluctuation regimes (Ginzburgmore » and mean field) can lead to an intermediate region with reversed scaling, and we verify experimentally this behavior for the structural transition in the series of multiferroic hexagonal manganites. Trends across the series allow us to identify additional intrinsic features of the defect formation beyond the original Kibble-Zurek paradigm.« less

Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects.

PubMed

Cheng, Shao-Wen; Lin, Zhong-Qin; Wang, Wei; Zhang, Wei; Kou, Dong-Quan; Ying, Xiao-Zhou; Chen, Qing-Yu; Shen, Yue; Cheng, Xiao-Jie; Peng, Lei; Lv, Chuan-Zhu

2011-01-01

To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs). ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP) staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN), osteopontin (OPN) were examined by reverse transcription-polymerase chain reaction (RT-PCR). In vivo, demineralized bone matrix (DBM)-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects.

Acousto-defect interaction in irradiated and non-irradiated silicon n+-p structures

NASA Astrophysics Data System (ADS)

Olikh, O. Ya.; Gorb, A. M.; Chupryna, R. G.; Pristay-Fenenkov, O. V.

2018-04-01

The influence of ultrasound on current-voltage characteristics of non-irradiated silicon n+-p structures as well as silicon structures exposed to reactor neutrons or 60Co gamma radiation has been investigated experimentally. It has been found that the ultrasound loading of the n+-p structure leads to the reversible change of shunt resistance, carrier lifetime, and ideality factor. Specifically, considerable acoustically induced alteration of the ideality factor and the space charge region lifetime was observed in the irradiated samples. The experimental results were described by using the models of coupled defect level recombination, Shockley-Read-Hall recombination, and dislocation-induced impedance. The experimentally observed phenomena are associated with the increase in the distance between coupled defects as well as the extension of the carrier capture coefficient of complex point defects and dislocations. It has been shown that divacancies and vacancy-interstitial oxygen pairs are effectively modified by ultrasound in contrast to interstitial carbon-interstitial oxygen complexes.

Global Formation of Topological Defects in the Multiferroic Hexagonal Manganites

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

Meier, Q. N.; Lilienblum, M.; Griffin, S. M.

The spontaneous transformations associated with symmetry-breaking phase transitions generate domain structures and defects that may be topological in nature. The formation of these defects can be described according to the Kibble-Zurek mechanism, which provides a generic relation that applies from cosmological to interatomic length scales. Its verification is challenging, however, in particular at the cosmological scale where experiments are impractical. While it has been demonstrated for selected condensed-matter systems, major questions remain regarding, e.g., its degree of universality. Here, we develop a global Kibble-Zurek picture from the condensed-matter level. We show theoretically that a transition between two fluctuation regimes (Ginzburgmore » and mean field) can lead to an intermediate region with reversed scaling, and we verify experimentally this behavior for the structural transition in the series of multiferroic hexagonal manganites. Trends across the series allow us to identify additional intrinsic features of the defect formation beyond the original Kibble-Zurek paradigm.« less

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

Lubeigt, E.; Laboratoire de Mecanique et d'Acoustique, CNRS UPR 7051, 13402 Marseille Cedex 20; Mensah, S.

The fourth generation of nuclear reactor can use liquid sodium as the core coolant. When the reactor is operating, sodium temperatures can reach up to 600 deg. C. During maintenance periods, when the reactor is shut down, the coolant temperature is reduced to 200 deg. C. Because molten sodium is optically opaque, ultrasonic imaging techniques are developed for maintenance activities. Under-sodium imaging aims at i) checking the health of immersed structures. It should also allow ii) to assess component degradation or damage as cracks and shape defects as well as iii) the detection of lost objects. The under-sodium imaging systemmore » has to sustain high temperature (up to 300 deg. C) and hostility of the sodium environment. Furthermore, specific constraints such as transducers characteristics or the limited sensor mobility in the reactor vessel have to be considered. This work focuses on developing a methodology for detecting damages such as crack defects with ultrasound devices. Surface-breaking cracks or deep cracks are sought in the weld area, as welds are more subject to defects. Traditional methods enabled us to detect emerging cracks of submillimeter size with sodium-compatible high-temperature transducer. The presented approach relies on making use of prior knowledge about the environment through the implementation of differential imaging and time-reversal techniques. Indeed, this approach allows to detect a change by comparison with a reference measurement and by focusing back to any change in the environment. It is a means of analysis and understanding of the physical phenomena making it possible to design more effective inspection strategies. Difference between the measured signals reveals the acoustic field scattered by a perturbation (a crack for instance), which may occur between periodical measurements. The imaging method relies on the adequate combination of two computed ultrasonic fields, one forward and one adjoint. The adjoint field, which carries the information about the defects, is analogous to a time-reversal operation. One of the interests of the presented method is that the time-reversal operation is not done experimentally but numerically. Numerical simulations have been carried out to validate the practical relevance of this approach. The preliminary numerical results show a nice agreement between the guessed and the actual positions of the defect. After water-tests, in sodium-tests must be done in order to validate the water/sodium transposition. For this purpose, an under-sodium device is under development, which can move the transducers with four degrees of freedom in a 1.5 m{sup 3} sodium pot. (authors)« less

Autoimmune retinopathy with RPE hypersensitivity and 'negative ERG' in X-linked hyper-IgM syndrome.

PubMed

Schuster, Andreas; Apfelstedt-Sylla, Eckart; Pusch, Carsten M; Zrenner, Eberhart; Thirkill, Charles E

2005-01-01

To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-IgM immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity. Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed. (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. Electrophysiology revealed a 'negative ERG' indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of approximately 27.6-32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition. The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both antiretinal activity and RPE hypersensitivity. In this case, peripheral stem-cell transfusion with its associated chemotherapy failed to benefit the patient's vision; indications of autoimmunity appeared to increase following this treatment.

Accurate reconstruction of discontinuous mandible using a reverse engineering/computer-aided design/rapid prototyping technique: a preliminary clinical study.

PubMed

Zhou, Li-bin; Shang, Hong-tao; He, Li-sheng; Bo, Bin; Liu, Gui-cai; Liu, Yan-pu; Zhao, Jin-long

2010-09-01

To improve the reconstructive surgical outcome of a discontinuous mandibular defect, we used reverse engineering (RE), computer-aided design (CAD), and rapid prototyping (RP) technique to fabricate customized mandibular trays to precisely restore the mandibular defects. Autogenous bone grafting was also used to restore the bony continuity for occlusion rehabilitation. Six patients who had undergone block resection of the mandible underwent reconstruction using a custom titanium tray combining autogenous iliac grafts. The custom titanium tray was made using a RE/CAD/RP technique. A virtual 3-dimensional model was obtained by spiral computed tomography scanning. The opposite side of the mandible was mirrored to cover the defect area to restore excellent facial symmetry. A bone grafting tray was designed from the mirrored image and manufactured using RP processing and casting. The mandibular defects were restored using the trays in combination of autologous iliac grafting. An implant denture was made for 1 of the 6 patients at 24 weeks postoperatively for occlusion rehabilitation. The trays fabricated using this technique fit well in all 6 patients. The reconstructive procedures were easy and time saving. Satisfactory facial symmetry was restored. No severe complications occurred in the 5 patients without occlusion rehabilitation during a mean 50-month follow-up period. The reconstruction in the patient with occlusion lasted for only 1 year and failed eventually because of bone resorption and infection. Mandibular reconstruction was facilitated using the RE/CAD/RP technique. Satisfactory esthetic results were achieved. However, the rigidity of the cast tray could cause severe stress shielding to the grafts, which could lead to disuse atrophy. Therefore, some modification is needed for functional reconstruction. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Generation and Characterization of a Defective HIV-1 Virus as an Immunogen for a Therapeutic Vaccine

PubMed Central

García-Pérez, Javier; García, Felipe; Blanco, Julia; Escribà-García, Laura; Gatell, Jose Maria; Alcamí, Jose; Plana, Montserrat; Sánchez-Palomino, Sonsoles

2012-01-01

Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles. PMID:23144996

High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from antiretroviral-naive patients.

PubMed

Bertine, Mélanie; Charpentier, Charlotte; Visseaux, Benoit; Storto, Alexandre; Collin, Gilles; Larrouy, Lucile; Damond, Florence; Matheron, Sophie; Brun-Vézinet, Françoise; Descamps, Diane

2015-04-24

In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.

Hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility

PubMed Central

Bae, Mihyun H.; Bissonette, Gregory B.; Mars, Wendy M.; Michalopoulos, George K.; Achim, Cristian L.; Depireux, Didier A.; Powell, Elizabeth M.

2009-01-01

Disrupted ontogeny of forebrain inhibitory interneurons leads to neurological disorders, including epilepsy. Adult mice lacking the urokinase plasminogen activator receptor (Plaur) have decreased numbers of neocortical GABAergic interneurons and spontaneous seizures, attributed to a reduction of hepatocyte growth factor/scatter factor (HGF/SF). We report that by increasing endogenous HGF/SF concentration in the postnatal Plaur null mouse brain maintains the interneuron populations in the adult, reverses the seizure behavior and stabilizes the spontaneous electroencephalogram activity. The perinatal intervention provides a pathway to reverse potential birth defects and ameliorate seizures in the adult. PMID:19853606

Regulation of β1- and β3-adrenergic agonist-stimulated lipolytic response in hyperthyroid and hypothyroid rat white adipocytes

PubMed Central

Germack, Renée; Starzec, Anna; Perret, Gérard Y

2000-01-01

This study examined the effects of thyroid status on the lipolytic responses of rat white adipocytes to β-adrenoceptor (β-AR) stimulation. The β1- and β3-AR mRNAs and proteins were measured by Northern and saturation analyses, respectively. Glycerol production and adenyl cyclase (AC) activity induced by various non-selective and selective β1/β3-AR agonists and drugs which act distal to the receptor in the signalling cascade were measured in cells from untreated, tri-iodothyronine (T3)-treated and thyroidectomized rats. The β3-AR density was enhanced (72%) by T3-treatment and reduced (50%) by introduction of a hypothyroid state while β1-AR number remained unaffected. The β1- and β3-AR density was correlated with the specific mRNA level in all thyroid status. The lipolytic responses to isoprenaline, noradrenaline (β1/β3/β3-AR agonists) and BRL 37344 (β3-AR agonist) were potentiated by 48, 58 and 48%, respectively in hyperthyroidism and reduced by about 80% in hypothyroidism. T3-treatment increased the maximal lipolytic response to the partial β3-AR (CGP 12177) and β1-AR (xamoterol) agonists by 234 and 260%, respectively, increasing their efficacy (intrinsic activity: 0.95 versus 0.43 and 1.02 versus 0.42). The maximal AC response to these agonists was increased by 84 and 58%, respectively, without changing their efficacy. In the hypothyroid state, the maximal lipolytic and AC responses were decreased with CGP (0.17±0.03 versus 0.41±0.08 μmol glycerol/106 adipocytes; 0.048±0.005 versus 0.114±0.006 pmol cyclic AMP min−1 mg−1) but not changed with xamoterol. The changes in lipolytic responses to postreceptor-acting agents (forskolin, enprofylline and dibutenyl cyclic AMP, (Bu)2cAMP) suggest the modifications on receptor coupling and phosphodiesterase levels in both thyroid states. Thyroid status affects lipolysis by modifying β3-AR density and postreceptor events without changes in the β1-AR functionality. PMID:10711342

Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

PubMed Central

Almeida, Sandra; Zhang, Zhijun; Coppola, Giovanni; Mao, Wenjie; Futai, Kensuke; Karydas, Anna; Geschwind, Michael D.; Tartaglia, M. Carmela; Gao, Fuying; Gianni, Davide; Sena-Esteves, Miguel; Geschwind, Daniel H.; Miller, Bruce L.; Farese, Robert V.; Gao, Fen-Biao

2012-01-01

SUMMARY The pathogenic mechanisms of frontotemporal dementia (FTD) remain poorly understood. Here we generated multiple induced pluripotent stem cell (iPSC) lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel GRN mutation (PGRN S116X). In neurons and microglia differentiated from PGRN S116X iPSCs, the levels of intracellular and secreted progranulin were reduced, establishing patient-specific cellular models of progranulin haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the PI3K and MAPK pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by progranulin expression. Our findings identify cell-autonomous, reversible defects in patient neurons with progranulin deficiency and provide a new model for studying progranulin-dependent pathogenic mechanisms and testing potential therapies. PMID:23063362

The reverse boomerang sign: a marker for first-trimester transposition of great arteries.

PubMed

Bravo-Valenzuela, Nathalie Jeanne; Peixoto, Alberto Borges; Araujo Júnior, Edward; Da Silva Costa, Fabricio; Meagher, Simon

2017-10-12

To describe a new sonographic marker of transposition of great arteries (TGA) during the first-trimester screening. We reviewed six cases of TGA from 2013 to 2016 in which an antenatal diagnosis of TGA at first-trimester screening (11-13 + 6 weeks of gestation) was confirmed postnatally. We specifically assessed images obtained by scanning the fetal heart in three vessels (3V) and three-vessel with trachea (3VT) views using color Doppler. The "reverse boomerang" sign was defined as a reverse curvature of right ventricle outflow tract (RVOT) at level of the 3VT view. We described six cases of confirmed TGA, five singletons and one twin pregnancy, among which only two vessels and the reverse curvature of RVOT (reverse boomerang sign) was demonstrated in the first-trimester screening at level of 3VT view. Ventricular septal defects were observed in three cases, and double outlet right ventricle in one case. No other cardiac or extracardiac anomalies were identified. Termination of pregnancy was not performed in any case. Our series case suggests that the reverse boomerang sign may improve the early prenatal screening for TGA.

Krypton-81m ventilation scanning: acute respiratory disease

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

Lavender, J.P.; Irving, H.; Armstrong, J.D. II

1981-02-01

From experience with 700 patients undergoing ventilation and perfusion lung scanning with krypton-81m/technetium-99m technique, 34 patients suffering from nonembolic acute respiratory disease were selected for review. In 16 patients with pneumonia, all had defects of ventilation corresponding to, or larger than, the radiologic consolidation. In 13 patients there was some preservation of perfusion in the consolidated region. In two of the three patients with matched defects, the pneumonia was of long standing. In seven patients with collapse or atelectasis and in 11 patients with acute reversible bronchial obstruction and normal volume lungs, a similar pattern or ventillation and perfusion wasmore » observed.« less

Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis

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

Fields, C.L.; Ossorio, M.A.; Roy, T.M.

1990-03-01

We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic reverse redistribution phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy.

Sublattice reversal in GaAs/Ge/GaAs (113)B heterostructures and its application to THz emitting devices based on a coupled multilayer cavity

NASA Astrophysics Data System (ADS)

Lu, Xiangmeng; Kumagai, Naoto; Minami, Yasuo; Kitada, Takahiro

2018-04-01

We fabricated a coupled multilayer cavity with a GaAs/Ge/GaAs sublattice reversal structure for terahertz emission application. Sublattice reversal in GaAs/Ge/GaAs was confirmed by comparing the anisotropic etching profile of an epitaxial sample with those of reference (113)A and (113)B GaAs substrates. The interfaces of GaAs/Ge/GaAs were evaluated at the atomic level by scanning transmission electron microscopy (STEM) and energy-dispersive X-ray spectroscopy (EDX) mapping. Defect-free GaAs/Ge/GaAs heterostructures were observed in STEM images and the sublattice lattice was directly seen through atomic arrangements in EDX mapping. A GaAs/AlAs coupled multilayer cavity with a sublattice reversal structure was grown on the (113)B GaAs substrate after the confirmation of sublattice reversal. Smooth GaAs/AlAs interfaces were formed over the entire region of the coupled multilayer cavity structure both below and above the Ge layer. Two cavity modes with a frequency difference of 2.9 THz were clearly observed.

Superoxide Dismutase 1 In Vivo Ameliorates Maternal Diabetes Mellitus-Induced Apoptosis and Heart Defects Through Restoration of Impaired Wnt Signaling.

PubMed

Wang, Fang; Fisher, Steven A; Zhong, Jianxiang; Wu, Yanqing; Yang, Peixin

2015-10-01

Oxidative stress is manifested in embryos exposed to maternal diabetes mellitus, yet specific mechanisms for diabetes mellitus-induced heart defects are not defined. Gene deletion of intermediates of Wingless-related integration (Wnt) signaling causes heart defects similar to those observed in embryos from diabetic pregnancies. We tested the hypothesis that diabetes mellitus-induced oxidative stress impairs Wnt signaling, thereby causing heart defects, and that these defects can be rescued by transgenic overexpression of the reactive oxygen species scavenger superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-overexpressing embryos from nondiabetic WT control dams and nondiabetic/diabetic WT female mice mated with SOD1 transgenic male mice were analyzed. No heart defects were observed in WT and SOD1 embryos under nondiabetic conditions. WT embryos of diabetic dams had a 26% incidence of cardiac outlet defects that were suppressed by SOD1 overexpression. Insulin treatment reduced blood glucose levels and heart defects. Diabetes mellitus increased superoxide production, canonical Wnt antagonist expression, caspase activation, and apoptosis and suppressed cell proliferation. Diabetes mellitus suppressed Wnt signaling intermediates and Wnt target gene expression in the embryonic heart, each of which were reversed by SOD1 overexpression. Hydrogen peroxide and peroxynitrite mimicked the inhibitory effect of high glucose on Wnt signaling, which was abolished by the SOD1 mimetic, tempol. The oxidative stress of diabetes mellitus impairs Wnt signaling and causes cardiac outlet defects that are rescued by SOD1 overexpression. This suggests that targeting of components of the Wnt5a signaling pathway may be a viable strategy for suppression of congenital heart defects in fetuses of diabetic pregnancies. © 2015 American Heart Association, Inc.

Optically reversible electrical soft-breakdown in wide-bandgap oxides—A factorial study

NASA Astrophysics Data System (ADS)

Zhou, Y.; Ang, D. S.; Kalaga, P. S.

2018-04-01

In an earlier work, we found that an electrical soft-breakdown region in wide-bandgap oxides, such as hafnium dioxide, silicon dioxide, etc., could be reversed when illuminated by white light. The effect is evidenced by a decrease in the breakdown leakage current, termed as a negative photoconductivity response. This finding raises the prospect for optical sensing applications based on these traditionally non-photo-responsive but ubiquitous oxide materials. In this study, we examine the statistical distribution for the rate of breakdown reversal as well as the influence of factors such as wavelength, light intensity, oxide stoichiometry (or oxygen content) and temperature on the reversal rate. The rate of breakdown reversal is shown to be best described by the lognormal distribution. Light in the range of ˜400-700 nm is found to have relatively little influence on the reversal rate. On the other hand, light intensity, oxygen content and temperature, each of them has a clear impact; a stronger light intensity, an oxide that is richer in oxygen content and a reduced temperature all speed up the reversal process substantially. These experimental results are consistent with the proposed phenomenological redox model involving photo-assisted recombination of the surrounding oxygen interstitials with vacancy defects in the breakdown path.

Controlling Metastable Native Point-Defect Populations in Cu(In,Ga)Se 2 and Cu 2ZnSnSe 4 Materials and Solar Cells through Voltage-Bias Annealing

DOE PAGES

Teeter, Glenn; Harvey, Steve P.; Johnston, Steve

2017-01-30

Our contribution describes the influence of low-temperature annealing with and without applied voltage bias on thin-film Cu 2ZnSnSe 4 (CZTSe), Cu(In,Ga)Se 2 (CIGS), and CdS material properties and solar cell performance. In order to quantify the effects of cation disorder on CZTSe device performance, completed devices were annealed under open-circuit conditions at various temperatures from 110 degrees C to 215 degrees C and subsequently quenched. Measurements on these devices document systematic, reversible changes in solar-cell performance consistent with a reduction in CZTSe band tails at lower annealing temperatures. CIGS and CZTSe solar cells were also annealed at various temperatures (200more » degrees C for CIGS and 110 degrees C-215 degrees C for CZTSe) and subsequently quenched with continuously applied voltage bias to explore the effects of non-equilibrium annealing conditions. For both absorbers, large reversible changes in device characteristics correlated with the magnitude and sign of the applied voltage bias were observed. For CZTSe devices, the voltage-bias annealing (VBA) produced reversible changes in open-circuit voltage (VOC) from 289 meV to 446 meV. For CIGS solar cells, even larger changes were observed in device performance: photovoltaic (PV) conversion efficiency of the CIGS device varied from below 3% to above 15%, with corresponding changes in CIGS hole density of about three orders of magnitude. Findings from these VBA experiments are interpreted in terms of changes to the metastable point-defect populations that control key properties in the absorber layers, and in the CdS buffer layer. Computational device modeling was performed to assess the impacts of cation disorder on the CZTSe VOC deficit, and to elucidate the effects of VBA treatments on metastable point defect populations in CZTSe, CIGS, and CdS. Our results indicate that band tails impose important limitations on CZTSe device performance. Device modeling results also indicate that non-equilibrium processing conditions including the effects of voltage bias can dramatically alter point-defect-mediated opto-electronic properties of semiconductors. Implications for optimization of PV materials and connections to long-term stability of PV devices are discussed.« less

Controlling metastable native point-defect populations in Cu(In,Ga)Se2 and Cu2ZnSnSe4 materials and solar cells through voltage-bias annealing

NASA Astrophysics Data System (ADS)

Teeter, G.; Harvey, S. P.; Johnston, S.

2017-01-01

This contribution describes the influence of low-temperature annealing with and without applied voltage bias on thin-film Cu2ZnSnSe4 (CZTSe), Cu(In,Ga)Se2 (CIGS), and CdS material properties and solar cell performance. To quantify the effects of cation disorder on CZTSe device performance, completed devices were annealed under open-circuit conditions at various temperatures from 110 °C to 215 °C and subsequently quenched. Measurements on these devices document systematic, reversible changes in solar-cell performance consistent with a reduction in CZTSe band tails at lower annealing temperatures. CIGS and CZTSe solar cells were also annealed at various temperatures (200 °C for CIGS and 110 °C-215 °C for CZTSe) and subsequently quenched with continuously applied voltage bias to explore the effects of non-equilibrium annealing conditions. For both absorbers, large reversible changes in device characteristics correlated with the magnitude and sign of the applied voltage bias were observed. For CZTSe devices, the voltage-bias annealing (VBA) produced reversible changes in open-circuit voltage (VOC) from 289 meV to 446 meV. For CIGS solar cells, even larger changes were observed in device performance: photovoltaic (PV) conversion efficiency of the CIGS device varied from below 3% to above 15%, with corresponding changes in CIGS hole density of about three orders of magnitude. Findings from these VBA experiments are interpreted in terms of changes to the metastable point-defect populations that control key properties in the absorber layers, and in the CdS buffer layer. Computational device modeling was performed to assess the impacts of cation disorder on the CZTSe VOC deficit, and to elucidate the effects of VBA treatments on metastable point defect populations in CZTSe, CIGS, and CdS. Results indicate that band tails impose important limitations on CZTSe device performance. Device modeling results also indicate that non-equilibrium processing conditions including the effects of voltage bias can dramatically alter point-defect-mediated opto-electronic properties of semiconductors. Implications for optimization of PV materials and connections to long-term stability of PV devices are discussed.

Controlling Metastable Native Point-Defect Populations in Cu(In,Ga)Se 2 and Cu 2ZnSnSe 4 Materials and Solar Cells through Voltage-Bias Annealing

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

Teeter, Glenn; Harvey, Steve P.; Johnston, Steve

Our contribution describes the influence of low-temperature annealing with and without applied voltage bias on thin-film Cu 2ZnSnSe 4 (CZTSe), Cu(In,Ga)Se 2 (CIGS), and CdS material properties and solar cell performance. In order to quantify the effects of cation disorder on CZTSe device performance, completed devices were annealed under open-circuit conditions at various temperatures from 110 degrees C to 215 degrees C and subsequently quenched. Measurements on these devices document systematic, reversible changes in solar-cell performance consistent with a reduction in CZTSe band tails at lower annealing temperatures. CIGS and CZTSe solar cells were also annealed at various temperatures (200more » degrees C for CIGS and 110 degrees C-215 degrees C for CZTSe) and subsequently quenched with continuously applied voltage bias to explore the effects of non-equilibrium annealing conditions. For both absorbers, large reversible changes in device characteristics correlated with the magnitude and sign of the applied voltage bias were observed. For CZTSe devices, the voltage-bias annealing (VBA) produced reversible changes in open-circuit voltage (VOC) from 289 meV to 446 meV. For CIGS solar cells, even larger changes were observed in device performance: photovoltaic (PV) conversion efficiency of the CIGS device varied from below 3% to above 15%, with corresponding changes in CIGS hole density of about three orders of magnitude. Findings from these VBA experiments are interpreted in terms of changes to the metastable point-defect populations that control key properties in the absorber layers, and in the CdS buffer layer. Computational device modeling was performed to assess the impacts of cation disorder on the CZTSe VOC deficit, and to elucidate the effects of VBA treatments on metastable point defect populations in CZTSe, CIGS, and CdS. Our results indicate that band tails impose important limitations on CZTSe device performance. Device modeling results also indicate that non-equilibrium processing conditions including the effects of voltage bias can dramatically alter point-defect-mediated opto-electronic properties of semiconductors. Implications for optimization of PV materials and connections to long-term stability of PV devices are discussed.« less

Domain walls and ferroelectric reversal in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

2017-01-01

Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180∘ domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall-mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond-valence sums. Our results thus provide both theoretical and empirical guidance for future searches for ferroelectric candidates in materials of the corundum derivative family.

Domain walls and ferroelectric reversal in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180° domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy, and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond valence sums. Our results thus provide both theoretical and empirical guidance to further search for ferroelectric candidates in materials of the corundum derivative family. The work is supported by ONR Grant N00014-12-1-1035.

Leakage current transport mechanism under reverse bias in Au/Ni/GaN Schottky barrier diode

NASA Astrophysics Data System (ADS)

Peta, Koteswara Rao; Kim, Moon Deock

2018-01-01

The leakage current transport mechanism under reverse bias of Au/Ni/GaN Schottky diode is studied using temperature dependent current-voltage (I-V-T) and capacitance-voltage (C-V) characteristics. I-V measurement in this study is in the range of 140 K-420 K in steps of 10 K. A reduction in voltage dependent barrier height and a strong internal electric field in depletion region under reverse bias suggested electric field enhanced thermionic emission in carrier transport via defect states in Au/Ni/GaN SBD. A detailed analysis of reverse leakage current revealed two different predominant transport mechanisms namely variable-range hopping (VRH) and Poole-Frenkel (PF) emission conduction at low (<260 K) and high (>260 K) temperatures respectively. The estimated thermal activation energies (0.20-0.39 eV) from Arrhenius plot indicates a trap assisted tunneling of thermally activated electrons from a deep trap state into a continuum of states associated with each conductive threading dislocation.

Water promotes the sealing of nanoscale packing defects in folding proteins.

PubMed

Fernández, Ariel

2014-05-21

A net dipole moment is shown to arise from a non-Debye component of water polarization created by nanoscale packing defects on the protein surface. Accordingly, the protein electrostatic field exerts a torque on the induced dipole, locally impeding the nucleation of ice at the protein-water interface. We evaluate the solvent orientation steering (SOS) as the reversible work needed to align the induced dipoles with the Debye electrostatic field and computed the SOS for the variable interface of a folding protein. The minimization of the SOS is shown to drive protein folding as evidenced by the entrainment of the total free energy by the SOS energy along trajectories that approach a Debye limit state where no torque arises. This result suggests that the minimization of anomalous water polarization at the interface promotes the sealing of packing defects, thereby maintaining structural integrity and committing the protein chain to fold.

Diminishing sign anomaly and scaling behavior of the mixed-state Hall resistivity in Tl2Ba2Ca2Cu3O10 films containing columnar defects

NASA Technical Reports Server (NTRS)

Budhani, R. C.; Liou, S. H.; Cai, Z. X.

1993-01-01

The issues of sign reversal of the Hall voltage and scaling between longitudinal (rho(xx)) and Hall (rho(xy)) resistivities are studied in Tl2Ba2Ca2Cu3O10 films in which the vortex dynamics is drastically changed by flux pinning at heavy-ion-irradiation-induced linear defects. While the sign anomaly diminishes with increasing defect concentration, the power law rho(xy) is approximately equal to rho(xx) exp beta, beta = 1.85 +/- 0.1, holds even after irradiation. This result shows that the scaling is a universal feature of the mixed state in this system. The sign anomaly, on the other hand, is not consistent with a model that invokes pinning-induced backflow in the vortex core as the mechanism for this effect.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.

PubMed

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C

2016-07-26

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.

System and method for floating-substrate passive voltage contrast

DOEpatents

Jenkins, Mark W [Albuquerque, NM; Cole, Jr., Edward I.; Tangyunyong, Paiboon [Albuquerque, NM; Soden, Jerry M [Placitas, NM; Walraven, Jeremy A [Albuquerque, NM; Pimentel, Alejandro A [Albuquerque, NM

2009-04-28

A passive voltage contrast (PVC) system and method are disclosed for analyzing ICs to locate defects and failure mechanisms. During analysis a device side of a semiconductor die containing the IC is maintained in an electrically-floating condition without any ground electrical connection while a charged particle beam is scanned over the device side. Secondary particle emission from the device side of the IC is detected to form an image of device features, including electrical vias connected to transistor gates or to other structures in the IC. A difference in image contrast allows the defects or failure mechanisms be pinpointed. Varying the scan rate can, in some instances, produce an image reversal to facilitate precisely locating the defects or failure mechanisms in the IC. The system and method are useful for failure analysis of ICs formed on substrates (e.g. bulk semiconductor substrates and SOI substrates) and other types of structures.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling

PubMed Central

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.

2016-01-01

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741

Why borrow from Peter when Paul can afford it? Reverse homodigital artery flap for fingertip reconstruction

PubMed Central

Sundaramurthy, Narayanamurthy; Venkata Mahipathy, Surya Rao Rao; Durairaj, Alagar Raja

2017-01-01

Background: Fingertip injuries that are complicated by pulp loss, bone or tendon exposure will need a flap cover. Cross finger flap is commonly used to cover such defects. However, patients are apprehensive about injuring the uninjured finger as a donor site. Reverse homodigital artery flap (RHAF) can provide reliable vascularised cover to such defects. Aims: This study aims to assess the functional and aesthetic outcomes along with the patient satisfaction of RHAFs done for fingertip defects. Materials and Methods: RHAFs done in 18 patients operated between August 2015 and October 2016 were retrospectively analysed on flap survival, sensory recovery, range of movements, hypersensitivity, cold intolerance, flexion contracture and donor site morbidity. Results: Seventeen of the 18 flaps done survived completely. One flap had partial necrosis of 3 mm that healed conservatively. Middle finger of the right hand was the most commonly injured finger. Touch, pain and pressure sensations recovered in 8–12 weeks. Two-point discrimination was 4.5 mm at 6 months. The deficit of 5° s was present at distal interphalangeal joint during active flexion at 6 months. Cold intolerance and flexion contracture were not seen and 2 instances of hypersensitivity at 2 months got cured conservatively after 4 months. Overall satisfaction of patients was 8/10. Conclusion: RHAF provides single staged well-vascularised cover for fingertip injuries with good sensory recovery without damaging the adjacent uninjured finger. Hence, it can be a reliable flap for fingertip reconstruction in selected cases. PMID:29343895

Reversible magnesium and aluminium ions insertion in cation-deficient anatase TiO2

NASA Astrophysics Data System (ADS)

Koketsu, Toshinari; Ma, Jiwei; Morgan, Benjamin J.; Body, Monique; Legein, Christophe; Dachraoui, Walid; Giannini, Mattia; Demortière, Arnaud; Salanne, Mathieu; Dardoize, François; Groult, Henri; Borkiewicz, Olaf J.; Chapman, Karena W.; Strasser, Peter; Dambournet, Damien

2017-11-01

In contrast to monovalent lithium or sodium ions, the reversible insertion of multivalent ions such as Mg2+ and Al3+ into electrode materials remains an elusive goal. Here, we demonstrate a new strategy to achieve reversible Mg2+ and Al3+ insertion in anatase TiO2, achieved through aliovalent doping, to introduce a large number of titanium vacancies that act as intercalation sites. We present a broad range of experimental and theoretical characterizations that show a preferential insertion of multivalent ions into titanium vacancies, allowing a much greater capacity to be obtained compared to pure TiO2. This result highlights the possibility to use the chemistry of defects to unlock the electrochemical activity of known materials, providing a new strategy for the chemical design of materials for practical multivalent batteries.

High-frequency Total Focusing Method (TFM) imaging in strongly attenuating materials with the decomposition of the time reversal operator associated with orthogonal coded excitations

NASA Astrophysics Data System (ADS)

Villaverde, Eduardo Lopez; Robert, Sébastien; Prada, Claire

2017-02-01

In the present work, the Total Focusing Method (TFM) is used to image defects in a High Density Polyethylene (HDPE) pipe. The viscoelastic attenuation of this material corrupts the images with a high electronic noise. In order to improve the image quality, the Decomposition of the Time Reversal Operator (DORT) filtering is combined with spatial Walsh-Hadamard coded transmissions before calculating the images. Experiments on a complex HDPE joint demonstrate that this method improves the signal-to-noise ratio by more than 40 dB in comparison with the conventional TFM.

Reversible pressure-induced crystal-amorphous structural transformation in ice Ih

NASA Astrophysics Data System (ADS)

English, Niall J.; Tse, John S.

2014-08-01

Molecular dynamics (MD) simulation of depressurised high-density amorphous ice (HDA) at 80 K and at negative pressures has been performed. Over several attempts, HDA recrystallised to a form close to hexagonal ice Ih, albeit with some defects. The results support the hypothesis that compression of ice-Ih to HDA is a reversible first-order phase transition, with a large hysteresis. Therefore, it would appear that LDA is not truly amorphous. The elastic energy estimated from the area of the hysteresis loop is ca. 4.5 kJ/mol, in some way consistent with experimentally-determined accumulated successive heats of transformations from recovered HDA → ice Ih.

Publisher Correction: Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes.

PubMed

Han, Longsen; Ren, Chao; Li, Ling; Li, Xiaoyan; Ge, Juan; Wang, Haichao; Miao, Yi-Liang; Guo, Xuejiang; Moley, Kelle H; Shu, Wenjie; Wang, Qiang

2018-05-01

In the version of this article originally published, the positions of Wenjie Shu and Qiang Wang in the author list were reversed and incorrect images were displayed in the HTML for Supplementary Figs. 1-12. The errors have been corrected in the HTML and PDF versions of the article.

Alternating Wolff-Parkinson-White syndrome associated with attack of angina

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

Mangiafico, R.A.; Petralito, A.; Grimaldi, D.R.

1990-07-01

In a patient with Wolff-Parkinson-White syndrome and an inferior-posterior bypass tract, transient restoration of normal conduction occurred during an attack of angina. The ECG pattern of inferior posterior ischemia was present when the conduction was normal. Thallium scintigraphy showed a reversible posterolateral perfusion defect. The possible mechanisms for production of intermittent preexcitation are discussed.

Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model

PubMed Central

Cheng, Ning; Dai, Jing; Cheng, Xiangrong; Li, Shu’e; Miron, Richard J.; Wu, Tao; Chen, Wenli; Zhang, Yufeng

2018-01-01

The most common complication for patients with postmenopausal osteoporosis is bone-related defects and fractures. While routine medication has a high probability of undesirable side effects, new approaches have aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss. Recently, we have synthesized a new hybrid CaP/silk scaffold with a CaP-phase distribution and pore architecture better suited to facilitate cell differentiation and bone formation. The aim of the present study was to compare the involved remodeling process and therapeutic effect of porous CaP/silk composite scaffolds upon local implantation into osteoporotic defects. Wistar rats were used to induce postmenopausal osteoporotic model by bilateral ovariectomy. The pure silk and hybrid CaP/silk scaffolds were implanted into critical sized defects created in distal femoral epiphysis. After 14 and 28 days, the in vivo osteogenetic efficiency was evaluated by μCT analysis, hematoxylin and eosin staining, Safranin O staining, tartrate-resistant acid phosphatase staining, and immunohistochemical assessment. Animals with or without critical-sized defects were used as drill or blank controls, respectively. The osteoporotic defect model was well established with significantly decreased μCT parameters of BV/TV, Tb.N and increased Tb.Sp, porosity, combined with changes in histological observations. During the healing process, the critical-sized drill control defects failed to regenerate appreciable bone tissue, while more significantly increased bone formation and mineralization with dynamic scaffold degradation and decreased osteoclastic bone resorption could be detected within defects with hybrid CaP/silk scaffolds compared to pure silk scaffolds. PMID:23674058

Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model.

PubMed

Cheng, Ning; Dai, Jing; Cheng, Xiangrong; Li, Shu'e; Miron, Richard J; Wu, Tao; Chen, Wenli; Zhang, Yufeng; Shi, Bin

2013-08-01

The most common complication for patients with postmenopausal osteoporosis is bone-related defects and fractures. While routine medication has a high probability of undesirable side effects, new approaches have aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss. Recently, we have synthesized a new hybrid CaP/silk scaffold with a CaP-phase distribution and pore architecture better suited to facilitate cell differentiation and bone formation. The aim of the present study was to compare the involved remodeling process and therapeutic effect of porous CaP/silk composite scaffolds upon local implantation into osteoporotic defects. Wistar rats were used to induce postmenopausal osteoporotic model by bilateral ovariectomy. The pure silk and hybrid CaP/silk scaffolds were implanted into critical sized defects created in distal femoral epiphysis. After 14 and 28 days, the in vivo osteogenetic efficiency was evaluated by μCT analysis, hematoxylin and eosin staining, Safranin O staining, tartrate-resistant acid phosphatase staining, and immunohistochemical assessment. Animals with or without critical-sized defects were used as drill or blank controls, respectively. The osteoporotic defect model was well established with significantly decreased μCT parameters of BV/TV, Tb.N and increased Tb.Sp, porosity, combined with changes in histological observations. During the healing process, the critical-sized drill control defects failed to regenerate appreciable bone tissue, while more significantly increased bone formation and mineralization with dynamic scaffold degradation and decreased osteoclastic bone resorption could be detected within defects with hybrid CaP/silk scaffolds compared to pure silk scaffolds.

