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Sample records for hyperphosphorylation detaches 3-repeat

  1. Retinal Detachment: Torn or Detached Retina Diagnosis

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Diagnosis Written by: Kierstan Boyd ...

  2. Retinal Detachment: Torn or Detached Retina Symptoms

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Symptoms Written by: Kierstan Boyd ...

  3. Divertor detachment

    NASA Astrophysics Data System (ADS)

    Krasheninnikov, Sergei

    2015-11-01

    The heat exhaust is one of the main conceptual issues of magnetic fusion reactor. In a standard operational regime the large heat flux onto divertor target reaches unacceptable level in any foreseeable reactor design. However, about two decades ago so-called ``detached divertor'' regimes were found. They are characterized by reduced power and plasma flux on divertor targets and look as a promising solution for heat exhaust in future reactors. In particular, it is envisioned that ITER will operate in a partly detached divertor regime. However, even though divertor detachment was studied extensively for two decades, still there are some issues requiring a new look. Among them is the compatibility of detached divertor regime with a good core confinement. For example, ELMy H-mode exhibits a very good core confinement, but large ELMs can ``burn through'' detached divertor and release large amounts of energy on the targets. In addition, detached divertor regimes can be subject to thermal instabilities resulting in the MARFE formation, which, potentially, can cause disruption of the discharge. Finally, often inner and outer divertors detach at different plasma conditions, which can lead to core confinement degradation. Here we discuss basic physics of divertor detachment including different mechanisms of power and momentum loss (ionization, impurity and hydrogen radiation loss, ion-neutral collisions, recombination, and their synergistic effects) and evaluate the roles of different plasma processes in the reduction of the plasma flux; detachment stability; and an impact of ELMs on detachment. We also evaluate an impact of different magnetic and divertor geometries on detachment onset, stability, in- out- asymmetry, and tolerance to the ELMs. Supported by the U.S. Department of Energy Office of Science, Office of Fusion Energy Sciences under Award Number DE-DE-FG02-04ER54739 at UCSD.

  4. Retinal detachment

    MedlinePlus

    ... separate from the underlying tissues, much like a bubble under wallpaper. This is most often caused by ... small detachment, the doctor may place a gas bubble in the eye. This is called pneumatic retinopexy. ...

  5. Retinal Detachment

    MedlinePlus

    ... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...

  6. Retinal detachment

    MedlinePlus

    ... of the first symptoms of new flashes of light and floaters. ... diabetes. See your eye care specialist once a year. You may need more frequent visits if you have risk factors for retinal detachment. Be alert to symptoms of new flashes of light and floaters.

  7. Retinal Detachment Vision Simulator

    MedlinePlus

    ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment Vision Simulator Mar. 01, 2016 How does a detached or torn retina affect your vision? If a retinal tear is occurring, you may ...

  8. Hyperphosphorylation results in tau dysfunction in DNA folding and protection.

    PubMed

    Lu, Yang; He, Hai-Jin; Zhou, Jun; Miao, Jun-Ye; Lu, Jing; He, Ying-Ge; Pan, Rong; Wei, Yan; Liu, Ying; He, Rong-Qiao

    2013-01-01

    Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies. PMID:24064506

  9. Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

    PubMed Central

    Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B.; Baillargeon, Joanie; Hébert, Sébastien S.; Planel, Emmanuel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro. PMID:22768202

  10. Hyperphosphorylation as a defense mechanism to reduce TDP-43 aggregation.

    PubMed

    Li, Huei-Ying; Yeh, Po-An; Chiu, Hsiu-Chiang; Tang, Chiou-Yang; Tu, Benjamin Pang-hsien

    2011-01-01

    Several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are characterized by inclusion bodies formed by TDP-43 (TDP). We established cell and transgenic Drosophila models expressing TDP carboxyl terminal fragment (ND251 and ND207), which developed aggregates recapitulating important features of TDP inclusions in ALS/FTLD-U, including hyperphosphorylation at previously reported serine(403,404,409,410) residues, polyubiquitination and colocalization with optineurin. These models were used to address the pathogenic role of hyperphosphorylation in ALS/FTLD-U. We demonstrated that hyperphosphorylation and ubiquitination occurred temporally later than aggregation in cells. Expression of CK2α which phosphorylated TDP decreased the aggregation propensity of ND251 or ND207; this effect could be blocked by CK2 inhibitor DMAT. Mutation of serines(379,403,404,409,410) to alanines (S5A) to eliminate phosphorylation increased the aggregation propensity and number of aggregates of TDP, but mutation to aspartic acids (S5D) or glutamic acids (S5E) to simulate hyperphosphorylation had the opposite effect. Functionally, ND251 or ND207 aggregates decreased the number of neurites of Neuro2a cells induced by retinoic acid or number of cells by MTT assay. S5A mutation aggravated, but S5E mutation alleviated these cytotoxic effects of aggregates. Finally, ND251 or ND251S5A developed aggregates in neurons, and salivary gland of transgenic Drosophila, but ND251S5E did not. Taken together, our data indicate that hyperphosphorylation may represent a compensatory defense mechanism to stop or prevent pathogenic TDP from aggregation. Therefore, enhancement of phosphorylation may serve as an effective therapeutic strategy against ALS/FTLD-U. PMID:21850253

  11. Descemet membrane detachment.

    PubMed

    Mackool, R J; Holtz, S J

    1977-03-01

    Four eyes of three patients had extensive postoperative Descemet membrane (DM) detachment. Blood was present just anterior to the DM in three of the four eyes and later converted to and persisted as pigment. Haziness of the cornea at the level of the DM could be seen with reattachment. Detachments of the DM are classified as planar when there is 1 mm or less separation of the DM from its overlying stroma in all areas. Nonplanar DM detachments exceed 1 mm of separation. Planar detachments have a much better prognosis than nonplanar detachments do, with or without descemetopexy. Repair of DM detachments, when necessary, should include air injection, with the lease possible instrumentation of the DM. PMID:843278

  12. Modeling of Detached Solidification

    NASA Technical Reports Server (NTRS)

    Regel, Liya L.; Wilcox, William R.; Popov, Dmitri

    1997-01-01

    Our long term goal is to develop techniques to achieve detached solidification reliably and reproducibly, in order to produce crystals with fewer defects. To achieve this goal it is necessary to understand thoroughly the physics of detached solidification. It was the primary objective of the current project to make progress toward this complete understanding. 'Me products of this grant are attached. These include 4 papers and a preliminary survey of the observations of detached solidification in space. We have successfully modeled steady state detached solidification, examined the stability of detachment, and determined the influence of buoyancy-driven convection under different conditions. Directional solidification in microgravity has often led to ingots that grew with little or no contact with the ampoule wall. When this occurred, crystallographic perfection was usually greatly improved -- often by several orders of magnitude. Indeed, under the Soviet microgravity program the major objective was to achieve detached solidification with its resulting improvement in perfection and properties. Unfortunately, until recently the true mechanisms underlying detached solidification were unknown. As a consequence, flight experiments yielded erratic results. Within the past three years, we have developed a new theoretical model that explains many of the flight results. This model gives rise to predictions of the conditions required to yield detached solidification.

  13. Divertor plasma detachment

    NASA Astrophysics Data System (ADS)

    Krasheninnikov, S. I.; Kukushkin, A. S.; Pshenov, A. A.

    2016-05-01

    Regime with the plasma detached from the divertor targets (detached divertor regime) is a natural continuation of the high recycling conditions to higher density and stronger impurity radiation loss. Both the theoretical considerations and experimental data show clearly that the increase of the impurity radiation loss and volumetric plasma recombination causes the rollover of the plasma flux to the target when the density increases, which is the manifestation of detachment. Plasma-neutral friction (neutral viscosity effects), although important for the sustainment of high density/pressure plasma upstream and providing the conditions for efficient recombination and power loss, is not directly involved in the reduction of the plasma flux to the targets. The stability of detachment is also discussed.

  14. Retinal detachment in pseudophakia.

    PubMed

    Galin, M A; Poole, T A; Obstbaum, S A

    1979-07-01

    In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively. PMID:464014

  15. VANISHING RETINAL DETACHMENT

    PubMed Central

    2015-01-01

    Purpose: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. Methods: Retrospective case report. Results: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow-up 8 months later. The workup of alternate etiologies was unrevealing. Conclusion: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised. PMID:26352323

  16. Detached rock evaluation device

    DOEpatents

    Hanson, David R.