Influence of Ga doping ratio on the saturable absorption mechanism in Ga doped ZnO thin solid films processed by sol-gel spin coating technique

NASA Astrophysics Data System (ADS)

Sandeep, K. M.; Bhat, Shreesha; Dharmaprakash, S. M.; Byrappa, K.

2017-03-01

In the present study, the nonlinear optical properties of sol-gel spin coated gallium doped zinc oxide (GZO) thin solid films are explored with nanosecond laser pulses using the z-scan technique. The higher doping ratios of Ga result in a large redshift of the energy gap (0.38 eV) due to the existence of enhanced grain boundary defects in GZO films. A positive nonlinear absorption coefficient is observed in undoped 1 at.wt.% GZO and 2 at.wt.% GZO films, and a negative nonlinear absorption coefficient in 3 at.wt.% GZO film. Fewer defects in undoped 1% GZO and 2% GZO films resulted in reverse saturable absorption (RSA), whereas a saturable absorption (SA) mechanism is observed in 3% GZO films and is attributed to the enhanced defect concentration in the band structure of GZO. However, all the films showed a self-defocusing mechanism, derived by a closed aperture z-scan technique. The present work sheds light on the defect mechanism involved in the observed nonlinear properties of GZO films.

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

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

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-01-19

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thalliummore » defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.« less

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.

Mobility scooter driving ability in visually impaired individuals.

PubMed

Cordes, Christina; Heutink, Joost; Brookhuis, Karel A; Brouwer, Wiebo H; Melis-Dankers, Bart J M

2018-06-01

To investigate how well visually impaired individuals can learn to use mobility scooters and which parts of the driving task deserve special attention. A mobility scooter driving skill test was developed to compare driving skills (e.g. reverse driving, turning) between 48 visually impaired (very low visual acuity = 14, low visual acuity = 10, peripheral field defects = 11, multiple visual impairments = 13) and 37 normal-sighted controls without any prior experience with mobility scooters. Performance on this test was rated on a three-point scale. Furthermore, the number of extra repetitions on the different elements were noted. Results showed that visually impaired participants were able to gain sufficient driving skills to be able to use mobility scooters. Participants with visual field defects combined with low visual acuity showed most problems learning different skills and needed more training. Reverse driving and stopping seemed to be most difficult. The present findings suggest that visually impaired individuals are able to learn to drive mobility scooters. Mobility scooter allocators should be aware that these individuals might need more training on certain elements of the driving task. Implications for rehabilitation Visual impairments do not necessarily lead to an inability to acquire mobility scooter driving skills. Individuals with peripheral field defects (especially in combination with reduced visual acuity) need more driving ability training compared to normal-sighted people - especially to accomplish reversing. Individual assessment of visually impaired people is recommended, since participants in this study showed a wide variation in ability to learn driving a mobility scooter.

Defect-rich TiO2-δ nanocrystals confined in a mooncake-shaped porous carbon matrix as an advanced Na ion battery anode

NASA Astrophysics Data System (ADS)

He, Hanna; Zhang, Qi; Wang, Haiyan; Zhang, Hehe; Li, Jiadong; Peng, Zhiguang; Tang, Yougen; Shao, Minhua

2017-06-01

Inferior electronic conductivity and sluggish sodium ion diffusion are still two big challenges for TiO2 anode material for Na ion batteries (SIBs). Herein, we synthesize TiO2/C composites by the pyrolysis of MIL-125(Ti) precursor and successfully introduce defects to TiO2/C composite by a simple magnesium reduction. The as-prepared defect-rich TiO2-δ/C composite shows mooncake-shaped morphology consisting of TiO2-δ nanocrystals with an average particle size of 5 nm well dispersed in the carbon matrix. When used as a SIBs anode, the defect-rich TiO2-δ/C composite exhibits a high reversible capacity of 330.2 mAh g-1 at 50 mA g-1 at the voltage range of 0.001-3.0 V and long-term cycling stability with negligible decay after 5000 cycles. Compared with other four TiO2/C samples, the electrochemical performance of defect-rich TiO2-δ/C is highly improved, which may benefit from the enhanced electronic/ionic conductivities owing to the defect-rich features, high surface area rendering shortened electronic and ionic diffusion path, and the suppress of the TiO2 crystal aggregation during sodiation and desodiation process by the carbon matrix.

Display Parameters and Requirements

NASA Astrophysics Data System (ADS)

Bahadur, Birendra

The following sections are included: * INTRODUCTION * HUMAN FACTORS * Anthropometry * Sensory * Cognitive * Discussions * THE HUMAN VISUAL SYSTEM - CAPABILITIES AND LIMITATIONS * Cornea * Pupil and Iris * Lens * Vitreous Humor * Retina * RODS - NIGHT VISION * CONES - DAY VISION * RODS AND CONES - TWILIGHT VISION * VISUAL PIGMENTS * MACULA * BLOOD * CHOROID COAT * Visual Signal Processing * Pathways to the Brain * Spatial Vision * Temporal Vision * Colour Vision * Colour Blindness * DICHROMATISM * Protanopia * Deuteranopia * Tritanopia * ANOMALOUS TRICHROMATISM * Protanomaly * Deuteranomaly * Tritanomaly * CONE MONOCHROMATISM * ROD MONOCHROMATISM * Using Colour Effectively * COLOUR MIXTURES AND THE CHROMATICITY DIAGRAM * Colour Matching Functions and Chromaticity Co-ordinates * CIE 1931 Colour Space * CIE PRIMARIES * CIE COLOUR MATCHING FUNCTIONS AND CHROMATICITY CO-ORDINATES * METHODS FOR DETERMINING TRISTIMULUS VALUES AND COLOUR CO-ORDINATES * Spectral Power Distribution Method * Filter Method * CIE 1931 CHROMATICITY DIAGRAM * ADDITIVE COLOUR MIXTURE * CIE 1976 Chromaticity Diagram * CIE Uniform Colour Spaces and Colour Difference Formulae * CIELUV OR L*u*v* * CIELAB OR L*a*b* * CIE COLOUR DIFFERENCE FORMULAE * Colour Temperature and CIE Standard Illuminants and source * RADIOMETRIC AND PHOTOMETRIC QUANTITIES * Photopic (Vλ and Scotopic (Vλ') Luminous Efficiency Function * Photometric and Radiometric Flux * Luminous and Radiant Intensities * Incidence: Illuminance and Irradiance * Exitance or Emittance (M) * Luminance and Radiance * ERGONOMIC REQUIREMENTS OF DISPLAYS * ELECTRO-OPTICAL PARAMETERS AND REQUIREMENTS * Contrast and Contrast Ratio * Luminance and Brightness * Colour Contrast and Chromaticity * Glare * Other Aspects of Legibility * SHAPE AND SIZE OF CHARACTERS * DEFECTS AND BLEMISHES * FLICKER AND DISTORTION * ANGLE OF VIEW * Switching Speed * Threshold and Threshold Characteristic * Measurement Techniques For Electro-optical Parameters * RADIOMETRIC MEASUREMENTS * Broadband Radiometry or Filtered Photodetector Radiometric Method * Spectroradiometric Method * PHOTOMETRIC MEASUREMENTS * COLOUR MEASUREMENTS * LUMINANCE, CONTRAST RATIO, THRESHOLD CHARACTERISTIC AND POLAR PLOT * SWITCHING SPEED * ELECTRICAL AND LIFE PARAMETERS AND REQUIREMENTS * Operating Voltage, Current Drainage and Power Consumption * Operating Frequency * Life Expectancy * LCD FAILURE MODES * Liquid Crystal Materials * Substrate Glass * Electrode Patterns * Alignment and Aligning Material * Peripheral and End Plug Seal * Spacers * Crossover Material * Polarizers and Reflectors * Connectors * Heater * Colour Filters * Backlighting System * Explanation For Some of the Observed Defects * BLOOMING PIXELS * POLARIZER RELATED DEFECTS * DIFFERENTIAL THERMAL EXPANSION RELATED DEFECTS * ELECTROCHEMICAL AND ELECTROHYDRODYNAMIC RELATED DEFECTS * REVERSE TWIST AND REVERSE TILT * MEMORY OR REMINISCENT CONTRAST * LCD RELIABILRY AND ACCELERATED LIFE TESTING * ACKNOWLEDGEMENTS * REFERENCES * APPENDIX

Bone Grafting the Glenoid Versus Use of Augmented Glenoid Baseplates with Reverse Shoulder Arthroplasty.

PubMed

Jones, Richard B; Wright, Thomas W; Roche, Christopher P

2015-12-01

Large glenoid defects are a difficult reconstructive problem for surgeons performing reverse shoulder arthroplasty (rTSA). Options to address glenoid defects include eccentric reaming, bone grafting, and augmented glenoid baseplates. Augmented glenoid baseplates may provide a simpler, cost-effective, bone-preserving option compared to other techniques. No studies report the use of augmented baseplates to correct glenoid deformity in rTSA relative to the use of glenoid bone graft. We retrospectively reviewed 80 patients that received a primary rTSA and received either a structural bone graft or an augmented glenoid baseplate to address a significant glenoid defect. There were 39 patients in the augmented baseplate cohort and 41 patients in the bone graft cohort. The augmented baseplate cohort contained 24 8° posterior augment implants and 15 10° superior augment baseplates. The bone graft cohort consisted of 36 autograft humeral heads and 5 allograft femoral heads. The average follow-up for rTSA patients with an augmented baseplate was 28.3 ± 5.7 months, and the average follow-up for rTSA patients with glenoid bone graft was 34.1 ± 15.0 months. Each patient was scored preoperatively and at latest follow-up using the SST, UCLA, ASES, Constant, and SPADI metrics. Range of motion data was obtained as well. All patients demonstrated significant improvements in pain, ROM, and functional scores following treatment with rTSA using either augmented baseplates or glenoid bone graft to correct glenoid defects. The database contained no complications for the augmented glenoid baseplate cohort, and six complications (14.6%) for the glenoid bone graft cohort (including two glenoid loosenings and graft failures). Additionally, the augmented baseplate cohort showed a lower scapular notching rate of 10% as compared to the bone graft cohort which had a notching rate of 18.5%. The results of this study suggest that either augmented glenoid baseplates or glenoid bone graft can be used to address large glenoid defects during rTSA with significant improvement in outcomes. Augmented glenoid baseplates may achieve a lower complication and scapular notching rate, but additional and longer-term clinical follow-up is required to confirm these results.

[Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains].

PubMed

Sabel, B A

2017-02-01

Visual field defects are considered irreversible because the retina and optic nerve do not regenerate. Nevertheless, there is some potential for recovery of the visual fields. This can be accomplished by the brain, which analyses and interprets visual information and is able to amplify residual signals through neuroplasticity. Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy. This is actually the neurobiological basis of normal learning. Plasticity is maintained throughout life and can be induced by repetitively stimulating (training) brain circuits. The question now arises as to how plasticity can be utilised to activate residual vision for the treatment of visual field loss. Just as in neurorehabilitation, visual field defects can be modulated by post-lesion plasticity to improve vision in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all patients have some residual vision, the goal is to strengthen residual capacities by enhancing synaptic efficacy. New treatment paradigms have been tested in clinical studies, including vision restoration training and non-invasive alternating current stimulation. While vision training is a behavioural task to selectively stimulate "relative defects" with daily vision exercises for the duration of 6 months, treatment with alternating current stimulation (30 min. daily for 10 days) activates and synchronises the entire retina and brain. Though full restoration of vision is not possible, such treatments improve vision, both subjectively and objectively. This includes visual field enlargements, improved acuity and reaction time, improved orientation and vision related quality of life. About 70 % of the patients respond to the therapies and there are no serious adverse events. Physiological studies of the effect of alternating current stimulation using EEG and fMRI reveal massive local and global changes in the brain. These include local activation of the visual cortex and global reorganisation of neuronal brain networks. Because modulation of neuroplasticity can strengthen residual vision, the brain deserves a better reputation in ophthalmology for its role in visual rehabilitation. For patients, there is now more light at the end of the tunnel, because vision loss in some areas of the visual field defect is indeed reversible. Georg Thieme Verlag KG Stuttgart · New York.

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.

Two different carbon-hydrogen complexes in silicon with closely spaced energy levels

NASA Astrophysics Data System (ADS)

Stübner, R.; Kolkovsky, Vl.; Weber, J.

2015-08-01

An acceptor and a single donor state of carbon-hydrogen defects (CHA and CHB) are observed by Laplace deep level transient spectroscopy at 90 K. CHA appears directly after hydrogenation by wet chemical etching or hydrogen plasma treatment, whereas CHB can be observed only after a successive annealing under reverse bias at about 320 K. The activation enthalpies of these states are 0.16 eV for CHA and 0.14 eV for CHB. Our results reconcile previous controversial experimental results. We attribute CHA to the configuration where substitutional carbon binds a hydrogen atom on a bond centered position between carbon and the neighboring silicon and CHB to another carbon-hydrogen defect.

Prototyped grafting plate for reconstruction of mandibular defects.

PubMed

Zhou, Libin; Wang, Peilin; Han, Haolun; Li, Baowei; Wang, Hongnan; Wang, Gang; Zhao, Jinlong; Liu, Yanpu; Wu, Wei

2014-12-01

To esthetically and functionally restore a 40-mm canine mandibular discontinuity defect using a custom-made titanium bone-grafting plate in combination with autologous iliac bone grafts. Individualized titanium bone-grafting plates were manufactured using a series of techniques, including reverse engineering, computer aided design, rapid prototyping and titanium casting. A 40-mm discontinuous defect in the right mandibular body was created in 9 hybrid dogs. The defect was restored immediately using the customized plate in combination with autologous cancellous iliac blocks. Sequential radionuclide bone imaging was performed to evaluate the bone metabolism and reconstitution of the grafts. The specimens were evaluated by biomechanical testing, 3-dimensional microcomputed tomographic scanning, and histological examination. The results revealed that the symmetry of the mandibles was reconstructed using the customized grafting plate, and the bony continuity of the mandibles was restored. By 12 weeks after the operation, the cancellous iliac grafts became a hard bone block, which was of comparable strength to native mandibles. A fibrous tissue intermediate was found between the remodelled bone graft and the titanium plate. The results indicate that the prototyped grafting plate can be used to restore mandibular discontinuous defects, and satisfactory aesthetical and functional reconstruction can be achieved. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

MD simulations of phase stability of PuGa alloys: Effects of primary radiation defects and helium bubbles

DOE PAGES

Dremov, V. V.; Sapozhnikov, F. A.; Ionov, G. V.; ...

2013-05-14

We present classical molecular dynamics (MD) with Modified Embedded Atom Model (MEAM) simulations to investigate the role of primary radiation defects and radiogenic helium as factors affecting the phase stability of PuGa alloys in cooling–heating cycles at ambient pressure. The models of PuGa alloys equilibrated at ambient conditions were subjected to cooling–heating cycles in which they were initially cooled down to 100 K and then heated up to 500 K at ambient pressure. The rate of temperature change in the cycles was 10 K/ns. The simulations showed that the initial FCC phase of PuGa alloys undergo polymorphous transition in coolingmore » to a lower symmetry α'-phase. All the alloys undergo direct and reverse polymorphous transitions in the cooling–heating cycles. The alloys containing vacancies shift in both transitions to lower temperatures relative to the defect-free alloys. The radiogenic helium has much less effect on the phase stability compared to that of primary radiation defects (in spite of the fact that helium concentration is twice of that for the primary radiation defects). Lastly, this computational result agrees with experimental data on unconventional stabilization mechanism of PuGa alloys.« less

A conduction model for contacts to Si-doped AlGaN grown on sapphire and single-crystalline AlN

NASA Astrophysics Data System (ADS)

Haidet, Brian B.; Bryan, Isaac; Reddy, Pramod; Bryan, Zachary; Collazo, Ramón; Sitar, Zlatko

2015-06-01

Ohmic contacts to AlGaN grown on sapphire substrates have been previously demonstrated for various compositions of AlGaN, but contacts to AlGaN grown on native AlN substrates are more difficult to obtain. In this paper, a model is developed that describes current flow through contacts to Si-doped AlGaN. This model treats the current through reverse-biased Schottky barriers as a consequence of two different tunneling-dependent conduction mechanisms in parallel, i.e., Fowler-Nordheim emission and defect-assisted Frenkel-Poole emission. At low bias, the defect-assisted tunneling dominates, but as the potential across the depletion region increases, tunneling begins to occur without the assistance of defects, and the Fowler-Nordheim emission becomes the dominant conduction mechanism. Transfer length method measurements and temperature-dependent current-voltage (I-V) measurements of Ti/Al-based contacts to Si-doped AlGaN grown on sapphire and AlN substrates support this model. Defect-assisted tunneling plays a much larger role in the contacts to AlGaN on sapphire, resulting in nearly linear I-V characteristics. In contrast, contacts to AlGaN on AlN show limited defect-assisted tunneling appear to be only semi-Ohmic.

Reversible magnesium and aluminium ions insertion in cation-deficient anatase TiO 2

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

Koketsu, Toshinari; Ma, Jiwei; Morgan, Benjamin J.

In contrast to monovalent lithium or sodium ions, the reversible insertion of multivalent ions such as Mg 2+ and Al 3+ into electrode materials remains an elusive goal. In this work, we demonstrate a new strategy to achieve reversible Mg 2+ and Al 3+ insertion in anatase TiO 2, achieved through aliovalent doping, to introduce a large number of titanium vacancies that act as intercalation sites. We present a broad range of experimental and theoretical characterizations that show a preferential insertion of multivalent ions into titanium vacancies, allowing a much greater capacity to be obtained compared to pure TiO 2.more » In conclusion, this result highlights the possibility to use the chemistry of defects to unlock the electrochemical activity of known materials providing a new strategy for the chemical design of materials for practical multivalent batteries.« less

Reversible magnesium and aluminium ions insertion in cation-deficient anatase TiO 2

DOE PAGES

Koketsu, Toshinari; Ma, Jiwei; Morgan, Benjamin J.; ...

2017-09-18

In contrast to monovalent lithium or sodium ions, the reversible insertion of multivalent ions such as Mg 2+ and Al 3+ into electrode materials remains an elusive goal. In this work, we demonstrate a new strategy to achieve reversible Mg 2+ and Al 3+ insertion in anatase TiO 2, achieved through aliovalent doping, to introduce a large number of titanium vacancies that act as intercalation sites. We present a broad range of experimental and theoretical characterizations that show a preferential insertion of multivalent ions into titanium vacancies, allowing a much greater capacity to be obtained compared to pure TiO 2.more » In conclusion, this result highlights the possibility to use the chemistry of defects to unlock the electrochemical activity of known materials providing a new strategy for the chemical design of materials for practical multivalent batteries.« less

Bidirectional juxtacrine ephrinB2/Ephs signaling promotes angiogenesis of ECs and maintains self-renewal of MSCs.

PubMed

Cao, Cen; Huang, Ying; Tang, Qingming; Zhang, Chenguang; Shi, Lei; Zhao, Jiajia; Hu, Li; Hu, Zhewen; Liu, Yun; Chen, Lili

2018-07-01

Co-transplantation of endothelial cells (ECs) and mesenchymal stem cells (MSCs) is an important strategy for repairing complex and large bone defects. However, the ways in which ECs and MSCs interact remain to be fully clarified. We found that forward ephrinB2/Ephs signaling from hBMSCs to hUVECs promoted the tube formation of hUVECs by activating the PI3K/AKT/mTOR pathway. Reverse ephrinB2/Ephs signaling from hUVECs to hBMSCs promoted the proliferation and maintenance of hBMSCs self-renewal via upregulation of OCT4, SOX2, and YAP1. Subcutaneous co-transplantation of ECs and MSCs in nude mice confirmed that forward ephrinB2/Ephs signaling could increase the cross-sectional area of blood vessels in the transplanted area, and reverse ephrinB2/Ephs signaling could maintain the self-renewal of transplanted hBMSCs in vivo. Based on these results, ephrinB2/Ephs bidirectional juxtacrine regulation between ECs and MSCs plays a pivotal role in improving the healing of bone defects by promoting angiogenesis and achieving a sufficient number of MSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Suspended animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature.

PubMed

Chan, Kin; Goldmark, Jesse P; Roth, Mark B

2010-07-01

The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment.

Suspended Animation Extends Survival Limits of Caenorhabditis elegans and Saccharomyces cerevisiae at Low Temperature

PubMed Central

Chan, Kin; Goldmark, Jesse P.

2010-01-01

The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment. PMID:20462960

Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.

PubMed

Wen, Gen; Wang, Chun-Yang; Chai, Yi-Min; Cheng, Liang; Chen, Ming; Yi-Min, L V

2013-11-01

The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc.

Resistance to thyroid hormone due to defective thyroid receptor alpha.

PubMed

Moran, Carla; Chatterjee, Krishna

2015-08-01

Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

L-phase variants of Agromyces ramosus. [cell wall defectives in soil

NASA Technical Reports Server (NTRS)

Horwitz, A. H.; Casida, L. E., Jr.

1975-01-01

Earlier results suggested that Agromyces ramosus possibly might exist naturally in soil as a cell-wall-defective form. The purpose of the present study was to test this hypothesis by determining whether the laboratory-adapted strains of A. ramosus could be artificially induced into the L-phase and, if so, to examine some parameters affecting induction and the stability of the L-forms. The hypothesis was also tested by attempting to revert the laboratory L-phase strains by subjecting them to the technique originally used for isolation of the bacterial form from soil. It is shown that A. ramosus is easily induced into the L-phase by growing it on an agar media containing low levels of penicillin or glycine. The L-forms are found to be stable after initial contact with the inducing agent and to be unable to be reverted to the bacterial form. However, this lack of reversion does not completely negate the hypothesis that L-forms might occur in nature, because it is possible that L-forms existing in the natural state are less stable than those found in the laboratory where there is little selective pressure toward reversion.

Targeting hypertension in patients with cardiorenal metabolic syndrome.

PubMed

Rojas, Edward; Velasco, Manuel; Bermúdez, Valmore; Israili, Zafar; Bolli, Peter

2012-10-01

Diabetes mellitus coexisting with hypertension is greater than chance alone would predict. Hypertensive patients have been shown to have altered composition of skeletal muscle tissue, decreased blood flow to skeletal muscle and post-receptor signaling alterations in the IRS insulin pathway, all inducing insulin resistance states, which partially explains why blood pressure goals in DM patients are lower than in normoglycemic patients. Although optimal first-step antihypertensive drug therapy in type 2 DM or impaired fasting glucose levels (IFG) should be individualized for each patient, converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been demonstrated in some but not all studies to decrease the rate of development of proteinuria and diabetic renal disease. According to the ACCF/AHA 2011 Expert Consensus, elderly persons with diabetes, hypertension, and nephropathy should be initially treated with ACEIs or ARBs, although the choice of a specific antihypertensive may also depend on other associated comorbidities.

The Verriest Lecture: Short-wave-sensitive cone pathways across the life span

PubMed Central

Werner, John S.

2017-01-01

Structurally and functionally, the short-wave-sensitive (S) cone pathways are thought to decline more rapidly with normal aging than the middle- and long-wave-sensitive cone pathways. This would explain the celebrated results by Verriest and others demonstrating that the largest age-related color discrimination losses occur for stimuli on a tritan axis. Here, we challenge convention, arguing from psychophysical data that selective S-cone pathway losses do not cause declines in color discrimination. We show substantial declines in chromatic detection and discrimination, as well as in temporal and spatial vision tasks, that are mediated by S-cone pathways. These functional losses are not, however, unique to S-cone pathways. Finally, despite reduced photon capture by S cones, their postreceptoral pathways provide robust signals for the visual system to renormalize itself to maintain nearly stable color perception across the life span. PMID:26974914

ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

PubMed

Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

1997-05-23

Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

[APPLICATION OF WRIST CREASE ISLAND FLAP BASED ON THE SUPERFICIAL PALMAR BRANCH OF THE RADIAL ARTERY FOR THUMB RECONSTRUCTION].

PubMed

Zheng Dawei; Li, Zhangcan; Xu, Li; Zhang, Xuyang; Shi, Rongjian; Sun, Feng; Shou, Kuishui

2015-04-01

To investigate the effectiveness of the island flaps based on the superficial palmar branch of the radial artery (SPBRA) to repair the thumb wound. Between February 2012 and November 2013, 8 cases of thumb defects and bilateral artery defect were treated. There were 5 males and 3 females with an average age of 30.5 years (range, 19-51 years). The injury was caused by crush (4 cases), avulsion (3 cases), and twist (1 case). The injury located at the metacarpophalangeal joints in 3 cases, at the proximal palmar side in 2 cases, and at the interphalangeal joints in 3 cases. The defect size ranged from 3.5 cm x 1.5 cm to 6.5 cm x 2.0 cm. The digital artery defect was 2.5-8.5 cm (mean, 5.3 cm). The disease duration was 2.0-4.5 hours (mean, 3.2 hours). The reversed island flaps based on the SPBRA were designed, which size was 4.0 cm x 2.0 cm to 7.5 cm x 3.0 cm. The donor sites were closed directly. The operation was successfully completed in 7 patients except 1 patient having vascular variation. All flaps survived completely. Wound and incision at the donor site healed by first intention. All patients were followed up 6-18 months (mean, 13 months). The flaps had similar color and texture to adjacent skin. Linear scar was seen at the donor site in 1 patient, with no functional limitation. According to the functional assessment criteria of upper limb by the Hand Surgery Branch of Chinese Medical Association, the results were excellent in 6 cases, good in 1 case, and fair in 1 case, with an excellent and good rate of 87.5%. The reversed island flap based on the SPBRA is an ideal flap for the thumb reconstruction because the advantages of reliable blood supply, easy dissection, less injury at donor site, and good repair results.

Structurally tailored graphene nanosheets as lithium ion battery anodes: an insight to yield exceptionally high lithium storage performance

NASA Astrophysics Data System (ADS)

Li, Xifei; Hu, Yuhai; Liu, Jian; Lushington, Andrew; Li, Ruying; Sun, Xueliang

2013-11-01

How to tune graphene nanosheets (GNSs) with various morphologies has been a significant challenge for lithium ion batteries (LIBs). In this study, three types of GNSs with varying size, edge sites, defects and layer numbers have been successfully achieved. It was demonstrated that controlling GNS morphology and microstructure has important effects on its cyclic performance and rate capability in LIBs. Diminished GNS layer number, decreased size, increased edge sites and increased defects in the GNS anode can be highly beneficial to lithium storage and result in increased electrochemical performance. Interestingly, GNSs treated with a hydrothermal approach delivered a high reversible discharge capacity of 1348 mA h g-1. This study demonstrates that the controlled design of high performance GNS anodes is an important concept in LIB applications.How to tune graphene nanosheets (GNSs) with various morphologies has been a significant challenge for lithium ion batteries (LIBs). In this study, three types of GNSs with varying size, edge sites, defects and layer numbers have been successfully achieved. It was demonstrated that controlling GNS morphology and microstructure has important effects on its cyclic performance and rate capability in LIBs. Diminished GNS layer number, decreased size, increased edge sites and increased defects in the GNS anode can be highly beneficial to lithium storage and result in increased electrochemical performance. Interestingly, GNSs treated with a hydrothermal approach delivered a high reversible discharge capacity of 1348 mA h g-1. This study demonstrates that the controlled design of high performance GNS anodes is an important concept in LIB applications. Electronic supplementary information (ESI) available: SEM morphologies of GNS-I-III at low magnification, the TEM image of GNSs hydrothermally treated with urea in a ratio of 1 : 0, XPS survey, and SEM morphology changes of the three GNS anodes at low magnification after 100 charge-discharge cycles. See DOI: 10.1039/c3nr04823c

Functional antigen binding by the defective B cells of CBA/N mice.

PubMed

Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

1982-01-01

CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

Is light-induced degradation of a-Si:H/c-Si interfaces reversible?

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

El Mhamdi, El Mahdi; Holovsky, Jakub; Demaurex, Bénédicte

2014-06-23

Thin hydrogenated amorphous silicon (a-Si:H) films deposited on crystalline silicon (c-Si) surfaces are sensitive probes for the bulk electronic properties of a-Si:H. Here, we use such samples during repeated low-temperature annealing and visible-light soaking to investigate the long-term stability of a-Si:H films. We observe that during annealing the electronic improvement of the interfaces follows stretched exponentials as long as hydrogen evolution in the films can be detected. Once such evolution is no longer observed, the electronic improvement occurs much faster. Based on these findings, we discuss how the reversibility of light-induced defects depends on (the lack of observable) hydrogen evolution.

One-way propagation of bulk states and robust edge states in photonic crystals with broken inversion and time-reversal symmetries

NASA Astrophysics Data System (ADS)

Lu, Jin-Cheng; Chen, Xiao-Dong; Deng, Wei-Min; Chen, Min; Dong, Jian-Wen

2018-07-01

The valley is a flexible degree of freedom for light manipulation in photonic systems. In this work, we introduce the valley concept in magnetic photonic crystals with broken inversion symmetry. One-way propagation of bulk states is demonstrated by exploiting the pseudo-gap where bulk states only exist at one single valley. In addition, the transition between Hall and valley-Hall nontrivial topological phases is also studied in terms of the competition between the broken inversion and time-reversal symmetries. At the photonic boundary between two topologically distinct photonic crystals, we illustrate the one-way propagation of edge states and demonstrate their robustness against defects.

[Properties of synthesized CdS nanoparticles by reverse micelle method].

PubMed

Li, Heng-Da; Wang, Qing-Wei; Zhai, Hong-Ju; Li, Wen-Lian

2008-07-01

Micelle system with reverse phase (water/CTAB/n-hexyl alcohol/n-heptane) is a weenie liquid-globelet of surface active agent molecule which can be stably and uniformly dispersed in continuous oil medium. The micelle system with reverse phase can work as a "micro-reactor" to synthesize CdS nano-particle with excellent performance. In the present article considering the effects of W value (W= [water]/[surface agent]) of the micelle system with reverse phase, we observed that the ratio of [Cd2+] and [S2-] ions to the original concentrations of the Cd2+ and S2- ions can affect the luminescent properties of CdS nano-particle. Using regurgitant treatment process the surface of CdS nano-particle can be modified, and as a result the defect emission was reduced and even disappeared, but exciton emissions markedly increased. On the other hand, a red-shift of the exciton emission peak with the increase in the particle size was observed, indicating considerable quantum confinement effect. A maximum quantum efficiency of 11% for the synthesized CdS nano-material was achieved.

Blistering of langmuir-blodgett bilayers containing anionic phospholipids as observed by atomic force microscopy.

PubMed Central

Rinia, H A; Demel, R A; van der Eerden, J P; de Kruijff, B

1999-01-01

Asymmetric bilayers of different phospholipid compositions have been prepared by the Langmuir-Blodgett (L-B) method, and imaged by atomic force microscopy (AFM). Such bilayers can function as a model for biological membranes. The first leaflet consisted of zwitterionic phospholipids phosphatidylcholine (PC) or phosphatidylethanolamine (PE). The second leaflet consisted of the anionic phospholipid phosphatidylglycerol (PG), in either the condensed or liquid phase or, for comparison, of PC. Different bilayers showed different morphology. In all bilayers defects in the form of holes were present. In some bilayers with a first leaflet consisting of PC, polygonal line-shaped defects were observed, whereas when the first leaflet consisted of PE, mainly round defects were seen. Not only the shape, but also the amount of defects varied, depending on the condition and the composition of the second leaflet. In most of the PG-containing systems the defects were surrounded by elevations, which reversibly disappeared in the presence of divalent cations. This is the first time that such elevations have been observed on phospholipid bilayers. We propose that they are induced by phospholipid exchange between the two leaflets around the defects, leading to the presence of negatively charged phospholipids in the first leaflet. Because the substrate is also negatively charged, the bilayer around the edges is repelled and lifted up. Since it was found that the elevations are indeed detached from the substrate, we refer to this effect as bilayer blistering. PMID:10465778

Out-of-equilibrium dynamics and extended textures of topological defects in spin ice

NASA Astrophysics Data System (ADS)

Udagawa, M.; Jaubert, L. D. C.; Castelnovo, C.; Moessner, R.

2016-09-01

Memory effects have been observed across a wide range of geometrically frustrated magnetic materials, possibly including Pr2Ir2O7 where a spontaneous Hall effect has been observed. Frustrated magnets are also famous for the emergence of topological defects. Here we explore how the interaction between these defects can be responsible for a rich diversity of out-of-equilibrium dynamics, dominated by topological bottlenecks and multiscale energy barriers. Our model is an extension of the spinice model on the pyrochlore lattice, where farther-neighbor spin interactions give rise to a nearest-neighbor coupling between topological defects. This coupling can be chosen to be "unnatural" or not, i.e., attractive or repulsive between defects carrying the same topological charge. After applying a field quench, our model supports, for example, long-lived magnetization plateaux, and allows for the metastability of a "fragmented" spin liquid, an unconventional phase of matter where long-range order co-exists with a spin liquid. Perhaps most strikingly, the attraction between same-sign charges produces clusters of these defects in equilibrium, whose stability is due to a combination of energy and topological barriers. These clusters may take the form of a "jellyfish" spin texture, centered on a hexagonal ring with branches of arbitrary length. The ring carries a clockwise or counterclockwise circular flow of magnetization. This emergent toroidal degrees of freedom provide a possibility for time-reversal symmetry breaking with potential relevance to the spontaneous Hall effect observed in Pr2Ir2O7 .

Electric-Field-Driven Dual Vacancies Evolution in Ultrathin Nanosheets Realizing Reversible Semiconductor to Half-Metal Transition.

PubMed

Lyu, Mengjie; Liu, Youwen; Zhi, Yuduo; Xiao, Chong; Gu, Bingchuan; Hua, Xuemin; Fan, Shaojuan; Lin, Yue; Bai, Wei; Tong, Wei; Zou, Youming; Pan, Bicai; Ye, Bangjiao; Xie, Yi

2015-12-02

Fabricating a flexible room-temperature ferromagnetic resistive-switching random access memory (RRAM) device is of fundamental importance to integrate nonvolatile memory and spintronics both in theory and practice for modern information technology and has the potential to bring about revolutionary new foldable information-storage devices. Here, we show that a relatively low operating voltage (+1.4 V/-1.5 V, the corresponding electric field is around 20,000 V/cm) drives the dual vacancies evolution in ultrathin SnO2 nanosheets at room temperature, which causes the reversible transition between semiconductor and half-metal, accompanyied by an abrupt conductivity change up to 10(3) times, exhibiting room-temperature ferromagnetism in two resistance states. Positron annihilation spectroscopy and electron spin resonance results show that the Sn/O dual vacancies in the ultrathin SnO2 nanosheets evolve to isolated Sn vacancy under electric field, accounting for the switching behavior of SnO2 ultrathin nanosheets; on the other hand, the different defect types correspond to different conduction natures, realizing the transition between semiconductor and half-metal. Our result represents a crucial step to create new a information-storage device realizing the reversible transition between semiconductor and half-metal with flexibility and room-temperature ferromagnetism at low energy consumption. The as-obtained half-metal in the low-resistance state broadens the application of the device in spintronics and the semiconductor to half-metal transition on the basis of defects evolution and also opens up a new avenue for exploring random access memory mechanisms and finding new half-metals for spintronics.

Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle

PubMed Central

Pirinen, Eija; Canto, Carles; Jo, Young-Suk; Morato, Laia; Zhang, Hongbo; Menzies, Keir; Williams, Evan G.; Mouchiroud, Laurent; Moullan, Norman; Hagberg, Carolina; Li, Wei; Timmers, Silvie; Imhof, Ralph; Verbeek, Jef; Pujol, Aurora; van Loon, Barbara; Viscomi, Carlo; Zeviani, Massimo; Schrauwen, Patrick; Sauve, Anthony; Schoonjans, Kristina; Auwerx, Johan

2014-01-01

SUMMARY We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial function remains to be explored. Here, we show tight negative correlation between Parp-1 expression and energy expenditure in heterogeneous mouse populations, indicating that variations in PARP-1 activity have an impact on metabolic homeostasis. Notably, these genetic correlations can be translated into pharmacological applications. Long-term treatment with PARP inhibitors enhances fitness in mice by increasing the abundance of mitochondrial respiratory complexes and boosting mitochondrial respiratory capacity. Furthermore, PARP inhibitors reverse mitochondrial defects in primary myotubes of obese humans and attenuate genetic defects of mitochondrial metabolism in human fibroblasts and C. elegans. Overall, our work validates in worm, mouse and human models that PARP inhibition may be used to treat both genetic and acquired muscle dysfunction linked to defective mitochondrial function. PMID:24814482

Defects of mitogen-activated protein kinase in ICOS signaling pathway lead to CD4(+) and CD8(+) T-cell dysfunction in patients with active SLE.

PubMed

Gang, Cai; Jiahui, Yang; Huaizhou, Wang; Qing, Cai; Dongbao, Zhao; Qian, Shen

2009-01-01

In this study, hypoproliferation and defects of effectors and cytokines in CD4(+) and CD8(+) T-cells via ICOS costimulation were found in active SLE patients, relative to normal individuals and RA patient controls. Exogenous IL-2 can partially reverse those defects. In addition, low level of ERK phosphorylation in ICOS-mediated signaling pathway was discovered in lupus CD4(+) and CD8(+) T-cells. When blocked with ERK-specific chemical inhibitor PD98059, cell proliferation and IL-2 production via ICOS costimulation from both CD4(+) and CD8(+) T-cells will be severely inhibited. These findings confirmed the dysfunction of both CD4(+) and CD8(+) T-cells after ICOS costimulation in lupus patients and most importantly pointed out that impairment of ERK activation might be one of the critical factors involved in ICOS-mediated IL-2 and T-cell hypoproliferation in active SLE.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices.

PubMed

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-25

Crystal-amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier-lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13-0.6 MA cm(-2)) compared with the melt-quench strategy (∼50 MA cm(-2)). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices

PubMed Central

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-01

Crystal–amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier–lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13–0.6 MA cm−2) compared with the melt-quench strategy (∼50 MA cm−2). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation. PMID:26805748

Defect States in InP/InGaAs/InP Heterostructures by Current-Voltage Characteristics and Deep Level Transient Spectroscopy.

PubMed

Vu, Thi Kim Oanh; Lee, Kyoung Su; Lee, Sang Jun; Kim, Eun Kyu

2018-09-01

We studied defect states in In0.53Ga0.47As/InP heterojunctions with interface control by group V atoms during metalorganic chemical vapor (MOCVD) deposition. From deep level transient spectroscopy (DLTS) measurements, two defects with activation energies of 0.28 eV (E1) and 0.15 eV (E2) below the conduction band edge, were observed. The defect density of E1 for In0.53Ga0.47As/InP heterojunctions with an addition of As and P atoms was about 1.5 times higher than that of the heterojunction added P atom only. From the temperature dependence of current- voltage characteristics, the thermal activation energies of In0.53Ga0.47As/InP of heterojunctions were estimated to be 0.27 and 0.25 eV, respectively. It appeared that the reverse light current for In0.53Ga0.47As/InP heterojunction added P atom increased only by illumination of a 940 nm-LED light source. These results imply that only the P addition at the interface can enhance the quality of InGaAs/InP heterojunction.

Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice

USDA-ARS?s Scientific Manuscript database

Supplemental vitamin E restores age-related defects in IL-2 production, T cell proliferation, and immune synapse formation. Here, we evaluated the effect of vitamin E on TCR-proximal signaling events. In aged murine CD4+ T cells stimulated via CD3 and CD28, tyrosine 191 of the adaptor protein LAT wa...

An integrated conceptual framework for selecting reverse logistics providers in the presence of vagueness

NASA Astrophysics Data System (ADS)

Fırdolaş, Tugba; Önüt, Semih; Kongar, Elif

2005-11-01

In recent years, relating organization's attitude towards sustainable development, environmental management is gaining an increasing interest among researchers in supply chain management. With regard to a long term requirement of a shift from a linear economy towards a cycle economy, businesses should be motivated to embrace change brought about by consumers, government, competition, and ethical responsibility. To achieve business goals and objectives, a company must reply to increasing consumer demand for "green" products and implement environmentally responsible plans. Reverse logistics is an activity within organizations delegated to the customer service function, where customers with warranted or defective products would return them to their supplier. Emergence of reverse logistics enables to provide a competitive advantage and significant return on investment with an indirect effect on profitability. Many organizations are hiring third-party providers to implement reverse logistics programs designed to retain value by getting products back. Reverse logistics vendors play an important role in helping organizations in closing the loop for products offered by the organizations. In this regard, the selection of third-party providers issue is increasingly becoming an area of reverse logistics concept and practice. This study aims to assist managers in determining which third-party logistics provider to collaborate in the reverse logistics process with an alternative approach based on an integrated model using neural networks and fuzzy logic. An illustrative case study is discussed and the best provider is identified through the solution of this model.

Septal and Anterior Reverse Mismatch of Myocardial Perfusion and Metabolism in Patients With Coronary Artery Disease and Left Bundle Branch Block

PubMed Central

Wang, Jian-Guang; Fang, Wei; Yang, Min-Fu; Tian, Yue-Qin; Zhang, Xiao-Li; Shen, Rui; Sun, Xiao-Xin; Guo, Feng; Wang, Dao-Yu; He, Zuo-Xiang

2015-01-01

Abstract The effects of left bundle branch block (LBBB) on left ventricular myocardial metabolism have not been well investigated. This study evaluated these effects in patients with coronary artery disease (CAD). Sixty-five CAD patients with complete LBBB (mean age, 61.8 ± 9.7 years) and 65 without LBBB (mean age, 59.9 ± 8.4 years) underwent single photon emission computed tomography, positron emission tomography, and contrast coronary angiography. The relationship between myocardial perfusion and metabolism and reverse mismatch score, and that between QRS length and reverse mismatch score and wall motion score were evaluated. The incidence of left ventricular septum and anterior wall reverse mismatching between the two groups was significantly different (P < 0.001 and P = 0.002, respectively). The incidences of normal myocardial perfusion and metabolism in the left ventricular lateral and inferior walls were also significantly different between the two groups (P < 0.001 and P < 0.001, respectively). The incidence of septal reverse mismatching in patients with mild to moderate perfusion was significantly higher among those with LBBB than among those without LBBB (P < 0.001). In CAD patients with LBBB, septal reverse mismatching was significantly more common among those with mild to moderate perfusion than among those with severe perfusion defects (P = 0.002). The correlation between the septal reverse mismatch score and QRS length was significant (P = 0.026). In patients with CAD and LBBB, septal and anterior reverse mismatching of myocardial perfusion and metabolism was frequently present; the septal reverse mismatch score negatively correlated with the QRS interval. PMID:25997045

Study of Bulk and Elementary Screw Dislocation Assisted Reverse Breakdown in Low-Voltage (less than 250 V) 4H-SiC p(+)n Junction diodes. Part 1; DC Properties

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Huang, Wei; Dudley, Michael

1998-01-01

Given the high density (approx. 10(exp 4)/sq cm) of elementary screw dislocations (Burgers vector = 1c with no hollow core) in commercial SiC wafers and epilayers, all appreciable current (greater than 1 A) SiC power devices will likely contain elementary screw dislocations for the foreseeable future. It is therefore important to ascertain the electrical impact of these defects, particularly in high-field vertical power device topologies where SiC is expected to enable large performance improvements in solid-state high-power systems. This paper compares the DC-measured reverse-breakdown characteristics of low-voltage (less than 250 V) small-area (less than 5 x 10(exp -4)/sq cm) 4H-SiC p(+)n diodes with and without elementary screw dislocations. Compared to screw dislocation-free devices, diodes containing elementary screw dislocations exhibited higher pre-breakdown reverse leakage currents, softer reverse breakdown I-V knees, and highly localized microplasmic breakdown current filaments. The observed localized 4H-SiC breakdown parallels microplasmic breakdowns observed in silicon and other semiconductors, in which space-charge effects limit current conduction through the local microplasma as reverse bias is increased.

Study of Bulk and Elementary Screw Dislocation Assisted Reverse Breakdown in Low-Voltage (<250 V) 4H-SiC p+n Junction Diodes - Part 1: DC Properties

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Huang, Wei; Dudley, Michael

1999-01-01

Given the high density (approx. 10(exp 4)/sq cm) of elementary screw dislocations (Burgers vector = lc with no hollow core) in commercial SiC wafers and epilayers, all appreciable current (greater than 1 A) SiC power devices will likely contain elementary screw dislocations for the foreseeable future. It is therefore important to ascertain the electrical impact of these defects, particularly in high-field vertical power device topologies where SiC is expected to enable large performance improvements in solid-state high-power systems. This paper compares the DC-measured reverse-breakdown characteristics of low-voltage (less than 250 V) small-area (less than 5 x 10(exp -4) sq cm) 4H-SiC p(+)n diodes with and without elementary screw dislocations. Compared to screw dislocation-free devices, diodes containing elementary screw dislocations exhibited higher pre-breakdown reverse leakage currents, softer reverse breakdown I-V knees, and highly localized microplasmic breakdown current filaments. The observed localized 4H-SiC breakdown parallels microplasmic breakdowns observed in silicon and other semiconductors, in which space-charge effects limit current conduction through the local microplasma as reverse bias is increased.

Topological defects control collective dynamics in neural progenitor cell cultures

NASA Astrophysics Data System (ADS)

Kawaguchi, Kyogo; Kageyama, Ryoichiro; Sano, Masaki

2017-04-01

Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and -1/2 (half-integer due to the nematic feature that arises from the head-tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from -1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.

Understanding ferromagnetic hysteresis: A theoretical approach

NASA Astrophysics Data System (ADS)

Gangopadhyay, Bijan Kumar

2018-05-01

This work presents a theoretical-mathematical model for the ferromagnetic hysteresis. Theoretical understanding on ferromagnetism can be achieved through addressing the self-interaction propensity between the magnetic dipole moments associated with the magnetic domains, in conjunction with the pinning effects of the dipoles with the defects in the domain sites. An expression which relates ferromagnetic magnetization to the effective magnetic field was established in our previous work (AIP Conference Proceedings 1665, 130042 (2015)). Using this relation and solving for the reversible and the irreversible components of the magnetization, we successfully show that the magnetic saturation and the magnetic remanence can be achieved theoretically. This work also estimates the range of the external field that can be used to trace a reversible M-H curve.

Acoustic Longitudinal Field NIF Optic Feature Detection Map Using Time-Reversal & MUSIC

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

Lehman, S K

2006-02-09

We developed an ultrasonic longitudinal field time-reversal and MUltiple SIgnal Classification (MUSIC) based detection algorithm for identifying and mapping flaws in fused silica NIF optics. The algorithm requires a fully multistatic data set, that is one with multiple, independently operated, spatially diverse transducers, each transmitter of which, in succession, launches a pulse into the optic and the scattered signal measured and recorded at every receiver. We have successfully localized engineered ''defects'' larger than 1 mm in an optic. We confirmed detection and localization of 3 mm and 5 mm features in experimental data, and a 0.5 mm in simulated datamore » with sufficiently high signal-to-noise ratio. We present the theory, experimental results, and simulated results.« less

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

PubMed

Saito, Akiko; Ooki, Akio; Nakamura, Takashi; Onodera, Shoko; Hayashi, Kamichika; Hasegawa, Daigo; Okudaira, Takahito; Watanabe, Katsuhito; Kato, Hiroshi; Onda, Takeshi; Watanabe, Akira; Kosaki, Kenjiro; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakamoto, Teruo; Yamaguchi, Akira; Sueishi, Kenji; Azuma, Toshifumi

2018-01-22

Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

Evaluation of a Computer-Assisted Dental Diagnostic System by Navy Hospital Corpsmen

DTIC Science & Technology

1989-06-23

hypersensitivity 1 Defective restoration Displace/mobility of tooth, favorable prognosis Displace/mobility of tooth, guarded prognosis 2 Endo / perio ... injury Osseous sequestrum 2 Occlusal trauma _1 Periodontal abscess 3 Periocoronitis/erupting tooth 2 Reversible pulpitis Root fracture Total...Trauma Related Injury 1 1 0 *Tooth, Specific 18 26 17 *Teeth, Generalized 1 1 0 *Gingiva, Specific Area 6 1 1 *Gingiva, Generalized Area 2 2 2 *Oral

Collision dynamics of two-dimensional non-Abelian vortices

NASA Astrophysics Data System (ADS)

Mawson, Thomas; Petersen, Timothy C.; Simula, Tapio

2017-09-01

We study computationally the collision dynamics of vortices in a two-dimensional spin-2 Bose-Einstein condensate. In contrast to Abelian vortex pairs, which annihilate or pass through each other, we observe non-Abelian vortex pairs to undergo rungihilation—an event that converts the colliding vortices into a rung vortex. The resulting rung defect subsequently decays to another pair of non-Abelian vortices of different type, accompanied by a magnetization reversal.

Metabolic profiling of PPARα−/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation

PubMed Central

Makowski, Liza; Noland, Robert C.; Koves, Timothy R.; Xing, Weibing; Ilkayeva, Olga R.; Muehlbauer, Michael J.; Stevens, Robert D.; Muoio, Deborah M.

2009-01-01

Peroxisome proliferator-activated receptor-α (PPARα) is a master transcriptional regulator of β-oxidation and a prominent target of hypolipidemic drugs. To gain deeper insights into the systemic consequences of impaired fat catabolism, we used quantitative, mass spectrometry-based metabolic profiling to investigate the fed-to-fasted transition in PPARα+/+ and PPARα−/− mice. Compared to PPARα+/+ animals, acylcarnitine profiles of PPARα−/− mice revealed 2- to 4-fold accumulation of long-chain species in the plasma, whereas short-chain species were reduced by as much as 69% in plasma, liver, and skeletal muscle. These results reflect a metabolic bottleneck downstream of carnitine palmitoyltransferase-1, a mitochondrial enzyme that catalyzes the first step in β-oxidation. Organic and amino acid profiles of starved PPARα−/− mice suggested compromised citric acid cycle flux, enhanced urea cycle activity, and increased amino acid catabolism. PPARα−/− mice had 40–50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARα−/− mice. In summary, comprehensive metabolic profiling revealed novel biomarkers of defective fat oxidation, while also highlighting the potential value of supplemental carnitine as a therapy and diagnostic tool for metabolic disorders.—Makowski, L., Noland, R. C., Koves, T. R., Xing, W., Ilkayeva, O. R., Muehlbauer, M. J., Stevens, R. D., Muoio, D. M. Metabolic profiling of PPARα−/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation. PMID:18945875

New insight into the assessment of asthma using xenon ventilation computed tomography.

PubMed

Jung, Jae-Woo; Kwon, Jae-Woo; Kim, Tae-Wan; Lee, So-Hee; Kim, Kyung-Mook; Kang, Hye-Ryun; Park, Heung-Woo; Lee, Chang-Hyun; Goo, Jin-Mo; Min, Kyung-Up; Cho, Sang-Heon

2013-08-01

Image analyses include computed tomography (CT), magnetic resonance imaging, and xenon ventilation CT, which is new modality to evaluate pulmonary functional imaging. To examine the usefulness of dual-energy xenon ventilation CT in asthmatic patients. A total of 43 patients 18 years or older who were nonsmokers were included in the study. Xenon CT images in wash-in and wash-out phases were obtained at baseline and after inhalation of methacholine and salbutamol. The degrees of ventilation defects and xenon trappings were evaluated through visual analysis. Ventilation defects and xenon trapping were significantly increased and decreased after methacholine challenge and salbutamol inhalation, respectively (P < .005). The ventilation abnormalities were not significantly related to the percentage of forced expiratory volume in 1 second (FEV1) or the ratio of FEV1 to forced vital capacity. Xenon trappings after salbutamol inhalation were negatively related to the scores of the asthma control test, wheezing, or night symptoms, with statistical significance (P < .05), whereas, FEV1 showed no significant correlation with symptom scores. Baseline FEV1 was significantly lower and dyspnea and wheezing were more severe in the non-full reversal group than in the full reversal group after salbutamol inhalation in xenon CT (P < .05). The degree of ventilation defects were positively correlated with FEV1 improvement after 3 months of treatment (P = .02). The results of this study suggest that xenon ventilation CT can be used as a new method to assess ventilation abnormalities in asthma, and these ventilation abnormalities can be used as novel parameters that reflect the status of asthma control and symptom severity. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse.

PubMed

Liu, Benny; Turley, Stephen D; Burns, Dennis K; Miller, Anna M; Repa, Joyce J; Dietschy, John M

2009-02-17

Niemann-Pick type C disease is largely attributable to an inactivating mutation of NPC1 protein, which normally aids movement of unesterified cholesterol (C) from the endosomal/lysosomal (E/L) compartment to the cytosolic compartment of cells throughout the body. This defect results in activation of macrophages in many tissues, progressive liver disease, and neurodegeneration. In the npc1(-/-) mouse, a model of this disease, the whole-animal C pool expands from 2,082 to 4,925 mg/kg body weight (bw) and the hepatic C pool increases from 132 to 1,485 mg/kg bw between birth and 49 days of age. A single dose of 2-hydroxypropyl-beta-cyclodextrin (CYCLO) administered at 7 days of age immediately caused this sequestered C to flow from the lysosomes to the cytosolic pool in many organs, resulting in a marked increase in cholesteryl esters, suppression of C but not fatty acid synthesis, down-regulation of genes controlled by sterol regulatory element 2, and up-regulation of many liver X receptor target genes. There was also decreased expression of proinflammatory proteins in the liver and brain. In the liver, where the rate of C sequestration equaled 79 mg x d(-1) x kg(-1), treatment with CYCLO within 24 h increased C movement out of the E/L compartment from near 0 to 233 mg x d(-1) x kg(-1). By 49 days of age, this single injection of CYCLO resulted in a reduction in whole-body C burden of >900 mg/kg, marked improvement in liver function tests, much less neurodegeneration, and, ultimately, significant prolongation of life. These findings suggest that CYCLO acutely reverses the lysosomal transport defect seen in NPC disease.

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report

PubMed Central

2011-01-01

Introduction Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. Case presentation We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. Conclusion The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment. PMID:21745362

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report.

PubMed

Cotta, Oana R; Santarpia, Libero; Curtò, Lorenzo; Aimaretti, Gianluca; Corneli, Ginevra; Trimarchi, Francesco; Cannavò, Salvatore

2011-07-11

Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment.

Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

PubMed Central

Staropoli, John F.; Haliw, Larissa; Biswas, Sunita; Garrett, Lillian; Hölter, Sabine M.; Becker, Lore; Skosyrski, Sergej; Da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Neff, Frauke; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adler, Thure; Puk, Oliver; Sun, Minxuan; Favor, Jack; Racz, Ildikó; Bekeredjian, Raffi; Busch, Dirk H.; Graw, Jochen; Klingenspor, Martin; Klopstock, Thomas; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Lopez, Edith; Harati, Hayat; Hill, Eric; Krause, Daniela S.; Guide, Jolene; Dragileva, Ella; Gale, Evan; Wheeler, Vanessa C.; Boustany, Rose-Mary; Brown, Diane E.; Breton, Sylvie; Ruether, Klaus; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Cotman, Susan L.

2012-01-01

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3 Δ ex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3 Δ ex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3 Δ ex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3 Δ ex7/8 mice that merit further study for JNCL biomarker development. PMID:22701626

Oxidant Induced Changes in Mitochondria and Calcium Dynamicsin the Pathophysiology of Alzheimer's Disease

PubMed Central

Gibson, Gary E.; Karuppagounder, Saravanan S.; Shi, Qingli

2009-01-01

Considerable data supports the hypothesis that mitochondrial abnormalities link gene defects and/or environmental insults to the neurodegenerative process The interaction of oxidants with calcium and the mitochondrial enzymes of the tricarboxylic acid (TCA) cycle are central to that relationship. Abnormalities that were discovered in brains or fibroblasts from patients with Alzheimer's Disease (AD) have been modeled in vitro and in vivo to assess their pathophysiological importance and to determine how they might be reversed. The conclusions are consistent with the hypothesis that the AD-related abnormalities result from oxidative stress. The selection of compounds for reversal is complex because the actions of the relevant compounds vary under different conditions such as cell redox states and acute vs chronic changes. However, the models that have been developed are useful for testing the effectiveness of the potential medications. The results suggest that the reversal of the mitochondrial deficits and a reduction in oxidative stress will reduce the clinical and pathological changes and benefit patients. PMID:19076444

Reversible adapting layer produces robust single-crystal electrocatalyst for oxygen evolution.

PubMed

Tung, Ching-Wei; Hsu, Ying-Ya; Shen, Yen-Ping; Zheng, Yixin; Chan, Ting-Shan; Sheu, Hwo-Shuenn; Cheng, Yuan-Chung; Chen, Hao Ming

2015-08-28

Electrochemically converting water into oxygen/hydrogen gas is ideal for high-density renewable energy storage in which robust electrocatalysts for efficient oxygen evolution play crucial roles. To date, however, electrocatalysts with long-term stability have remained elusive. Here we report that single-crystal Co3O4 nanocube underlay with a thin CoO layer results in a high-performance and high-stability electrocatalyst in oxygen evolution reaction. An in situ X-ray diffraction method is developed to observe a strong correlation between the initialization of the oxygen evolution and the formation of active metal oxyhydroxide phase. The lattice of skin layer adapts to the structure of the active phase, which enables a reversible facile structural change that facilitates the chemical reactions without breaking the scaffold of the electrocatalysts. The single-crystal nanocube electrode exhibits stable, continuous oxygen evolution for >1,000 h. This robust stability is attributed to the complementary nature of defect-free single-crystal electrocatalyst and the reversible adapting layer.

Rho-associated kinase (ROCK) inhibition reverses low cell activity on hydrophobic surfaces.

PubMed

Tian, Yu Shun; Kim, Hyun Jung; Kim, Hyun-Man

2009-08-28

Hydrophobic polymers do not offer an adequate scaffold surface for cells to attach, migrate, proliferate, and differentiate. Thus, hydrophobic scaffolds for tissue engineering have traditionally been physicochemically modified to enhance cellular activity. However, modifying the surface by chemical or physical treatment requires supplementary engineering procedures. In the present study, regulation of a cell signal transduction pathway reversed the low cellular activity on a hydrophobic surface without surface modification. Inhibition of Rho-associated kinase (ROCK) by Y-27632 markedly enhanced adhesion, migration, and proliferation of osteoblastic cells cultured on a hydrophobic polystyrene surface. ROCK inhibition regulated cell-cycle-related molecules on the hydrophobic surface. This inhibition also decreased expression of the inhibitors of cyclin-dependent kinases such as p21(cip1) and p27(kip1) and increased expression of cyclin A and D. These results indicate that defective cellular activity on the hydrophobic surface can be reversed by the control of a cell signal transduction pathway without physicochemical surface modification.

Epidermal growth factor in alkali-burned corneal epithelial wound healing.

PubMed

Singh, G; Foster, C S

1987-06-15

We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

Myocardial infarction with Moyamoya disease and pituitary gigantism in a young female patient.

PubMed

Ahn, Y K; Jeong, M H; Bom, H S; Park, J C; Kim, J K; Chung, D J; Chung, M Y; Cho, J G; Kang, J C

1999-08-01

Myocardial infarction is very rare in young female patients with systemic vascular disorders. Moyamoya disease is a cerebrovascular disease associated with an abnormal vascular network. This report presents a 19-year-old female patient who suffered from chest pain and exertional dyspnea for 2 months prior to admission. She had a history of Moyamoya disease and pituitary gigantism since childhood. Her ejection fraction on echocardiogram was 20% and a perfusion defect with partial reversibility in the anterior wall was demonstrated on stress single photon emission computed tomography (SPECT). Diagnostic coronary angiogram revealed critical stenosis in the middle left anterior descending artery, which was treated by coronary stenting. Her subjective symptoms were relieved and the perfusion defect seen on SPECT decreased after coronary intervention.

Restoration of Motor Defects Caused by Loss of Drosophila TDP-43 by Expression of the Voltage-Gated Calcium Channel, Cacophony, in Central Neurons.

PubMed

Lembke, Kayly M; Scudder, Charles; Morton, David B

2017-09-27

Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the Drosophila TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae. Furthermore, loss of TBPH caused a reduction in cacophony , a Type II voltage-gated calcium channel, expression and that genetically restoring cacophony in motor neurons in TBPH mutant animals was sufficient to rescue the locomotion defects. In the present study, we examined the relative contributions of neuromuscular junction physiology and the motor program to the locomotion defects and identified subsets of neurons that require cacophony expression to rescue the defects. At the neuromuscular junction, we showed mEPP amplitudes and frequency require TBPH. Cacophony expression in motor neurons rescued mEPP frequency but not mEPP amplitude. We also showed that TBPH mutants displayed reduced motor neuron bursting and coordination during crawling and restoring cacophony selectively in two pairs of cells located in the brain, the AVM001b/2b neurons, also rescued the locomotion and motor defects, but not the defects in neuromuscular junction physiology. These results suggest that the behavioral defects associated with loss of TBPH throughout the nervous system can be associated with defects in a small number of genes in a limited number of central neurons, rather than peripheral defects. SIGNIFICANCE STATEMENT TDP-43 dysfunction is a common feature in neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar dementia, and Alzheimer's disease. Loss- and gain-of-function models have shown that neurons are sensitive to TDP-43 expression levels, but the specific defects caused by TDP-43 loss of function have not been described in detail. A Drosophila loss-of-function model displays pronounced locomotion defects that can be reversed by restoring the expression levels of a voltage-gated calcium channel, cacophony. We show these defects can be rescued by expression of cacophony in motor neurons and by expression in two pairs of neurons in the brain. These data suggest that loss of TDP-43 can disrupt the central circuitry of the CNS, opening up identification of alternative therapeutic targets for TDP-43 proteinopathies. Copyright © 2017 the authors 0270-6474/17/379486-12$15.00/0.

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

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

Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Functionmore » was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.« less

Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

PubMed

Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

2014-03-21

It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

Magnetization dynamics of single-domain nanodots and minimum energy dissipation during either irreversible or reversible switching

NASA Astrophysics Data System (ADS)

Madami, Marco; Gubbiotti, Gianluca; Tacchi, Silvia; Carlotti, Giovanni

2017-11-01

Single- or multi-layered planar magnetic dots, with lateral dimensions ranging from tens to hundreds of nanometers, are used as elemental switches in current and forthcoming devices for information and communication technology (ICT), including magnetic memories, spin-torque oscillators and nano-magnetic logic gates. In this review article, we will first discuss energy dissipation during irreversible switching protocols of dots of different dimensions, ranging from a few tens of nanometers to the micrometric range. Then we will focus on the fundamental energy limits of adiabatic (slow) erasure and reversal of a magnetic nanodot, showing that dissipationless operation is achievable, provided that both dynamic reversibility (arbitrarily slow application of external fields) and entropic reversibility (no free entropy increase) are insured. However, recent theoretical and experimental tests of magnetic-dot erasure reveal that intrinsic defects related to materials imperfections such as roughness or polycrystallinity, may cause an excess of dissipation if compared to the minimum theoretical limit. We will conclude providing an outlook on the most promising strategies to achieve a new generation of power-saving nanomagnetic logic devices based on clusters of interacting dots and on straintronics.

Designing a multistage supply chain in cross-stage reverse logistics environments: application of particle swarm optimization algorithms.

PubMed

Chiang, Tzu-An; Che, Z H; Cui, Zhihua

2014-01-01

This study designed a cross-stage reverse logistics course for defective products so that damaged products generated in downstream partners can be directly returned to upstream partners throughout the stages of a supply chain for rework and maintenance. To solve this reverse supply chain design problem, an optimal cross-stage reverse logistics mathematical model was developed. In addition, we developed a genetic algorithm (GA) and three particle swarm optimization (PSO) algorithms: the inertia weight method (PSOA_IWM), V(Max) method (PSOA_VMM), and constriction factor method (PSOA_CFM), which we employed to find solutions to support this mathematical model. Finally, a real case and five simulative cases with different scopes were used to compare the execution times, convergence times, and objective function values of the four algorithms used to validate the model proposed in this study. Regarding system execution time, the GA consumed more time than the other three PSOs did. Regarding objective function value, the GA, PSOA_IWM, and PSOA_CFM could obtain a lower convergence value than PSOA_VMM could. Finally, PSOA_IWM demonstrated a faster convergence speed than PSOA_VMM, PSOA_CFM, and the GA did.

Designing a Multistage Supply Chain in Cross-Stage Reverse Logistics Environments: Application of Particle Swarm Optimization Algorithms

PubMed Central

Chiang, Tzu-An; Che, Z. H.

2014-01-01

This study designed a cross-stage reverse logistics course for defective products so that damaged products generated in downstream partners can be directly returned to upstream partners throughout the stages of a supply chain for rework and maintenance. To solve this reverse supply chain design problem, an optimal cross-stage reverse logistics mathematical model was developed. In addition, we developed a genetic algorithm (GA) and three particle swarm optimization (PSO) algorithms: the inertia weight method (PSOA_IWM), V Max method (PSOA_VMM), and constriction factor method (PSOA_CFM), which we employed to find solutions to support this mathematical model. Finally, a real case and five simulative cases with different scopes were used to compare the execution times, convergence times, and objective function values of the four algorithms used to validate the model proposed in this study. Regarding system execution time, the GA consumed more time than the other three PSOs did. Regarding objective function value, the GA, PSOA_IWM, and PSOA_CFM could obtain a lower convergence value than PSOA_VMM could. Finally, PSOA_IWM demonstrated a faster convergence speed than PSOA_VMM, PSOA_CFM, and the GA did. PMID:24772026

Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

PubMed

Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

2018-07-01

Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

PubMed

Allavena, C; Rodallec, A; Leplat, A; Hall, N; Luco, C; Le Guen, L; Bernaud, C; Bouchez, S; André-Garnier, E; Boutoille, D; Ferré, V; Raffi, F

2018-01-01

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses. Copyright © 2017 Elsevier B.V. All rights reserved.

Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues.

PubMed

Dravis, Christopher; Henkemeyer, Mark

2011-07-01

We report that the disruption of bidirectional signaling between ephrin-B2 and EphB receptors impairs morphogenetic cell-cell septation and closure events during development of the embryonic midline. A novel role for reverse signaling is identified in tracheoesophageal foregut septation, as animals lacking the cytoplasmic domain of ephrin-B2 present with laryngotracheoesophageal cleft (LTEC), while both EphB2/EphB3 forward signaling and ephrin-B2 reverse signaling are shown to be required for midline fusion of the palate. In a third midline event, EphB2/EphB3 are shown to mediate ventral abdominal wall closure by acting principally as ligands to stimulate ephrin-B reverse signaling. Analysis of new ephrin-B2(6YFΔV) and ephrin-B2(ΔV) mutants that specifically ablate ephrin-B2 tyrosine phosphorylation- and/or PDZ domain-mediated signaling indicates there are at least two distinct phosphorylation-independent components of reverse signaling. These involve both PDZ domain interactions and a non-canonical SH2/PDZ-independent form of reverse signaling that may utilize associations with claudin family tetraspan molecules, as EphB2 and activated ephrin-B2 molecules are specifically co-localized with claudins in epithelia at the point of septation. Finally, the developmental phenotypes described here mirror common human midline birth defects found with the VACTERL association, suggesting a molecular link to bidirectional signaling through B-subclass Ephs and ephrins. Copyright © 2011 Elsevier Inc. All rights reserved.

Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary Epithelial Cell Differentiation

DTIC Science & Technology

2006-03-01

1-0322 TITLE: Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary Epithelial Cell Differentiation PRINCIPAL...Summary 3. DATES COVERED (From - To) 1 MAR 2005 - 28 FEB 2006 4. TITLE AND SUBTITLE Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary...reverse the phenotype of differentiation-defective breast cancer cells bearing reduced BRCA1 functions. This result implies BRCA1 is involved in

Inversion of chalcogen defect levels in silicon - An MNDO study. [modified neglect of diatomic overlap

NASA Technical Reports Server (NTRS)

Singh, R. K.; Sahu, S. N.; Singh, V. A.; Corbett, J. W.

1985-01-01

MNDO (modified neglect of diatomic overlap) calculations have been carried out for substitutional oxygen and sulfur impurities in silicon. The calculations of the gap levels reveal a reversal of trend with atomic ionization energies in agreement with self-consistent Green function results, and analysis of the MNDO charge distribution supports the view that the electronegativity difference between oxygen and sulfur gives rise to this shallower energy level.

Conference on Semi-Insulating III-V Materials (2nd), held 19-21 Apr 82, Evian (France),

DTIC Science & Technology

1983-02-28

Dist Special 19. KEY WORDS (Continue on reverse side If neceary mud Identity by block numb ) Semiconductor devices Field effect transitors Integrated...doped GaAs sub- 4 strates. The results showed no The catalog of defects includes statistically significant differ- vacancies, interstitials, anti...orientation also had high level profiles of GaAs active transconductance. In addition,the statistical scatter-uni-layers and their correlation to o m

Comment on ’Single Pentacene Molecules Detected by Fluorescence Excitation in a P-Terphenyl Crystal’

DTIC Science & Technology

1990-12-10

8217 NO 11 TITLE (include Security Classification) Comment on "Single Pentacene Molecules Detected by Fluorescence Excitation in a p-Terphenyl Crystal" 12...8217 {Continue on reverse it necessary and identify by block numboer) Using h--,Ihly efficient Fluorescence excitation spectroscov of individual pentacene ...molecular impurities in p-terphenvl crystals, we have observed that some pentacene defects exhibit spcntaneous spectral jumps in their resonance frequency at

Elucidating cdc25’s Oncogenic Mechanism in Breast Cancer Using Pin1, a Negative Mitotic Regulator

DTIC Science & Technology

2000-07-01

inhibitor aphidicolin. This defect in replication checkpoint function was reversed after addition of recombinant wild type Pin 1, but not an isomerase... inhibitor , aphidicolin. Mock-depleted extracts effectively postponed mitotic entry in response to replication inhibition, while depletion of Pin 1 from...fail to haft mitotic entry in response to the DNA polymerase inhibitor , aphidicolin. The addition of recombinant Pin1 restores the appropriate G2

Fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation in an adolescent.

PubMed

Nourse, Jamie P; Jones, Kimberley; Dua, Ujjwal; Runnegar, Naomi; Looke, David; Schmidt, Chris; Tey, Siok-Keen; Kennedy, Glen; Gandhi, Maher K

2010-03-15

We describe a unique case of fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation presenting in an adolescent. Detailed assays of Epstein-Barr virus-specific T cell immunity revealed defects in the patient's T cell receptor signalling pathway characterized by a lack of interleukin-2 and CD25 expression, which may have contributed to her clinical course. Allogeneic stem cell transplantation reversed the clinical and laboratory phenotype.

Studies of Altered Response to Infection Induced by Thermal Injury.

DTIC Science & Technology

1984-05-01

beginning to examine various prophylactic treatments for their efficacy in reversing a number of burn mediated immune defects. We expect even more interesting...with fluoresceinated antibody (OKM5) and FACS sorting or negative selection by Sephadex G-l0 passage and/or antibody and -3- complement treatment ... infectious episode. This mitogen hyperimmunity is typical of a normal immune system dealing with an infectious challenge. The Group II patients have a

Evolutionary Algorithm Based Automated Reverse Engineering and Defect Discovery

DTIC Science & Technology

2007-09-21

a previous application of a GP as a data mining function to evolve fuzzy decision trees symbolically [3-5], the terminal set consisted of fuzzy...of input and output information is required. In the case of fuzzy decision trees, the database represented a collection of scenarios about which the...fuzzy decision tree to be evolved would make decisions . The database also had entries created by experts representing decisions about the scenarios

Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

PubMed Central

Shao, Hongwei; Xu, Qiyuan; Wu, Qiuling; Ma, Qi; Salgueiro, Luis; Wang, Jian’An; Eton, Darwin; Webster, Keith A; Yu, Hong

2011-01-01

The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34+ progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses. PMID:21143386

Reverse Transcription of a Self-Primed Retrotransposon Requires an RNA Structure Similar to the U5-IR Stem-Loop of Retroviruses

PubMed Central

Lin, Jia-Hwei; Levin, Henry L.

1998-01-01

An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV. The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop. Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of Tf1 does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak U5-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the U5-IR structure. However, all of the mutations in the U5-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5′ end of Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer. Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. PMID:9774699

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

PubMed Central

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

Metal-Organic Nanosheets Formed via Defect-Mediated Transformation of a Hafnium Metal-Organic Framework.

PubMed

Cliffe, Matthew J; Castillo-Martínez, Elizabeth; Wu, Yue; Lee, Jeongjae; Forse, Alexander C; Firth, Francesca C N; Moghadam, Peyman Z; Fairen-Jimenez, David; Gaultois, Michael W; Hill, Joshua A; Magdysyuk, Oxana V; Slater, Ben; Goodwin, Andrew L; Grey, Clare P

2017-04-19

We report a hafnium-containing MOF, hcp UiO-67(Hf), which is a ligand-deficient layered analogue of the face-centered cubic fcu UiO-67(Hf). hcp UiO-67 accommodates its lower ligand:metal ratio compared to fcu UiO-67 through a new structural mechanism: the formation of a condensed "double cluster" (Hf 12 O 8 (OH) 14 ), analogous to the condensation of coordination polyhedra in oxide frameworks. In oxide frameworks, variable stoichiometry can lead to more complex defect structures, e.g., crystallographic shear planes or modules with differing compositions, which can be the source of further chemical reactivity; likewise, the layered hcp UiO-67 can react further to reversibly form a two-dimensional metal-organic framework, hxl UiO-67. Both three-dimensional hcp UiO-67 and two-dimensional hxl UiO-67 can be delaminated to form metal-organic nanosheets. Delamination of hcp UiO-67 occurs through the cleavage of strong hafnium-carboxylate bonds and is effected under mild conditions, suggesting that defect-ordered MOFs could be a productive route to porous two-dimensional materials.

Reversible wettability of electron-beam deposited indium-tin-oxide driven by ns-UV irradiation

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

Persano, Luana; Center for Biomolecular Nanotechnologies UNILE, Istituto Italiano di Tecnologia, Via Barsanti, I-73010 Arnesano-LE; Del Carro, Pompilio

2012-04-09

Indium tin oxide (ITO) is one of the most widely used semiconductor oxides in the field of organic optoelectronics, especially for the realization of anode contacts. Here the authors report on the control of the wettability properties of ITO films deposited by reactive electron beam deposition and irradiated by means of nanosecond-pulsed UV irradiation. The enhancement of the surface water wettability, with a reduction of the water contact angle larger than 50 deg., is achieved by few tens of seconds of irradiation. The analyzed photo-induced wettability change is fully reversible in agreement with a surface-defect model, and it can bemore » exploited to realize optically transparent, conductive surfaces with controllable wetting properties for sensors and microfluidic circuits.« less

Mechanism of the α -ɛ phase transformation in iron

NASA Astrophysics Data System (ADS)

Dewaele, A.; Denoual, C.; Anzellini, S.; Occelli, F.; Mezouar, M.; Cordier, P.; Merkel, S.; Véron, M.; Rausch, E.