    1986-01-01

    A rock detachment evaluation device (10) having an energy transducer unit 1) for sensing vibrations imparted to a subject rock (172) for converting the sensed vibrations into electrical signals, a low band pass filter unit (12) for receiving the electrical signal and transmitting only a low frequency segment thereof, a high band pass filter unit (13) for receiving the electrical signals and for transmitting only a high frequency segment thereof, a comparison unit (14) for receiving the low frequency and high frequency signals and for determining the difference in power between the signals, and a display unit (16) for displaying indicia of the difference, which provides a quantitative measure of rock detachment.

  17. Disruption of Myc-Tubulin Interaction by Hyperphosphorylation of c-Myc during Mitosis or by Constitutive Hyperphosphorylation of Mutant c-Myc in Burkitt's Lymphoma

    PubMed Central

    Niklinski, Jacek; Claassen, Gisela; Meyers, Cheryl; Gregory, Mark A.; Allegra, Carmen J.; Kaye, Frederic J.; Hann, Stephen R.; Zajac-Kaye, Maria

    2000-01-01

    Somatic mutations at Thr-58 of c-Myc have been detected in Burkitt's lymphoma (BL) tumors and have been shown to affect the transforming potential of the Myc oncoprotein. In addition, the N-terminal domain of c-Myc has been shown to interact with microtubules in vivo, and the binding of c-Myc to α-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with α-tubulin. In addition, we show that wild-type c-Myc–α-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells. PMID:10866684

  18. Hypothermia-induced hyperphosphorylation: a new model to study tau kinase inhibitors

    PubMed Central

    Bretteville, Alexis; Marcouiller, François; Julien, Carl; El Khoury, Noura B.; Petry, Franck R.; Poitras, Isabelle; Mouginot, Didier; Lévesque, Georges; Hébert, Sébastien S.; Planel, Emmanuel

    2012-01-01

    Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells. We have shown that hypothermia induces tau hyperphosphorylation in vitro and in vivo. Here, we hypothesized that hypothermia could be used to assess tau kinase inhibitors efficacy. Hypothermia applied to models of biological gradual complexity such as neuronal-like cells, ex vivo brain slices and adult non-transgenic mice leads to tau hyperphosphorylation at multiple AD-related phospho-epitopes. We show that Glycogen Synthase Kinase-3 inhibitors LiCl and AR-A014418, as well as roscovitine, a cyclin-dependent kinase 5 inhibitor, decrease hypothermia-induced tau hyperphosphorylation, leading to different tau phosphorylation profiles. Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors. PMID:22761989

  19. Stability of Detached Solidification

    NASA Technical Reports Server (NTRS)

    Mazuruk, K.; Volz, M. P.; Croell, A.

    2009-01-01

    Bridgman crystal growth can be conducted in the so-called "detached" solidification regime, where the growing crystal is detached from the crucible wall. A small gap between the growing crystal and the crucible wall, of the order of 100 micrometers or less, can be maintained during the process. A meniscus is formed at the bottom of the melt between the crystal and crucible wall. Under proper conditions, growth can proceed without collapsing the meniscus. The meniscus shape plays a key role in stabilizing the process. Thermal and other process parameters can also affect the geometrical steady-state stability conditions of solidification. The dynamic stability theory of the shaped crystal growth process has been developed by Tatarchenko. It consists of finding a simplified autonomous set of differential equations for the radius, height, and possibly other process parameters. The problem then reduces to analyzing a system of first order linear differential equations for stability. Here we apply a modified version of this theory for a particular case of detached solidification. Approximate analytical formulas as well as accurate numerical values for the capillary stability coefficients are presented. They display an unexpected singularity as a function of pressure differential. A novel approach to study the thermal field effects on the crystal shape stability has been proposed. In essence, it rectifies the unphysical assumption of the model that utilizes a perturbation of the crystal radius along the axis as being instantaneous. It consists of introducing time delay effects into the mathematical description and leads, in general, to stability over a broader parameter range. We believe that this novel treatment can be advantageously implemented in stability analyses of other crystal growth techniques such as Czochralski and float zone methods.

  20. Insulin resistance and muscle insulin receptor substrate‐1 serine hyperphosphorylation

    PubMed Central

    Stuart, Charles A.; Howell, Mary E. A.; Cartwright, Brian M.; McCurry, Melanie P.; Lee, Michelle L.; Ramsey, Michael W.; Stone, Michael H.

    2014-01-01

    Abstract Insulin resistance in metabolic syndrome subjects is profound in spite of muscle insulin receptor and insulin‐responsive glucose transporter (GLUT4) expression being nearly normal. Insulin receptor tyrosine kinase phosphorylation of insulin receptor substrate‐1 (IRS‐1) at Tyr896 is a necessary step in insulin stimulation of translocation of GLUT4 to the cell surface. Serine phosphorylation of IRS‐1 by some kinases diminishes insulin action in mice. We evaluated the phosphorylation status of muscle IRS‐1 in 33 subjects with the metabolic syndrome and seventeen lean controls. Each underwent euglycemic insulin clamps and a thigh muscle biopsy before and after 8 weeks of either strength or endurance training. Muscle IRS‐1 phosphorylation at six sites was quantified by immunoblots. Metabolic syndrome muscle IRS‐1 had excess phosphorylation at Ser337 and Ser636 but not at Ser307, Ser789, or Ser1101. Ser337 is a target for phosphorylation by glycogen synthase kinase 3 (GSK3) and Ser636 is phosphorylated by c‐Jun N‐terminal kinase 1 (JNK1). Exercise training without weight loss did not change the IRS‐1 serine phosphorylation. These data suggest that baseline hyperphosphorylation of at least two key serines within muscle IRS‐1 diminishes the transmission of the insulin signal and thereby decreases the insulin‐stimulated translocation of GLUT4. Excess fasting phosphorylation of muscle IRS‐1 at Ser636 may be a major cause of the insulin resistance seen in obesity and might prevent improvement in insulin responsiveness when exercise training is not accompanied by weight loss. PMID:25472611

  1. Cytoplasmic SET induces tau hyperphosphorylation through a decrease of methylated phosphatase 2A

    PubMed Central

    2014-01-01

    Background The neuronal cytoplasmic localization of SET, an inhibitor of the phosphatase 2A (PP2A), results in tau hyperphosphorylation in the brains of Alzheimer patients through mechanisms that are still not well defined. Results We used primary neurons and mouse brain slices to show that SET is translocated to the cytoplasm in a manner independent of both its cleavage and over-expression. The localization of SET in the cytoplasm, either by the translocation of endogenous SET or by internalization of the recombinant full-length SET protein, induced tau hyperphosphorylation. Cytoplasmic recombinant full-length SET in mouse brain slices induced a decrease of PP2A activity through a decrease of methylated PP2A levels. The levels of methylated PP2A were negatively correlated with tau hyperphosphorylation at Ser-202 but not with the abnormal phosphorylation of tau at Ser-422. Conclusions The presence of full-length SET in the neuronal cytoplasm is sufficient to impair PP2A methylation and activity, leading to tau hyperphosphorylation. In addition, our data suggest that tau hyperphosphorylation is regulated by different mechanisms at distinct sites. The translocation of SET to the neuronal cytoplasm, the low activity of PP2A, and tau hyperphosphorylation are associated in the brains of Alzheimer patients. Our data show a link between the translocation of SET in the cytoplasm and the decrease of methylated PP2A levels leading to a decrease of PP2A activity and tau hyperphosphorylation. This chain of events may contribute to the pathogenesis of Alzheimer disease. PMID:24981783

  2. Sediment detachment by rain power

    NASA Astrophysics Data System (ADS)

    Gabet, Emmanuel J.; Dunne, Thomas

    2003-01-01

    In interrill areas, overland flow is often incapable of detaching soil particles so detachment is primarily by raindrop impact. We derive a mathematical expression, rain power (R, W m-2), relating the energy expenditure of raindrops impacting a soil surface to the rate of detachment of soil particles. Rain power incorporates rainfall, hillslope, and vegetation characteristics and is modulated by flow depths. Rainfall simulation experiments on natural hillslopes were performed to measure detachment rates and across-slope flow depth distributions in surface runoff. Our results indicate that flow depths follow a Poisson distribution, and this observation is used to develop a dimensionless function, A(?, d), that accounts for the interaction of flow depths (h) and raindrop diameter (d) in moderating detachment rates. Rain power correlates well with the detachment rate of fine-grained particles (ψ, g m-2 s-1) so that ψ = 0.011R1.4A(?, d) (n = 44, R2 = 0.88, p < 0.005). We generalize this result to represent natural rainfall conditions and present a method for modeling sediment detachment rates and sediment discharge along entire lengths of hillslopes under the range of conditions where detached sediment is transported as wash load. Modeling simulations demonstrate the temporal and spatial variation in detachment rates caused by increases in flow depth.