2015-05-01

The α -Fe↔ɛ -Fe pressure-induced transformation under pure hydrostatic static compression has been characterized with in situ x-ray diffraction using α -Fe single crystals as starting samples. The forward transition starts at 14.9 GPa, and the reverse at 12 GPa, with a width of α -ɛ coexistence domain of the order of 2 GPa. The elastic stress in the sample increases in this domain, and partially relaxes after completion of the transformation. Orientation relations between parent α -Fe and child ɛ -Fe have been determined, which definitely validates the Burgers path for the direct transition. On the reverse transition, an unexpected variant selection is observed. X-ray diffraction data, complemented with ex situ microstructural observations, suggest that this selection is caused by defects and stresses accumulated during the direct transition.

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

PubMed Central

Tannour-Louet, Mounia; Han, Shuo; Corbett, Sean T.; Louet, Jean-Francois; Yatsenko, Svetlana; Meyers, Lindsay; Shaw, Chad A.; Kang, Sung-Hae L.; Cheung, Sau Wai; Lamb, Dolores J.

2010-01-01

Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10−12). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development. PMID:21048976

Repair of bony lateral skull base defects equal to or larger than 10 mm by extracorporeally sewed unit-sandwich graft.

PubMed

Indorewala, Shabbir; Nemade, Gaurav; Indorewala, Abuzar; Mahajan, Gauri

2018-06-23

To see effectiveness of the senior author's repair technique for repair of large (equal to or larger than 10 mm) bony lateral skull base defects. Retrospective. Secondary/tertiary care center. We performed retrospective review of 9 surgeries done in our institution between January 2010 and December 2013 for repair of large lateral bony skull base defects. We defined skull base defects extra-cranially and repaired them intra-cranially. We made an extracorporeal sandwich of autologous fascia-bone-fascia (fascia lata and nasal septal bone) and sewed it together to make it into a unit-sandwich graft. This extracorporeally sewed unit-sandwich graft was then inserted to close the large skull base defects either via (1) a cranial slit-window, or (2) the skull base defect itself. Since skull base is bony, bony repair is preferred. Bone plates that are easily available for skull base repair are calvarial and nasal septal bone. Occasionally, harvest of split calvarial bone carries risk of major complications. We preferred nasal septal bone. Harvesting of septal bone even in children using a posterior incision should not disturb the cartilage growth centers. All nine patients were operated by this technique. We had four patients with cerebrospinal fluid leak, and five patients with brain herniation. All these patients had complete reversal of herniation of cranial contents and cessation of cerebrospinal fluid leak. On imaging, in 6 cases the bone graft remained in original intended position after 12 months of surgery. The bone graft was not identifiable in 3 cases. The senior author's technique using autologous multi-layered graft is simple to master, repeatable and very effective.

Quantitative 3D evolution of colloidal nanoparticle oxidation in solution

DOE PAGES

Sun, Yugang; Zuo, Xiaobing; Sankaranarayanan, Subramanian K. R. S.; ...

2017-04-21

Real-time tracking three-dimensional (3D) evolution of colloidal nanoparticles in solution is essential for understanding complex mechanisms involved in nanoparticle growth and transformation. We simultaneously use time-resolved small-angle and wide-angle x-ray scattering to monitor oxidation of highly uniform colloidal iron nanoparticles, enabling the reconstruction of intermediate 3D morphologies of the nanoparticles with a spatial resolution of ~5 Å. The in-situ probing combined with large-scale reactive molecular dynamics simulations reveals the transformational details from the solid metal nanoparticles to hollow metal oxide nanoshells via nanoscale Kirkendall process, for example, coalescence of voids upon their growth, reversing of mass diffusion direction depending onmore » crystallinity, and so forth. In conclusion, our results highlight the complex interplay between defect chemistry and defect dynamics in determining nanoparticle transformation and formation.« less

Two different carbon-hydrogen complexes in silicon with closely spaced energy levels

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

Stübner, R., E-mail: ronald.stuebner@physik.tu-dresden.de, E-mail: kolkov@ifpan.edu.pl; Kolkovsky, Vl., E-mail: ronald.stuebner@physik.tu-dresden.de, E-mail: kolkov@ifpan.edu.pl; Weber, J.

An acceptor and a single donor state of carbon-hydrogen defects (CH{sub A} and CH{sub B}) are observed by Laplace deep level transient spectroscopy at 90 K. CH{sub A} appears directly after hydrogenation by wet chemical etching or hydrogen plasma treatment, whereas CH{sub B} can be observed only after a successive annealing under reverse bias at about 320 K. The activation enthalpies of these states are 0.16 eV for CH{sub A} and 0.14 eV for CH{sub B}. Our results reconcile previous controversial experimental results. We attribute CH{sub A} to the configuration where substitutional carbon binds a hydrogen atom on a bond centered position between carbonmore » and the neighboring silicon and CH{sub B} to another carbon-hydrogen defect.« less

Identification of a limiting mechanism in GaSb-rich superlattice midwave infrared detector

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

Delmas, Marie; Rodriguez, Jean-Baptiste; Rossignol, Rémi

2016-05-07

GaSb-rich superlattice (SL) p-i-n photodiodes grown by molecular beam epitaxy were studied theoretically and experimentally in order to understand the poor dark current characteristics typically obtained. This behavior, independent of the SL-grown material quality, is usually attributed to the presence of defects due to Ga-related bonds, limiting the SL carrier lifetime. By analyzing the photoresponse spectra of reverse-biased photodiodes at 80 K, we have highlighted the presence of an electric field, breaking the minibands into localized Wannier-Stark states. Besides the influence of defects in such GaSb-rich SL structures, this electric field induces a strong tunneling current at low bias which canmore » be the main limiting mechanism explaining the high dark current density of the GaSb-rich SL diode.« less

Replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus and isolation of a td mutant from duck-adapted PR-RSV-C.

PubMed

Geryk, J; Mazo, A; Svoboda, J; Hlozánek, I

1980-01-01

The replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus subgroup C was studied using roller cultures. Under such conditions, 10(5)--10(6) infectous units of virus per 0.2 ml were produced, as revealed in both the reverse transcriptase and 16Q complementation tests. A new td daPR-RSV-C mutant was isolated from duck-adapted PR-RSV-C. This mutant replicated in roller cultures with equal efficiency as the original td PR-RSV-C. It was verified that td daPR-RSV-C does not transform chicken fibroblasts, is not oncogenic for 3-week-old chickens and has subgroup C host-range specificity. Both td mutants replicate in duck cells and reach the same titres.

Highly Nitrogen-Doped Three-Dimensional Carbon Fibers Network with Superior Sodium Storage Capacity.

PubMed

Lei, Wen; Xiao, Weiping; Li, Jingde; Li, Gaoran; Wu, Zexing; Xuan, Cuijuan; Luo, Dan; Deng, Ya-Ping; Wang, Deli; Chen, Zhongwei

2017-08-30

Inspired by the excellent absorption capability of spongelike bacterial cellulose (BC), three-dimensional hierarchical porous carbon fibers doped with an ultrahigh content of N (21.2 atom %) (i.e., nitrogen-doped carbon fibers, NDCFs) were synthesized by an adsorption-swelling strategy using BC as the carbonaceous material. When used as anode materials for sodium-ion batteries, the NDCFs deliver a high reversible capacity of 86.2 mAh g -1 even after 2000 cycles at a high current density of 10.0 A g -1 . It is proposed that the excellent Na + storage performance is mainly due to the defective surface of the NDCFs created by the high content of N dopant. Density functional theory (DFT) calculations show that the defect sites created by N doping can strongly "host" Na + and therefore contribute to the enhanced storage capacity.

Quantitative 3D evolution of colloidal nanoparticle oxidation in solution

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

Sun, Yugang; Zuo, Xiaobing; Sankaranarayanan, Subramanian K. R. S.

Real-time tracking three-dimensional (3D) evolution of colloidal nanoparticles in solution is essential for understanding complex mechanisms involved in nanoparticle growth and transformation. We simultaneously use time-resolved small-angle and wide-angle x-ray scattering to monitor oxidation of highly uniform colloidal iron nanoparticles, enabling the reconstruction of intermediate 3D morphologies of the nanoparticles with a spatial resolution of ~5 Å. The in-situ probing combined with large-scale reactive molecular dynamics simulations reveals the transformational details from the solid metal nanoparticles to hollow metal oxide nanoshells via nanoscale Kirkendall process, for example, coalescence of voids upon their growth, reversing of mass diffusion direction depending onmore » crystallinity, and so forth. In conclusion, our results highlight the complex interplay between defect chemistry and defect dynamics in determining nanoparticle transformation and formation.« less

Glyceraldehyde 3-phosphate dehydrogenase negatively regulates human immunodeficiency virus type 1 infection

PubMed Central

2012-01-01

Background Host proteins are incorporated inside human immunodeficiency virus type 1 (HIV-1) virions during assembly and can either positively or negatively regulate HIV-1 infection. Although the identification efficiency of host proteins is improved by mass spectrometry, how those host proteins affect HIV-1 replication has not yet been fully clarified. Results In this study, we show that virion-associated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) does not allosterically inactivate HIV-1 reverse transcriptase (RT) but decreases the efficiency of reverse transcription reactions by decreasing the packaging efficiency of lysyl-tRNA synthetase (LysRS) and tRNALys3 into HIV-1 virions. Two-dimensional (2D) gel electrophoresis demonstrated that some isozymes of GAPDH with different isoelectric points were expressed in HIV-1-producing CEM/LAV-1 cells, and a proportion of GAPDH was selectively incorporated into the virions. Suppression of GAPDH expression by RNA interference in CEM/LAV-1 cells resulted in decreased GAPDH packaging inside the virions, and the GAPDH-packaging-defective virus maintained at least control levels of viral production but increased the infectivity. Quantitative analysis of reverse transcription products indicated that the levels of early cDNA products of the GAPDH-packaging-defective virus were higher than those of the control virus owing to the higher packaging efficiencies of LysRS and tRNALys3 into the virions rather than the GAPDH-dependent negative allosteric modulation for RT. Furthermore, immunoprecipitation assay using an anti-GAPDH antibody showed that GAPDH directly interacted with Pr55gag and p160gag-pol and the overexpression of LysRS in HIV-1-producing cells resulted in a decrease in the efficiency of GAPDH packaging in HIV particles. In contrast, the viruses produced from cells expressing a high level of GAPDH showed decreased infectivity in TZM-bl cells and reverse transcription efficiency in TZM-bl cells and peripheral blood mononuclear cells (PBMCs). Conclusions These findings indicate that GAPDH negatively regulates HIV-1 infection and provide insights into a novel function of GAPDH in the HIV-1 life cycle and a new host defense mechanism against HIV-1 infection. PMID:23237566

The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model

PubMed Central

Curado, Silvia; Ober, Elke A.; Walsh, Susan; Cortes-Hernandez, Paulina; Verkade, Heather; Koehler, Carla M.; Stainier, Didier Y. R.

2010-01-01

SUMMARY Understanding liver development should lead to greater insights into liver diseases and improve therapeutic strategies. In a forward genetic screen for genes regulating liver development in zebrafish, we identified a mutant – oliver – that exhibits liver-specific defects. In oliver mutants, the liver is specified, bile ducts form and hepatocytes differentiate. However, the hepatocytes die shortly after their differentiation, and thus the resulting mutant liver consists mainly of biliary tissue. We identified a mutation in the gene encoding translocase of the outer mitochondrial membrane 22 (Tomm22) as responsible for this phenotype. Mutations in tomm genes have been associated with mitochondrial dysfunction, but most studies on the effect of defective mitochondrial protein translocation have been carried out in cultured cells or unicellular organisms. Therefore, the tomm22 mutant represents an important vertebrate genetic model to study mitochondrial biology and hepatic mitochondrial diseases. We further found that the temporary knockdown of Tomm22 levels by morpholino antisense oligonucleotides causes a specific hepatocyte degeneration phenotype that is reversible: new hepatocytes repopulate the liver as Tomm22 recovers to wild-type levels. The specificity and reversibility of hepatocyte ablation after temporary knockdown of Tomm22 provides an additional model to study liver regeneration, under conditions where most hepatocytes have died. We used this regeneration model to analyze the signaling commonalities between hepatocyte development and regeneration. PMID:20483998

Homologous recombination between overlapping thymidine kinase gene fragments stably inserted into a mouse cell genome.

PubMed

Lin, F L; Sternberg, N

1984-05-01

We have constructed a substrate to study homologous recombination between adjacent segments of chromosomal DNA. This substrate, designated lambda tk2 , consists of one completely defective and one partially defective herpes simplex virus thymidine kinase (tk) gene cloned in bacteriophage lambda DNA. The two genes have homologous 984-base-pair sequences and are separated by 3 kilobases of largely vector DNA. When lambda tk2 DNA was transferred into mouse LMtk- cells by the calcium phosphate method, rare TK+ transformants were obtained that contained many (greater than 40) copies of the unrecombined DNA. Tk- revertants, which had lost most of the copies of unrecombined DNA, were isolated from these TK+-transformed lines. Two of these Tk- lines were further studied by analysis of their reversion back to the Tk+ phenotype. They generated ca. 200 Tk+ revertants per 10(8) cells after growth in nonselecting medium for 5 days. All of these Tk+ revertants have an intact tk gene reconstructed by homologous recombination; they also retain various amounts of unrecombined lambda tk2 DNA. Southern blot analysis suggested that at least some of the recombination events involve unequal sister chromatid exchanges. We also tested three agents, mitomycin C, 12-O-tetradecanoyl-phorbol-13-acetate, and mezerein, that are thought to stimulate recombination to determine whether they affect the reversion from Tk- to Tk+. Only mitomycin C increased the number of Tk+ revertants.

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

NASA Technical Reports Server (NTRS)

Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

2003-01-01

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.

PubMed

Tejani, Furqan H; Thompson, Randall C; Iskandrian, Ami E; McNutt, Bruce E; Franks, Billy

2011-02-01

Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

Experience of low-dose aminophylline use to relieve minor adverse effects of dipyridamole in patients undergoing stress myocardial perfusion imaging.

PubMed

Lin, Li-Fan; Cheng, Cheng-Yi; Hou, Cheng-Han; Ku, Chih-Hung; Tseng, Neng-Chuan; Shen, Daniel H Y

2014-06-01

Intravenous administration of aminophylline is widely adopted to reverse dipyridamole-related adverse effects (AEs) during stress myocardial perfusion imaging (MPI). The study aimed to investigate the efficacy of lower-dose aminophylline to relieve minor AEs. 2,250 consecutive patients undergoing dipyridamole-stressed MPI were enrolled. Information concerning AE occurrence and dosages of aminophylline was collected to evaluate the efficacy of lower-dose aminophylline. A logistic regression was used to determine independent predictors of dipyridamole-related AE occurrence. No severe AE was noted. Overall mild AE incidence was 37.0% (833/2,250 patients). Initial low-dose (25 mg) aminophylline relieved symptoms in 98.8% of patients with mild AEs (823/833 patients). An extra 25 mg aminophylline sufficed to reverse all such AEs. Mean body mass index (BMI) differed significantly between patients with and without any AE [25.6 vs 25.1 (P = .009)]. There was no significant difference between two subgroups in mean age, male gender prevalence, body height and weight, dipyridamole dose/BMI, or prevalence of significant perfusion defect(s) on MPI. Multivariable logistic regression demonstrated BMI remained the independent predictor of dipyridamole-related AE occurrence (odds ratio 1.028, 95% confidence interval 1.007-1.049, P = .01). Low-dose (≦50 mg, and usually 25 mg) aminophylline seems sufficient to relieve mild dipyridamole-related AEs during stress MPI.

Unified Numerical Solver for Device Metastabilities in CdTe Thin-Film PV

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

Vasileska, Dragica

Thin-film modules of all technologies often suffer from performance degradation over time. Some of the performance changes are reversible and some are not, which makes deployment, testing, and energy-yield prediction more challenging. Manufacturers de-vote significant empirical efforts to study these phenomena and to improve semiconduc-tor device stability. Still, understanding the underlying reasons of these instabilities re-mains clouded due to the lack of ability to characterize materials at atomistic levels and the lack of interpretation from the most fundamental material science. The most com-monly alleged causes of metastability in CdTe device, such as “migration of Cu,” have been investigated rigorously overmore » the past fifteen years. Still, the discussion often ended prematurely with stating observed correlations between stress conditions and changes in atomic profiles of impurities or CV doping concentration. Multiple hypotheses sug-gesting degradation of CdTe solar cell devices due to interaction and evolution of point defects and complexes were proposed, and none of them received strong theoretical or experimental confirmation. It should be noted that atomic impurity profiles in CdTe pro-vide very little intelligence on active doping concentrations. The same elements could form different energy states, which could be either donors or acceptors, depending on their position in crystalline lattice. Defects interact with other extrinsic and intrinsic de-fects; for example, changing the state of an impurity from an interstitial donor to a sub-stitutional acceptor often is accompanied by generation of a compensating intrinsic in-terstitial donor defect. Moreover, all defects, intrinsic and extrinsic, interact with the elec-trical potential and free carriers so that charged defects may drift in the electric field and the local electrical potential affects the formation energy of the point defects. Such complexity of interactions in CdTe makes understanding of temporal changes in device performance even more challenging and a closed solution that can treat the entire sys-tem and its interactions is required.« less

Metastability and reliability of CdTe solar cells

NASA Astrophysics Data System (ADS)

Guo, Da; Brinkman, Daniel; Shaik, Abdul R.; Ringhofer, Christian; Vasileska, Dragica

2018-04-01

Thin-film modules of all technologies often suffer from performance degradation over time. Some of the performance changes are reversible and some are not, which makes deployment, testing, and energy-yield prediction more challenging. Manufacturers devote significant empirical efforts to study these phenomena and to improve semiconductor device stability. Still, understanding the underlying reasons of these instabilities remains clouded due to the lack of ability to characterize materials at atomistic levels and the lack of interpretation from the most fundamental material science. The most commonly alleged causes of metastability in CdTe devices, such as ‘migration of Cu’, have been investigated rigorously over the past fifteen years. Still, the discussion often ended prematurely with stating observed correlations between stress conditions and changes in atomic profiles of impurities or CV doping concentration. Multiple hypotheses suggesting degradation of CdTe solar cell devices due to interaction and evolution of point defects and complexes were proposed, and none of them received strong theoretical or experimental confirmation. It should be noted that atomic impurity profiles in CdTe provide very little intelligence on active doping concentrations. The same elements could form different energy states, which could be either donors or acceptors, depending on their position in crystalline lattice. Defects interact with other extrinsic and intrinsic defects; for example, changing the state of an impurity from an interstitial donor to a substitutional acceptor often is accompanied by generation of a compensating intrinsic interstitial donor defect. Moreover, all defects, intrinsic and extrinsic, interact with the electrical potential and free carriers so that charged defects may drift in the electric field and the local electrical potential affects the formation energy of the point defects. Such complexity of interactions in CdTe makes understanding of temporal changes in device performance even more challenging and a closed solution that can treat the entire system and its interactions is required.

Materials for energy, drug, and information storage

NASA Astrophysics Data System (ADS)

Cheng, Peifu

It is generally recognized that H2O adsorption on a porous material would inhibit H2 adsorption. However, Chapter 3 reports that stable H2O-functionalized ZIF-8(a representative MOF), which was obtained by the simple water treatment of ZIF-8 at ambient temperature, can increase its H2 adsorption heat from 5.2 to 10.1 kJ/mol. As a result, the reversible H2 capacity at ambient temperature increased by 77%. A suitable isotherm equation for C2H2 adsorption on various MOFs has not been found. Chapter 4 demonstrates that Dubinin-Astakhov equation can be exploited as a general isotherm model to depict C2H 2 adsorption on MOF-5, ZIF-8, HKUST-1, and MIL-53. Furthermore, it was found that the adsorption of C2H2 on the defected MIL-53 is stronger than that on MIL-53 without defection, reflected by adsorption-heat increase from 19.3 to 25.1 kJ/mol. Chapter 5 finds that the adsorption of CO2 on the defected ZIF-8 is stronger than that on ZIF-8 without defection, reflected by initial adsorption-heat increase from 16.0 to 22.8 kJ/mol. As a result, the specific reversible CO2 capacity per surface area increased with increasing defects. A novel strategy was developed to enhance the hydrophilicity on the external surface of ZIF-8 without reducing or blocking the internal pores in Chapter 6. A simple ball-milling approach combined with water treatment results in a significantly higher cell viability without compromising its hydroxyurea loading and release capacity. It's a challenge to build a memristor with odd-symmetric I--V features. In Chapter 7, a novel strategy, in which two same asymmetric switch components can be combined as a symmetric device, is reported to create an odd-symmetric memristor. Furthermore, with this strategy, the surface-sulphurization was performed on both sides of a Ag foil, leading to a Ag2S/Ag/Ag2S odd-symmetric memristor consisting of two asymmetric Ag2S/Ag memristive switches. Chapter 8 demonstrate that 2H phase of bulk MoS2 possessed an ohmic feature, whereas 1T phase of exfoliated MoS2 nanosheets exhibited a unique memristive behaviour due to voltage-dependent resistance change. Furthermore, an ideal odd-symmetric memristor with odd-symmetric I--V characteristics was successfully fabricated by the 1T phase MoS2 nanosheets via combining two asymmetric switches anti-serially.

Dietary fructose causes defective insulin signalling and ceramide accumulation in the liver that can be reversed by gut microbiota modulation

PubMed Central

Crescenzo, Raffaella; Mazzoli, Arianna; Di Luccia, Blanda; Bianco, Francesca; Cancelliere, Rosa; Cigliano, Luisa; Liverini, Giovanna; Baccigalupi, Loredana; Iossa, Susanna

2017-01-01

ABSTRACT Objective: The link between metabolic derangement of the gut–2013liver–visceral white adipose tissue (v-WAT) axis and gut microbiota was investigated. Methods: Rats were fed a fructose-rich diet and treated with an antibiotic mix. Inflammation was measured in portal plasma, ileum, liver, and v-WAT, while insulin signalling was analysed by measuring levels of phosphorylated kinase Akt. The function and oxidative status of hepatic mitochondria and caecal microbiota composition were also evaluated. Results: Ileal inflammation, increase in plasma transaminases, plasma peroxidised lipids, portal concentrations of tumour necrosis factor alpha, lipopolysaccharide, and non-esterified fatty acids, were induced by fructose and were reversed by antibiotic. The increased hepatic ceramide content, inflammation and decreased insulin signaling in liver and v-WAT induced by fructose was reversed by antibiotic. Antibiotic also blunted the increase in hepatic mitochondrial efficiency and oxidative damage of rats fed fructose-rich diet. Three genera, Coprococcus, Ruminococcus, and Clostridium, significantly increased, while the Clostridiaceae family significantly decreased in rats fed a fructose-rich diet, and antibiotic abolished these variations Conclusions: When gut microbiota modulation by fructose is prevented by antibiotic, inflammatory flow from the gut to the liver and v-WAT are reversed. PMID:28659742

Dietary fructose causes defective insulin signalling and ceramide accumulation in the liver that can be reversed by gut microbiota modulation.

PubMed

Crescenzo, Raffaella; Mazzoli, Arianna; Di Luccia, Blanda; Bianco, Francesca; Cancelliere, Rosa; Cigliano, Luisa; Liverini, Giovanna; Baccigalupi, Loredana; Iossa, Susanna

2017-01-01

Objective : The link between metabolic derangement of the gut-2013liver-visceral white adipose tissue (v-WAT) axis and gut microbiota was investigated. Methods : Rats were fed a fructose-rich diet and treated with an antibiotic mix. Inflammation was measured in portal plasma, ileum, liver, and v-WAT, while insulin signalling was analysed by measuring levels of phosphorylated kinase Akt. The function and oxidative status of hepatic mitochondria and caecal microbiota composition were also evaluated. Results : Ileal inflammation, increase in plasma transaminases, plasma peroxidised lipids, portal concentrations of tumour necrosis factor alpha, lipopolysaccharide, and non-esterified fatty acids, were induced by fructose and were reversed by antibiotic. The increased hepatic ceramide content, inflammation and decreased insulin signaling in liver and v-WAT induced by fructose was reversed by antibiotic. Antibiotic also blunted the increase in hepatic mitochondrial efficiency and oxidative damage of rats fed fructose-rich diet. Three genera, Coprococcus, Ruminococcus, and Clostridium, significantly increased, while the Clostridiaceae family significantly decreased in rats fed a fructose-rich diet, and antibiotic abolished these variations Conclusions : When gut microbiota modulation by fructose is prevented by antibiotic, inflammatory flow from the gut to the liver and v-WAT are reversed.

Long-range activation of Sox9 in Odd Sex (Ods) mice.

PubMed

Qin, Yangjun; Kong, Ling-kun; Poirier, Christophe; Truong, Cavatina; Overbeek, Paul A; Bishop, Colin E

2004-06-15

The Odd Sex mouse mutation arose in a transgenic line of mice carrying a tyrosinase minigene driven by the dopachrome tautomerase (Dct) promoter region. The minigene integrated 0.98 Mb upstream of Sox9 and was accompanied by a deletion of 134 kb. This mutation causes female to male sex reversal in XX Ods/+ mice, and a characteristic eye phenotype of microphthalmia with cataracts in all mice carrying the transgene. Ods causes sex reversal in the absence of Sry by upregulating Sox9 expression and maintaining a male pattern of Sox9 expression in XX Ods/+ embryonic gonads. This expression, which begins at E11.5, triggers downstream events leading to the formation of a testis. We report here that the 134 kb deletion, in itself, is insufficient to cause sex reversal. We demonstrate that in Ods, the Dct promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium of the eye, causing the observed microphthalmia. In addition, it induces Sox9 expression in the melanocytes where it causes pigmentation defects. We propose that Ods sex reversal is due to the Dct promoter element interacting with gonad-specific enhancer elements to produce the observed male pattern expression of Sox9 in the embryonic gonads.

Analytical reverse time migration: An innovation in imaging of infrastructures using ultrasonic shear waves.

PubMed

Asadollahi, Aziz; Khazanovich, Lev

2018-04-11

The emergence of ultrasonic dry point contact (DPC) transducers that emit horizontal shear waves has enabled efficient collection of high-quality data in the context of a nondestructive evaluation of concrete structures. This offers an opportunity to improve the quality of evaluation by adapting advanced imaging techniques. Reverse time migration (RTM) is a simulation-based reconstruction technique that offers advantages over conventional methods, such as the synthetic aperture focusing technique. RTM is capable of imaging boundaries and interfaces with steep slopes and the bottom boundaries of inclusions and defects. However, this imaging technique requires a massive amount of memory and its computation cost is high. In this study, both bottlenecks of the RTM are resolved when shear transducers are used for data acquisition. An analytical approach was developed to obtain the source and receiver wavefields needed for imaging using reverse time migration. It is shown that the proposed analytical approach not only eliminates the high memory demand, but also drastically reduces the computation time from days to minutes. Copyright © 2018 Elsevier B.V. All rights reserved.

Impairment of probabilistic reward-based learning in schizophrenia.

PubMed

Weiler, Julia A; Bellebaum, Christian; Brüne, Martin; Juckel, Georg; Daum, Irene

2009-09-01

Recent models assume that some symptoms of schizophrenia originate from defective reward processing mechanisms. Understanding the precise nature of reward-based learning impairments might thus make an important contribution to the understanding of schizophrenia and the development of treatment strategies. The present study investigated several features of probabilistic reward-based stimulus association learning, namely the acquisition of initial contingencies, reversal learning, generalization abilities, and the effects of reward magnitude. Compared to healthy controls, individuals with schizophrenia exhibited attenuated overall performance during acquisition, whereas learning rates across blocks were similar to the rates of controls. On the group level, persons with schizophrenia were, however, unable to learn the reversal of the initial reward contingencies. Exploratory analysis of only the subgroup of individuals with schizophrenia who showed significant learning during acquisition yielded deficits in reversal learning with low reward magnitudes only. There was further evidence of a mild generalization impairment of the persons with schizophrenia in an acquired equivalence task. In summary, although there was evidence of intact basic processing of reward magnitudes, individuals with schizophrenia were impaired at using this feedback for the adaptive guidance of behavior.

EPR reversible signature of self-trapped holes in fictive temperature-treated silica glass

NASA Astrophysics Data System (ADS)

Lancry, Matthieu; Ollier, Nadège; Babu, B. H.; Herrero, Christian; Poumellec, Bertrand

2018-03-01

Post-mortem electron paramagnetic resonance spectroscopy experiments have been carried out between room temperature and 20 K to examine the radiation-induced defects in fictive temperature (Tf) treated Heraeus F300 silica (0.1 ppm OH, 1500 ppm Cl2). In particular, we focus our attention on Self-Trapped Hole (STH) centers detected in 1000 °C, 1100 °C, and 1200 °C Tf treated samples irradiated at room temperature by gamma rays at 6 kGy. By repeating annealing cycles between 77 and 300 K on the same samples, we observed that the EPR signal attributed to STH decreases as the temperature increases but in a reversible manner. We evidenced a deviation from the Curie law for T > 70 K and suggested an interpretation based on the decrease in the "strain-assisted TH" population by reversible excitation of the trapped hole to a delocalized state with an activation energy of 7.8 meV. This also means that the precursors of hole trapping sites (a local strain atomic configuration) remain stable until 300 K at least.

[Neurological Disorders and Pregnancy].

PubMed

Berlit, P

2016-02-01

Neurological disorders caused by pregnancy and puerperium include the posterior reversible encephalopathy syndrome, the amniotic fluid embolism syndrome (AFES), the postpartum angiopathy due to reversible vasoconstriction syndrome, and the Sheehan syndrome. Hypertension and proteinuria are the hallmarks of preeclampsia, seizures define eclampsia. Hemolysis, elevated liver enzymes and low platelets constitute the HELLP syndrome. Vision disturbances including cortical blindness occur in the posterior reversible encephalopathy syndrome (PRES). The Sheehan syndrome presents with panhypopituitarism post partum due to apoplexia of the pituitary gland in severe peripartal blood loss leading to longstanding hypotension. Some neurological disorders occur during pregnancy and puerperium with an increased frequency. These include stroke, sinus thrombosis, the restless legs syndrome and peripheral nerve syndromes, especially the carpal tunnel syndrome. Chronic neurologic diseases need an interdisciplinary approach during pregnancy. Some anticonvulsants double the risk of birth defects. The highest risk exists for valproic acid, the lowest for lamotrigine and levetiracetam. For MS interval treatment, glatiramer acetate and interferones seem to be safe during pregnancy. All other drugs should be avoided. © Georg Thieme Verlag KG Stuttgart · New York.

Pharmacological correction of a defect in PPAR-gamma signaling ameliorates disease severity in Cftr-deficient mice.

PubMed

Harmon, Gregory S; Dumlao, Darren S; Ng, Damian T; Barrett, Kim E; Dennis, Edward A; Dong, Hui; Glass, Christopher K

2010-03-01

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (encoded by Cftr) that impair its role as an apical chloride channel that supports bicarbonate transport. Individuals with cystic fibrosis show retained, thickened mucus that plugs airways and obstructs luminal organs as well as numerous other abnormalities that include inflammation of affected organs, alterations in lipid metabolism and insulin resistance. Here we show that colonic epithelial cells and whole lung tissue from Cftr-deficient mice show a defect in peroxisome proliferator-activated receptor-gamma (PPAR-gamma, encoded by Pparg) function that contributes to a pathological program of gene expression. Lipidomic analysis of colonic epithelial cells suggests that this defect results in part from reduced amounts of the endogenous PPAR-gamma ligand 15-keto-prostaglandin E(2) (15-keto-PGE(2)). Treatment of Cftr-deficient mice with the synthetic PPAR-gamma ligand rosiglitazone partially normalizes the altered gene expression pattern associated with Cftr deficiency and reduces disease severity. Rosiglitazone has no effect on chloride secretion in the colon, but it increases expression of the genes encoding carbonic anhydrases 4 and 2 (Car4 and Car2), increases bicarbonate secretion and reduces mucus retention. These studies reveal a reversible defect in PPAR-gamma signaling in Cftr-deficient cells that can be pharmacologically corrected to ameliorate the severity of the cystic fibrosis phenotype in mice.

High Throughput Sequencing Identifies Misregulated Genes in the Drosophila Polypyrimidine Tract-Binding Protein (hephaestus) Mutant Defective in Spermatogenesis.

PubMed

Sridharan, Vinod; Heimiller, Joseph; Robida, Mark D; Singh, Ravinder

2016-01-01

The Drosophila polypyrimidine tract-binding protein (dmPTB or hephaestus) plays an important role during spermatogenesis. The heph2 mutation in this gene results in a specific defect in spermatogenesis, causing aberrant spermatid individualization and male sterility. However, the array of molecular defects in the mutant remains uncharacterized. Using an unbiased high throughput sequencing approach, we have identified transcripts that are misregulated in this mutant. Aberrant transcripts show altered expression levels, exon skipping, and alternative 5' ends. We independently verified these findings by reverse-transcription and polymerase chain reaction (RT-PCR) analysis. Our analysis shows misregulation of transcripts that have been connected to spermatogenesis, including components of the actomyosin cytoskeletal apparatus. We show, for example, that the Myosin light chain 1 (Mlc1) transcript is aberrantly spliced. Furthermore, bioinformatics analysis reveals that Mlc1 contains a high affinity binding site(s) for dmPTB and that the site is conserved in many Drosophila species. We discuss that Mlc1 and other components of the actomyosin cytoskeletal apparatus offer important molecular links between the loss of dmPTB function and the observed developmental defect in spermatogenesis. This study provides the first comprehensive list of genes misregulated in vivo in the heph2 mutant in Drosophila and offers insight into the role of dmPTB during spermatogenesis.

[Closure of wide patent ductus arteriosus using a fenestrated muscular VSD occluder device in a pediatric patient with Down syndrome and pulmonary hypertension].

PubMed

Güvenç, Osman; Saygı, Murat; Demir, İbrahim Halil; Ödemiş, Ender

2017-06-01

Patients with wide patent ductus arteriosus and significant pulmonary hypertension not treated in time constitute a significant problem for cardiologists. For these patients, tests that could aid in decision-making for further planning include reversibility and balloon occlusion tests performed in the catheterization laboratory. Devices developed for the closure of ductus as well as different devices with off-label use may be employed in patients scheduled for transcatheter occlusion. When result of reversibility test is borderline positive, the use of fenestrated device may be applicable for selected patients. Presently described is case of a 10-year-old patient with Down syndrome who had a wide ductus and systemic pulmonary hypertension. Transcatheter closure procedure was performed with off-label use of a fenestrated muscular ventricular septal defect occluder device.

Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations*

PubMed Central

Martin, Gregory M.; Rex, Emily A.; Devaraneni, Prasanna; Denton, Jerod S.; Boodhansingh, Kara E.; DeLeon, Diva D.; Stanley, Charles A.; Shyng, Show-Ling

2016-01-01

ATP-sensitive potassium (KATP) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by KATP channel openers. Cross-linking experiments showed that KATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the KATP channel opener diazoxide. Our study expands the list of KATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. PMID:27573238

Electrical characterisation of SiGe heterojunction bipolar transistors and Si pseudo-HBTS

NASA Astrophysics Data System (ADS)

De Barros, O.; Le Tron, B.; Woods, R. C.; Giroult-Matlakowski, G.; Vincent, G.; Brémond, G.

1996-08-01

This paper reports an electrical characterisation of the emitter-base junction of Si pseudo-HBTs and SiGe HBTs fabricated in a CMOS compatible single polysilicon self-aligned process. From the reverse characteristics it appears that the definition of the emitter-base junction by plasma etching induces peripheral defects that increase the base current of the transistors. Deep level transient spectroscopy measurements show a deep level in the case of SiGe base, whose spatial origin is not fully determinate up to now.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2015-10-01

practical examination of current methods,” J. Biomech., Oct. 2015. [8] R. J. Nesbitt, S . T. Herfat, D. V. Boguszewski, A . J. Engel, M . T. Galloway, and J... a Sheep Model 5b. GRANT NUMBER W81XWH-13-1-0324 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Christopher H. Evans, Ph.D. 5d. PROJECT NUMBER...interfragmentary movement ( IFM ) through the separated bone cortices (fracture gap). In research funded by a CDMRP Idea Development Award, we used a

Electric field-induced emission enhancement and modulation in individual CdSe nanowires.

PubMed

Vietmeyer, Felix; Tchelidze, Tamar; Tsou, Veronica; Janko, Boldizsar; Kuno, Masaru

2012-10-23

CdSe nanowires show reversible emission intensity enhancements when subjected to electric field strengths ranging from 5 to 22 MV/m. Under alternating positive and negative biases, emission intensity modulation depths of 14 ± 7% are observed. Individual wires are studied by placing them in parallel plate capacitor-like structures and monitoring their emission intensities via single nanostructure microscopy. Observed emission sensitivities are rationalized by the field-induced modulation of carrier detrapping rates from NW defect sites responsible for nonradiative relaxation processes. The exclusion of these states from subsequent photophysics leads to observed photoluminescence quantum yield enhancements. We quantitatively explain the phenomenon by developing a kinetic model to account for field-induced variations of carrier detrapping rates. The observed phenomenon allows direct visualization of trap state behavior in individual CdSe nanowires and represents a first step toward developing new optical techniques that can probe defects in low-dimensional materials.

Dynamic defect annealing in wurtzite MgZnO implanted with Ar ions

NASA Astrophysics Data System (ADS)

Azarov, A. Yu.; Wendler, E.; Du, X. L.; Kuznetsov, A. Yu.; Svensson, B. G.

2015-09-01

Successful implementation of ion beams for modification of ternary ZnO-based oxides requires understanding and control of radiation-induced defects. Here, we study structural disorder in wurtzite ZnO and MgxZn1-xO (x ⩽ 0.3) samples implanted at room and 15 K temperatures with Ar ions in a wide fluence range (5 × 1012-3 × 1016 cm-2). The samples were characterized by Rutherford backscattering/channeling spectrometry performed in-situ without changing the sample temperature. The results show that all the samples exhibit high radiation resistance and cannot be rendered amorphous even for high ion fluences. Increasing the Mg content leads to some damage enhancement near the surface region; however, irrespective of the Mg content, the fluence dependence of bulk damage in the samples displays the so-called IV-stage evolution with a reverse temperature effect for high ion fluences.

Au/n-InP Schottky diodes using an Al2O3 interfacial layer grown by atomic layer deposition

NASA Astrophysics Data System (ADS)

Kim, Hogyoung; Kim, Min Soo; Yoon, Seung Yu; Choi, Byung Joon

2017-02-01

We investigated the effect of an Al2O3 interfacial layer grown by atomic layer deposition on the electrical properties of Au Schottky contacts to n-type InP. Considering barrier inhomogeneity, modified Richardson plots yielded a Richardson constant of 8.4 and 7.5 Acm-2K-2, respectively, for the sample with and without the Al2O3 interlayer (theoretical value of 9.4 Acm-2K-2 for n-type InP). The dominant reverse current flow for the sample with an Al2O3 interlayer was found to be Poole-Frenkel emission. From capacitance-voltage measurements, it was observed that the capacitance for the sample without the Al2O3 interlayer was frequency dependent. Sputter-induced defects as well as structural defects were passivated effectively with an Al2O3 interlayer.

Photoluminescence quenching processes by NO2 adsorption in ZnO nanostructured films

NASA Astrophysics Data System (ADS)

Cretı, A.; Valerini, D.; Taurino, A.; Quaranta, F.; Lomascolo, M.; Rella, R.

2012-04-01

The optical response by NO2 gas adsorption at different concentrations has been investigated, at room temperature, in ZnO nanostructured films grown by controlled vapor phase deposition. The variation (quenching) in the photoluminescence signal from excitonic and defects bands, due to the interactions between the oxidizing gas molecules and the sample surface, has been detected and dynamic responses and calibration curves as a function of gas concentration have been obtained and analyzed for each band. We showed that the sensing response results larger in excitonic band than in defect one and that the emission signal rises from two different quenchable and unquenchable states. A simple model was proposed in order to explain the quenching processes on the emission intensity and to correlate them to the morphological features of the samples. Finally, the reversibility of the quenching effects has also been tested at high gas concentration.

Determination of bone and tissue concentrations of teicoplanin mixed with hydroxyapatite cement to repair cortical defects.

PubMed

Eggenreich, K; Zeipper, U; Schwendenwein, E; Hadju, S; Kaltenecker, G; Laslo, I; Lang, S; Roschger, P; Vecsei, V; Wintersteiger, R

2002-01-01

A highly specific and sensitive isocratic reversed-phase high performance liquid chromatography (HPLC) method for the determination of the major component of teicoplanin in tissue is reported. Comparing fluorescamine and o-phthalaldehyde (OPA) as derivatizing agents, the derivative formed with the latter exhibits superior fluorescence intensity allowing detection of femtomole quantities. Pretreatment for tissue samples is by solid-phase extraction which uses Bakerbond PolarP C(18) cartridges and gives effective clean up from endogenous by-products. Linearity was given from 0.6 to 100 ng per injection. The coefficient of variation did not exceed 5.8% for both interday and intraday assays. It was found that when bone defects are repaired with a hydroxyapatite-teicoplanin mixture, the antibiotic does not degrade, even when it is in the cement for several months. The stability of teicoplanin in bone cement was determined fluorodensitometrically.

The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

PubMed Central

Ziegler, Christopher M.; Eisenhauer, Philip; Bruce, Emily A.; Weir, Marion E.; King, Benjamin R.; Klaus, Joseph P.; Krementsov, Dimitry N.; Shirley, David J.; Ballif, Bryan A.; Botten, Jason

2016-01-01

Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation. PMID:27010636

Observation of self-excited acoustic vortices in defect-mediated dust acoustic wave turbulence.

PubMed

Tsai, Ya-Yi; I, Lin

2014-07-01

Using the self-excited dust acoustic wave as a platform, we demonstrate experimental observation of self-excited fluctuating acoustic vortex pairs with ± 1 topological charges through spontaneous waveform undulation in defect-mediated turbulence for three-dimensional traveling nonlinear longitudinal waves. The acoustic vortex pair has helical waveforms with opposite chirality around the low-density hole filament pair in xyt space (the xy plane is the plane normal to the wave propagation direction). It is generated through ruptures of sequential crest surfaces and reconnections with their trailing ruptured crest surfaces. The initial rupture is originated from the amplitude reduction induced by the formation of the kinked wave crest strip with strong stretching through the undulation instability. Increasing rupture causes the separation of the acoustic vortex pair after generation. A similar reverse process is followed for the acoustic vortex annihilating with the opposite-charged acoustic vortex from the same or another pair generation.

Enhancement of venous drainage with vein stripper for reversed pedicled neurocutaneous flaps.

PubMed

Sonmez, Erhan; Silistireli, Özlem Karataş; Karaaslan, Önder; Kamburoğlu, Haldun Onuralp; Safak, Tunc

2013-05-01

The flaps based on the vascular axis of superficial sensitive cutaneous nerves had gained increased popularity in reconstructive surgery because of such major advantages as preservation of major extremity arteries and avoidance of microsurgical procedures. However, postoperative venous congestion resulting in partial or total necrosis is still a common problem for these flaps. The aim of the current study is to introduce a new method for reducing the postoperative venous congestion of neural island flap with the results of reconstruction of the soft tissue defects of foot and ankle. This method was used to treat 19 patients with various chronic soft tissue defects of the foot and ankle between 2011 and 2012. We observed that the novel method presented in this report enables effective venous drainage, solving the postoperative venous congestion problem of these flaps. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

In situ spectroscopic study of the plastic deformation of amorphous silicon under non-hydrostatic conditions induced by indentation

PubMed Central

Gerbig, Y.B; Michaels, C.A.; Bradby, J.E.; Haberl, B.; Cook, R.F.

2016-01-01

Indentation-induced plastic deformation of amorphous silicon (a-Si) thin films was studied by in situ Raman imaging of the deformed contact region of an indented sample, employing a Raman spectroscopy-enhanced instrumented indentation technique. Quantitative analyses of the generated in situ Raman maps provide unique, new insight into the phase behavior of as-implanted a-Si. In particular, the occurrence and evolving spatial distribution of changes in the a-Si structure caused by processes, such as polyamorphization and crystallization, induced by indentation loading were measured. The experimental results are linked with previously published work on the plastic deformation of a-Si under hydrostatic compression and shear deformation to establish a sequence for the development of deformation of a-Si under indentation loading. The sequence involves three distinct deformation mechanisms of a-Si: (1) reversible deformation, (2) increase in coordination defects (onset of plastic deformation), and (3) phase transformation. Estimated conditions for the occurrence of these mechanisms are given with respect to relevant intrinsic and extrinsic parameters, such as indentation stress, volumetric strain, and bond angle distribution (a measure for the structural order of the amorphous network). The induced volumetric strains are accommodated solely by reversible deformation of the tetrahedral network when exposed to small indentation stresses. At greater indentation stresses, the increased volumetric strains in the tetrahedral network lead to the formation of predominately five-fold coordination defects, which seems to mark the onset of irreversible or plastic deformation of the a-Si thin film. Further increase in the indentation stress appears to initiate the formation of six-fold coordinated atomic arrangements. These six-fold coordinated arrangements may maintain their amorphous tetrahedral structure with a high density of coordination defects or nucleate as a new crystalline β-tin phase within the a-Si network. PMID:26924926

Poole-Frenkel effect on electrical characterization of Al-doped ZnO films deposited on p-type GaN

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

Huang, Bohr-Ran; Liao, Chung-Chi; Ke, Wen-Cheng, E-mail: wcke@saturn.yzu.edu.tw

2014-03-21

This paper presents the electrical properties of Al-doped ZnO (AZO) films directly grown on two types of p-type GaN thin films. The low-pressure p-GaN thin films (LP-p-GaN) exhibited structural properties of high-density edge-type threading dislocations (TDs) and compensated defects (i.e., nitrogen vacancy). Compared with high-pressure p-GaN thin films (HP-p-GaN), X-ray photoemission spectroscopy of Ga 3d core levels indicated that the surface Fermi-level shifted toward the higher binding-energy side by approximately 0.7 eV. The high-density edge-type TDs and compensated defects enabled surface Fermi-level shifting above the intrinsic Fermi-level, causing the surface of LP-p-GaN thin films to invert to n-type semiconductor. A highlymore » nonlinear increase in leakage current regarding reverse-bias voltage was observed for AZO/LP-p-GaN. The theoretical fits for the reverse-bias voltage region indicated that the field-assisted thermal ionization of carriers from defect associated traps, which is known as the Poole-Frenkel effect, dominated the I-V behavior of AZO/LP-p-GaN. The fitting result estimated the trap energy level at 0.62 eV below the conduction band edge. In addition, the optical band gap increased from 3.50 eV for as-deposited AZO films to 3.62 eV for 300 °C annealed AZO films because of the increased carrier concentration. The increasing Fermi-level of the 300 °C annealed AZO films enabled the carrier transport to move across the interface into the LP-p-GaN thin films without any thermal activated energy. Thus, the Ohmic behavior of AZO contact can be achieved directly on the low-pressure p-GaN films at room temperature.« less

Poole-Frenkel effect on electrical characterization of Al-doped ZnO films deposited on p-type GaN

NASA Astrophysics Data System (ADS)

Huang, Bohr-Ran; Liao, Chung-Chi; Ke, Wen-Cheng; Chang, Yuan-Ching; Huang, Hao-Ping; Chen, Nai-Chuan

2014-03-01

This paper presents the electrical properties of Al-doped ZnO (AZO) films directly grown on two types of p-type GaN thin films. The low-pressure p-GaN thin films (LP-p-GaN) exhibited structural properties of high-density edge-type threading dislocations (TDs) and compensated defects (i.e., nitrogen vacancy). Compared with high-pressure p-GaN thin films (HP-p-GaN), X-ray photoemission spectroscopy of Ga 3d core levels indicated that the surface Fermi-level shifted toward the higher binding-energy side by approximately 0.7 eV. The high-density edge-type TDs and compensated defects enabled surface Fermi-level shifting above the intrinsic Fermi-level, causing the surface of LP-p-GaN thin films to invert to n-type semiconductor. A highly nonlinear increase in leakage current regarding reverse-bias voltage was observed for AZO/LP-p-GaN. The theoretical fits for the reverse-bias voltage region indicated that the field-assisted thermal ionization of carriers from defect associated traps, which is known as the Poole-Frenkel effect, dominated the I-V behavior of AZO/LP-p-GaN. The fitting result estimated the trap energy level at 0.62 eV below the conduction band edge. In addition, the optical band gap increased from 3.50 eV for as-deposited AZO films to 3.62 eV for 300 °C annealed AZO films because of the increased carrier concentration. The increasing Fermi-level of the 300 °C annealed AZO films enabled the carrier transport to move across the interface into the LP-p-GaN thin films without any thermal activated energy. Thus, the Ohmic behavior of AZO contact can be achieved directly on the low-pressure p-GaN films at room temperature.

Irradiation-induced Ag nanocluster nucleation in silicate glasses: Analogy with photography

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

Espiau de Lamaestre, R.; Fontainebleau Research Center, Corning SA, 77210 Avon; Bea, H.

2007-11-15

The synthesis of Ag nanoclusters in soda lime silicate glasses and silica was studied by optical absorption and electron spin resonance experiments under both low (gamma ray) and high (MeV ion) deposited energy density irradiation conditions. Both types of irradiation create electrons and holes whose density and thermal evolution--notably via their interaction with defects--are shown to determine the clustering and growth rates of Ag nanocrystals. We thus establish the influence of redox interactions of defects and silver (poly)ions. The mechanisms are similar to the latent image formation in photography: Irradiation-induced photoelectrons are trapped within the glass matrix, notably on dissolvedmore » noble metal ions and defects, which are thus neutralized (reverse oxidation reactions are also shown to exist). Annealing promotes metal atom diffusion, which, in turn, leads to cluster nuclei formation. The cluster density depends not only on the irradiation fluence but also--and primarily--on the density of deposited energy and the redox properties of the glass. Ion irradiation (i.e., large deposited energy density) is far more effective in cluster formation, despite its lower neutralization efficiency (from Ag{sup +} to Ag{sup 0}) as compared to gamma photon irradiation.« less

A coverage and slicing dependencies analysis for seeking software security defects.

PubMed

He, Hui; Zhang, Dongyan; Liu, Min; Zhang, Weizhe; Gao, Dongmin

2014-01-01

Software security defects have a serious impact on the software quality and reliability. It is a major hidden danger for the operation of a system that a software system has some security flaws. When the scale of the software increases, its vulnerability has becoming much more difficult to find out. Once these vulnerabilities are exploited, it may lead to great loss. In this situation, the concept of Software Assurance is carried out by some experts. And the automated fault localization technique is a part of the research of Software Assurance. Currently, automated fault localization method includes coverage based fault localization (CBFL) and program slicing. Both of the methods have their own location advantages and defects. In this paper, we have put forward a new method, named Reverse Data Dependence Analysis Model, which integrates the two methods by analyzing the program structure. On this basis, we finally proposed a new automated fault localization method. This method not only is automation lossless but also changes the basic location unit into single sentence, which makes the location effect more accurate. Through several experiments, we proved that our method is more effective. Furthermore, we analyzed the effectiveness among these existing methods and different faults.

Metal–Organic Nanosheets Formed via Defect-Mediated Transformation of a Hafnium Metal–Organic Framework

PubMed Central

2017-01-01

We report a hafnium-containing MOF, hcp UiO-67(Hf), which is a ligand-deficient layered analogue of the face-centered cubic fcu UiO-67(Hf). hcp UiO-67 accommodates its lower ligand:metal ratio compared to fcu UiO-67 through a new structural mechanism: the formation of a condensed “double cluster” (Hf12O8(OH)14), analogous to the condensation of coordination polyhedra in oxide frameworks. In oxide frameworks, variable stoichiometry can lead to more complex defect structures, e.g., crystallographic shear planes or modules with differing compositions, which can be the source of further chemical reactivity; likewise, the layered hcp UiO-67 can react further to reversibly form a two-dimensional metal–organic framework, hxl UiO-67. Both three-dimensional hcp UiO-67 and two-dimensional hxl UiO-67 can be delaminated to form metal–organic nanosheets. Delamination of hcp UiO-67 occurs through the cleavage of strong hafnium-carboxylate bonds and is effected under mild conditions, suggesting that defect-ordered MOFs could be a productive route to porous two-dimensional materials. PMID:28343394

Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation.

PubMed

Vladar, Eszter K; Nayak, Jayakar V; Milla, Carlos E; Axelrod, Jeffrey D

2016-08-18

Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease.

In-field implementation of impedance-based structural health monitoring for insulated rail joints

NASA Astrophysics Data System (ADS)

Albakri, Mohammad I.; Malladi, V. V. N. Sriram; Woolard, Americo G.; Tarazaga, Pablo A.

2017-04-01

Track defects are a major safety concern for the railroad industry. Among different track components, insulated rail joints, which are widely used for signaling purposes, are considered a weak link in the railroad track. Several joint-related defects have been identified by the railroad community, including rail wear, torque loss, and joint bar breakage. Current track inspection techniques rely on manual and visual inspection or on specially equipped testing carts, which are costly, timeconsuming, traffic disturbing, and prone to human error. To overcome the aforementioned limitations, the feasibility of utilizing impedance-based structural health monitoring for insulated rail joints is investigated in this work. For this purpose, an insulated joint, provided by Koppers Inc., is instrumented with piezoelectric transducers and assembled with 136 AREA rail plugs. The instrumented joint is then installed and tested at the Facility for Accelerated Service Testing, Transportation Technology Center Inc. The effects of environmental and operating conditions on the measured impedance signatures are investigated through a set of experiments conducted at different temperatures and loading conditions. The capabilities of impedance-based SHM to detect several joint-related damage types are also studied by introducing reversible mechanical defects to different joint components.

Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres.

PubMed

Morrish, Tammy A; Garcia-Perez, José Luis; Stamato, Thomas D; Taccioli, Guillermo E; Sekiguchi, JoAnn; Moran, John V

2007-03-08

Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long-terminal-repeat (non-LTR) retrotransposons that comprise approximately 17% of human DNA. The average human genome contains approximately 80-100 retrotransposition-competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription. We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (EN(i)) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end-joining (NHEJ) pathway of DNA double-strand-break repair. Here we have characterized EN(i) retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, approximately 30% of EN(i) retrotransposition events insert in an orientation-specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among EN(i) retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 (also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated EN(i) retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of EN(i) retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends. Thus, we propose that EN(i) retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

PubMed Central

Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

The Application of a Homologous Recombination Assay Revealed Amino Acid Residues in an LTR-Retrotransposon That Were Critical for Integration

PubMed Central

Atwood, Angela; Choi, Jeannie; Levin, Henry L.

1998-01-01

Retroviruses and their relatives, the LTR-retrotransposons, possess an integrase protein (IN) that is required for the insertion of reverse transcripts into the genome of host cells. Schizosaccharomyces pombe is the host of Tf1, an LTR-retrotransposon with integration activity that can be studied by using techniques of yeast genetics. In this study, we sought to identify amino acid substitutions in Tf1 that specifically affected the integration step of transposition. In addition to seeking amino acid substitutions in IN, we also explored the possibility that other Tf1 proteins contributed to integration. By comparing the results of genetic assays that monitored both transposition and reverse transcription, we were able to seek point mutations throughout Tf1 that blocked transposition but not the synthesis of reverse transcripts. These mutant versions of Tf1 were candidates of elements that possessed defects in the integration step of transposition. Five mutations in Tf1 that resulted in low levels of integration were found to be located in the IN protein: two substitutions in the N-terminal Zn domain, two in the catalytic core, and one in the C-terminal domain. These results suggested that each of the three IN domains was required for Tf1 transposition. The potential role of these five amino acid residues in the function of IN is discussed. Two of the mutations that reduced integration mapped to the RNase H (RH) domain of Tf1 reverse transcriptase. The Tf1 elements with the RH mutations produced high levels of reverse transcripts, as determined by recombination and DNA blot analysis. These results indicated that the RH of Tf1 possesses a function critical for transposition that is independent of the accumulation of reverse transcripts. PMID:9445033

A study on fatigue strength reduction factor for small diameter socket welded pipe joints

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

Higuchi, Makoto; Nakagawa, Akira; Hayashi, Makoto

1996-12-01

Factors that may exert influence on the fatigue strength of small diameter socket welded joints of nominal diameter in the 20--50 mm range have been investigated by the fully reversed four-point bending fatigue test with the material, diameter, pipe schedule, throat depth, bead shape, slip-on gap, and root defect as the testing parameters. The fatigue strength of socket joints depended acutely on the diameter. When the diameter is large, the fatigue strength tended to be low and the fracture is of the root-failure mode; when it is small, on the other hand, the fatigue strength is high and the fracturemore » is of the toe-failure mode. Stainless steel proved to be superior to carbon steel; it gave rise to 1.37 times the fatigue strength of the latter for socket joints of nominal diameter 50 mm; the fatigue strength reduction factor determined at 10{sup 7} cycles with respect to the fatigue strength of smooth base metal in the fully reversed fatigue was about 4 for stainless steel and about 5 for carbon steel. The fatigue strength was higher, the larger the Sche number (i.e., the thicker the pipe wall); it was improved markedly by placing one final refinement pass on the toe or by eliminating the slip-on gap. An empirical formula relating the size of the root defect to the fatigue strength reduction has been proposed.« less

Homologous recombination between overlapping thymidine kinase gene fragments stably inserted into a mouse cell genome.

PubMed Central

Lin, F L; Sternberg, N

1984-01-01

We have constructed a substrate to study homologous recombination between adjacent segments of chromosomal DNA. This substrate, designated lambda tk2 , consists of one completely defective and one partially defective herpes simplex virus thymidine kinase (tk) gene cloned in bacteriophage lambda DNA. The two genes have homologous 984-base-pair sequences and are separated by 3 kilobases of largely vector DNA. When lambda tk2 DNA was transferred into mouse LMtk- cells by the calcium phosphate method, rare TK+ transformants were obtained that contained many (greater than 40) copies of the unrecombined DNA. Tk- revertants, which had lost most of the copies of unrecombined DNA, were isolated from these TK+-transformed lines. Two of these Tk- lines were further studied by analysis of their reversion back to the Tk+ phenotype. They generated ca. 200 Tk+ revertants per 10(8) cells after growth in nonselecting medium for 5 days. All of these Tk+ revertants have an intact tk gene reconstructed by homologous recombination; they also retain various amounts of unrecombined lambda tk2 DNA. Southern blot analysis suggested that at least some of the recombination events involve unequal sister chromatid exchanges. We also tested three agents, mitomycin C, 12-O-tetradecanoyl-phorbol-13-acetate, and mezerein, that are thought to stimulate recombination to determine whether they affect the reversion from Tk- to Tk+. Only mitomycin C increased the number of Tk+ revertants. Images PMID:6328272

Common and Specific Protein Accumulation Patterns in Different Albino/Pale-Green Mutants Reveals Regulon Organization at the Proteome Level1[W

PubMed Central

Motohashi, Reiko; Rödiger, Anja; Agne, Birgit; Baerenfaller, Katja; Baginsky, Sacha

2012-01-01

Research interest in proteomics is increasingly shifting toward the reverse genetic characterization of gene function at the proteome level. In plants, several distinct gene defects perturb photosynthetic capacity, resulting in the loss of chlorophyll and an albino or pale-green phenotype. Because photosynthesis is interconnected with the entire plant metabolism and its regulation, all albino plants share common characteristics that are determined by the switch from autotrophic to heterotrophic growth. Reverse genetic characterizations of such plants often cannot distinguish between specific consequences of a gene defect from generic effects in response to perturbations in photosynthetic capacity. Here, we set out to define common and specific features of protein accumulation in three different albino/pale-green plant lines. Using quantitative proteomics, we report a common molecular phenotype that connects the loss of photosynthetic capacity with other chloroplast and cellular functions, such as protein folding and stability, plastid protein import, and the expression of stress-related genes. Surprisingly, we do not find significant differences in the expression of key transcriptional regulators, suggesting that substantial regulation occurs at the posttranscriptional level. We examine the influence of different normalization schemes on the quantitative proteomics data and report all identified proteins along with their fold changes and P values in albino plants in comparison with the wild type. Our analysis provides initial guidance for the distinction between general and specific adaptations of the proteome in photosynthesis-impaired plants. PMID:23027667

Ion irradiation induced effects and magnetization reversal mechanism in (Ni80Fe20)1-xCox nanowires and nanotubes

NASA Astrophysics Data System (ADS)

Ahmad, Naeem; Iqbal, Javed; Chen, J. Y.; Hussain, Asim; Shi, D. W.; Han, X. F.

2015-03-01

The effect of Co on the ferromagnetic characteristics of the Ni80Fe20 nanocylinders having zero magnetostriction and soft magnetic nature is an interesting field of research. The (Ni80Fe20)1-xCox nanocylinders have been prepared by electrodeposition into commercially available anodized aluminum oxide (AAO) nanoporous templates. The analysis of magnetization reversal from the angular dependence of coercivity has been studied in detail. This angular dependence of coercivity has shown a transition from curling to nucleation mode as a function of field angle for all (Ni80Fe20)1-xCox nanocylinders depending upon the critical angle. The shape anisotropy, dipole-dipole interactions, surface effects and magnetocrystalline anisotropy have been found to play an effective role for the spontaneous magnetization in nanowires and nanotubes. It has been interestingly observed that the magnetostatic interactions or dipole-dipole interactions are dominant in nanocylinders regardless of its geometry. Furthermore, the prepared samples have been irradiated with He2+ ions (energy E=2 MeV, fluence=1014 ions/cm2 and ion current=16 nA) at room temperature using a 5-UDH-2pelletron tandem accelerator. The irradiations have created defects and these defects have induced changes in magnetization as a result an increase in coercivity as function of the ion fluences is observed. Such kind of behavior in coercivity enhancement and magnetization reduction can also be attributed to the stress relaxation and percolation in nonuniform states of ferromagnetic alloys, respectively.

Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

PubMed Central

Khawaja, Tuba; Greer, Christine; Thadani, Samir R.; Kato, Tomoko S.; Bhatia, Ketan; Shimbo, Daichi; Konkak, Andrew; Bokhari, Sabahat; Einstein, Andrew J.; Schulze, P. Christian

2015-01-01

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease. PMID:25339129

A comparison of interocular differences in patients with pigment dispersion syndrome.

PubMed

Yip, Leonard W; Sothornwit, Nisa; Berkowitz, Jonathan; Mikelberg, Frederick S

2009-01-01

Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are characterized by loss of iris pigment because of reverse pupillary block. The loss of iris pigment is manifested as transillumination defects. Differences in ocular anatomy have been found between subjects with PDS and controls. Our study aims to see if differences in interocular anatomic features are also related to differences in the quantity of transillumination defects between eyes. This is an observational case series of 30 eyes of 15 subjects with PDS/PG in at least 1 eye. Patients underwent refraction, exophthalmometry, corneal and anterior chamber analysis by Pentacam, biometry, A-scan, ultrasound biomicroscopy, and anterior segment digital photography. The Pentacam mean central radii of the posterior corneal surface (cornea back Rm), vertical central radius of curvature of the posterior corneal surface (cornea back Rv), and keratometric power deviation (influence of the posterior surface of the cornea on refractive power) were statistically different between eyes with greater pigment loss and eyes with lesser pigment loss. Eyes with greater pigment loss had a larger back radius of corneal curvature and a correspondingly numerically smaller keratometric power deviation. Other measurements of ocular anatomy were not statistically significant. A flatter curvature of the posterior corneal surface of the eye is associated with increased pigment loss in PDS and PG. The authors postulate that this could result in a difference in the biomechanical properties of the cornea, increased deformation with blinking, and a pumping action resulting in the reverse pupil block of PDS.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle.

PubMed

Chen, Zhong; Gallie, Daniel R

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle

PubMed Central

Chen, Zhong; Gallie, Daniel R.

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity. PMID:26630486

Mitochondrial DNA replication, nucleoside reverse-transcriptase inhibitors, and AIDS cardiomyopathy.

PubMed

Lewis, William

2003-01-01

Nucleoside reverse-transcriptase inhibitors (NRTIs) in combination with other antiretrovirals (HAART) are the cornerstones of current AIDS therapy, but extensive use brought mitochondrial side effects to light. Clinical experience, pharmacological, cell, and molecular biological evidence links altered mitochondrial (mt-) DNA replication to the toxicity of NRTIs in many tissues, and conversely, mtDNA replication defects and mtDNA depletion in target tissues are observed. Organ-specific pathological changes or diverse systemic effects result from and are frequently attributed to HAART in which NRTIs are included. The shared features of mtDNA depletion and energy depletion became key observations and related the clinical and in vivo experimental findings to inhibition of mtDNA replication by NRTI triphosphates in vitro. Subsequent to those findings, other observations suggested that mitochondrial energy deprivation is concomitant with or the result of mitochondrial oxidative stress in AIDS (from HIV, for example) or from NRTI therapy itself. Copyright 2003, Elsevier Science (USA)

Reversible MRI lesions after seizures.

PubMed

Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

1997-06-01

After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

Fast Risetime Reverse Bias Pulse Failures in SiC PN Junction Diodes

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Fazi, Christian; Parsons, James D.

1996-01-01

SiC-based high temperature power devices are being developed for aerospace systems which will require high reliability. One behavior crucial to power device reliability. To date, it has necessarily been assumed to date is that the breakdown behavior of SiC pn junctions will be similar to highly reliable silicon-based pn junctions. Challenging this assumption, we report the observation of anomalous unreliable reverse breakdown behavior in moderately doped (2-3 x 10(exp 17) cm(exp -3)) small-area 4H- and 6H-SiC pn junction diodes at temperatures ranging from 298 K (25 C) to 873 K (600 C). We propose a mechanism in which carrier emission from un-ionized dopants and deep level defects leads to this unstable behavior. The fundamental instability mechanism is applicable to all wide bandgap semiconductors whose dopants are significantly un-ionized at typical device operating temperatures.

Role of associated defects in oxygen ion conduction and surface exchange reaction for epitaxial samaria-doped ceria thin films as catalytic coatings

DOE PAGES

Yang, Nan; Shi, Yanuo; Schweiger, Sebastian; ...

2016-05-18

Samaria-doped ceria (SDC) thin films are particularly important for energy and electronic applications such as micro-solid oxide fuel cells, electrolysers, sensors and memristors. In this paper we report a comparative study investigating ionic conductivity and surface reactions for well-grown epitaxial SDC films varying the samaria doping concentration. With increasing doping above 20 mol% of samaria, an enhancement in the defect association was observed by Raman spectroscopy. The role of such defect associates on the films` oxygen ion transport and exchange was investigated by electrochemical impedance spectroscopy and electrochemical strain microscopy (ESM). The measurements reveal that the ionic transport has amore » sharp maximum in ionic conductivity and drop in its activation energy down to 0.6 eV for 20 mol% doping. Increasing the doping concentration further up to 40 mol%, raises the activation energy substantially by a factor of two. We ascribe the sluggish transport kinetics to the "bulk" ionic-near ordering in case of the heavily doped epitaxial films. Analysis of the ESM first order reversal curve measurements indicate that these associated defects may have a beneficial role by lowering the activation of the oxygen exchange "surface" reaction for heavily doped 40 mol% of samaria. We reveal in a model experiment through a solid solution series of samaria doped ceria epitaxial films that the occurrence of associate defects in the bulk affects the surface charging state of the films to increase the exchange rates. Lastly, the implication of these findings are the design of coatings with tuned oxygen surface exchange by control of bulk associate clusters for future electro-catalytic applications.« less

Cartilage repair and joint preservation: medical and surgical treatment options.

PubMed

Madry, Henning; Grün, Ulrich Wolfgang; Knutsen, Gunnar

2011-10-01

Articular cartilage defects are most often caused by trauma and osteoarthritis and less commonly by metabolic disorders of the subchondral bone, such as osteonecrosis and osteochondritis dissecans. Such defects do not heal spontaneously in adults and can lead to secondary osteoarthritis. Medications are indicated for symptomatic relief. Slow-acting drugs in osteoarthritis (SADOA), such as glucosamine and chondroitin, are thought to prevent cartilage degeneration. Reconstructive surgical treatment strategies aim to form a repair tissue or to unload compartments of the joint with articular cartilage damage. In this article, we selectively review the pertinent literature, focusing on original publications of the past 5 years and older standard texts. Particular attention is paid to guidelines and clinical studies with a high level of evidence, along with review articles, clinical trials, and book chapters. There have been only a few randomized trials of medical versus surgical treatments. Pharmacological therapies are now available that are intended to treat the cartilage defect per se, rather than the associated symptoms, yet none of them has yet been shown to slow or reverse the progression of cartilage destruction. Surgical débridement of cartilage does not prevent the progression of osteoarthritis and is thus not recommended as the sole treatment. Marrow-stimulating procedures and osteochondral grafts are indicated for small focal articular cartilage defects, while autologous chondrocyte implantationis mainly indicated for larger cartilage defects. These surgical reconstructive techniques play a lesser role in the treatment of osteoarthritis. Osteotomy near the knee joint is indicated for axial realignment when unilateral osteoarthritis of the knee causes axis deviation. Surgical reconstructive techniques can improve joint function and thereby postpone the need for replacement of the articular surface with an artificial joint.

Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.

PubMed

Chantarawaratit, P; Sangvanich, P; Banlunara, W; Soontornvipart, K; Thunyakitpisal, P

2014-04-01

Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate biomolecule for periodontal tissue regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations.

PubMed

Martin, Gregory M; Rex, Emily A; Devaraneni, Prasanna; Denton, Jerod S; Boodhansingh, Kara E; DeLeon, Diva D; Stanley, Charles A; Shyng, Show-Ling

2016-10-14

ATP-sensitive potassium (K ATP ) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of K ATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by K ATP channel openers. Cross-linking experiments showed that K ATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the K ATP channel opener diazoxide. Our study expands the list of K ATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection.

PubMed Central

Murray, H W; Hariprashad, J; McDermott, D F; Stoeckle, M Y

1996-01-01

Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection. A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact. New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy. Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration. While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted. Together, these observations suggest that the failure of PE mice to resolve visceral L. donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness. PMID:8557335

A PATO-compliant zebrafish screening database (MODB): management of morpholino knockdown screen information.

PubMed

Knowlton, Michelle N; Li, Tongbin; Ren, Yongliang; Bill, Brent R; Ellis, Lynda Bm; Ekker, Stephen C

2008-01-07

The zebrafish is a powerful model vertebrate amenable to high throughput in vivo genetic analyses. Examples include reverse genetic screens using morpholino knockdown, expression-based screening using enhancer trapping and forward genetic screening using transposon insertional mutagenesis. We have created a database to facilitate web-based distribution of data from such genetic studies. The MOrpholino DataBase is a MySQL relational database with an online, PHP interface. Multiple quality control levels allow differential access to data in raw and finished formats. MODBv1 includes sequence information relating to almost 800 morpholinos and their targets and phenotypic data regarding the dose effect of each morpholino (mortality, toxicity and defects). To improve the searchability of this database, we have incorporated a fixed-vocabulary defect ontology that allows for the organization of morpholino affects based on anatomical structure affected and defect produced. This also allows comparison between species utilizing Phenotypic Attribute Trait Ontology (PATO) designated terminology. MODB is also cross-linked with ZFIN, allowing full searches between the two databases. MODB offers users the ability to retrieve morpholino data by sequence of morpholino or target, name of target, anatomical structure affected and defect produced. MODB data can be used for functional genomic analysis of morpholino design to maximize efficacy and minimize toxicity. MODB also serves as a template for future sequence-based functional genetic screen databases, and it is currently being used as a model for the creation of a mutagenic insertional transposon database.

Effect of 10% sodium ascorbate on the calcium: Phosphorus ratio of enamel bleached with 35% hydrogen peroxide: an in vitro quantitative energy-dispersive X-ray analysis.

PubMed

Poorni, Saravanan; Kumar, R Anil; Shankar, P; Indira, Rajamani; Ramachandran, S

2010-10-01

The study assessed quantitatively the calcium and phosphorous loss from the enamel surface following bleaching with 35% hydrogen peroxide and reversal with 10% sodium ascorbate using energy-dispersive X-ray analysis (EDAX). Eight non-carious, freshly extracted human permanent maxillary central incisors without any visible defects were used. Each specimen was bleached with 35% hydrogen peroxide activated by light and reversed with sodium ascorbate antioxidant gel. The calcium and phosphorous content in weight percent of sound, bleached and reversed enamel was acquired using EDAX. The Ca/P ratio was calculated from the obtained data. One-way ANOVA followed by Post Hoc Tukey test was used for comparing the Ca/P ratio of sound, bleached and reversed enamel. All the samples subjected to bleaching using 35% hydrogen peroxide showed a statistically significant decrease in the Ca/P ratio as compared with samples in which no bleaching procedure was performed (P-value < 0.01). The striking finding was that there was a significant increase in the Ca/P ratio on application of sodium ascorbate antioxidant gel when compared with the bleached enamel (P-value < 0.01). The authors concluded that 35% hydrogen peroxide causes a significant decrease in the Ca/P ratio. This decrease in the Ca/P ratio can be restored by the application of 10% sodium ascorbate antioxidant gel.

Cardiovascular Pressures with Venous Gas Embolism and Decompression

NASA Technical Reports Server (NTRS)

Butler, B. D.; Robinson, R.; Sutton, T.; Kemper, G. B.

1995-01-01

Venous gas embolism (VGE) is reported with decompression to a decreased ambient pressure. With severe decompression, or in cases where an intracardiac septal defect (patent foramen ovale) exists, the venous bubbles can become arterialized and cause neurological decompression illness. Incidence rates of patent foramen ovale in the general population range from 25-34% and yet aviators, astronauts, and deepsea divers who have decompression-induced venous bubbles do not demonstrate neurological symptoms at these high rates. This apparent disparity may be attributable to the normal pressure gradient across the atria of the heart that must be reversed for there to be flow potency. We evaluated the effects of: venous gas embolism (0.025, 0.05 and 0.15 ml/ kg min for 180 min.) hyperbaric decompression; and hypobaric decompression on the pressure gradient across the left and right atria in anesthetized dogs with intact atrial septa. Left ventricular end-diastolic pressure was used as a measure of left atrial pressure. In a total of 92 experimental evaluations in 22 dogs, there were no reported reversals in the mean pressure gradient across the atria; a total of 3 transient reversals occurred during the peak pressure gradient changes. The reasons that decompression-induced venous bubbles do not consistently cause serious symptoms of decompression illness may be that the amount of venous gas does not always cause sufficient pressure reversal across a patent foramen ovale to cause arterialization of the venous bubbles.

A Long Terminal Repeat-Containing Retrotransposon of Schizosaccharomyces pombe Expresses a Gag-Like Protein That Assembles into Virus-Like Particles Which Mediate Reverse Transcription

PubMed Central

Teysset, Laure; Dang, Van-Dinh; Kim, Min Kyung; Levin, Henry L.