  3. Hyperphosphorylation of Intrinsically Disordered Tau Protein Induces an Amyloidogenic Shift in Its Conformational Ensemble

    PubMed Central

    Zhu, Shaolong; Shala, Agnesa; Bezginov, Alexandr; Sljoka, Adnan; Audette, Gerald; Wilson, Derek J.

    2015-01-01

    Tau is an intrinsically disordered protein (IDP) whose primary physiological role is to stabilize microtubules in neuronal axons at all stages of development. In Alzheimer's and other tauopathies, tau forms intracellular insoluble amyloid aggregates known as neurofibrillary tangles, a process that appears in many cases to be preceded by hyperphosphorylation of tau monomers. Understanding the shift in conformational bias induced by hyperphosphorylation is key to elucidating the structural factors that drive tau pathology, however, as an IDP, tau is not amenable to conventional structural characterization. In this work, we employ a straightforward technique based on Time-Resolved ElectroSpray Ionization Mass Spectrometry (TRESI-MS) and Hydrogen/Deuterium Exchange (HDX) to provide a detailed picture of residual structure in tau, and the shifts in conformational bias induced by hyperphosphorylation. By comparing the native and hyperphosphorylated ensembles, we are able to define specific conformational biases that can easily be rationalized as enhancing amyloidogenic propensity. Representative structures for the native and hyperphosphorylated tau ensembles were generated by refinement of a broad sample of conformations generated by low-computational complexity modeling, based on agreement with the TRESI-HDX profiles. PMID:25767879

  4. SIL1 Rescued Bip Elevation-Related Tau Hyperphosphorylation in ER Stress.

    PubMed

    Liu, Zan-Chao; Chu, Jiang; Lin, Li; Song, Jie; Ning, Lin-Na; Luo, Hong-Bin; Yang, Shu-Sheng; Shi, Yan; Wang, Qun; Qu, Na; Zhang, Qi; Wang, Jian-Zhi; Tian, Qing

    2016-03-01

    Endoplasmic reticulum (ER) stress has been indicated in the early stage of Alzheimer's disease (AD), in which tau hyperphosphorylation is one major pathological alteration. The elevation of binding immunoglobulin protein (Bip), an important ER chaperon, was reported in AD brain. It is important to study the roles of ER-related chaperons in tau hyperphosphorylation. In this research, increased Bip was found in the brains of the AD model mice (Tg2576) compared to the age-matched control mice. Meanwhile, deficiency of SIL1, an important co-chaperon of Bip, was observed in brains of Tg2576 mice and in ER stress both in vivo and in vitro. Then, we transfected Bip-EGFP plasmid into HEK293 cells stably expressing the longest human tau (HEK293/tau) or N2a cells and found that increased Bip induced tau hyperphosphorylation via activating glycogen synthase kinase-3β (GSK-3β), an important tau kinase, and increased the association with tau and GSK-3β. When we overexpressed SIL1 in Bip-transfected HEK293/tau cells and thapsigargin-treated HEK293/tau cells, significantly reduced tau hyperphosphorylation and GSK-3β activation were observed. These results suggested the important roles of ER-related chaperons, Bip and SIL1, in AD-like tau hyperphosphorylation. PMID:25575678

  5. The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer's Disease

    PubMed Central

    Liu, Zhenzhen; Li, Tao; Li, Ping; Wei, Nannan; Zhao, Zhiquan; Liang, Huimin; Ji, Xinying; Chen, Wenwu; Xue, Mengzhou; Wei, Jianshe

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid-beta (Aβ)] and neurofibrillary tangles (aggregates of tau). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than Aβ plaques. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagic pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between oxidative stress, tau protein hyperphosphorylation, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on oxidative stress, tau hyperphosphorylation, and autophagy. We also discuss the relationship of these three factors in AD. PMID:26171115

  6. PIMASERTIB AND SEROUS RETINAL DETACHMENTS

    PubMed Central

    AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem

    2016-01-01

    Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523

  7. Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

    SciTech Connect

    Miklossy, J.; Miller, L.; Qing, H.; Radenovic, A.; Kis, A.; Vileno, B.; Laszlo, F.; Martins, R.N.; Waeber, G.; Mooser, V.; Bosman, F.; Khalili, K.; Darbinian, N.; McGeer, P.L.

    2008-08-25

    Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (A{beta}) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated A{beta}, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. A{beta} was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that A{beta} deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that A{beta} deposits and hyperphosphorylated tau may also occur in other organs than the brain.

  8. Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay

    PubMed Central

    Durand, Sébastien; Franks, Tobias M.; Lykke-Andersen, Jens

    2016-01-01

    Many gene expression factors contain repetitive phosphorylation sites for single kinases, but the functional significance is poorly understood. Here we present evidence for hyperphosphorylation as a mechanism allowing UPF1, the central factor in nonsense-mediated decay (NMD), to increasingly attract downstream machinery with time of residence on target mRNAs. Indeed, slowing NMD by inhibiting late-acting factors triggers UPF1 hyperphosphorylation, which in turn enhances affinity for factors linking UPF1 to decay machinery. Mutational analyses reveal multiple phosphorylation sites contributing to different extents to UPF1 activity with no single site being essential. Moreover, the ability of UPF1 to undergo hyperphosphorylation becomes increasingly important for NMD when downstream factors are depleted. This hyperphosphorylation-dependent feedback mechanism may serve as a molecular clock ensuring timely degradation of target mRNAs while preventing degradation of non-targets, which, given the prevalence of repetitive phosphorylation among central gene regulatory factors, may represent an important general principle in gene expression. PMID:27511142

  9. Detachable acoustic electric feedthrough

    NASA Astrophysics Data System (ADS)

    Moss, Scott; Skippen, Jeremy; Konak, Michael; Powlesland, Ian; Galea, Steve

    2010-04-01

    This paper outlines the development and characterisation of a detachable acoustic electric feedthrough (DAEF) to transfer power and data across a metal (or composite) plate. The DAEF approach is being explored as a potential means of wirelessly powering in-situ structural health monitoring systems embedded within aircraft and other high value engineering assets. The DAEF technique operates via two axially aligned piezoelectric-magnet structures mounted on opposite sides of a plate. Magnetic force is used to align the two piezoelectric-magnet structures, to create an acoustic path across a plate. The piezoelectric-magnet structures consisted of Pz26 piezoelectric disk elements bonded to NdFeB magnets, with a standard ultrasonic couplant (High-Z) used between the magnet and plate to facilitate the passage of ultrasound. Measured impedance curves are matched to modeled curves using the Comsol multi-physics software coupled with a particle-swarm approach, allowing optimised Pz26 material parameters to be found (i.e. stiffness, coupling and permittivity matrices). The optimised Pz26 parameters are then used in an axi-symmetric Comsol model to make predictions about the DAEF power transfer, which is then experimentally confirmed. With an apparent input power of 1 VA and 4.2 MHz drive frequency, the measured power transfer efficiency across a 1.6 mm Al plate is ~34%. The effect of various system parameters on power transfer is explored, including bondline thickness and plate thickness. DAEF data communication is modelled using LTspice with three-port one-dimensional piezoelectric models, indicating that data rates of 115 kBit/s are feasible.

  10. Retinal detachment repair - series (image)

    MedlinePlus

    ... scleral buckle is applied. This consists of a silicone patch wrapped around the eye, compressing the globe ... of the eye, and sealing the detachment. The silicone patch is usually left in place permanently, unless ...

  11. detached_shells_carbon_stars

    NASA Astrophysics Data System (ADS)

    Hony, Sacha; Bouwman, Jeroen; Waters, Laurens

    2004-09-01

    We propose to obtain 19-37 micrometer IRS spectra of the detached shells around nearby carbon-stars. We have selected a small (11) sample of bright, well studied, carbon-stars with known detached shells. The sample covers a range of angular diameters of the detached shells from 8-200" and stellar effective temperatures between 800-2600 K. With the spectra of the dust in the detached shell we aim to establish: i) The location of the shell. ii) The chemistry of the shell in order to constrain it's origin. iii) Test the MgS identification for the ``30'' micrometer emission feature. iv) Determine observationally the relationship between the ``30'' micrometer feature peak-position and the distance to the star. These observations will contribute greatly to the understanding AGB-star mass loss, in general, and the phenomenon of detached shells around carbon-stars, in particular. They will also be used to develop a diagnostic tool that allows to study detached shell properties of distant carbon-stars, that cannot be spatially resolved, based on their IR spectrum alone. The total requested time is 2.5h.

  12. Activation of Asparaginyl Endopeptidase Leads to Tau Hyperphosphorylation in Alzheimer Disease*

    PubMed Central

    Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Tung, Yunn Chyn; Liu, Fei; Iqbal, Khalid

    2013-01-01

    Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2PP2A, except when I2PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. PMID:23640887

  13. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

    PubMed Central

    Chen, Yanxing; Run, Xiaoqin; Liang, Zhihou; Zhao, Yang; Dai, Chun-ling; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2014-01-01

    Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD). Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. Methods: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75 U/day) for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight). Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and 2 h after propofol injection were then investigated by using Western blots and immunohistochemistry. Results: Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase. Conclusion: Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia. PMID:24910612

  14. Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies?

    PubMed Central

    Alavi Naini, Seyedeh Maryam; Soussi-Yanicostas, Nadia

    2015-01-01

    Hyperphosphorylation and aggregation of the microtubule-associated protein tau in brain, are pathological hallmarks of a large family of neurodegenerative disorders, named tauopathies, which include Alzheimer's disease. It has been shown that increased phosphorylation of tau destabilizes tau-microtubule interactions, leading to microtubule instability, transport defects along microtubules, and ultimately neuronal death. However, although mutations of the MAPT gene have been detected in familial early-onset tauopathies, causative events in the more frequent sporadic late-onset forms and relationships between tau hyperphosphorylation and neurodegeneration remain largely elusive. Oxidative stress is a further pathological hallmark of tauopathies, but its precise role in the disease process is poorly understood. Another open question is the source of reactive oxygen species, which induce oxidative stress in brain neurons. Mitochondria have been classically viewed as a major source for oxidative stress, but microglial cells were recently identified as reactive oxygen species producers in tauopathies. Here we review the complex relationships between tau pathology and oxidative stress, placing emphasis on (i) tau protein function, (ii) origin and consequences of reactive oxygen species production, and (iii) links between tau phosphorylation and oxidative stress. Further, we go on to discuss the hypothesis that tau hyperphosphorylation and oxidative stress are two key components of a vicious circle, crucial in neurodegenerative tauopathies. PMID:26576216

  15. Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration.

    PubMed

    Li, Liang; Sengupta, Amitabha; Haque, Niloufar; Grundke-Iqbal, Inge; Iqbal, Khalid

    2004-05-21

    Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, reduces the clinical deterioration in moderate-to-severe Alzheimer disease (AD) for which other treatments are not available. The activity of protein phosphatase (PP)-2A is compromised in AD brain and is believed to be a cause of the abnormal hyperphosphorylation of tau and the consequent neurofibrillary degeneration. Here we show that memantine inhibits and reverses the PP-2A inhibition-induced abnormal hyperphosphorylation and accumulation of tau in organotypic culture of rat hippocampal slices. Such restorative effects of memantine were not detected either with 5,7-dichlorokynurenic acid or with D(-)-2-amino-5-phosphopentanoic acid, NMDA receptor antagonists active at the glycine binding site and at the glutamate binding site, respectively. These findings show (1) that memantine inhibits and reverses the PP-2A inhibition-induced abnormal hyperphosphorylation of tau/neurofibrillary degeneration and (2) that this drug might be useful for the treatment of AD and related tauopathies. PMID:15147906

  16. The mechanics of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2013-03-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular, and retinal pigment epithelium (RPE) pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed tissue within which e.g., the hydraulic conductivities of the retina or choroid increase, the RPE pumps fail, or the adhesion properties change. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. This work supported by the Army Research Office through grant 58386MA

  17. Size distribution of detached drops

    NASA Astrophysics Data System (ADS)

    Baluev, V. V.; Stepanov, V. M.

    1989-10-01

    The law governing the size distribution of detached gas-liquid streams of drops has been determined analytically, and a comparison is carried out against experimental data existing in the literature. The derived theoretical relationships offer an excellent description of existing experimental results.

  18. Detached Growth of Germanium by Directional Solidification

    NASA Technical Reports Server (NTRS)

    Palosz, W.; Volz, M. P.; Cobb, S.; Motakef, S.; Szofran, F. R.

    2004-01-01

    The conditions of detached solidification under controlled pressure differential across the meniscus were investigated. Uncoated and graphite- or BN-coated silica and pBN crucibles were used. Detached and partly detached growth was achieved in pBN and BN-coated crucibles, respectively. The results of the experiments are discussed based on the theory of Duffar et al.

  19. Detached growth of germanium by directional solidification

    NASA Astrophysics Data System (ADS)

    Palosz, W.; Volz, M. P.; Cobb, S.; Motakef, S.; Szofran, F. R.

    2005-04-01

    The conditions of detached solidification under controlled pressure differential across the meniscus were investigated. Uncoated and graphite- or BN-coated silica and pBN crucibles were used. Detached and partly detached growth was achieved in pBN and BN-coated crucibles, respectively. The results of the experiments are discussed based on the theory of Duffar et al.

  20. Kinematic Fitting of Detached Vertices

    SciTech Connect

    Paul Mattione

    2007-05-01

    The eg3 experiment at the Jefferson Lab CLAS detector aims to determine the existence of the $\\Xi_{5}$ pentaquarks and investigate the excited $\\Xi$ states. Specifically, the exotic $\\Xi_{5}^{--}$ pentaquark will be sought by first reconstructing the $\\Xi^{-}$ particle through its weak decays, $\\Xi^{-}\\to\\pi^{-}\\Lambda$ and $\\Lambda\\to\\pi^{-}$. A kinematic fitting routine was developed to reconstruct the detached vertices of these decays, where confidence level cuts on the fits are used to remove background events. Prior to fitting these decays, the exclusive reaction $\\gamma D\\rightarrow pp\\pi^{-}$ was studied in order to correct the track measurements and covariance matrices of the charged particles. The $\\Lambda\\rightarrow p\\pi^{-}$ and $\\Xi^{-}\\to\\pi^{-}\\Lambda$ decays were then investigated to demonstrate that the kinematic fitting routine reconstructs the decaying particles and their detached vertices correctly.

  1. Hyperphosphorylation of tau protein in the ipsilateral thalamus after focal cortical infarction in rats.

    PubMed

    Dong, Da-Wei; Zhang, Yu-Sheng; Yang, Wan-Yong; Wang-Qin, Run-Qi; Xu, An-Ding; Ruan, Yi-Wen

    2014-01-16

    Hyperphosphorylation of tau has been considered as an important risk factor for neurodegenerative diseases. It has been found also in the cortex after focal cerebral ischemia. The present study is aimed at investigating changes of tau protein expression in the ipsilateral thalamus remote from the primary ischemic lesion site after distal middle cerebral artery occlusion (MCAO). The number of neurons in the ventroposterior thalamic nucleus (VPN) was evaluated using Nissl staining and neuronal nuclei (NeuN) immunostaining. Total tau and phosphorylated tau at threonine 231 (p-T231-tau) and serine 199 (p-S199-tau) levels, respectively, in the thalamus were measured using immunostaining and immunoblotting. Moreover, apoptosis was detected with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay. It was found that the numbers of intact neurons and NeuN(+) cells within the ipsilateral VPN were reduced significantly compared with the sham-operated group, but the levels of p-T231-tau and p-S199-tau in the ipsilateral thalamus were increased significantly in rats subjected to ischemia for 3 days, 7 days and 28 days. Furthermore, the number of TUNEL-positive cells was increased in the ipsilateral VPN at 7 days and 28 days after MCAO. Thus, hyperphosphorylated tau protein is observed in ipsilateral thalamus after focal cerebral infarction in this study. Our findings suggest that the expression of hyperphosphorylated tau protein induced by ischemia may be associated with the secondary thalamic damage after focal cortical infarction via an apoptotic pathway. PMID:24216136

  2. Extensive RPA2 hyperphosphorylation promotes apoptosis in response to DNA replication stress in CHK1 inhibited cells.

    PubMed

    Zuazua-Villar, Pedro; Ganesh, Anil; Phear, Geraldine; Gagou, Mary E; Meuth, Mark

    2015-11-16

    The replication protein A (RPA)-ssDNA complex formed at arrested replication forks recruits key proteins to activate the ATR-CHK1 signalling cascade. When CHK1 is inhibited during DNA replication stress, RPA2 is extensively hyperphosphorylated. Here, we investigated the role of RPA2 hyperphosphorylation in the fate of cells when CHK1 is inhibited. We show that proteins normally involved in DNA repair (RAD51) or control of RPA phosphorylation (the PP4 protein phosphatase complex) are not recruited to the genome after treatment with CHK1 and DNA synthesis inhibitors. This is not due to RPA2 hyperphosphorylation as suppression of this response does not restore loading suggesting that recruitment requires active CHK1. To determine whether RPA2 hyperphosphorylation protects stalled forks from collapse or induction of apoptosis in CHK1 inhibited cells during replication stress, cells expressing RPA2 genes mutated at key phosphorylation sites were characterized. Mutant RPA2 rescued cells from RPA2 depletion and reduced the level of apoptosis induced by treatment with CHK1 and replication inhibitors however the incidence of double strand breaks was not affected. Our data indicate that RPA2 hyperphosphorylation promotes cell death during replication stress when CHK1 function is compromised but does not appear to be essential for replication fork integrity. PMID:26271993