2003-01-01

The Tf1 element of Schizosaccharomyces pombe is a long terminal repeat-containing retrotransposon that encodes functional protease, reverse transcriptase, and integrase proteins. Although these proteins are known to be necessary for protein processing, reverse transcription, and integration, respectively, the function of the protein thought to be Gag has not been determined. We present here the first electron microscopy of Tf1 particles. We tested whether the putative Gag of Tf1 was required for particle formation, packaging of RNA, and reverse transcription. We generated deletions of 10 amino acids in each of the four hydrophilic domains of the protein and found that all four mutations reduced transposition activity. The N-terminal deletion removed a nuclear localization signal and inhibited nuclear import of the transposon. The two mutations in the center of Gag destabilized the protein and resulted in no virus-like particles. The C-terminal deletion caused a defect in RNA packaging and, as a result, low levels of cDNA. The electron microscopy of cells expressing a truncated Tf1 showed that Gag alone was sufficient for the formation of virus-like particles. Taken together, these results indicate that Tf1 encodes a Gag protein that is a functional equivalent of the Gag proteins of retroviruses. PMID:12692246

Damage imaging in a laminated composite plate using an air-coupled time reversal mirror

DOE PAGES

Le Bas, P. -Y.; Remillieux, M. C.; Pieczonka, L.; ...

2015-11-03

We demonstrate the possibility of selectively imaging the features of a barely visible impact damage in a laminated composite plate by using an air-coupled time reversal mirror. The mirror consists of a number of piezoelectric transducers affixed to wedges of power law profiles, which act as unconventional matching layers. The transducers are enclosed in a hollow reverberant cavity with an opening to allow progressive emission of the ultrasonic wave field towards the composite plate. The principle of time reversal is used to focus elastic waves at each point of a scanning grid spanning the surface of the plate, thus allowingmore » localized inspection at each of these points. The proposed device and signal processing removes the need to be in direct contact with the plate and reveals the same features as vibrothermography and more features than a C-scan. More importantly, this device can decouple the features of the defect according to their orientation, by selectively focusing vector components of motion into the object, through air. For instance, a delamination can be imaged in one experiment using out-of-plane focusing, whereas a crack can be imaged in a separate experiment using in-plane focusing. As a result, this capability, inherited from the principle of time reversal, cannot be found in conventional air-coupled transducers.« less

IGF-1 and insulin as growth hormones.

PubMed

Laron, Zvi

2004-01-01

IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

PubMed Central

Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

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

St. Denny, I.H.; Glinka, K.G.; Nemecek, G.M.

1987-05-01

Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected bymore » 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.« less

Bioactive peptides derived from natural proteins with respect to diversity of their receptors and physiological effects.

PubMed

Yoshikawa, Masaaki

2015-10-01

We have found various bioactive peptides derived from animal and plant proteins, which interact with receptors for endogenous bioactive peptides such as opioids, neurotensin, complements C3a and C5a, oxytocin, and formyl peptides etc. Among them, rubiscolin, a δ opioid peptide derived from plant RuBisCO, showed memory-consolidating, anxiolytic-like, and food intake-modulating effects. Soymorphin, a μ opioid peptide derived from β-conglycinin showed anxiolytic-like, anorexigenic, hypoglycemic, and hypotriglyceridemic effects. β-Lactotensin derived from β-lactoglobulin, the first natural ligand for the NTS2 receptor, showed memory-consolidating, anxiolytic-like, and hypocholesterolemic effects. Weak agonist peptides for the complements C3a and C5a receptors were released from many proteins and exerted various central effects. Peptides showing anxiolytic-like antihypertensive and anti-alopecia effects via different types of receptors such as OT, FPR and AT2 were also obtained. Based on these study, new functions and post-receptor mechanisms of receptor commom to endogenous and exogenous bioactive peptides have been clarified. Copyright © 2015 Elsevier Inc. All rights reserved.

E-waste management and sustainability: a case study in Brazil.

PubMed

Azevedo, Luís Peres; da Silva Araújo, Fernando Gabriel; Lagarinhos, Carlos Alberto Ferreira; Tenório, Jorge Alberto Soares; Espinosa, Denise Crocce Romano

2017-11-01

The advancement of technology and development of new electronic and electrical equipment with a reduced life cycle has increased the need for the disposal of them (called Waste of Electric and Electronic Equipment or simply e-waste) due to defects presented during use, replacement of obsolete equipment, and ease of acquisition of new equipment. There is a lack of consumer awareness regarding the use, handling storage, and disposal of this equipment. In Brazil, the disposal of post-consumer waste is regulated by the National Solid Waste Policy, established by Law No. 12305 and regulated on the 23rd December 2010. Under this legislation, manufacturers and importers are required to perform a project for the Reverse Logistics of e-waste, though its implementation is not well defined. This work focuses on the verification of the sustainability of reverse logistics suggested by the legislation and the mandatory points, evaluating its costs and the possible financial gain with recycling of the waste. The management of reverse logistics and recycling of waste electrical and electronic equipment, or simply recycling of e-waste, as suggested by the government, will be the responsibility of the managing organization to be formed by the manufacturers/importers in Brazil.

Casein Kinase 2 Reverses Tail-Independent Inactivation of Kinesin-1

NASA Astrophysics Data System (ADS)

Xu, Jing

2013-03-01

Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-based transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a head-tail interaction, but is believed to be active otherwise. Here we report a tail-independent inactivation of kinesin, reversible by the disease-relevant signalling protein, casein kinase 2 (CK2). The majority of initially active kinesin (native or tail-less) loses its ability to interact with microtubules in vitro, and CK2 reverses this inactivation (approximately fourfold) without altering kinesin's single motor properties. This activation pathway does not require motor phosphorylation, and is independent of head-tail auto-inhibition. In cultured mammalian cells, reducing CK2 expression, but not its kinase activity, decreases the force required to stall lipid droplet transport, consistent with a decreased number of active kinesin motors. Our results (Nat. Commun., 3:754, 2012) provide the first direct evidence of a protein kinase upregulating kinesin-based transport, and suggest a novel pathway for regulating the activity of cargo-bound kinesin. Work supported by NIGMS grants GM64624 to SPG, GM74830-06A1 to LH, GM76516 to LB, NS048501 to SJK, and AHA grant 825278F to JX.

Correlation of pattern reversal visual evoked potential parameters with the pattern standard deviation in primary open angle glaucoma.

PubMed

Kothari, Ruchi; Bokariya, Pradeep; Singh, Ramji; Singh, Smita; Narang, Purvasha

2014-01-01

To evaluate whether glaucomatous visual field defect particularly the pattern standard deviation (PSD) of Humphrey visual field could be associated with visual evoked potential (VEP) parameters of patients having primary open angle glaucoma (POAG). Visual field by Humphrey perimetry and simultaneous recordings of pattern reversal visual evoked potential (PRVEP) were assessed in 100 patients with POAG. The stimulus configuration for VEP recordings consisted of the transient pattern reversal method in which a black and white checker board pattern was generated (full field) and displayed on VEP monitor (colour 14″) by an electronic pattern regenerator inbuilt in an evoked potential recorder (RMS EMG EP MARK II). The results of our study indicate that there is a highly significant (P<0.001) negative correlation of P100 amplitude and a statistically significant (P<0.05) positive correlation of N70 latency, P100 latency and N155 latency with the PSD of Humphrey visual field in the subjects of POAG in various age groups as evaluated by Student's t-test. Prolongation of VEP latencies were mirrored by a corresponding increase of PSD values. Conversely, as PSD increases the magnitude of VEP excursions were found to be diminished.

Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes

PubMed Central

Dong, Tao; He, Jing; Wang, Shiqing; Wang, Lianzhang; Cheng, Yuqi; Zhong, Yi

2016-01-01

The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes. PMID:27335463

Electroluminescence from metal-oxide-semiconductor devices with erbium-doped CeO{sub 2} films on silicon

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

Lv, Chunyan; Department of Chemistry, Huzhou University, Zhejiang, Huzhou 313000; Zhu, Chen

2015-04-06

We report on erbium (Er)-related electroluminescence (EL) in the visible and near-infrared (NIR) from metal-oxide-semiconductor (MOS) devices with Er-doped CeO{sub 2} (CeO{sub 2}:Er) films on silicon. The onset voltage of such EL under either forward or reverse bias is smaller than 10 V. Moreover, the EL quenching can be avoidable for the CeO{sub 2}:Er-based MOS devices. Analysis on the current-voltage characteristic of the device indicates that the electron transportation at the EL-enabling voltages under either forward or reverse bias is dominated by trap-assisted tunneling mechanism. Namely, electrons in n{sup +}-Si/ITO can tunnel into the conduction band of CeO{sub 2} host viamore » defect states at sufficiently high forward/reverse bias voltages. Then, a fraction of such electrons are accelerated by electric field to become hot electrons, which impact-excite the Er{sup 3+} ions, thus leading to characteristic emissions. It is believed that this work has laid the foundation for developing viable silicon-based emitters using CeO{sub 2}:Er films.« less

Percutaneous fetoscopic closure of large open spina bifida using a bilaminar skin substitute.

PubMed

Lapa Pedreira, Denise A; Acacio, Gregório L; Gonçalves, Rodrigo T; Sá, Renato Augusto M; Brandt, Reynaldo A; Chmait, Ramen; Kontopoulos, Eftichia; Quintero, Ruben A

2018-01-04

We have previously described our percutaneous fetoscopic technique for the treatment of open spina bifida (OSB). However, approximately 20-30% of OSB defects are too large to allow primary skin closure. We hereby describe a modification of our standard technique using a bilaminar skin substitute to allow closure of such large spinal defects. The aim of this study was to report our clinical experience with the use of a bilaminar skin substitute and a percutaneous fetoscopic technique for the prenatal closure of large spina bifida defects. Surgeries were performed between 24.0 and 28.9 gestational weeks under general anesthesia, using an entirely percutaneous fetoscopic approach with partial CO2 insufflation of the uterine cavity, as previously described. If there was enough skin to be sutured in the midline, only a biocellulose patch was placed over the placode. In cases where skin approximation was not possible, a bilaminar skin substitute (two layers: one silicone and one dermal matrix) was placed over the biocellulose. The surgical site was assessed at birth, and long-term follow-up was performed. Forty-seven consecutive fetuses underwent percutaneous fetoscopic OSB repair. Premature preterm rupture of membranes (PPROM) occurred in 38 (84%), and the mean gestational age at delivery was 32,8 + 2.5 weeks. A bilaminar skin substitute was required in 13 (29%), of which 5 was associated with myeloschisis. In all cases the skin substitute was found at the surgical site, at birth. In 3 (15%) of these cases, postnatal additional repair was needed. In the other 10 cases, the silicone layer detached spontaneously from the dermal matrix (average 25 days after birth), and the lesion healed by secondary-intention. Operating time was significantly longer in cases requiring the bilaminar skin substitute (additional 42 minutes). The subgroup with bilaminar skin substitute had similar PPROM rate and delivery gestational age compared to the one patch group. Complete reversal of hindbrain herniation occurred in 68% of the one patch and in 33% (p < 0.05) of the two patches group. In 4 cases there was no reversal and 3 of them were myeloschisis cases. Large OSB defects may be successfully treated in utero using a bilaminar skin substitute over a biocellulose patch through an entirely percutaneous approach. Although the operating time is longer, surgical outcomes are similar to cases closed primarily. Myeloschisis seems to have a worse prognosis then myelomeningocele cases. PPROM and preterm birth continue to be a challenge. Further experience is needed to assess the risks and benefits of this technique for management of large OSB defects. This article is protected by copyright. All rights reserved.

Treatment of The Posterior Unstable Shoulder

PubMed Central

Alepuz, Eduardo Sánchez

2017-01-01

Background: It is estimated that approximately 5% of glenohumeral instabilities are posterior. There are a number of controversies regarding therapeutic approaches for these patients. Methods: We analyse the main surgery alternatives for the treatment of the posterior shoulder instability. We did a research of the publications related with posterior glenohumeral instability. Results: There are conservative and surgical treatment options. Conservative treatment has positive results in most patients, with around 65 to 80% of cases showing recurrent posterior dislocation. There are multiple surgical techniques, both open and arthroscopic, for the treatment of posterior glenohumeral instability. There are procedures that aim to repair bone defects and others that aim to repair soft tissues and capsulolabral injuries. The treatment should be planned according to each case on an individual basis according to the patient characteristics and the injury type. Surgical treatment is indicated in patients with functional limitations arising from instability and/or pain that have not improved with rehabilitation treatment. The indications for arthroscopic treatment are recurrent posterior subluxation caused by injury of the labrum or the capsulolabral complex; recurrent posterior subluxation caused by capsuloligamentous laxity or capsular redundancy; and multidirectional instability with posterior instability as a primary component. Arthroscopic assessment will help identify potential injuries associated with posterior instability such as bone lesions or defects and lesions or defects of soft tissues. The main indications for open surgery would be in cases of Hill Sachs lesions or broad reverse Bankart lesions not accessible by arthroscopy. We indicated non-anatomical techniques (McLaughlin or its modifications) for reverse Hill-Sachs lesions with impairment of the articular surface between 20% and 50%. Disimpaction of the fracture and placement of bone graft (allograft or autograft) is a suitable treatment for acute lesions that do not exceed 50% of the articular surface and with articular cartilage in good condition. Reconstruction with allograft may be useful in lesions affecting up to 50% of the humeral surface and should be considered when there is a situation of non-viable cartilage at the fracture site. For defects greater than 50% of the articular surface or in the case of dislocations over 6 months in duration where there is poor bone quality, some authors advocate substitution techniques as a treatment of choice. The main techniques for treating glenoid bone defects are posterior bone block and posterior opening osteotomy of the glenoid. Conclusions: The treatment of the posterior glenohumeral instability has to be individualized based on the patient´s injuries, medical history, clinical exam and goals. The most important complications in the treatment of posterior glenohumeral instability are recurrent instability, avascular necrosis and osteoarthritis. PMID:28979596

2017 NEPP Tasks Update for Ceramic and Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander A.

2017-01-01

This presentation gives an overview of current NEPP tasks on ceramic and tantalum capacitors and plans for the future. It includes tasks on leakage currents, gas generation and case deformation in wet tantalum capacitors; ESR degradation and acceleration factors in MnO2 and polymer cathode capacitors. Preliminary results on the effect of moisture on degradation of reverse currents in MnO2 tantalum capacitors are discussed. Latest results on mechanical characteristics of MLCCs and modeling of degradation of leakage currents in BME capacitors with defects are also presented.

Positronics of radiation-induced effects in chalcogenide glassy semiconductors

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

Shpotyuk, O.; Kozyukhin, S. A., E-mail: sergkoz@igic.ras.ru; Shpotyuk, M.

2015-03-15

Using As{sub 2}S{sub 3} and AsS{sub 2} glasses as an example, the principal possibility of using positron annihilation spectroscopy methods for studying the evolution of the free volume of hollow nanoobjects in chalcogenide glassy semiconductors exposed to radiation is shown. The results obtained by measurements of the positron annihilation lifetime and Doppler broadening of the annihilation line in reverse chronological order are in full agreement with the optical spectroscopy data in the region of the fundamental absorption edge, being adequately described within coordination defect-formation and physical-aging models.

Analysis of a retrieved delta III total shoulder prosthesis.

PubMed

Nyffeler, R W; Werner, C M L; Simmen, B R; Gerber, C

2004-11-01

A reversed Delta III total shoulder prosthesis was retrieved post-mortem, eight months after implantation. A significant notch was evident at the inferior pole of the scapular neck which extended beyond the inferior fixation screw. This bone loss was associated with a corresponding, erosive defect of the polyethylene cup. Histological examination revealed a chronic foreign-body reaction in the joint capsule. There were, however, no histological signs of loosening of the glenoid base plate and the stability of the prosthetic articulation was only slightly reduced by the eroded rim of the cup.

Quantum random walks on congested lattices and the effect of dephasing.

PubMed

Motes, Keith R; Gilchrist, Alexei; Rohde, Peter P

2016-01-27

We consider quantum random walks on congested lattices and contrast them to classical random walks. Congestion is modelled on lattices that contain static defects which reverse the walker's direction. We implement a dephasing process after each step which allows us to smoothly interpolate between classical and quantum random walks as well as study the effect of dephasing on the quantum walk. Our key results show that a quantum walker escapes a finite boundary dramatically faster than a classical walker and that this advantage remains in the presence of heavily congested lattices.

Effects induced by high and low intensity laser plasma on SiC Schottky detectors

NASA Astrophysics Data System (ADS)

Sciuto, Antonella; Torrisi, Lorenzo; Cannavò, Antonino; Mazzillo, Massimo; Calcagno, Lucia

2018-01-01

Silicon-Carbide detectors are extensively employed as diagnostic devices in laser-generated plasma, allowing the simultaneous detection of photons, electrons and ions, when used in time-of-flight configuration. The plasma generated by high intensity laser (1016 W/cm2) producing high energy ions was characterized by SiC detector with a continuous front-electrode, and a very thick active depth, while SiC detector with an Interdigit front-electrode was used to measure the low energy ions of plasma generated by low intensity laser (1010 W/cm2). Information about ion energy, number of charge states, plasma temperature can be accurately obtained. However, laser exposure induces the formation of surface and bulk defects whose concentration increases with increasing the time to plasma exposure. The surface defects consist of clusters with a main size of the order of some microns and they modify the diode barrier height and the efficiency of the detector as checked by alpha spectrometry. The bulk defects, due to the energy loss of detected ions, strongly affect the electrical properties of the device, inducing a relevant increase of the leakage (reverse) current and decrease the forward current related to a deactivation of the dopant in the active detector region.

Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

PubMed Central

Muldoon, L. L.; Neuwelt, E. A.; Pagel, M. A.; Weiss, D. L.

1994-01-01

The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8178934

Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).

PubMed

Muldoon, L L; Neuwelt, E A; Pagel, M A; Weiss, D L

1994-05-01

The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy.

Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E.

PubMed

Baumgartner, Matthias R

2013-01-01

The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

PubMed Central

Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

2016-01-01

Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

PubMed

Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

2009-04-23

We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Development of an airway mucus defect in the cystic fibrosis rat

PubMed Central

Birket, Susan E.; Davis, Joy M.; Fernandez, Courtney M.; Tuggle, Katherine L.; Oden, Ashley M.; Chu, Kengyeh K.; Tearney, Guillermo J.; Fanucchi, Michelle V.; Sorscher, Eric J.

2018-01-01

The mechanisms underlying the development and natural progression of the airway mucus defect in cystic fibrosis (CF) remain largely unclear. New animal models of CF, coupled with imaging using micro-optical coherence tomography, can lead to insights regarding these questions. The Cftr–/– (KO) rat allows for longitudinal examination of the development and progression of airway mucus abnormalities. The KO rat exhibits decreased periciliary depth, hyperacidic pH, and increased mucus solid content percentage; however, the transport rates and viscoelastic properties of the mucus are unaffected until the KO rat ages. Airway submucosal gland hypertrophy develops in the KO rat by 6 months of age. Only then does it induce increased mucus viscosity, collapse of the periciliary layer, and delayed mucociliary transport; stimulation of gland secretion potentiates this evolution. These findings could be reversed by bicarbonate repletion but not pH correction without counterion donation. These studies demonstrate that abnormal surface epithelium in CF does not cause delayed mucus transport in the absence of functional gland secretions. Furthermore, abnormal bicarbonate transport represents a specific target for restoring mucus clearance, independent of effects on periciliary collapse. Thus, mature airway secretions are required to manifest the CF defect primed by airway dehydration and bicarbonate deficiency. PMID:29321377

Hydrogen Passivation of Interstitial Zn Defects in Heteroepitaxial InP Cell Structures and Influence on Device Characteristics

NASA Technical Reports Server (NTRS)

Ringel, S. A.; Chatterjee, B.

2004-01-01

Hydrogen passivation of heteroepitaxial InP solar cells is of recent interest for deactivation of dislocations and other defects caused by the cell/substrate lattice mismatch that currently limit the photovoltaic performance of these devices. In this paper we present strong evidence that, in addition to direct hydrogen-dislocation interactions, hydrogen forms complexes with the high concentration of interstitial Zn defects present within the p(+) Zn-doped emitter of MOCVD-grown heteroepitaxial InP devices, resulting in a dramatic increase of the forward bias turn-on voltage by as much as 280 mV, from 680 mV to 960 mV. This shift is reproducible and thermally reversible and no such effect is observed for either n(+)p structures or homoepitaxial p(+)n structures grown under identical conditions. A combination of photoluminescence (PL), electrochemical C-V dopant profiling, SIMS and I-V measurements were performed on a set of samples having undergone a matrix of hydrogenation and post-hydrogenation annealing conditions to investigate the source of this voltage enhancement and confirm the expected role of interstitial Zn and hydrogen. A precise correlation between all measurements is demonstrated which indicates that Zn interstitials within the p(+) emitter and their interaction with hydrogen are indeed responsible for this device behavior.

Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription through Interaction with Its Integrase Protein

PubMed Central

Jayappa, Kallesh Danappa; Ao, Zhujun; Wang, Xiaoxia; Mouland, Andrew J.; Shekhar, Sudhanshu; Yang, Xi

2015-01-01

ABSTRACT In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs 52GQVD and 250VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1INQ53A/Q252A) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1INQ53A/Q252A mutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1. IMPORTANCE Host cellular DYNLL1, DYNLT1, and p150Glued proteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral replication steps. PMID:25568209

iPSC-derived cardiomyocytes reveal abnormal TGFβ signaling in left ventricular non-compaction cardiomyopathy

PubMed Central

Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D.; Shukla, Praveen; Abilez, Oscar J.; Churko, Jared M.; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M.; Snyder, Michael P.; Bernstein, Daniel; Wu, Joseph C.

2016-01-01

Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC. PMID:27642787

Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis

PubMed Central

Ngo, Lisa Y.; Kasahara, Shinji; Kumasaka, Debra K.; Knoblaugh, Sue E.; Jhingran, Anupam; Hohl, Tobias M.

2014-01-01

Candida albicans is a commensal fungus that can cause systemic disease in patients with breaches in mucosal integrity, indwelling catheters, and defects in phagocyte function. Although circulating human and murine monocytes bind C. albicans and promote inflammation, it remains unclear whether C-C chemokine receptor 2 (CCR2)– and Ly6C-expressing inflammatory monocytes exert a protective or a deleterious function during systemic infection. During murine systemic candidiasis, interruption of CCR2-dependent inflammatory monocyte trafficking into infected kidneys impaired fungal clearance and decreased murine survival. Depletion of CCR2-expressing cells led to uncontrolled fungal growth in the kidneys and brain and demonstrated an essential antifungal role for inflammatory monocytes and their tissue-resident derivatives in the first 48 hours postinfection. Adoptive transfer of purified inflammatory monocytes in depleted hosts reversed the defect in fungal clearance to a substantial extent, indicating a compartmentally and temporally restricted protective function that can be transferred to enhance systemic innate antifungal immunity. PMID:23922372

Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication

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

Cullen, M.R.; Kayne, R.D.; Robins, J.M.

In an attempt to define a postulated effect of lead on male endocrine function, seven men with symptomatic occupational lead intoxication (maximum whole blood lead levels 66-139 ..mu..g/dl) underwent in-patient endocrine evaluation at the time of diagnosis. Defects in thyroid function probably of central origin, were present in three patients. Six patients had subnormal glucocorticoid production measured by 24-hr urinary 17-hydroxy-corticosteroids and plasma cortisol responses to vasopressin- and/or insulin-induced hypoglycemia. Although serum testosterone concentration was normal in six patients, five had defects in spermatogenesis, including two with ologospermia and two with azoospermia. Repeat examinations after chelation therapy showed only partialmore » improvement. It is concluded that heavy occupational exposure to lead, sufficient to cause clinical poisoning, may be associated with diffuse disturbances of endocrine and reproductive functions in men which are not rapidly reversible with standard treatment. Since men without overt poisoning have not been studied, these results cannot yet be included as sequelae of low-dose exposures.« less

Characterization of Cytokinetic Mutants Using Small Fluorescent Probes.

PubMed

Smertenko, Andrei; Moschou, Panagiotis; Zhang, Laining; Fahy, Deirdre; Bozhkov, Peter

2016-01-01

Cytokinesis is a powerful paradigm for addressing fundamental questions of plant biology including molecular mechanisms of development, cell division, cell signaling, membrane trafficking, cell wall synthesis, and cytoskeletal dynamics. Genetics was instrumental in identification of proteins regulating cytokinesis. Characterization of mutant lines generated using forward or reverse genetics includes microscopic analysis for defects in cell division. Typically, failure of cytokinesis results in appearance of multinucleate cells, formation of cell wall stubs, and isotropic cell expansion in the root elongation zone. Small fluorescent probes served as a very effective tool for the detection of cytokinetic defects. Such probes stain living or formaldehyde-fixed specimens avoiding complex preparatory steps. Although resolution of the fluorescence probes is inferior to electron microscopy, the procedure is fast, easy, and does not require expensive materials or equipment. This chapter describes techniques for staining DNA with the probes DAPI and SYTO82, for staining membranes with FM4-64, and for staining cell wall with propidium iodide.

Origin of phase transition in VO2

NASA Astrophysics Data System (ADS)

Basu, Raktima; Sardar, Manas; Dhara, Sandip

2018-04-01

Vanadium dioxide (VO2) exhibits a reversible first-order metal to insulator transition (MIT) along with a structural phase transition (SPT) from monoclinic M1 to rutile tetragonal R via another two intermediate phases of monoclinic M2 and triclinic T at a technologically important temperature of 340K. In the present work, besides synthesizing M1 phase of VO2, we also stabilized M2 and T phases at room temperature by introducing native defects in the system and observed an increase in transition temperature with increase in native defects. Raman spectroscopic measurements were carried out to confirm the pure VO2 phases. Since the MIT is accompanied by SPT in these systems, the origin of the phase transition is still under debate. The controversy between MIT and SPT, whether electron-phonon coupling or strong electron-electron correlation triggers the phase transition in VO2 is also resolved by examining the presence of intermediate phase M2 during phase transition.

Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

PubMed

Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

2015-07-21

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria

PubMed Central

Hsu, FoSheng; Spannl, Stephanie; Ferguson, Charles; Hyman, Anthony A; Parton, Robert G

2018-01-01

Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. Thus, it is fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosomal contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to mitochondria upon oxidative stress. This process is reversible and accompanied by an increase in Rab5-positive endosomes in contact with mitochondria. Interestingly, activation of Rab5 on mitochondria depends on the Rab5-GEF ALS2/Alsin, encoded by a gene mutated in amyotrophic lateral sclerosis (ALS). Alsin-deficient human-induced pluripotent stem cell-derived spinal motor neurons are defective in relocating Rab5 to mitochondria and display increased susceptibility to oxidative stress. These findings define a novel pathway whereby Alsin catalyzes the assembly of the Rab5 endocytic machinery on mitochondria. Defects in stress-sensing by endosomes could be crucial for mitochondrial quality control during the onset of ALS. PMID:29469808

Additively manufactured sub-periosteal jaw implants.

PubMed

Mommaerts, M Y

2017-07-01

Severe bone atrophy jeopardizes the success of endosseous implants. This technical note aims to present the innovative concept of additively manufactured sub-periosteal jaw implants (AMSJIs). Digital datasets of the patient's jaws and wax trial in occlusion are used to segment the bone and dental arches, for the design of a sub-periosteal frame and abutments in the optimal location related to the dental arch and for the design of the suprastructure. The implants and suprastructure are three-dimensionally (3D) printed in titanium alloy. The provisional denture is 3D-printed in polymer. AMSJIs offer an alternative approach for patients with extreme jaw bone atrophy. This report refers to the use of this technique for full maxillary rehabilitation, but partial defects in either jaw and extended post-resection defects may also be approached using the same technique. This customized, prosthesis-driven reverse-engineering approach avoids bone grafting and provides immediate functional restoration with one surgical session. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

PubMed Central

Salomon, Julie; Gaston, Cécile; Magescas, Jérémy; Duvauchelle, Boris; Canioni, Danielle; Sengmanivong, Lucie; Mayeux, Adeline; Michaux, Grégoire; Campeotto, Florence; Lemale, Julie; Viala, Jérôme; Poirier, Françoise; Minc, Nicolas; Schmitz, Jacques; Brousse, Nicole; Ladoux, Benoit; Goulet, Olivier; Delacour, Delphine

2017-01-01

Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture. PMID:28084299

Aqueous proton transfer across single-layer graphene

DOE PAGES

Achtyl, Jennifer L.; Unocic, Raymond R.; Xu, Lijun; ...

2015-03-17

Proton transfer across single-layer graphene proceeds with large computed energy barriers and is thought to be unfavourable at room temperature unless nanoscale holes or dopants are introduced, or a potential bias is applied. Here we subject single-layer graphene supported on fused ​silica to cycles of high and low pH, and show that protons transfer reversibly from the aqueous phase through the graphene to the other side where they undergo acid–base chemistry with the silica hydroxyl groups. After ruling out diffusion through macroscopic pinholes, the protons are found to transfer through rare, naturally occurring atomic defects. Computer simulations reveal low energymore » barriers of 0.61–0.75 eV for aqueous proton transfer across hydroxyl-terminated atomic defects that participate in a Grotthuss-type relay, while ​pyrylium-like ether terminations shut down proton exchange. In conclusion, unfavourable energy barriers to helium and ​hydrogen transfer indicate the process is selective for aqueous protons.« less

Cancer-associated Isocitrate Dehydrogenase Mutations Inactivate NADPH-dependent Reductive Carboxylation*

PubMed Central

Leonardi, Roberta; Subramanian, Chitra; Jackowski, Suzanne; Rock, Charles O.

2012-01-01

Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP+-dependent oxidative decarboxylation of isocitrate (ICT) to α-ketoglutarate (αKG) and the NADPH/CO2-dependent reductive carboxylation of αKG to ICT. Reductive carboxylation by IDH1 was potently inhibited by NADP+ and, to a lesser extent, by ICT. IDH1 and IDH2 with cancer-associated mutations at the active site arginines were unable to carry out the reductive carboxylation of αKG. These mutants were also defective in ICT decarboxylation and converted αKG to 2-hydroxyglutarate using NADPH. These mutant proteins were thus defective in both of the normal reactions of IDH. Biochemical analysis of heterodimers between wild-type and mutant IDH1 subunits showed that the mutant subunit did not inactivate reductive carboxylation by the wild-type subunit. Cells expressing the mutant IDH are thus deficient in their capacity for reductive carboxylation and may be compromised in their ability to produce acetyl-CoA under hypoxia or when mitochondrial function is otherwise impaired. PMID:22442146

Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development

PubMed Central

Qu, Xiuxia; Hertzler, Kristina; Pan, Yi; Grobe, Kay; Robinson, Michael L.; Zhang, Xin

2011-01-01

Vertebrate lens development depends on a complex network of signaling molecules to coordinate cell proliferation, migration and differentiation. In this study, we have studied the role of heparan sulfate in lens specific signaling by generating a conditional ablation of heparan sulfate modification genes, Ndst1 and Ndst2. In this mutant, N-sulfation of heparan sulfate was disrupted after the lens induction stage, resulting in reduced lens cell proliferation, increased cell death and defective lens fiber differentiation in later lens development. The loss of Ndst function also prevented the assembly of Fgf/Fgfr complexes on the lens cell surface and disrupted ERK signaling within the lens. We further demonstrated that Ndst mutation completely inhibited the FGF1 and Fgf3 overexpression phenotypes, but Kras reactivation was sufficient to reverse the Ndst deficient lens differentiation defect. The epistatic relationship between Ndst and FGF-Ras signaling demonstrates that FGF signaling is the predominant signaling pathway controlled by Ndst in lens development. PMID:21536023

The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

PubMed

Douglas, Lois M; Wang, Hong X; Konopka, James B

2013-11-26

Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane contributes to virulence, we analyzed a set of eight genes encoding MARVEL family proteins that are predicted to function in membrane organization. Interestingly, deletion of one gene, NCE102, caused a strong defect in formation of invasive hyphal growth in vitro and decreased virulence in mice. The nce102Δ mutant cells showed defects in actin organization that underlie the morphogenesis defect, since mutation of a known regulator of actin organization caused a similar defect. These studies identify a novel way in which the plasma membrane regulates the actin cytoskeleton and contributes to pathogenesis.

Insulin resistance and improvements in signal transduction.

PubMed

Musi, Nicolas; Goodyear, Laurie J

2006-02-01

Type 2 diabetes and obesity are common metabolic disorders characterized by resistance to the actions of insulin to stimulate skeletal muscle glucose disposal. Insulin-resistant muscle has defects at several steps of the insulin-signaling pathway, including decreases in insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. One approach to increase muscle glucose disposal is to reverse/improve these insulin-signaling defects. Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity. In contrast, physical training and metformin improve whole-body glucose disposal but have minimal effects on proximal insulin-signaling steps. A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs). A different strategy to increase muscle glucose disposal is by stimulating insulin-independent glucose transport. AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge and becomes activated in situations of energy consumption, such as muscle contraction. Several studies have shown that pharmacologic activation of AMPK increases glucose transport in muscle, independent of the actions of insulin. AMPK activation is also involved in the mechanism of action of metformin and adiponectin. Moreover, in the hypothalamus, AMPK regulates appetite and body weight. The effect of AMPK to stimulate muscle glucose disposal and to control appetite makes it an important pharmacologic target for the treatment of type 2 diabetes and obesity.

Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

PubMed Central

Ortiz-Abalia, Jon; Sahún, Ignasi; Altafaj, Xavier; Andreu, Núria; Estivill, Xavier; Dierssen, Mara; Fillat, Cristina

2008-01-01

Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whether functional CNS defects could be corrected with an inhibitory RNA against Dyrk1A, delivered by bilateral intrastriatal injections of adeno-associated virus type 2 (AAVshDyrk1A). We report that AAVshDyrk1A efficiently transduced HEK293 cells and primary neuronal cultures, triggering the specific inhibition of Dyrk1A expression. Injecting the vector into the striata of TgDyrk1A mice resulted in a restricted, long-term transduction of the striatum. This gene therapy was found to be devoid of toxicity and succeeded in normalizing Dyrk1A protein levels in TgDyrk1A mice. Importantly, the behavioral studies of the adult TgDyrk1A mice treated showed a reversal of corticostriatal-dependent phenotypes, as revealed by the attenuation of their hyperactive behavior, the restoration of motor-coordination defects, and an improvement in sensorimotor gating. Taken together, the data demonstrate that normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment. Furthermore, these results identify Dyrk1A as a potential target for therapy in DS. PMID:18940310

The Argonaute protein TbAGO1 contributes to large and mini-chromosome segregation and is required for control of RIME retroposons and RHS pseudogene-associated transcripts.

PubMed

Durand-Dubief, Mickaël; Absalon, Sabrina; Menzer, Linda; Ngwabyt, Sandra; Ersfeld, Klaus; Bastin, Philippe

2007-12-01

The protist Trypanosoma brucei possesses a single Argonaute gene called TbAGO1 that is necessary for RNAi silencing. We previously showed that in strain 427, TbAGO1 knock-out leads to a slow growth phenotype and to chromosome segregation defects. Here we report that the slow growth phenotype is linked to defects in segregation of both large and mini-chromosome populations, with large chromosomes being the most affected. These phenotypes are completely reversed upon inducible re-expression of TbAGO1 fused to GFP, demonstrating their link with TbAGO1. Trypanosomes that do not express TbAGO1 show a general increase in the abundance of transcripts derived from the short retroposon RIME (Ribosomal Interspersed Mobile Element). Supplementary large RIME transcripts emerge in the absence of RNAi, a phenomenon coupled to the disappearance of short transcripts. These fluctuations are reversed by inducible expression of GFP::TbAGO1. Furthermore, we use a combination of Northern blots, RT-PCR and sequencing to reveal that RNAi controls expression of transcripts derived from RHS (Retrotransposon Hot Spot) pseudogenes (RHS genes with retro-element(s) integrated within their coding sequence). Absence of RNAi also leads to an increase of steady-state transcripts from regular RHS genes (those without retro-element), indicating a role for pseudogene in control of gene expression. However, analysis of retroposon abundance and arrangement in the genome of multiple clonal cell lines of TbAGO1-/- failed to reveal movement of mobile elements despite the increased amounts of retroposon transcripts.

Measuring colour rivalry suppression in amblyopia.

PubMed

Hofeldt, T S; Hofeldt, A J

1999-11-01

To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes. To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed. In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1. 8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (beta=1.21, p<0.0001), and negatively related to stereoacuity (beta=-0.16, p=0.019). The interocular difference in logMAR acuity was negatively related to stereoacuity (beta=-0.13, p=0.009). Colour rivalry suppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.

Candida albicans CHT3 encodes the functional homolog of the Cts1 chitinase of Saccharomyces cerevisiae.

PubMed

Dünkler, Alexander; Walther, Andrea; Specht, Charles A; Wendland, Jürgen

2005-11-01

Chitin synthesis and chitin degradation play an important role in cellular morphogenesis and influence the cell shape of fungal organisms. The Candida albicans genome contains four chitinase genes, CHT1, CHT2, and CHT3, which are homologous to the Saccharomyces cerevisiae CTS1 gene and C. albicans CHT4, which is homologous to S. cerevisiae CTS2. To determine which of the C. albicans CHT genes represents the functional homolog of the S. cerevisiae CTS1 gene we constructed mutants of these genes and characterized the resulting phenotypes using morphological assays such as in vivo time lapse microscopy and enzymatic assays to determine the chitinase activity. Deletion of CaCHT1 and CaCHT2 provided no phenotypic alterations in liquid culture but resulted in increased hyphal growth on solid media. Deletion of CaCHT3 generated chains of unseparated cells in the yeast growth phase strongly resembling the cts1 deletion phenotype of S. cerevisiae cells. Expression of CHT3 under control of the regulatable MAL2-promoter in C. albicans resulted in the reversion of the cell separation defect when cells were grown in maltose. Cht3, but not Cht2 when expressed in S. cerevisiae was also able to reverse the cell separation defect of the S. cerevisiae c ts1 deletion strain. Measurements of chitinase activity from yeast cells of C. albicans showed that Cht2 is bound to cells, consistent with it being GPI-anchored while Cht3 is secreted into growth medium; Cht3 is also the principal, observed activity.