  3. Deregulation of Protein Phosphatase 2A and Hyperphosphorylation of τ Protein Following Onset of Diabetes in NOD Mice

    PubMed Central

    Papon, Marie-Amélie; El Khoury, Noura B.; Marcouiller, François; Julien, Carl; Morin, Françoise; Bretteville, Alexis; Petry, Franck R.; Gaudreau, Simon; Amrani, Abdelaziz; Mathews, Paul M.; Hébert, Sébastien S.; Planel, Emmanuel

    2013-01-01

    The histopathological hallmarks of Alzheimer disease (AD) include intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated τ protein. Insulin dysfunction might influence AD pathology, as population-based and cohort studies have detected higher AD incidence rates in diabetic patients. But how diabetes affects τ pathology is not fully understood. In this study, we investigated the impact of insulin dysfunction on τ phosphorylation in a genetic model of spontaneous type 1 diabetes: the nonobese diabetic (NOD) mouse. Brains of young and adult female NOD mice were examined, but young NOD mice did not display τ hyperphosphorylation. τ phosphorylation at τ-1 and pS422 epitopes was slightly increased in nondiabetic adult NOD mice. At the onset of diabetes, τ was hyperphosphorylated at the τ-1, AT8, CP13, pS262, and pS422. A subpopulation of diabetic NOD mice became hypothermic, and τ hyperphosphorylation further extended to paired helical filament-1 and TG3 epitopes. Furthermore, elevated τ phosphorylation correlated with an inhibition of protein phosphatase 2A (PP2A) activity. Our data indicate that insulin dysfunction in NOD mice leads to AD-like τ hyperphosphorylation in the brain, with molecular mechanisms likely involving a deregulation of PP2A. This model may be a useful tool to address further mechanistic association between insulin dysfunction and AD pathology. PMID:22961084

  4. Identification of Oncogenic Point Mutations and Hyperphosphorylation of Anaplastic Lymphoma Kinase in Lung Cancer12

    PubMed Central

    Wang, Yi-Wei; Tu, Pang-Hsien; Lin, Kuen-Tyng; Lin, Shu-Chen; Ko, Jenq-Yuh; Jou, Yuh-Shan

    2011-01-01

    The oncogenic property of anaplastic lymphoma kinase (ALK) plays an essential role in the pathogenesis of various cancers and serves as an important therapeutic target. In this study, we identified frequent intragenic loss of heterozygosity and six novel driver mutations within ALK in lung adenocarcinomas. Overexpression of H694R or E1384K mutant ALK leads to hyperphosphorylation of ALK, and activation of its downstream mediators STAT3, AKT, and ERK resulted in enhanced cell proliferation, colony formation, cell migration, and tumor growth in xenograft models. Furthermore, the activated phospho-Y1604 ALK was increasingly detected in 13 human lung cancer cell lines and 263 lung cancer specimens regardless of tumor stages and types. Treatment of two different ALK inhibitors, WHI-P154 and NVP-TAE684, resulted in the down-regulation of aberrant ALK signaling, shrinkage of tumor, and suppression of metastasis and significantly improved survival of ALK mutant-bearing mice. Together, we identified that novel ALK point mutations possessed tumorigenic effects mainly through hyperphosphorylation of Y1604 and activation of downstream oncogenic signaling. The upregulated phospho-Y1604 ALK could serve as a diagnostic biomarker for lung cancer. Furthermore, targeting oncogenic mutant ALKs with inhibitors could be a promising strategy to improve the therapeutic efficacy of fatal lung cancers. PMID:21847362

  5. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

    PubMed

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B

    2015-09-01

    Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1 hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to decreased amino acid availability. PMID:25957086

  6. Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway

    PubMed Central

    Gong, Wei-Gang; Wu, Di; Tang, Xiang; Li, Xiao-Li; Wu, Fang-Fang; Bai, Feng; Xu, Lin; Zhang, Zhi-Jun

    2016-01-01

    Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1–42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1–42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1–42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1–42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway. PMID:26950279

  7. Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

    PubMed

    Wang, Yan-Juan; Ren, Qing-Guo; Gong, Wei-Gang; Wu, Di; Tang, Xiang; Li, Xiao-Li; Wu, Fang-Fang; Bai, Feng; Xu, Lin; Zhang, Zhi-Jun

    2016-03-22

    Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1-42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1-42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1-42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1-42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway. PMID:26950279

  8. Dynamic stability of detached solidification

    NASA Astrophysics Data System (ADS)

    Mazuruk, K.; Volz, M. P.

    2016-06-01

    A dynamic stability analysis model is developed for meniscus-defined crystal growth processes. The Young-Laplace equation is used to analyze the response of a growing crystal to perturbations to its radius and a thermal transport model is used to analyze the effect of perturbations on the evolution of the crystal-melt interface. A linearized differential equation is used to analyze radius perturbations but a linear integro-differential equation is required for the height perturbations. The stability model is applied to detached solidification under zero-gravity and terrestrial conditions. A numerical analysis is supplemented with an approximate analytical analysis, valid in the limit of small Bond numbers. For terrestrial conditions, a singularity is found to exist in the capillary stability coefficients where, at a critical value of the pressure differential across the meniscus, there is a transition from stability to instability. For the zero-gravity condition, exact formulas for the capillary stability coefficients are derived.

  9. MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer’s disease

    PubMed Central

    Wang, Gang; Huang, Yue; Wang, Li-Ling; Zhang, Yong-Fang; Xu, Jing; Zhou, Yi; Lourenco, Guinevere F.; Zhang, Bei; Wang, Ying; Ren, Ru-Jing; Halliday, Glenda M.; Chen, Sheng-Di

    2016-01-01

    MicroRNA-146a is upregulated in the brains of patients with Alzheimer’s disease (AD). Here, we show that the rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is a target of microRNA-146a in neural cells. Knockdown of ROCK1 mimicked the effects of microRNA-146a overexpression and induced abnormal tau phosphorylation, which was associated with inhibition of phosphorylation of the phosphatase and tensin homolog (PTEN). The ROCK1/PTEN pathway has been implicated in the neuronal hyperphosphorylation of tau that occurs in AD. To determine the function of ROCK1 in AD, brain tissue from 17 donors with low, intermediate or high probability of AD pathology were obtained and analyzed. Data showed that ROCK1 protein levels were reduced and ROCK1 colocalised with hyperphosphorylated tau in early neurofibrillary tangles. Intra-hippocampal delivery of a microRNA-146a specific inhibitor (antagomir) into 5xFAD mice showed enhanced hippocampal levels of ROCK1 protein and repressed tau hyperphosphorylation, partly restoring memory function in the 5xFAD mice. Our in vitro and in vivo results confirm that dysregulation of microRNA-146a biogenesis contributes to tau hyperphosphorylation and AD pathogenesis, and inhibition of this microRNA could be a viable novel in vivo therapy for AD. PMID:27221467

  10. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5

    PubMed Central

    Ahlijanian, Michael K.; Barrezueta, Nestor X.; Williams, Robert D.; Jakowski, Amy; Kowsz, Kim P.; McCarthy, Sheryl; Coskran, Timothy; Carlo, Anthony; Seymour, Patricia A.; Burkhardt, John E.; Nelson, Robert B.; McNeish, John D.

    2000-01-01

    Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3β. Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5. The p25 transgenic mice display silver-positive neurons using the Bielschowsky stain. Disturbances in neuronal cytoskeletal organization are apparent at the ultrastructural level. These changes are localized predominantly to the amygdala, thalamus/hypothalamus, and cortex. The p25 transgenic mice display increased spontaneous locomotor activity and differences from control in the elevated plus-maze test. The overexpression of an activator of cdk5 in transgenic mice results in increased cdk5 activity that is sufficient to produce hyperphosphorylation of tau and neurofilament as well as cytoskeletal disruptions reminiscent of Alzheimer's disease and other neurodegenerative diseases. PMID:10706614

  11. Indirubin-3′-monoxime suppresses amyloid-beta-induced apoptosis by inhibiting tau hyperphosphorylation

    PubMed Central

    Zhang, Shu-gang; Wang, Xiao-shan; Zhang, Ying-dong; Di, Qing; Shi, Jing-ping; Qian, Min; Xu, Li-gang; Lin, Xing-jian; Lu, Jie

    2016-01-01

    Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer's disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SH-SY5Y cells exposed to amyloid-beta 25–35 (Aβ25–35), and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β (GSK-3β). Our results suggest that indirubin-3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer's disease. PMID:27482230

  12. Experimental results from detached plasmas in TFTR

    SciTech Connect

    Strachan, J.D.; Boody, F.P.; Bush, C.E.; Cohen, S.A.; Grek, B.; Grisham, L.; Jobes, F.C.; Johnson, D.W.; Mansfield, D.K.; Medley, S.S.

    1986-10-01

    Detached plasmas are formed in TFTR which have the principal property of the boundary to the high temperature plasma core being defined by a radiating layer. This paper documents the properties of TFTR ohmic-detached plasmas with a range of plasma densities at two different plasma currents.

  13. Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice

    PubMed Central

    Jung, Ga-young; Won, Sae-Bom; Kim, Juhae; Jeon, Sookyoung; Han, Anna

    2013-01-01

    Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/db+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress. PMID:24278623

  14. Loss of Prohibitin Membrane Scaffolds Impairs Mitochondrial Architecture and Leads to Tau Hyperphosphorylation and Neurodegeneration

    PubMed Central

    Merkwirth, Carsten; Morbin, Michela; Brönneke, Hella S.; Jordan, Sabine D.; Rugarli, Elena I.; Langer, Thomas

    2012-01-01

    Fusion and fission of mitochondria maintain the functional integrity of mitochondria and protect against neurodegeneration, but how mitochondrial dysfunctions trigger neuronal loss remains ill-defined. Prohibitins form large ring complexes in the inner membrane that are composed of PHB1 and PHB2 subunits and are thought to function as membrane scaffolds. In Caenorhabditis elegans, prohibitin genes affect aging by moderating fat metabolism and energy production. Knockdown experiments in mammalian cells link the function of prohibitins to membrane fusion, as they were found to stabilize the dynamin-like GTPase OPA1 (optic atrophy 1), which mediates mitochondrial inner membrane fusion and cristae morphogenesis. Mutations in OPA1 are associated with dominant optic atrophy characterized by the progressive loss of retinal ganglion cells, highlighting the importance of OPA1 function in neurons. Here, we show that neuron-specific inactivation of Phb2 in the mouse forebrain causes extensive neurodegeneration associated with behavioral impairments and cognitive deficiencies. We observe early onset tau hyperphosphorylation and filament formation in the hippocampus, demonstrating a direct link between mitochondrial defects and tau pathology. Loss of PHB2 impairs the stability of OPA1, affects mitochondrial ultrastructure, and induces the perinuclear clustering of mitochondria in hippocampal neurons. A destabilization of the mitochondrial genome and respiratory deficiencies manifest in aged neurons only, while the appearance of mitochondrial morphology defects correlates with tau hyperphosphorylation in the absence of PHB2. These results establish an essential role of prohibitin complexes for neuronal survival in vivo and demonstrate that OPA1 stability, mitochondrial fusion, and the maintenance of the mitochondrial genome in neurons depend on these scaffolding proteins. Moreover, our findings establish prohibitin-deficient mice as a novel genetic model for tau pathologies

  15. Imatinib methanesulfonate reduces hyperphosphorylation of tau following repeated peripheral exposure to lipopolysaccharide.

    PubMed

    Gardner, L E; White, J D; Eimerbrink, M J; Boehm, G W; Chumley, M J

    2016-09-01

    For years, the prevailing hypothesis for Alzheimer's Disease (AD) has proposed a mechanism by which deposition of amyloid-beta (Aβ) in the brain is independent of tau-pathologies and cognitive decline. However, despite extensive research on the disease, the mechanisms underlying the etiology of tau-pathology remain unknown. Previous research in our lab has shown that imatinib methanesulfonate (IM) blocks the peripheral production of Aβ in response to LPS, thereby preventing the buildup of Aβ in the hippocampus, and rescuing the cognitive dysfunction that normally follows. The present study aimed to examine the link between Aβ and tau following inflammation, and to expand our understanding of how IM affects AD pathology. Specifically, we hypothesized that the IM-mediated inhibition of Aβ production following inflammation would successfully protect against the hyperphosphorylation of tau (ptau). Here we show that 7days of LPS treatment in male C57BL/6J mice, which normally produces elevations in peripheral and central Aβ, also produces hyperphosphorylation of tau. However, just as pre-treatment and concurrent treatment with IM blocks Aβ production, it also blocks the phosphorylation of tau. In addition, 7days of LPS-induced inflammation and Aβ production also leads to elevated total tau protein expression. Our results may provide support for the hypothesis that enhanced expression of tau following LPS administration is a protective measure by hippocampal neurons to compensate for the loss of the microtubule-stabilizing protein due to phosphorylation. More importantly, our results support the hypothesis that blocking the production of Aβ that follows inflammation also leads to reduced tau phosphorylation, lending credence to a model in which Aβ initiates tau phosphorylation. PMID:27320209

  16. Intraretinal proliferation induced by retinal detachment

    SciTech Connect

    Fisher, S.K.; Erickson, P.A.; Lewis, G.P.; Anderson, D.H. )

    1991-05-01

    Cellular proliferation after retinal detachment was studied by {sup 3}H-thymidine light microscopic autoradiography in cats that had experimental detachments of 0.5-180 days duration. The animals underwent labeling 2 hr before death with an intraocular injection of 200 microCi of {sup 3}H-thymidine. The number of labeled nuclei were counted in 1-micron thick tissue sections in regions of detachment, in regions of the experimental eyes that remained attached, and in control eyes that had no detachments. In the normal eye, in one that had only the lens and vitreous removed, and in the eyes with 0.5- and 1-day detachments, the number of labeled nuclei ranged from 0/mm (0.5-day detachment) to 0.38/mm (lens and vitreous removed only). By 2 days postdetachment, the number of labeled nuclei increased to 2.09/mm. The highest levels of labeling occurred in two animals with detachments of 3 (7.86/mm) and 4 (7.09/mm) days. Thereafter, the numbers declined steadily until near-baseline counts were obtained at 14 days. The number of labeled nuclei was slightly elevated in the attached regions of two animals with 3-day detachments. Labeled cell types included: Mueller cells, astrocytes, pericytes, and endothelial cells of the retinal vasculature, and both resident (microglial cells) and invading macrophages. In an earlier study RPE cells were also shown to proliferate in response to detachment. Thus, these data show that proliferation is a rapid response to detachment, reaching a maximum within 4 days, and that virtually every nonneuronal cell type in the retina can participate in this response. The data suggest that events leading to such clinical manifestations as proliferative vitreoretinopathy and subretinal fibrosis may have their beginnings in this very early proliferative response.

  17. Detachment of stretched viscoelastic fibrils

    NASA Astrophysics Data System (ADS)

    Glassmaker, N. J.; Hui, C. Y.; Yamaguchi, T.; Creton, C.

    2008-03-01

    New experimental results are presented about the final stage of failure of soft viscoelastic adhesives. A microscopic view of the detachment of the adhesive shows that after cavity growth and expansion, well adhered soft adhesives form a network of fibrils connected to expanded contacting feet which fail via a sliding mechanism, sensitive to interfacial shear stresses rather than by a fracture mechanism as sometimes suggested in earlier work. A mechanical model of this stretching and sliding failure phenomenon is presented which treats the fibril as a nonlinear elastic or viscoelastic rod and the foot as an elastic layer subject to a friction force proportional to the local displacement rate. The force on the stretched rod drives the sliding of the foot against the substrate. The main experimental parameter controlling the failure strain and stress during the sliding process is identified by the model as the normalized probe pull speed, which also depends on the magnitude of the friction and PSA modulus. In addition, the material properties, viscoelasticity and finite extensibility of the polymer chains, are shown to have an important effect on both the details of the sliding process and the ultimate failure strain and stress. Appendix B is only available in electronic form at 10.1140/epje/i2007-10287-y and are accessible for authorised users.