A zebrafish model of manganism reveals reversible and treatable symptoms that are independent of neurotoxicity

PubMed Central

Bakthavatsalam, Subha; Das Sharma, Shreya; Sonawane, Mahendra; Thirumalai, Vatsala; Datta, Ankona

2014-01-01

Manganese (manganese ion; referred to as Mn) is essential for neuronal function, yet it is toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson’s disease (PD). However, manganism is distinct from PD and the neural basis of its pathology is poorly understood. To address this issue, we generated a zebrafish model of manganism by incubating larvae in rearing medium containing Mn. We find that Mn-treated zebrafish larvae exhibit specific postural and locomotor defects. Larvae begin to float on their sides, show a curved spine and swim in circles. We discovered that treatment with Mn causes postural defects by interfering with mechanotransduction at the neuromasts. Furthermore, we find that the circling locomotion could be caused by long-duration bursting in the motor neurons, which can lead to long-duration tail bends in the Mn-treated larvae. Mn-treated larvae also exhibited fewer startle movements. Additionally, we show that the intensity of tyrosine hydroxylase immunoreactivity is reversibly reduced after Mn-treatment. This led us to propose that reduced dopamine neuromodulation drives the changes in startle movements. To test this, when we supplied an external source of dopamine to Mn-treated larvae, the larvae exhibited a normal number of startle swims. Taken together, these results indicate that Mn interferes with neuronal function at the sensory, motor and modulatory levels, and open avenues for therapeutically targeted studies on the zebrafish model of manganism. PMID:25261567

Organometallic chemical vapor deposition and characterization of ZnGe(1-x)Si(x)P2-Ge alloys on GaP substrates

NASA Technical Reports Server (NTRS)

Xing, G. C.; Bachmann, Klaus J.; Posthill, J. B.; Timmons, M. L.

1993-01-01

The epitaxial growth of ZnGe(1-x)Si(x)P2-Ge alloys on GaP substrates by open tube organometallic chemical vapor deposition (OMCVD) is reported. The chemical composition of the alloys characterized by energy dispersive X-ray spectroscopy shows that alloys with x up to 0.13 can be deposited on (001) GaP. Epitaxial growth with mirror smooth surface morphology was achieved for x less than or equal to 0.05. Transmission electron microscopy (TEM) micrographs of these alloys show specular epitaxy and the absence of microstructural defects indicating a defect density of less than 10(exp 7) cm(sup -2). Selected area electron diffraction pattern of the alloy shows that the epitaxial layer crystallizes in the chalcopyrite structure with relatively weak superlattice reflections indicating certain degree of randomness in the cation sublattice. Hall measurements show that the alloys are p-type, like the unalloyed films; the carrier concentration, however, dropped about 10 times from 2 x 10(exp 18) to 2 x 10(exp 17) cm(sup -3). Absorption measurements indicate that the band tailing in the absorption spectra of the alloy was shifted about 0.04 eV towards shorter wavelength as compared to the unalloyed material. Diodes fabricated from the n(+)-GaP/p-ZnSiP2-ZnGeP2-Ge heterostructure at x = 0.05 have a reverse break-down voltage of -10.8 V and a reverse saturation current density of approximately 6 x 10(exp -8) A/sq cm.

[Follow-up of patients with good exercise capacity in stress test with myocardial single-photon emission computed tomography (SPECT)].

PubMed

González, Javiera; Prat, Hernán; Swett, Eduardo; Berrocal, Isabel; Fernández, René; Zhindon, Juan Pablo; Castro, Ariel; Massardo, Teresa

2015-11-01

The evaluation of coronary artery disease (CAD) can be performed with stress test and myocardial SPECT tomography. To assess the predictive value of myocardial SPECT using stress test for cardiovascular events in patients with good exercise capacity. We included 102 males aged 56 ± 10 years and 19 females aged 52 ± 10 years, all able to achieve 10 METs and ≥ 85% of the theoretical maximum heart rate and at least 8 min in their stress test with gated 99mTc-sestamibi SPECT. Eighty two percent of patients were followed clinically for 33 ± 17 months. Sixty seven percent of patients were studied for CAD screening and the rest for known disease assessment. Treadmill stress test was negative in 75.4%; 37% of patients with moderate to severe Duke Score presented ischemia. Normal myocardial perfusion SPECT was observed in 70.2%. Reversible defects appeared in 24.8% of cases, which were of moderate or severe degree (> 10% left ventricular extension) in 56.6%. Only seven cases had coronary events after the SPECT. Two major (myocardial infarction and emergency coronary revascularization) and 5 minor events (elective revascularization) ere observed in the follow-up. In a multivariate analysis, SPECT ischemia was the only statistically significant parameter that increased the probability of having a major or minor event. Nearly a quarter of our patients with good exercise capacity demonstrated reversible defects in their myocardial perfusion SPECT. In the intermediate-term follow-up, a low rate of cardiac events was observed, being the isotopic ischemia the only significant predictive parameter.

Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry.

PubMed

Weed, Darin J; Pritchard, Suzanne M; Gonzalez, Floricel; Aguilar, Hector C; Nicola, Anthony V

2017-03-01

Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions. IMPORTANCE HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a class III fusion protein, undergoes reversible conformational changes in response to low-pH exposure. Here, we show that low-pH inactivation of HSV is irreversible and due to a defect in virion fusion activity. We identified an irreversible change in the fusion domain of gB following multiple sequential low-pH exposures or following prolonged low-pH treatment. This change appears to be separable from the alteration in gB quaternary structure. Together, the results are consistent with a model by which low pH can have an activating or inactivating effect on HSV depending on the presence of a target membrane. Copyright © 2017 American Society for Microbiology.

Methionine biosynthesis is essential for infection in the rice blast fungus Magnaporthe oryzae.

PubMed

Saint-Macary, Marie Emmanuelle; Barbisan, Crystel; Gagey, Marie Josèphe; Frelin, Océane; Beffa, Roland; Lebrun, Marc Henri; Droux, Michel

2015-01-01

Methionine is a sulfur amino acid standing at the crossroads of several biosynthetic pathways. In fungi, the last step of methionine biosynthesis is catalyzed by a cobalamine-independent methionine synthase (Met6, EC 2.1.1.14). In the present work, we studied the role of Met6 in the infection process of the rice blast fungus, Magnaporthe oryzae. To this end MET6 null mutants were obtained by targeted gene replacement. On minimum medium, MET6 null mutants were auxotrophic for methionine. Even when grown in presence of excess methionine, these mutants displayed developmental defects, such as reduced mycelium pigmentation, aerial hypha formation and sporulation. They also displayed characteristic metabolic signatures such as increased levels of cysteine, cystathionine, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine while methionine and glutathione levels remained unchanged. These metabolic perturbations were associated with the over-expression of MgCBS1 involved in the reversed transsulfuration pathway that metabolizes homocysteine into cysteine and MgSAM1 and MgSAHH1 involved in the methyl cycle. This suggests a physiological adaptation of M. oryzae to metabolic defects induced by the loss of Met6, in particular an increase in homocysteine levels. Pathogenicity assays showed that MET6 null mutants were non-pathogenic on both barley and rice leaves. These mutants were defective in appressorium-mediated penetration and invasive infectious growth. These pathogenicity defects were rescued by addition of exogenous methionine and S-methylmethionine. These results show that M. oryzae cannot assimilate sufficient methionine from plant tissues and must synthesize this amino acid de novo to fulfill its sulfur amino acid requirement during infection.

The First Dorsal Metatarsal Artery Perforator Propeller Flap.

PubMed

Hallock, Geoffrey G

2016-06-01

Distal foot and toe defects requiring a vascularized flap for coverage have very limited options, oftentimes justifying even a free flap. Perforator flaps in general and propeller flaps in particular have opened up an entirely new subset of local tissue transfer alternatives that can potentially avoid the difficulties that accompany microvascular tissue transfers. The first dorsal metatarsal artery (FDMA) perforator propeller flap represents another variation of this theme. A standard FDMA flap from the dorsum of the foot was raised in reversed fashion based on the distal communicating branch or "perforator" from the plantar foot circulation in 2 patients with great toe defects. All distal skin tissue between this perforator and the defect was kept with the FDMA flap as an attached minor blade, to thereby create an FDMA propeller flap. Salvage of the great toe in both patients was achieved. The benefit of the minor blade of the propeller was to fill a portion of the donor site defect of the traditional FDMA major blade, to permit tension-free donor site closure of the dorsal foot without sequela. The distal-based FDMA flap can be useful as a local flap for coverage of distal foot and toe wounds, but direct donor site closure can be problematic as mirrored by its relative the dorsalis pedis flap. The FDMA perforator propeller flap variation can achieve the same reconstructive goals while simultaneously transferring vascularized tissue into the dorsal foot donor site to thereby minimize the tension if direct closure is possible or minimize the need for a skin graft in this notoriously difficult region.

Both nuclear and cytoplasmic components are defective in oocytes of the B6.Y(TIR) sex-reversed female mouse.

PubMed

Amleh, A; Smith, L; Chen, H; Taketo, T

2000-03-15

In the mammalian gonadal primordium, activation of the Sry gene on the Y chromosome initiates a cascade of genetic events leading to testicular organization whereas its absence results in ovarian differentiation. An exception occurs when the Y chromosome of Mus musculus domesticus from Tirano, Italy (Y(TIR)), is placed on the C57BL/6J (B6) genetic background. The B6.Y(TIR) progeny develop only ovaries or ovotestes despite Sry transcription in fetal life. Consequently, the XY offspring with bilateral ovaries develop into apparently normal females, but their eggs fail to develop after fertilization. Our previous studies have shown that the primary cause of infertility can be attributed to oocytes rather than their surrounding somatic cells in the XY ovary. This study attempted to identify the defects in oocytes from the B6.Y(TIR) female mouse. We examined the developmental potential of embryos from XY and XX females after exchanging their nuclear components by microsurgery following in vitro maturation and fertilization. The results suggest that both nuclear and cytoplasmic components are defective in oocytes from XY females. In the XY fetal ovary, most germ cells entered meiosis and their autosomes appeared to synapse normally while the X and Y chromosomes remained unpaired during meiotic prophase. This lack of X-Y pairing probably caused aneuploidy in some secondary oocytes following in vitro maturation. However, normal numbers of chromosomes in the rest of the secondary oocytes indicate that aneuploidy alone can not explain the nuclear defect in oocytes. Copyright 2000 Academic Press.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

PubMed

Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

2007-02-01

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

PubMed

Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

2016-07-15

The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation.

FGFR2 mutation in 46,XY sex reversal with craniosynostosis

PubMed Central

Bagheri-Fam, Stefan; Ono, Makoto; Li, Li; Zhao, Liang; Ryan, Janelle; Lai, Raymond; Katsura, Yukako; Rossello, Fernando J.; Koopman, Peter; Scherer, Gerd; Bartsch, Oliver; Eswarakumar, Jacob V.P.; Harley, Vincent R.

2015-01-01

Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe a patient whose features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to-female sex reversal or CSR. The craniosynostosis patient was chromosomally XY, but presented as a phenotypic female due to complete GD. DNA sequencing identified the FGFR2c heterozygous missense mutation, c.1025G>C (p.Cys342Ser). Substitution of Cys342 by Ser or other amino acids (Arg/Phe/Try/Tyr) has been previously reported in Crouzon and Pfeiffer syndrome. We show that the ‘knock-in’ Crouzon mouse model Fgfr2cC342Y/C342Y carrying a Cys342Tyr substitution displays XY gonadal sex reversal with variable expressivity. We also show that despite FGFR2c-Cys342Tyr being widely considered a gain-of-function mutation, Cys342Tyr substitution in the gonad leads to loss of function, as demonstrated by sex reversal in Fgfr2cC342Y/− mice carrying the knock-in allele on a null background. The rarity of our patient suggests the influence of modifier genes which exacerbated the testicular phenotype. Indeed, patient whole exome analysis revealed several potential modifiers expressed in Sertoli cells at the time of testis determination in mice. In summary, this study identifies the first FGFR2 mutation in a 46,XY GD patient. We conclude that, in certain rare genetic contexts, maintaining normal levels of FGFR2 signaling is important for human testis determination. PMID:26362256

The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

PubMed

van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T; Benarous, Richard; Berkhout, Ben

2014-01-01

The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

Self-Assembly of Topological Solitons and Functional Nanoparticles in Liquid Crystals

NASA Astrophysics Data System (ADS)

Ackerman, Paul Jeffrey

As a result of their intrinsic orientational order, soft elasticity, and facile response to external stimuli, liquid crystals (LCs) provide a rich environment for both fundamental science and viable technological applications. In this thesis I explore the emergent properties of confinement-frustrated chiral nematic LCs and nanoparticle-LC composites. Due to a complex free energy landscape, con- fined LCs exhibit a large number of local and global energy minima and can facilitate self-assembly of many types of topological solitons. These localized configurations of molecular orientation field are useful for technological applications, have properties that are enhanced by colloidal inclusions and enable the fundamental studies of nanoparticle interactions. Experimental and numerical ex- ploration of these topologically nontrivial solitons may influence the experimental realization of their analogs in physical systems ranging from elementary particles to cosmology. The delicate interplay of topology, chirality and confinement of LCs can enable spontaneous or optical vortex initiated self-assembly of solitons. In turn, the optical generation and patterning of reconfigurable LC solitons can enable the production of optical vortices in laser beams, demon- strating hierarchical control of defects in matter and light with potential technological applications. The elasticity and facile response of LCs to applied fields facilitates the self-assembly of crystals and chains of solitons, giant electrostriction, as well as electrically driven nonequilibrium dynamics in the form of reversible directional motion of stable defect pairs. Concepts of chirality and topo- logical invariants, such as Hopf index and Skyrmion number, are invoked to examine and classify a variety of spatial solitons, including Skyrmions, Hopfions, and torons, as well as to analyze the role of chirality and the unexpected observation of twist handedness reversal that enables soliton stability. By introducing colloidal particles to the confined chiral LCs, we probe how new composite material properties can emerge spontaneously or be pre-designed and then probed by combining the facile response of the LC host and the unique properties of nanoparticles. This allows us to achieve polar ferromagnetic response in chiral ferromagnetic LC colloids as well as to probe plasmon- exciton interactions through controlling metal and semiconductor quantum dot nanoparticles within topological defects.

Defects in tRNA processing and nuclear export induce GCN4 translation independently of phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2.

PubMed

Qiu, H; Hu, C; Anderson, J; Björk, G R; Sarkar, S; Hopper, A K; Hinnebusch, A G

2000-04-01

Induction of GCN4 translation in amino acid-starved cells involves the inhibition of initiator tRNA(Met) binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2. It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant tRNA(AAC)(Val) (tRNA(Val*)) or the RNA component of RNase MRP encoded by NME1. Here we show that overexpression of the tRNA pseudouridine 55 synthase encoded by PUS4 also leads to translational derepression of GCN4 (Gcd(-) phenotype) independently of eIF2 phosphorylation. Surprisingly, the Gcd(-) phenotype of high-copy-number PUS4 (hcPUS4) did not require PUS4 enzymatic activity, and several lines of evidence indicate that PUS4 overexpression did not diminish functional initiator tRNA(Met) levels. The presence of hcPUS4 or hcNME1 led to the accumulation of certain tRNA precursors, and their Gcd(-) phenotypes were reversed by overexpressing the RNA component of RNase P (RPR1), responsible for 5'-end processing of all tRNAs. Consistently, overexpression of a mutant pre-tRNA(Tyr) that cannot be processed by RNase P had a Gcd(-) phenotype. Interestingly, the Gcd(-) phenotype of hcPUS4 also was reversed by overexpressing LOS1, required for efficient nuclear export of tRNA, and los1Delta cells have a Gcd(-) phenotype. Overproduced PUS4 appears to impede 5'-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively. The mutant tRNA(Val*) showed nuclear accumulation in otherwise wild-type cells, suggesting a defect in export to the cytoplasm. We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNA(Met) binding to the ribosome.

Defects in tRNA Processing and Nuclear Export Induce GCN4 Translation Independently of Phosphorylation of the α Subunit of Eukaryotic Translation Initiation Factor 2

PubMed Central

Qiu, Hongfang; Hu, Cuihua; Anderson, James; Björk, Glenn R.; Sarkar, Srimonti; Hopper, Anita K.; Hinnebusch, Alan G.

2000-01-01

Induction of GCN4 translation in amino acid-starved cells involves the inhibition of initiator tRNAMet binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2. It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant tRNAAACVal (tRNAVal*) or the RNA component of RNase MRP encoded by NME1. Here we show that overexpression of the tRNA pseudouridine 55 synthase encoded by PUS4 also leads to translational derepression of GCN4 (Gcd− phenotype) independently of eIF2 phosphorylation. Surprisingly, the Gcd− phenotype of high-copy-number PUS4 (hcPUS4) did not require PUS4 enzymatic activity, and several lines of evidence indicate that PUS4 overexpression did not diminish functional initiator tRNAMet levels. The presence of hcPUS4 or hcNME1 led to the accumulation of certain tRNA precursors, and their Gcd− phenotypes were reversed by overexpressing the RNA component of RNase P (RPR1), responsible for 5′-end processing of all tRNAs. Consistently, overexpression of a mutant pre-tRNATyr that cannot be processed by RNase P had a Gcd− phenotype. Interestingly, the Gcd− phenotype of hcPUS4 also was reversed by overexpressing LOS1, required for efficient nuclear export of tRNA, and los1Δ cells have a Gcd− phenotype. Overproduced PUS4 appears to impede 5′-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively. The mutant tRNAVal* showed nuclear accumulation in otherwise wild-type cells, suggesting a defect in export to the cytoplasm. We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNAMet binding to the ribosome. PMID:10713174

[Oral contraception, glucid metabolism and monitoring criteria].

PubMed

Gaspard, U

1988-02-01

Combined oral contraceptives (OCs) entail insulin resistence and decreased glucose tolerance proportional to their dose and type of progestin. Derivatives of 19-nortestosterone have more deleterious effects than do derivatives of 17-acetoxy progesterone. The effects are usually reversible and limited, and the diabetogenic role of currently available low-dose OCs is small. Metabolic and vascular risks must still be taken into account in prescribing OCs because hyperglycemia and hyperinsulinemia are significant vascular risk factors. Women with histories of OC use have increased risks of fatal and nonfatal myocardial infarct, cerebrovascular accidents, and peripheral vascular disease, but the increases are not always significant. Age and smoking are known to be primary risk factors whose effects are increased by OCs. Reduction of the estrogen dose of OCs may have resulted in a significant reduction of the venous thromboembolic risk, while reduction of the progestin dose may have resulted in a decreased incidence of venous accidents. The mechanisms of action by which OCs amplify existing vascular risks are largely unknown. Research with methods capable of quantifying insulin resistence suggests that a post-receptor intracellular effect is responsible for insulin resistence and diminished intracellular metabolism of glucose in users of OCs. Because OCs are ordinarily used by healthy young women over long periods of time with minimal medical supervision, it is desirable to identify cases in which cardiovascular and other undesirable secondary effects are likely. OCs are contraindicated for any woman with a history of cardiac accidents, venous or arterial vascular problems, or hypertension. Obesity is a relative contraindication because it may coexist with a problem of glucose metabolism and constitute a diabetic risk factor. Other diabetic risk factors that must be evaluated are age, family or personal history of gestational diabetics, and transitory problems of glucose tolerance. Low dose combined OCs have little effect on carbohydrate metabolism or glucose tolerance, but women with diabetic risk factors may be more sensitive to the vascular impact of OCs than other women. Weight, blood pressure, and fasting or nonfasting blood sugar should be assessed annually OC users. Obese women should undergo an endocrinologic and metabolic examination in the interests of general prevention before receiving a prescription for combined OCs. Women with family or personal histories of diabetic risk should be evaluated from a metabolic and vascular standpoint.

Characterization of a Poly(styrene-block-methylacrylate-random-octadecylacrylate-block-styrene) Shape Memory ABA Triblock Copolymer

NASA Astrophysics Data System (ADS)

Fei, Pengzhan; Cavicchi, Kevin

2011-03-01

A new ABA triblock copolymer of poly(styrene-block- methylacrylate-random-octadecylacrylate-block-styrene) (PS-b- PMA-r-PODA-b-PS) was synthesized by reversible addition fragmentation chain transfer polymerization. The triblock copolymer can generate a three-dimensional, physically crosslinked network by self-assembly, where the glassy PS domains physically crosslink the midblock chains. The side chain crystallization of the polyoctadecylacrylare (PODA) side chain generates a second reversible network enabling shape memory properties. Shape memory tests by uniaxial deformation and recovery of molded dog-bone shape samples demonstrate that shape fixities above 96% and shape recoveries above 98% were obtained for extensional strains up to 300%. An outstanding advantage of this shape memory material is that it can be very easily shaped and remolded by elevating the temperature to 140circ; C, and after remolding the initial shape memory properties are totally recovered by eliminating the defects introduced by the previous deformation cycling.

Tension pneumocephalus mimicking septic shock: a case report.

PubMed

Miranda, Caroline; Mahta, Ali; Wheeler, Lee Adam; Tsiouris, A John; Kamel, Hooman

2018-02-01

Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

Divacancy-hydrogen complexes in dislocation-free high-purity germanium. [Annealing, Hall effect, steady-state concentration energy dependence

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

Haller, E.E.; Hubbard, G.S.; Hansen, W.L.

1976-09-01

A defect center with a single acceptor level at E/sub v/ + 0.08 eV appears in H/sub 2/-grown dislocation-free high-purity germanium. Its concentration changes reversibly upon annealing up to 650 K. By means of Hall-effect and conductivity measurements over a large temperature range the temperature dependence of the steady-state concentration between 450 and 720 K as well as the transients following changes in temperature were determined. The observed acceptor level is attributed to the divacancy-hydrogen complex V/sub 2/H. The complex reacts with hydrogen, dissolved in the Ge lattice or stored in traps, according to V/sub 2/H + H reversible V/submore » 2/H/sub 2/. An energy level associated with the divacancy-dihydrogen complex was not observed. These results are in good agreement with the idea that hydrogen in germanium forms a ''very deep donor'' (i.e., the energy level lies inside the valence band).« less

Topologically robust sound propagation in an angular-momentum-biased graphene-like resonator lattice

NASA Astrophysics Data System (ADS)

Khanikaev, Alexander B.; Fleury, Romain; Mousavi, S. Hossein; Alù, Andrea

2015-10-01

Topological insulators do not allow conduction in the bulk, yet they support edge modes that travel along the boundary only in one direction, determined by the carried electron spin, with inherent robustness to defects and disorder. Topological insulators have inspired analogues in photonics and optics, in which one-way edge propagation in topologically protected two-dimensional materials is achieved breaking time-reversal symmetry with a magnetic bias. Here, we introduce the concept of topological order in classical acoustics, realizing robust topological protection and one-way edge propagation of sound in a suitably designed resonator lattice biased with angular momentum, forming the acoustic analogue of a magnetically biased graphene layer. Extending the concept of an acoustic nonreciprocal circulator based on angular-momentum bias, time-reversal symmetry is broken here using moderate rotational motion of air within each element of the lattice, which takes the role of the electron spin in determining the direction of modal edge propagation.

Fabrication of n-ZnO:Al/p-Si(100) heterojunction diode and its characterization

NASA Astrophysics Data System (ADS)

Parvathy Venu, M.; Dharmaprakash, S. M.; Byrappa, K.

2018-04-01

Aluminum doped ZnO (n-ZnO:Al) nanostructured thin films were grown on ZnO seed layer coated p-Si(100) substrate employing hydrothermal technique. X-ray diffraction pattern revealed that the ZnO:Al film possess hexagonal wurtzite structure with preferential orientation along (002) direction. Photoluminescence of the sample displayed near band edge emission peak in the ultra-violet region and defect level emission peak in the visible region. The as grown thin film was used in the fabrication of n-ZnO:Al/p-Si heterojunction diode and the room temperature current-voltage (I-V) and capacitance-voltage (C-V) characteristics were studied. The heterojunction exhibited fairly good rectification with an ideality of 2.49 and reverse saturation current of 2 nA. The barrier height was found to be 0.668 eV from the I-V measurements. The C-V measurements showed a decrease in the capacitance of the heterojunction with an increase in the reverse bias voltage.

Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling

PubMed Central

Wasser, Catherine R; Ertunc, Mert; Liu, Xinran; Kavalali, Ege T

2007-01-01

Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-β-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-β-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis. PMID:17170046

Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.

PubMed

Cheng, Chia-Wei; Adams, Gregor B; Perin, Laura; Wei, Min; Zhou, Xiaoying; Lam, Ben S; Da Sacco, Stefano; Mirisola, Mario; Quinn, David I; Dorff, Tanya B; Kopchick, John J; Longo, Valter D

2014-06-05

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration. Copyright © 2014 Elsevier Inc. All rights reserved.

Rigid clamp

DOEpatents

Benavides, G.L.; Burt, J.D.

1994-07-12

The invention relates to a clamp mechanism that can be used to attach or temporarily support objects inside of tubular goods. The clamp mechanism can also be modified so that it grips objects. The clamp has a self-centering feature to accommodate out-of-roundness or other internal defections in tubular objects such as pipe. A plurality of clamping shoes are expanded by a linkage which is preferably powered by a motor to contact the inside of a pipe. The motion can be reversed and jaw elements can be connected to the linkage so as to bring the jaws together to grab an object. 12 figs.

Rigid clamp

DOEpatents

Benavides, Gilbert L.; Burt, Jack D.

1994-01-01

The invention relates to a clamp mechanism that can be used to attach or temporarily support objects inside of tubular goods. The clamp mechanism can also be modified so that it grips objects. The clamp has a self-centering feature to accommodate out-of-roundness or other internal defections in tubular objects such as pipe. A plurality of clamping shoes are expanded by a linkage which is preferably powered by a motor to contact the inside of a pipe. The motion can be reversed and jaw elements can be connected to the linkage so as to bring the jaws together to grab an object.

Pigment dispersion syndrome and pigmentary glaucoma--a major review.

PubMed

Niyadurupola, Nuwan; Broadway, David C

2008-12-01

Pigment dispersion syndrome (PDS) is an interesting condition that can lead to secondary open angle glaucoma. Pigmentary glaucoma is primarily a disease of young people, myopes and men. PDS is characterized by the presence of Krukenberg spindles, iris trans-illumination defects, trabecular meshwork pigmentation and backward bowing of the iris. Posterior bowing of the iris causes rubbing of the pigmented iris epithelium against lens structures, liberation of pigment and trabecular meshwork changes that result in reduced aqueous outflow with the risk of glaucoma. Peripheral laser iridotomy can reverse backward bowing of the iris and may prevent progression of pigmentary glaucoma.

Quantum random walks on congested lattices and the effect of dephasing

PubMed Central

Motes, Keith R.; Gilchrist, Alexei; Rohde, Peter P.

2016-01-01

We consider quantum random walks on congested lattices and contrast them to classical random walks. Congestion is modelled on lattices that contain static defects which reverse the walker’s direction. We implement a dephasing process after each step which allows us to smoothly interpolate between classical and quantum random walks as well as study the effect of dephasing on the quantum walk. Our key results show that a quantum walker escapes a finite boundary dramatically faster than a classical walker and that this advantage remains in the presence of heavily congested lattices. PMID:26812924

Casein Kinase 2 Reverses Tail-Independent Inhibition of Kinesin-1

NASA Astrophysics Data System (ADS)

Xu, Jing; Shu, Zhanyong; Anand, Preetha; Reddy, Babu; Cermelli, Silvia; Whisenant, Thomas; King, Stephen; Bardwell, Lee; Huang, Lan; Gross, Steven

2011-03-01

Kinesin-1 is a plus-end microtubule-based molecular motor, and defects in kinesin transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a direct head-tail interaction, but is believed to be active otherwise. In contrast, this study uncovers a fast but reversible inhibition distinct from the canonical auto-inhibition pathway. The majority of the initially active kinesin (full-length or tail-less) loses its ability to bind/interact with microtubule, and Casein Kinase 2 (CK2) reverses this inactivation (up to 4-fold) without altering kinesin's single motor properties. Motor phosphorylation is not required for this CK2 -mediated kinesin activation. In cultured mammalian cells, knockdown of CK2 level, but not kinase activity, was sufficient to decrease the force required to stall lipid droplet transport, consistent with a reduction in the number of active motors. We propose that CK2 forms a positive regulating complex with the motor. This study provides the first direct evidence of a protein kinase positively regulating kinesin-transport, and uncovers a pathway whereby inactive cargo-bound kinesin can be activated. This work is supported by NIGMS grants GM64624 and GM079156 to SPG, GM-74830 to LH, NIH grants GM76516 and GM60366 to LB, and AHA grant 825278F to JX.

Nonmyeloablative Conditioning with Busulfan before Matched Littermate Bone Marrow Transplantation Results in Reversal of the Disease Phenotype in Canine Leukocyte Adhesion Deficiency

PubMed Central

Sokolic, Robert A.; Bauer, Thomas R.; Gu, Yu-Chen; Hai, Mehreen; Tuschong, Laura M.; Burkholder, Tanya; Colenda, Lyn; Bacher, John; Starost, Matthew F.; Hickstein, Dennis D.

2005-01-01

Leukocyte adhesion deficiency (LAD)–1, a primary immunodeficiency disease caused by molecular defects in the leukocyte integrin CD18 molecule, is characterized by recurrent, life-threatening bacterial infections. Myeloablative hematopoietic stem cell transplantation is the only curative treatment for LAD-1. Recently, canine LAD (CLAD) has been shown to be a valuable animal model for the preclinical testing of nonmyeloablative transplantation regimens for the treatment of children with LAD-1. To develop new allogeneic transplantation approaches for LAD-1, we assessed a nonmyeloablative conditioning regimen consisting of busulfan as a single agent before matched littermate allogeneic bone marrow transplantation in CLAD. Three CLAD dogs received busulfan 10 mg/kg intravenously before infusion of matched littermate bone marrow, and all dogs received posttransplantation immunosuppression with cyclosporin A and mycophenolate mofetil. Initially, all 3 dogs became mixed chimeras, and levels of donor chimerism sufficient to reverse the CLAD phenotype persisted in 2 animals. The third dog maintained donor microchimerism with an attenuated CLAD phenotype. These 3 dogs have all been followed up for at least 1 year after transplantation. These results indicate that a nonmyeloablative conditioning regimen with chemotherapy alone is capable of generating stable mixed chimerism and reversal of the disease phenotype in CLAD. PMID:16182176

Tracking gas-liquid coexistence in fluids of charged soft dumbbells.

PubMed

Braun, Heiko; Hentschke, Reinhard

2009-10-01

The existence of gas-liquid coexistence in dipolar fluids with no other contribution to attractive interaction than dipole-dipole interaction is a basic and open question in the theory of fluids. Recent Monte Carlo work by Camp and co-workers indicates that a fluid of charged hard dumbbells does exhibit gas-liquid (g-l) coexistence. This system has the potential to answer the above fundamental question because the charge-to-charge separation, d , on the dumbbells may be reduced to, at least in principle, yield the dipolar fluid limit. Using the molecular-dynamics technique we present simulation results for the g-l critical point of charged soft dumbbells at fixed dipole moment as function of d . We do find a g-l critical point at finite temperature even at the smallest d value (10;{-4}) . Reversible aggregation appears to play less a role than in related model systems as d becomes small. Consequently attempts to interpret the simulation results using either an extension of Flory's lattice theory for polymer systems, which includes reversible assembly of monomers into chains, or the defect model for reversible networks proposed by Tlusty and Safran are not successful. The overall best qualitative interpretation of the critical parameters is obtained by considering the dumbbells as dipoles immersed in a continuum dielectric.

FOXL2 is a female sex-determining gene in the goat.

PubMed

Boulanger, Laurent; Pannetier, Maëlle; Gall, Laurence; Allais-Bonnet, Aurélie; Elzaiat, Maëva; Le Bourhis, Daniel; Daniel, Nathalie; Richard, Christophe; Cotinot, Corinne; Ghyselinck, Norbert B; Pailhoux, Eric

2014-02-17

The origin of sex reversal in XX goats homozygous for the polled intersex syndrome (PIS) mutation was unclear because of the complexity of the mutation that affects the transcription of both FOXL2 and several long noncoding RNAs (lncRNAs). Accumulating evidence suggested that FOXL2 could be the sole gene of the PIS locus responsible for XX sex reversal, the lncRNAs being involved in transcriptional regulation of FOXL2. In this study, using zinc-finger nuclease-directed mutagenesis, we generated several fetuses, of which one XX individual bears biallelic mutations of FOXL2. Our analysis demonstrates that FOXL2 loss of function dissociated from loss of lncRNA expression is sufficient to cause an XX female-to-male sex reversal in the goat model and, as in the mouse model, an agenesis of eyelids. Both developmental defects were reproduced in two newborn animals cloned from the XX FOXL2(-/-) fibroblasts. These results therefore identify FOXL2 as a bona fide female sex-determining gene in the goat. They also highlight a stage-dependent role of FOXL2 in the ovary, different between goats and mice, being important for fetal development in the former but for postnatal maintenance in the latter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mutations That Affect the Efficiency of Translation of mRNA for the cII Gene of Coliphage Lambda

PubMed Central

Dul, Ed; Mahoney, Michael E.; Wulff, Daniel L.

1987-01-01

Starting with the λ pRE- strain λctr1 cy3008, which forms clear plaques, we have isolated two mutant strains, λdya2 ctr1 cy3008 and λ dya3 ctr1 cy3008, that form plaques with very slightly turbid centers. The dya2 and dya3 mutations lie in the region of overlap between the PRE promoter and the ribosome recognition region of the cII gene, and have nucleotide alterations at positions -1 and +5 of pRE, and alterations of cII mRNA at -16 and -21 nucleotides before the initial AUG codon of the gene. Both mutations destabilize a stem structure that may be formed by cII mRNA, and dya2 also changes the sequence on cII mRNA that is complementary to the 3'-end of 16 S rRNA from 5'-UAAGGA-3' to 5'-UGAGGA-3'.—The dya2 and dya3 mutations, along with the ctr1 mutation, which destabilizes either of two alternate stem structures which may be formed by cII mRNA (these being more stable stem structures than the one affected by dya2 and dya3), were tested for their ability to reverse two cII- mutations that are characterized by inefficient translation of cII mRNA. These are cII3088, an A → G mutation four bases before the initial AUG codon, and cII3059 , a GUU → GAU (Val2 → Asp) second codon mutation. It was found that ctr1 completely reverses the translation defects of these two mutations, while dya2 partially reverses these translation defects. The dya3 mutation has no effect on translation efficiency under any condition tested. However neither the ctr1 mutation nor the dya2 mutation has much effect on translation efficiency in an otherwise cII+ background, indicating that other factors must limit the rate of translation of cII mRNA under these conditions. PMID:2953647

Defects in Gallbladder Emptying and Bile Acid Homeostasis in Mice With Cystic Fibrosis Transmembrane Conductance Regulator Deficiencies

PubMed Central

Debray, Dominique; Rainteau, Dominique; Barbu, Véronique; Rouahi, Myriam; Mourabit, Haquima El; Lerondel, Stéphanie; Rey, Colette; Humbert, Lydie; Wendum, Dominique; Cottart, Charles-Henry; Dawson, Paul; Chignard, Nicolas; Housset, Chantal

2013-01-01

Background & Aims Patients with cystic fibrosis (CF) have poorly defined defects in biliary function. We evaluated the effects of cystic fibrosis transmembrane conductance regulator (CFTR) deficiency on the enterohepatic disposition of bile acids (BAs). Methods Bile secretion and BA homeostasis were investigated in Cftrtm1Unc (Cftr−/−) and CftrΔF508 (ΔF508) mice. Results Cftr−/− and ΔF508 mice did not grow to normal size, but did not have liver abnormalities. The gallbladders of Cftr−/− mice were enlarged and had defects in emptying, based on99mtechnetiummebrofenin scintigraphy or post-prandial variationsn gallbladder volume; gallbladder contraction in response to cholecystokinin-8 was normal. Cftr−/− mice had abnormal gallbladder bile and duodenal acidity, and overexpressed the vasoactive intestinal peptide—a myorelaxant factor for the gallbladder. The BA pool was larger in Cftr−/− than wild-type mice, although there were no differences in fecal loss of BAs. Amounts of secondary BAs in portal blood, liver, and bile of Cftr−/− mice were much lower than normal. Expression of genes that are induced by BAs, including fibroblast growth factor-15 and BA transporters, was lower in the ileum but higher in the gallbladders of Cftr−/− mice, compared with wild-type mice, whereas enzymes that synthesize BA were down-regulated in livers of Cftr−/− mice. This indicates that BAs underwent a cholecystohepatic shunt, which was confirmed using cholyl-(Ne-NBD)-lysine as a tracer. In Cftr−/− mice, cholecystectomy reversed most changes in gene expression and partially restored circulating levels of secondary BAs. The ΔF508 mice overexpressed vasoactive intestinal peptide and had defects in gallbladder emptying and in levels of secondary BAs, but these features were less severe than in Cftr−/− mice. Conclusions Cftr−/− and CftrΔF508 mice have defects in gallbladder emptying that disrupt enterohepatic circulation of BAs. These defects create a shunt pathway that restricts the amount of toxic secondary BAs that enter the liver. PMID:22370478

Reconstitution of wild type viral DNA in simian cells transfected with early and late SV40 defective genomes.