  18. Dynamics of mussel plaque detachment.

    PubMed

    Desmond, Kenneth W; Zacchia, Nicholas A; Waite, J Herbert; Valentine, Megan T

    2015-09-14

    Mussels are well known for their ability to generate and maintain strong, long-lasting adhesive bonds under hostile conditions. Many prior studies attribute their adhesive strength to the strong chemical interactions between the holdfast and substrate. While chemical interactions are certainly important, adhesive performance is also determined by contact geometry, and understanding the coupling between chemical interactions and the plaque shape and mechanical properties is essential in deploying bioinspired strategies when engineering improved adhesives. To investigate how the shape and mechanical properties of the mussel's plaque contribute to its adhesive performance, we use a custom built load frame capable of fully characterizing the dynamics of the detachment. With this, we can pull on samples along any orientation, while at the same time measuring the resulting force and imaging the bulk deformations of the plaque as well as the holdfast-substrate interface where debonding occurs. We find that the force-induced yielding of the mussel plaque improves the bond strength by two orders of magnitude and that the holdfast shape improves bond strength by an additional order of magnitude as compared to other simple geometries. These results demonstrate that optimizing the contact geometry can play as important a role on adhesive performance as optimizing the chemical interactions as observed in other organisms and model systems. PMID:26223522

  19. Stability of Detached Grown Germanium Single Crystals

    NASA Technical Reports Server (NTRS)

    Schweizer, M.; Volz, M. P.; Cobb, S. D.; Vujisic, L.; Szofran, F. R.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    Detachment of the melt meniscus from the crucible during semiconductor Bridgman growth experiments has been observed in recent years, especially under microgravity experiments. Under earth conditions, the hydrostatic pressure counteracts the mechanism, whereby it is more difficult to achieve detached Bridgman growth. Attempts to get stable detached growth under terrestrial conditions have been discussed in the literature and have been the subject of recent experiments in our own group. The advantage of crystals grown without wall contact is obvious: In general, they possess a higher crystal quality than conventional Bridgman grown crystals with wall contact. However, due to the interaction of different parameters such as the wetting behavior of the melt with the crucible, and the dependence of the growth angle with the shape of the melt meniscus, the mechanism leading to detachment is very complicated and not completely understood. We have grown several doped and undoped Germanium crystals with the detached Bridgman and the normal Bridgman growth technique. Pyrolytic boron nitride containers were used for all growth experiments. In the detached grown crystals the typical gap thickness between the pBN crucible and the crystal is in the range of 10 to 100 micrometers, which was determined by performing profilometer measurements. Etch pit density measurements were also performed and a comparison between detached and attached grown crystals will be given. An interesting feature was detected on the surface of a detached grown crystal. Strong surface striations with an average axial distance of 0.5 mm were observed around the whole circumference. The maximum fluctuation of the gap thickness is in the range of 5-10 micrometers. These variations of the detached gap along the crystal axis can be explained by a kind of stiction of the melt/crucible interface and thus by a variation of the meniscus shape. This phenomenon leading to the fluctuation of the gap thickness will be

  20. Stability of Detached Grown Germanium Single Crystals

    NASA Technical Reports Server (NTRS)

    Schweizer, M.; Volz, M. P.; Cobb, S. D.; Motakef, S.; Szofran, F. R.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Detachment of the melt meniscus from the crucible during semiconductor Bridgman growth experiments has been observed in recent years especially, under microgravity experiments. Under earth conditions, the hydrostatic pressure counteracts the mechanism, whereby it is more difficult to achieve detached Bridgman growth. Attempts to get stable detached growth under terrestrial conditions have been discussed in the literature and have been the subject of recent experiments in our own group. The advantage of crystals grown without wall contact is obvious: In general, they possess a higher crystal quality than conventional Bridgman grown crystals with wall contact. However, due to the interaction of different parameters such as the wetting behavior of the melt with the crucible, and the dependence of the growth angle with the shape of the melt meniscus, the mechanism leading to detachment is very complicated and not completely understood. We have grown several doped and undoped Germanium crystals with the detached Bridgman and the normal Bridgman growth technique. Pyrolytic boron nitride containers were used for all growth experiments. In the detached grown crystals the typical gap thickness between the pBN crucible and the crystal is in the range of 10 to 100 microns, which was determined by performing profilometer measurements. Etch pit density measurements were also performed and a comparison between detached and attached grown crystals will be given. An interesting feature was detected on the surface of a detached grown crystal. Strong surface striations with an average axial distance of 0.5mm were observed around the whole circumference. The maximum fluctuation of the gap thickness is in the range of 5-10 microns. These variations of the detached gap along the crystal axis can be explained by a kind of stiction of the melt/crucible interface and thus by a variation of the meniscus shape. This phenomenon leading to the fluctuation of the gap thickness will be

  1. E1A Blocks Hyperphosphorylation of p130 and p107 without Affecting the Phosphorylation Status of the Retinoblastoma Protein

    PubMed Central

    Parreño, Matilde; Garriga, Judit; Limón, Ana; Mayol, Xavier; Beck, George R.; Moran, Elizabeth; Graña, Xavier

    2000-01-01

    The phosphorylation status of the pRB family of growth suppressor proteins is regulated in a cell cycle entry-, progression-, and exit-dependent manner in normal cells. We have shown previously that p130, a member of this family, exhibits patterns of phosphorylated forms associated with various cell growth and differentiation stages. However, human 293 cells, which are transformed cells that express the adenoviral oncoproteins E1A and E1B, exhibit an abnormal pattern of p130 phosphorylated forms. Here we report that, unlike pRB, the phosphorylation status of both p130 and p107 is not modulated during the cell cycle in 293 cells as it is in other cells. Conditional overexpression of individual G1/S cyclins in 293 cells does not alter the phosphorylation status of p130, suggesting that the expression of E1A and/or E1B blocks hyperphosphorylation of p130. In agreement with these observations, transient cotransfection of vectors expressing E1A 12S, but not E1B, in combination with pocket proteins into U-2 OS cells blocks hyperphosphorylation of both p130 and p107. However, the phosphorylation status of pRB is not altered by cotransfection of E1A 12S vectors. Moreover, MC3T3-E1 preosteoblasts stably expressing E1A 12S also exhibit a block in hyperphosphorylation of endogenous p130 and p107. Direct binding of E1A to p130 and p107 is not required for the phosphorylation block since E1A 12S mutants defective in binding to the pRB family also block hyperphosphorylation of p130 and p107. Our data reported here identify a novel function of E1A, which affects p130 and p107 but does not affect pRB. Since E1A does not bind the hyperphosphorylated forms of p130, this function of E1A might prevent the existence of “free” hyperphosphorylated p130, which could act as a CDK inhibitor. PMID:10708433

  2. On plasma detachment in propulsive magnetic nozzles

    SciTech Connect

    Ahedo, Eduardo; Merino, Mario

    2011-05-15

    Three detachment mechanisms proposed in the literature (via resistivity, via electron inertia, and via induced magnetic field) are analyzed with an axisymmetric model of the expansion of a small-beta, weakly collisional, near-sonic plasma in a diverging magnetic nozzle. The model assumes cold, partially magnetized ions and hot, isothermal, fully magnetized electrons. Different conditions of the plasma beam at the nozzle throat are considered. A central feature is that a positive thrust gain in the nozzle of a plasma thruster is intimately related to the azimuthal current in the plasma being diamagnetic. Then, and contrary to existing expectations, the three aforementioned detachment mechanisms are divergent, that is, the plasma beam diverges outwards of the guide nozzle, further hindering its axial expansion and the thrust efficiency. The rate of divergent detachment is quantified for the small-parameter range of the three mechanisms. Alternative mechanisms for a convergent detachment of the plasma beam are suggested.