PubMed

O'Neill, F J; Gao, Y; Xu, X

1993-11-01

The DNAs of polyomaviruses ordinarily exist as a single circular molecule of approximately 5000 base pairs. Variants of SV40, BKV and JCV have been described which contain two complementing defective DNA molecules. These defectives, which form a bipartite genome structure, contain either the viral early region or the late region. The defectives have the unique property of being able to tolerate variable sized reiterations of regulatory and terminus region sequences, and portions of the coding region. They can also exchange coding region sequences with other polyomaviruses. It has been suggested that the bipartite genome structure might be a stage in the evolution of polyomaviruses which can uniquely sustain genome and sequence diversity. However, it is not known if the regulatory and terminus region sequences are highly mutable. Also, it is not known if the bipartite genome structure is reversible and what the conditions might be which would favor restoration of the monomolecular genome structure. We addressed the first question by sequencing the reiterated regulatory and terminus regions of E- and L-SV40 DNAs. This revealed a large number of mutations in the regulatory regions of the defective genomes, including deletions, insertions, rearrangements and base substitutions. We also detected insertions and base substitutions in the T-antigen gene. We addressed the second question by introducing into permissive simian cells, E- and L-SV40 genomes which had been engineered to contain only a single regulatory region. Analysis of viral DNA from transfected cells demonstrated recombined genomes containing a wild type monomolecular DNA structure. However, the complete defectives, containing reiterated regulatory regions, could often compete away the wild type genomes. The recombinant monomolecular genomes were isolated, cloned and found to be infectious. All of the DNA alterations identified in one of the regulatory regions of E-SV40 DNA were present in the recombinant monomolecular genomes. These and other findings indicate that the bipartite genome state can sustain many mutations which wtSV40 cannot directly sustain. However, the mutations can later be introduced into the wild type genomes when the E- and L-SV40 DNAs recombine to generate a new monomolecular genome structure.

The influence of void and porosity on deformation behaviour of nanocrystalline Ni under tensile followed by compressive loading

NASA Astrophysics Data System (ADS)

Meraj, Md.; Nayak, Shradha; Krishanjeet, Kumar; Pal, Snehanshu

2018-03-01

In this paper, we present a lucid understanding about the deformation behaviour of nanocrystalline (NC) Ni with and without defects subjected to tensile followed by compressive loading using molecular dynamic (MD) simulations. The embedded atom method (EAM) potential have been incorporated in the simulation for three kinds of samples-i.e. for NC Ni (without any defect), porous NC Ni and NC Ni containing a centrally located void. All the three samples, which have been prepared by implementing the Voronoi method and using Atom Eye software, consist of 16 uniform grains. The total number of atoms present in NC Ni, porous NC Ni and NC Ni containing a void are 107021, 105968 and 107012 respectively. The stress-strain response of NC Ni under tensile followed by compressive loading are simulated at a high strain rate of 107 s-1 and at a constant temperature of 300K. The stress-strain curves for the NC Ni with and without defects have been plotted for three different types of loading: (a) tensile loading (b) compressive loading (c) forward tensile loading followed by reverse compressive loading. Prominent change in yield strength of the NC Ni is observed due to the introduction of defects. For tensile followed by compressive loading (during forward loading), the yield point for NC Ni with void is lesser than the yield point of NC Ni and porous NC Ni. The saw tooth shape or serration portion of the stress-strain curve is mainly due to three characteristic phenomena, dislocation generation and its movement, dislocation pile-up at the junctions, and dislocation annihilation. Both twins and stacking faults are observed due to plastic deformation as the deformation mechanism progresses. The dislocation density, number of clusters and number of vacancy of the NC sample with and without defects are plotted against the strain developed in the sample. It is seen that introduction of defects brings about change in mechanical properties of the NC Ni. The crystalline nature of NC Ni is found to decrease with introduction of defects. The findings of this work can thus be extended in bringing a whole new insight related to the deformation behaviour and properties of Nano- materials during cyclic deformation at various temperatures.

Genome-Enabled Studies of Anaerobic, Nitrate-Dependent Iron Oxidation in the Chemolithoautotrophic Bacterium Thiobacillus denitrificans

NASA Astrophysics Data System (ADS)

Beller, H. R.; Zhou, P.; Legler, T. C.; Chakicherla, A.; O'Day, P. A.

2013-12-01

Thiobacillus denitrificans is a chemolithoautotrophic bacterium capable of anaerobic, nitrate-dependent U(IV) and Fe(II) oxidation, both of which can strongly influence the long-term efficacy of in situ reductive immobilization of uranium in contaminated aquifers. We previously identified two c-type cytochromes involved in nitrate-dependent U(IV) oxidation in T. denitrificans and hypothesized that c-type cytochromes would also catalyze Fe(II) oxidation, as they have been found to play this role in anaerobic phototrophic Fe(II)-oxidizing bacteria. Here we report on efforts to identify genes associated with nitrate-dependent Fe(II) oxidation, namely (a) whole-genome transcriptional studies [using FeCO3, Fe2+, and U(IV) oxides as electron donors under denitrifying conditions], (b) Fe(II) oxidation assays performed with knockout mutants targeting primarily highly expressed or upregulated c-type cytochromes, and (c) random transposon-mutagenesis studies with screening for Fe(II) oxidation. Assays of mutants for 26 target genes, most of which were c-type cytochromes, indicated that none of the mutants tested were significantly defective in nitrate-dependent Fe(II) oxidation. The non-defective mutants included the c1-cytochrome subunit of the cytochrome bc1 complex (complex III), which has relevance to a previously proposed role for this complex in nitrate-dependent Fe(II) oxidation and to current concepts of reverse electron transfer. Of the transposon mutants defective in Fe(II) oxidation, one mutant with a disrupted gene associated with NADH:ubiquinone oxidoreductase (complex I) was ~35% defective relative to the wild-type strain; this strain was similarly defective in nitrate reduction with thiosulfate as the electron donor. Overall, our results indicate that nitrate-dependent Fe(II) oxidation in T. denitrificans is not catalyzed by the same c-type cytochromes involved in U(IV) oxidation, nor have other c-type cytochromes yet been implicated in the process.

A study of thermal conductivity in graphene diodes and transistors with intrinsic defects and subjected to metal impurities

NASA Astrophysics Data System (ADS)

Sadeghzadeh, Sadegh; Rezapour, Navid

2016-12-01

In this paper, the effect of the presence of cavities resulting from the fabrication process and the effect of common metal impurities added during the synthesis process on the thermal conductivity of single-layer graphene sheets, diodes and transistors have been investigated by using the Reverse Non Equilibrium Molecular Dynamics (RNEMD) method. The obtained results show that thermal conductivity generally diminishes by increasing the concentration of nanoparticles and increases when porosities and impurities are at the edges of sheets. Regarding a better thermal management in graphene with the addition of nanoparticles, and considering its existing porosity, a lower thermal conductivity is achieved by adding more nanoparticles. By increasing the diameter of pores from 0.5 nm to 4.4 nm in a specific single-layer graphene sheet, thermal conductivity diminishes from 67 W/mk to 1.43 W/mk; while it diminishes from 45 to 1.0 W/mk for the same structure containing both the defects and nanoparticles over the defects. In evaluating the influences of cavities and metallic nanoparticles on thermal conductivity, it was observed that changing the share of cavities or nanoparticles has a significant effect on the thermal conductivity of graphene diodes and transistors. The rectification efficiency of diodes diminished from about 100% for the defect-free diode to about 19% for the diode containing 2 nm cavities and then increased to 75% for the diode with 5 nm cavities. While, with the increase in the concentration of iron nanoparticles, the rectification efficiency increased from about 100% for the diode with no iron particles to about 255% for the diode containing 13 wt % of iron particles. Final results demonstrate that the metallic nanoparticles and also defects with specific diameters can be effectively exploited to increase or decrease the efficiency of nanodiodes and nanotransistors. This leads to engineered design of nanodiodes and nanotransistors for various applications.

Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

PubMed Central

Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

2016-01-01

Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis Formation and Heart Development

PubMed Central

2017-01-01

The formation of the asymmetric left-right (LR) body axis is one of the fundamental aspects of vertebrate embryonic development, and one still raising passionate discussions among scientists. Although the conserved role of nodal is unquestionable in this process, several of the details around this signaling cascade are still unanswered. To further understand this mechanism, we have been studying Cerberus-like 2 (Cerl2), an inhibitor of Nodal, and its role in the generation of asymmetries in the early vertebrate embryo. The absence of Cerl2 results in a wide spectrum of malformations commonly known as heterotaxia, which comprises defects in either global organ position (e.g., situs inversus totalis), reversed orientation of at least one organ (e.g., situs ambiguus), and mirror images of usually asymmetric paired organs (e.g., left or right isomerisms of the lungs). Moreover, these laterality defects are frequently associated with congenital heart diseases (e.g., transposition of the great arteries, or atrioventricular septal defects). Here, reviewing the knowledge on the establishment of LR asymmetry in mouse embryos, the emerging conclusion is that as necessary as is the activation of the Nodal signaling cascade, the tight control that Cerl2-mediates on Nodal signaling is equally important, and that generates a further regionalized LR genetic program in the proper time and space. PMID:29367552

Bifilm Defect Formation in Hydraulic Jump of Liquid Aluminum

NASA Astrophysics Data System (ADS)

Hsu, Fu-Yuan

2016-06-01

In aluminum gravity casting, as liquid aluminum fell through a vertical sprue and impacted on the horizontal flat surface, a phenomenon known as hydraulic jump ( i.e., flow transition from super-critical to sub-critical flows) was observed. As the jump was transformed, a reverse eddy motion on the surface of the jump was created. This motion entrained aluminum oxide film from the surface into aluminum melt. This folded film (so-called "bifilm" defect) was engulfed by the melt and caused its quality to deteriorate. To understand this phenomenon, aluminum casting experiments and computational modeling were conducted. In the casting experiment, a radius ( R j) to the point where the circular hydraulic jump occurred was measured. This is the circular region of `irregular surface feature', a rough oxidized surface texture near the center area of the castings. To quantify contents of the bifilm defects in the outer region of the jump, the samples in this region were sectioned and re-melted for doing re-melted reduced pressure test (re-melt RPT). An "area-normalized" bifilm index map was plotted to analyze bifilms' population in the samples. The flow transition in the hydraulic jump of liquid aluminum depended on three pressure heads: inertial, gravitational, and surface-tension pressures. A new theoretical equation containing surface tension for describing the flow transition of liquid metal was proposed.

Controlled manipulation of flexible carbon nanotubes through shape-dependent pushing by atomic force microscopy.

PubMed

Yang, Seung-Cheol; Qian, Xiaoping

2013-09-17

A systematic approach to manipulating flexible carbon nanotubes (CNTs) has been developed on the basis of atomic force microscope (AFM) based pushing. Pushing CNTs enables efficient transport and precise location of individual CNTs. A key issue for pushing CNTs is preventing defective distortion in repetitive bending and unbending deformation. The approach presented here controls lateral movement of an AFM tip to bend CNTs without permanent distortion. The approach investigates possible defects caused by tensile strain of the outer tube under uniform bending and radial distortion by kinking. Using the continuum beam model and experimental bending tests, dependency of maximum bending strain on the length of bent CNTs and radial distortion on bending angles at a bent point have been demonstrated. Individual CNTs are manipulated by limiting the length of bent CNTs and the bending angle. In our approach, multiwalled CNTs with 5-15 nm diameter subjected to bending deformation produce no outer tube breakage under uniform bending and reversible radial deformation with bending angles less than 110°. The lateral tip movement is determined by a simple geometric model that relies on the shape of multiwalled CNTs. The model effectively controls deforming CNT length and bending angle for given CNT shape. Experimental results demonstrate successful manipulation of randomly dispersed CNTs without visual defects. This approach to pushing can be extended to develop a wide range of CNT based nanodevice applications.

Room temperature ferromagnetism in liquid-phase pulsed laser ablation synthesized nanoparticles of nonmagnetic oxides

NASA Astrophysics Data System (ADS)

Singh, S. C.; Kotnala, R. K.; Gopal, R.

2015-08-01

Intrinsic Room Temperature Ferromagnetism (RTF) has been observed in undoped/uncapped zinc oxide and titanium dioxide spherical nanoparticles (NPs) obtained by a purely green approach of liquid phase pulsed laser ablation of corresponding metal targets in pure water. Saturation magnetization values observed for zinc oxide (average size, 9 ± 1.2 nm) and titanium dioxide (average size, 4.4 ± 0.3 nm) NPs are 62.37 and 42.17 memu/g, respectively, which are several orders of magnitude larger than those of previous reports. In contrast to the previous works, no postprocessing treatments or surface modification is required to induce ferromagnetism in the case of present communication. The most important result, related to the field of intrinsic ferromagnetism in nonmagnetic materials, is the observation of size dependent ferromagnetism. Degree of ferromagnetism in titanium dioxide increases with the increase in particle size, while it is reverse for zinc oxide. Surface and volume defects play significant roles for the origin of RTF in zinc oxide and titanium dioxide NPs, respectively. Single ionized oxygen and neutral zinc vacancies in zinc oxide and oxygen and neutral/ionized titanium vacancies in titanium dioxide are considered as predominant defect centres responsible for observed ferromagnetism. It is expected that origin of ferromagnetism is a consequence of exchange interactions between localized electron spin moments resulting from point defects.

Room temperature ferromagnetism in liquid-phase pulsed laser ablation synthesized nanoparticles of nonmagnetic oxides

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

Singh, S. C., E-mail: subhash.laserlab@gmail.com; Gopal, R.; Kotnala, R. K.

2015-08-14

Intrinsic Room Temperature Ferromagnetism (RTF) has been observed in undoped/uncapped zinc oxide and titanium dioxide spherical nanoparticles (NPs) obtained by a purely green approach of liquid phase pulsed laser ablation of corresponding metal targets in pure water. Saturation magnetization values observed for zinc oxide (average size, 9 ± 1.2 nm) and titanium dioxide (average size, 4.4 ± 0.3 nm) NPs are 62.37 and 42.17 memu/g, respectively, which are several orders of magnitude larger than those of previous reports. In contrast to the previous works, no postprocessing treatments or surface modification is required to induce ferromagnetism in the case of present communication. The most important result, relatedmore » to the field of intrinsic ferromagnetism in nonmagnetic materials, is the observation of size dependent ferromagnetism. Degree of ferromagnetism in titanium dioxide increases with the increase in particle size, while it is reverse for zinc oxide. Surface and volume defects play significant roles for the origin of RTF in zinc oxide and titanium dioxide NPs, respectively. Single ionized oxygen and neutral zinc vacancies in zinc oxide and oxygen and neutral/ionized titanium vacancies in titanium dioxide are considered as predominant defect centres responsible for observed ferromagnetism. It is expected that origin of ferromagnetism is a consequence of exchange interactions between localized electron spin moments resulting from point defects.« less

Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation

PubMed Central

Grond, Susanne; Radner, Franz P.W.; Eichmann, Thomas O.; Kolb, Dagmar; Grabner, Gernot F.; Wolinski, Heimo; Gruber, Robert; Hofer, Peter; Heier, Christoph; Schauer, Silvia; Rülicke, Thomas; Hoefler, Gerald; Schmuth, Matthias; Elias, Peter M.; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

2017-01-01

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism. PMID:27725204

Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

PubMed Central

Koppe, Laetitia; Nyam, Elsa; Vivot, Kevin; Manning Fox, Jocelyn E.; Dai, Xiao-Qing; Nguyen, Bich N.; Attané, Camille; Moullé, Valentine S.; MacDonald, Patrick E.; Ghislain, Julien

2016-01-01

Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis. PMID:27525435

Calcium signals act through histone deacetylase to mediate pronephric kidney morphogenesis.

PubMed

Rothschild, Sarah C; Lee, Hunter J; Ingram, Sarah R; Mohammadi, Daniel K; Walsh, Gregory S; Tombes, Robert M

2018-06-01

Autosomal dominant polycystic kidney disease is the most common monogenetic kidney disorder and is linked to mutations in PKD1 and PKD2. PKD2, a Ca 2+ -conducting TRP channel enriched in ciliated cells and gated by extracellular signals, is necessary to activate the multifunctional Ca 2+/ calmodulin-dependent protein kinase type 2 (CaMK-II), enabling kidney morphogenesis and cilia stability. In this study, antisense morpholino oligonucleotides and pharmacological compounds were employed to investigate the roles of class II HDAC family members (HDAC 4, 5, and 6) in Zebrafish kidney development. While all three class II HDAC genes were expressed throughout the embryo during early development, HDAC5-morphant embryos exhibited anterior cysts and destabilized cloacal cilia, similar to PKD2 and CaMK-II morphants. In contrast, HDAC4-morphant embryos exhibited elongated cloacal cilia and lacked anterior kidney defects. Suppression of HDAC4 partially reversed the cilia shortening and anterior convolution defects caused by CaMK-II deficiency, whereas HDAC5 loss exacerbated these defects. EGFP-HDAC4, but not EGFP-HDAC5, translocated into the nucleus upon CaMK-II suppression in pronephric kidney cells. These results support a model by which activated CaMK-II sequesters HDAC4 in the cytosol to enable primary cilia formation and kidney morphogenesis. Developmental Dynamics 247:807-817, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Type 2 diabetes mellitus and exercise impairment.

PubMed

Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G

2013-03-01

Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.

Exploiting Photo-induced Reactions in Polymer Blends to Create Hierarchically Ordered, Defect-free Materials

ScienceCinema

Balazs, Anna [University of Pittsburgh, Pittsburgh, Pennsylvania, United States

2017-12-09

Computer simulations reveal how photo-induced chemical reactions can be exploited to create long-range order in binary and ternary polymeric materials. The process is initiated by shining a spatially uniform light over a photosensitive AB binary blend, which undergoes both a reversible chemical reaction and phase separation. We then introduce a well-collimated, higher-intensity light source. Rastering this secondary light over the sample locally increases the reaction rate and causes formation of defect-free, spatially periodic structures. These binary structures resemble either the lamellar or hexagonal phases of microphase-separated di-block copolymers. We measure the regularity of the ordered structures as a function of the relative reaction rates for different values of the rastering speed and determine the optimal conditions for creating defect-free structures in the binary systems. We then add a non-reactive homo-polymer C, which is immiscible with both A and B. We show that this component migrates to regions that are illuminated by the secondary, higher-intensity light, allowing us to effectively write a pattern of C onto the AB film. Rastering over the ternary blend with this collimated light now leads to hierarchically ordered patterns of A, B, and C. The findings point to a facile, non-intrusive process for manufacturing high-quality polymeric devices in a low-cost, efficient manner.

Point mutation in D8C domain of Tamm-Horsfall protein/uromodulin in transgenic mice causes progressive renal damage and hyperuricemia

PubMed Central

Landry, Nichole K.; El-Achkar, Tarek M.; Lieske, John C.

2017-01-01

Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys’ thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance. Both the young and the old transgenic mice had significantly higher serum uric acid and its catabolic product, allantoin, than age-matched wild-type mice. This THP mutation apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1. Our results strongly suggest that the progressive worsening of kidney functions reflects the accumulation of the deleterious effects of the misfolded mutant THP and the compensatory responses. Transgenic mice recapitulating human THP/uromodulin-associated kidney diseases could be used to elucidate their pathogenesis and test novel therapeutic strategies. PMID:29145399

Point mutation in D8C domain of Tamm-Horsfall protein/uromodulin in transgenic mice causes progressive renal damage and hyperuricemia.

PubMed

Ma, Lijie; Liu, Yan; Landry, Nichole K; El-Achkar, Tarek M; Lieske, John C; Wu, Xue-Ru

2017-01-01

Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance. Both the young and the old transgenic mice had significantly higher serum uric acid and its catabolic product, allantoin, than age-matched wild-type mice. This THP mutation apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1. Our results strongly suggest that the progressive worsening of kidney functions reflects the accumulation of the deleterious effects of the misfolded mutant THP and the compensatory responses. Transgenic mice recapitulating human THP/uromodulin-associated kidney diseases could be used to elucidate their pathogenesis and test novel therapeutic strategies.

Assembly of oligomeric death domain complexes during Toll receptor signaling.

PubMed

Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

2008-11-28

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

PubMed Central

Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

2008-01-01

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

Receptoral and postreceptoral visual processes in recovery from chromatic adaptation.

PubMed Central

Jameson, D; Hurvich, L M; Varner, F D

1979-01-01

The time course of recovery from chromatic adaptation in human vision was tracked by determining the wavelength of light that appears uniquely yellow (neither red nor green) both before and after exposure to yellowish green and yellowish red adapting lights. Recovery is complete within 5 min after steady light exposure. After exposure to the alternating repeated sequence 10-sec light/10-sec dark, the initial magnitude of the aftereffect is reduced but recovery is retarded. The results are interpreted in terms of two processes located at different levels in the hierarchical organization of the visual system. One is a change in the balance of cone receptor sensitivities; the second is a shift in the equilibrium baseline between opposite-signed responses of the red/green channel at the opponent-process neural level. The baseline-shift mechanism is effective in the condition in which repeated input signals originating at the receptors are of sufficient strength to activate the system effectively. Hence, this process is revealed in the alternating adaptation condition when the receptors undergo partial recovery after each light exposure, but receptor adaptation during continued steady light exposure effectively protects the subsequent neural systems from continued strong activation. PMID:288087

The behavioral pharmacology of hallucinogens

PubMed Central

Fantegrossi, William E.; Murnane, Aeneas C.; Reissig, Chad J.

2008-01-01

Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds. PMID:17977517

Spatial imaging in color and HDR: prometheus unchained

NASA Astrophysics Data System (ADS)

McCann, John J.

2013-03-01

The Human Vision and Electronic Imaging Conferences (HVEI) at the IS and T/SPIE Electronic Imaging meetings have brought together research in the fundamentals of both vision and digital technology. This conference has incorporated many color disciplines that have contributed to the theory and practice of today's imaging: color constancy, models of vision, digital output, high-dynamic-range imaging, and the understanding of perceptual mechanisms. Before digital imaging, silver halide color was a pixel-based mechanism. Color films are closely tied to colorimetry, the science of matching pixels in a black surround. The quanta catch of the sensitized silver salts determines the amount of colored dyes in the final print. The rapid expansion of digital imaging over the past 25 years has eliminated the limitations of using small local regions in forming images. Spatial interactions can now generate images more like vision. Since the 1950's, neurophysiology has shown that post-receptor neural processing is based on spatial interactions. These results reinforced the findings of 19th century experimental psychology. This paper reviews the role of HVEI in color, emphasizing the interaction of research on vision and the new algorithms and processes made possible by electronic imaging.

Effects of choline on sodium arsenite-induced neural tube defects in chick embryos.

PubMed

Song, Ge; Cui, Yi; Han, Zhong-Ji; Xia, Hong-Fei; Ma, Xu

2012-12-01

Arsenic passes through the placenta and accumulates in the neuroepithelium of embryo, whereby inducing congenital malformations such as neural tube defects (NTDs) in animals. Choline (CHO), a methyl-rich nutrient, functions as a methyl donor to participate in methyl group metabolism. Arsenic methylation has been regarded as a detoxification process and choline (CHO) is the major source of methyl-groups. However, whether CHO intake reverses the abnormal embryo development induced by sodium arsenite (SA) and the relationship between CHO intake and arsenite-induced NTDs are still unclear. In this study, we used chick embryos as animal model to investigate the effects of SA and CHO supplementation on the early development of nervous system. Our results showed that the administration of SA led to reduction in embryo viability, embryo body weight and extraembryonic vascular area, accompanied by a significantly increased incidence of the failed closure of the caudal end of the neural tube. CHO, at low dose (25 μg/μL), reversed the decrease in embryo viability and the increase in the failed closure of the caudal end of the neural tube, which were induced by SA. In addition, CHO (25 μg/μL) inhibited not only the SA-induced cell apoptosis by up-regulating Bcl-2 level, but also the global DNA methylation by increasing the expressions of DNMT1 and DNMT3a. However, less significant difference was found between the embryos co-treated with SA and CHO (50 μg/μL) and the ones treated with SA alone. Taken together, these findings suggest that low dose CHO could protect chick embryos from arsenite-induced NTDs by a possible mechanism related to the methyl metabolism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

PubMed Central

Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

2015-01-01

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

Modeling the instability behavior of thin film devices: Fermi Level Pinning

NASA Astrophysics Data System (ADS)

Moeini, Iman; Ahmadpour, Mohammad; Gorji, Nima E.

2018-05-01

We investigate the underlying physics of degradation/recovery of a metal/n-CdTe Schottcky junction under reverse or forward bias stressing conditions. We used Sah-Noyce-Shockley (SNS) theory to investigate if the swept of Fermi level pinning at different levels (under forward/reverse bias) is the origin of change in current-voltage characteristics of the device. This theory is based on Shockley-Read-Hall recombination within the depletion width and takes into account the interface defect levels. Fermi Level Pinning theory was primarily introduced by Ponpon and developed to thin film solar cells by Dharmadasa's group in Sheffield University-UK. The theory suggests that Fermi level pinning at multiple levels occurs due to high concentration of electron-traps or acceptor-like defects at the interface of a Schottky or pn junction and this re-arranges the recombination rate and charage collection. Shift of these levels under stress conditions determines the change in current-voltage characteristics of the cell. This theory was suggested for several device such as metal/n-CdTe, CdS/CdTe, CIGS/CdS or even GaAs solar cells without a modeling approach to clearly explain it's physics. We have applied the strong SNS modeling approach to shed light on Fermi Level Pinning theory. The modeling confirms that change in position of Fermi Level and it's pining in a lower level close to Valence band increases the recombination and reduces the open-circuit voltage. In contrast, Fermi Level pinning close to conduction band strengthens the electric field at the junction which amplifies the carrier collection and boosts the open-circuit voltage. This theory can well explain the stress effect on device characteristics of various solar cells or Schottky junctions by simply finding the right Fermi level pinning position at every specific stress condition.

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome.

PubMed

Suvrathan, Aparna; Hoeffer, Charles A; Wong, Helen; Klann, Eric; Chattarji, Sumantra

2010-06-22

Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased paired-pulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework.

Controlling depinning and propagation of single domain-walls in magnetic microwires

NASA Astrophysics Data System (ADS)

Jiménez, Alejandro; del Real, Rafael P.; Vázquez, Manuel

2013-03-01

The magnetization reversal in magnetostrictive amorphous microwires takes place by depinning and propagation of a single domain wall. This is a consequence of the particular domain structure determined by the strong uniaxial anisotropy from the reinforcement of magnetoelastic and shape contributions. In the present study, after an overview on the current state-of-the art on the topic, we introduce the general behaviour of single walls in 30 to 40 cm long Fe-base microwires propagating under homogeneous field. Depending on the way the walls are generated, we distinguish among three different walls namely, standard wall, DWst, depinned and propagating from the wire's end under homogeneous field which motion is the first one to switch on; reverse wall, DWrev, propagating from the opposite end under non-homogeneous field, and defect wall, DWdef, nucleated around local defect. Both, DWrev and DWdef are observed only under large enough applied field. In the subsequent section, we study the propagation of a wall under applied field smaller than the switching field. There, we conclude that a minimum field, Hdep,0, is needed to depin the DWst, as well as that a minimum field, Hprop,0, is required for the wall to propagate long distances. In the last section, we analyse the shape of induced signals in the pickup coils upon the crossing of the walls and its correlation to the domain walls shape. We conclude that length and shape of the wall are significantly distorted by the fact that the wall is typically as long as the measuring coils. Contribution to the Topical Issue "New Trends in Magnetism and Magnetic Materials", edited by Francesca Casoli, Massimo Solzi and Paola Tiberto.

BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease.

PubMed

Burke, Rebecca M; Norman, Timothy A; Haydar, Tarik F; Slack, Barbara E; Leeman, Susan E; Blusztajn, Jan Krzysztof; Mellott, Tiffany J

2013-11-26

Bone morphogenetic protein 9 (BMP9) promotes the acquisition of the cholinergic phenotype in basal forebrain cholinergic neurons (BFCN) during development and protects these neurons from cholinergic dedifferentiation following axotomy when administered in vivo. A decline in BFCN function occurs in patients with Alzheimer's disease (AD) and contributes to the AD-associated memory deficits. We infused BMP9 intracerebroventricularly for 7 d in transgenic AD model mice expressing green fluorescent protein specifically in cholinergic neurons (APP.PS1/CHGFP) and in wild-type littermate controls (WT/CHGFP). We used 5-mo-old mice, an age when the AD transgenics display early amyloid deposition and few cholinergic defects, and 10-mo-old mice, by which time these mice exhibit established disease. BMP9 infusion reduced the number of Aβ42-positive amyloid plaques in the hippocampus and cerebral cortex of 5- and 10-mo-old APP.PS1/CHGFP mice and reversed the reductions in choline acetyltransferase protein levels in the hippocampus of 10-mo-old APP.PS1/CHGFP mice. The treatment increased cholinergic fiber density in the hippocampus of both WT/CHGFP and APP.PS1/CHGFP mice at both ages. BMP9 infusion also increased hippocampal levels of neurotrophin 3, insulin-like growth factor 1, and nerve growth factor and of the nerve growth factor receptors, tyrosine kinase receptor A and p75/NGFR, irrespective of the genotype of the mice. These data show that BMP9 administration is effective in reducing the Aβ42 amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for BFCN in a mouse model of AD and provide evidence that the BMP9-signaling pathway may constitute a therapeutic target for AD.

Integrated arc suppression unit for defect reduction in PVD applications

NASA Astrophysics Data System (ADS)

Li, Jason; Narasimhan, Murali K.; Pavate, Vikram; Loo, David; Rosenblum, Steve; Trubell, Larry; Scholl, Richard; Seamons, Scott; Hagerty, Chris; Ramaswami, Sesh

1997-09-01

Arcing between the target and plasma during PVD deposition causes substantial damage to the target and splats and other contamination on the deposited films. Arc-related damages and defects are frequently encountered in microelectronics manufacturing and contributes largely to reduced wafer yields. Arcing is caused largely by the charge buildup at the contaminated sites on the target surface that contains either nonconducting inclusions or nodules. Arc suppression is a key issue for defect reduction, yield improvement and for reliable high quality metallization. An Integrated Arc Suppression Unit (IASU) has been designed for Endura HP PVDTM sputtering sources. The integrated design reduces cable length from unit to source and reduces electrical energy stored in the cable. Active arc handling mode, proactive arc prevention mode, and passive by-pass arc counting mode are incorporated into the same unit. The active mode is designed to quickly respond to chamber conditions, like a large chamber voltage drop, that signals a arc. The self run mode is designed to proactively prevent arc formation by pulsing and reversing target voltage at 50 kHz. The design of the IASU, also called mini small package arc repression circuit--low energy unit (mini Sparc-le), has been optimized for various DC magnetron sources, plasma stability, chamber impedance, power matching, CE MARK test, and power dissipation. Process characterization with Ti, TiN and Al sputtering indicates that the unit has little adverse impact on film properties. Mini Sparc-le unit has been shown here to significantly reduce splats occurrence in Al sputtering. Marathon test of the unit with Ti/TiN test demonstrated the unit's reliability and its ability to reduce sensitivity of defects to target characteristics.

The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels

PubMed Central

2011-01-01

Background The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of Foxg1 null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed Foxg1+/+↔Foxg1-/- chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells. Results Our analysis showed that the Foxg1-/- cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in Foxg1-/- dorsal telencephalic cells. We went on to show that the introduction into Foxg1-/- embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects. Conclusions We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner. PMID:21418559

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

PubMed Central

Sabbagh, Sébastien C.; Lepage, Christine; McClelland, Michael; Daigle, France

2012-01-01

The human-adapted Salmonella enterica serovar Typhi (S. Typhi) causes a systemic infection known as typhoid fever. This disease relies on the ability of the bacterium to survive within macrophages. In order to identify genes involved during interaction with macrophages, a pool of approximately 105 transposon mutants of S. Typhi was subjected to three serial passages of 24 hours through human macrophages. Mutants recovered from infected macrophages (output) were compared to the initial pool (input) and those significantly underrepresented resulted in the identification of 130 genes encoding for cell membrane components, fimbriae, flagella, regulatory processes, pathogenesis, and many genes of unknown function. Defined deletions in 28 genes or gene clusters were created and mutants were evaluated in competitive and individual infection assays for uptake and intracellular survival during interaction with human macrophages. Overall, 26 mutants had defects in the competitive assay and 14 mutants had defects in the individual assay. Twelve mutants had defects in both assays, including acrA, exbDB, flhCD, fliC, gppA, mlc, pgtE, typA, waaQGP, SPI-4, STY1867-68, and STY2346. The complementation of several mutants by expression of plasmid-borne wild-type genes or gene clusters reversed defects, confirming that the phenotypic impairments within macrophages were gene-specific. In this study, 35 novel phenotypes of either uptake or intracellular survival in macrophages were associated with Salmonella genes. Moreover, these results reveal several genes encoding molecular mechanisms not previously known to be involved in systemic infection by human-adapted typhoidal Salmonella that will need to be elucidated. PMID:22574205

Methionine Biosynthesis is Essential for Infection in the Rice Blast Fungus Magnaporthe oryzae

PubMed Central

Gagey, Marie Josèphe; Frelin, Océane; Beffa, Roland; Lebrun, Marc Henri; Droux, Michel

2015-01-01

Methionine is a sulfur amino acid standing at the crossroads of several biosynthetic pathways. In fungi, the last step of methionine biosynthesis is catalyzed by a cobalamine-independent methionine synthase (Met6, EC 2.1.1.14). In the present work, we studied the role of Met6 in the infection process of the rice blast fungus, Magnaporthe oryzae. To this end MET6 null mutants were obtained by targeted gene replacement. On minimum medium, MET6 null mutants were auxotrophic for methionine. Even when grown in presence of excess methionine, these mutants displayed developmental defects, such as reduced mycelium pigmentation, aerial hypha formation and sporulation. They also displayed characteristic metabolic signatures such as increased levels of cysteine, cystathionine, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine while methionine and glutathione levels remained unchanged. These metabolic perturbations were associated with the over-expression of MgCBS1 involved in the reversed transsulfuration pathway that metabolizes homocysteine into cysteine and MgSAM1 and MgSAHH1 involved in the methyl cycle. This suggests a physiological adaptation of M. oryzae to metabolic defects induced by the loss of Met6, in particular an increase in homocysteine levels. Pathogenicity assays showed that MET6 null mutants were non-pathogenic on both barley and rice leaves. These mutants were defective in appressorium-mediated penetration and invasive infectious growth. These pathogenicity defects were rescued by addition of exogenous methionine and S-methylmethionine. These results show that M. oryzae cannot assimilate sufficient methionine from plant tissues and must synthesize this amino acid de novo to fulfill its sulfur amino acid requirement during infection. PMID:25856162

Transforming growth factor-beta1 promotes articular cartilage repair through canonical Smad and Hippo pathways in bone mesenchymal stem cells.

PubMed

Ying, Jun; Wang, Pinger; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Dong, Rui; Xu, Shibing; Tong, Peijian; Wu, Chengliang; Jin, Hongting

2018-01-01

Transforming growth factor-β1 (TGF-β1) is a chondrogenic factor and has been reported to be able to enhance chondrocyte differentiation from bone marrow mesenchymal stem cells (BMSCs). Here we investigate the molecular mechanism through which TGF-β1 chronically promotes the repair of cartilage defect and inhibit chondrocyte hypertrophy. Animal models of full thickness cartilage defects were divided into three groups: model group, BMSCs group (treated with BMSCs/calcium alginate gel) and BMSCs+TGF-β1 group (treated with Lentivirus-TGF-β1-EGFP transduced BMSCs/calcium alginate gel). 4 and 8weeks after treatment, macroscopic observation, histopathological study and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were done to analyze phenotypes of the animals. BMSCs were transduced with Lentivirus-TGF-β1-EGFP in vitro and Western blot analysis was performed. We found that TGF-β1-expressiing BMSCs improved the repair of the cartilage defect. The impaired cartilage contained higher amount of GAG and type II collagen and was integrated to the surrounding normal cartilage and higher content of GAG and type II collagen. The major events include increased expression of type II collagen following Smad2/3 phosphorylation, and inhibition of cartilage hypertrophy by increasing Yes-associated protein-1 (YAP-1) and inhibiting Runx2 and Col10 after the completion of chondrogenic differentiation. We conclude that TGF-β1 is beneficial to chondrogenic differentiation of BMSCs via canonical Smad pathway to promote early-repairing of cartilage defect. Furthermore, TGF-β1 inhibits chondrocyte hypertrophy by decreasing hypertrophy marker gene expression via Hippo signaling. Long-term rational use of TGF-β1 may be an alternative approach in clinic for cartilage repair and regeneration. Copyright © 2017. Published by Elsevier Inc.

Late Maternal Folate Supplementation Rescues from Methyl Donor Deficiency-Associated Brain Defects by Restoring Let-7 and miR-34 Pathways.

PubMed

Geoffroy, Andréa; Kerek, Racha; Pourié, Grégory; Helle, Déborah; Guéant, Jean-Louis; Daval, Jean-Luc; Bossenmeyer-Pourié, Carine

2017-09-01

The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid. However, the question about the duration and periodicity of supplementation remains. We therefore tested maternal supply (3 mg/kg/day) during the last third of gestation from embryonic days (E) 13 to 20. Methyl donor deficiency-related developmental disorders at E20, including cerebellar and interhemispheric suture defects and atrophy of selective cerebral layers, were associated with increased brain expression (by 2.5-fold) of let-7a and miR-34a, with subsequent downregulation of their regulatory targets such as Trim71 and Notch signaling partners, respectively. These processes could be reversed by siRNA strategy in differentiating neuroprogenitors lacking folate, with improvement of their morphological characteristics. While folic acid supplementation helped restoring the levels of let-7a and miR-34a and their downstream targets, it led to a reduction of structural and functional defects taking place during the perinatal period. Our data outline the potential role of let-7 and miR-34 and their related signaling pathways in the developmental defects following gestational methyl donor deficiency and support the likely usefulness of late folate supplementation in at risk women.