  3. Ouabain enhances lung cancer cell detachment.

    PubMed

    Ruanghirun, Thidarat; Pongrakhananon, Varisa; Chanvorachote, Pithi

    2014-05-01

    A human steroid hormone, ouabain, has been shown to play a role in several types of cancer cell behavior; however, its effects on cancer metastasis are largely unknown. Herein, we demonstrate that sub-toxic concentrations of ouabain facilitate cancer cell detachment from the extracellular matrix in human lung cancer cells. Ouabain at concentrations of 0-10 pM significantly enhanced cell detachment in dose- and time- dependent manners, while having minimal effect on cell viability. The detachment-inducing effect of ouabain was found to be mediated through focal-adhesion kinase and ATP-dependent tyrosine kinase pathways. Alpha-5 and beta-1 integrins were found to be down-regulated in response to ouabain treatment. Since detachment of cancer cells is a prerequisite process for metastasis to begin, these insights benefit our understanding over the molecular basis of cancer biology. PMID:24778025

  4. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

    PubMed

    Shultz, Sandy R; Wright, David K; Zheng, Ping; Stuchbery, Ryan; Liu, Shi-Jie; Sashindranath, Maithili; Medcalf, Robert L; Johnston, Leigh A; Hovens, Christopher M; Jones, Nigel C; O'Brien, Terence J

    2015-05-01

    Traumatic brain injury is a common and serious neurodegenerative condition that lacks a pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau is implicated in some of the consequences of traumatic brain injury and is a potential pharmacological target. Protein phosphatase 2A is a heterotrimeric protein that regulates key signalling pathways, and protein phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major tau phosphatase in the brain. Here we investigated whether traumatic brain injury in rats and humans would induce changes in protein phosphatase 2A and phosphorylated tau, and whether treatment with sodium selenate-a potent PR55 activator-would reduce phosphorylated tau and improve traumatic brain injury outcomes in rats. Ninety young adult male Long-Evans rats were administered either a fluid percussion injury or sham-injury. A proportion of rats were killed at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A and tau. Other rats were given either sodium selenate or saline-vehicle treatment that was continuously administered via subcutaneous osmotic pump for 12 weeks. Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12 weeks post-injury to assess evolving structural brain damage and axonal injury. Behavioural impairments were assessed at 12 weeks post-injury. The results showed that traumatic brain injury in rats acutely reduced PR55 expression and protein phosphatase 2A activity, and increased the expression of phosphorylated tau and the ratio of phosphorylated tau to total tau. Similar findings were seen in post-mortem brain samples from acute human traumatic brain injury patients, although many did not reach statistical significance. Continuous sodium selenate treatment for 12 weeks after sham or fluid percussion injury in rats increased protein phosphatase 2A activity and PR55 expression, and reduced the ratio of phosphorylated tau to total tau

  5. Detached plasma in Saturn's front side magnetosphere

    NASA Technical Reports Server (NTRS)

    Goertz, C. K.

    1983-01-01

    Plasma observations in the outer front side Saturnian magnetosphere are discussed which indicate the existence of dense flux tubes outside the plasma sheets. It is suggested that flux tubes are detached from the plasma sheet by a centifugally driven flute instability. The same instability leads to a dispersal of Titan-injected plasma. It is shown that the detached flux tubes will probably break open as they convect into the nightside magnetotail and lose their content in the form of a planetary wind.

  6. Pericellular Innervation of Neurons Expressing Abnormally Hyperphosphorylated Tau in the Hippocampal Formation of Alzheimer's Disease Patients

    PubMed Central

    Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; DeFelipe, Javier

    2010-01-01

    Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered. PMID:20631843

  7. Magnetic Nozzle and Plasma Detachment Scenario

    NASA Astrophysics Data System (ADS)

    Breizman, Boris

    2007-11-01

    Some plasma propulsion concepts rely on a strong magnetic field to guide the plasma flow through the thruster nozzle. The question then arises of how the magnetically controlled plasma can detach from the spacecraft. This talk presents a magnetohydrodynamic detachment scenario in which the plasma stretches the magnetic field lines to infinity [1]. Such a scenario is of particular interest for high-power thrusters. As plasma flows along the magnetic field lines, the originally sub-Alfv'enic flow becomes super-Alfv'enic: this transition is similar to what occurs in the solar wind [2]. In order to describe the detachment quantitatively, the ideal MHD equations have been solved analytically for a plasma flow in a slowly diverging nozzle. The solution exhibits a well-behaved transition from sub- to super- Alfv'enic flow inside the nozzle and a rarefaction wave at the edge of the outgoing flow. The magnetic field in the detached plume is almost entirely due to the plasma currents. It is shown that efficient detachment is feasible if the nozzle is sufficiently long. In order to extend the detachment model beyond the idealizations of analytical theory, a Lagrangian fluid code has been developed to solve steady-stated MHD equations and to optimize nozzle efficiency by adjusting the magnetic coil configuration. This numerical tool enables broad parameter scan with modest computational requirements (single workstation). The code has been benchmarked against the idealized analytical picture of plasma detachment and then used to investigate more realistic nozzle configurations that are not analytically tractable. Most recently, the code has been used to interpret experimental data from the Detachment Demonstration Experiment (DDEX) [3] facility at NASA Marshall Space Flight Center. In collabotation with: M. Tushentsov, A. Arefiev, R. Bengtson, J.Meyers (University of Texas at Austin), D. Chavers, C. Dobson, J. Jones (Marshall Space Flight Center), B.Schuettpelz, (University of

  8. A mechanical model of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2012-08-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate, typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular and RPE pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed lesions in which the tissue has a higher choroidal hydraulic conductivity, has insufficient RPE pump activity, or has defective adhesion bonds. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. The corresponding stable blister radius and shape are calculated. Our analysis provides a quantitative description of the physical mechanisms involved in exudative retinal detachments and can help guide the development of retinal reattachment protocols or preventative procedures.

  9. Retinal detachment associated with atopic dermatitis.

    PubMed Central

    Takahashi, M; Suzuma, K; Inaba, I; Ogura, Y; Yoneda, K; Okamoto, H

    1996-01-01

    BACKGROUND: Retinal detachment associated with atopic dermatitis, one of the most common forms of dermatitis in Japan, has markedly increased in Japan in the past 10 years. To clarify pathogenic mechanisms of retinal detachment in such cases, we retrospectively studied clinical characteristics of retinal detachment associated with atopic dermatitis. METHODS: We examined the records of 80 patients (89 eyes) who had retinal detachment associated with atopic dermatitis. The patients were classified into three groups according to lens status: group A, eyes with clear lenses (40 eyes); group B, eyes with cataract (38 eyes), and group C, aphakic or pseudophakic eyes (11 eyes). RESULTS: No significant differences were noted in the ratio of males to females, age distribution, refractive error, or characteristic of retinal detachment among the three groups. The types of retinal breaks, however, were different in eyes with and without lens changes. While atrophic holes were dominant in group A, retinal dialysis was mainly seen in groups B and C. CONCLUSION: These findings suggested that anterior vitreoretinal traction may play an important role in the pathogenesis of retinal breaks in eyes with atopic cataract and that the same pathological process may affect the formation of cataract and tractional retinal breaks in patients with atopic dermatitis. PMID:8664234

  10. Plume detachment from a magnetic nozzle

    SciTech Connect

    Deline, Christopher A.; Bengtson, Roger D.; Breizman, Boris N.; Tushentsov, Mikhail R.; Jones, Jonathan E.; Chavers, D. Greg; Dobson, Chris C.; Schuettpelz, Branwen M.

    2009-03-15

    High-powered electric propulsion thrusters utilizing a magnetized plasma require that plasma exhaust detach from the applied magnetic field in order to produce thrust. This paper presents experimental results demonstrating that a sufficiently energetic and flowing plasma can indeed detach from a magnetic nozzle. Microwave interferometer and probe measurements provide plume density, electron temperature, and ion flux measurements in the nozzle region. Measurements of ion flux show a low-beta plasma plume which follows applied magnetic field lines until the plasma kinetic pressure reaches the magnetic pressure and a high-beta plume expanding ballistically afterward. Several magnetic configurations were tested including a reversed field nozzle configuration. Despite the dramatic change in magnetic field profile, the reversed field configuration yielded little measurable change in plume trajectory, demonstrating the plume is detached. Numerical simulations yield density profiles in agreement with the experimental results.

  11. Hyperphosphorylation of RyRs Underlies Triggered Activity in Transgenic Rabbit Model of LQT2 Syndrome

    PubMed Central

    Terentyev, Dmitry; Rees, Colin M.; Li, Weiyan; Cooper, Leroy L.; Jindal, Hitesh K.; Peng, Xuwen; Lu, Yichun; Terentyeva, Radmila; Odening, Katja E.; Daley, Jean; Bist, Kamana; Choi, Bum-Rak; Karma, Alain; Koren, Gideon

    2015-01-01

    Rationale Loss-of function mutations in HERG potassium channels underlie long QT syndrome (LQTS) type 2 (LQT2), and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasmamembrane-related pathways involved in arrhythmogenesis in LQTS, while pro-arrhythmic changes in intracellular Ca2+ handling remained unexplored. Objective We investigated the remodeling of Ca2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 in order to determine whether these changes contribute to triggered activity in the form of early afterdepolarizations (EADs). Methods and Results Confocal Ca2+ imaging revealed decrease in amplitude of Ca2+ transients and SR Ca2+ content in LQT2 myocytes. Experiments using SR-entrapped Ca2+ indicator demonstrated enhanced RyR-mediated SR Ca2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR in LQT2 myocytes vs. controls. Co-immunoprecipitation experiments demonstrated loss of protein phosphatases type 1 and type 2 from the RyR complex. Stimulation of LQT2 cells with β-adrenergic agonist isoproterenol resulted in prolongation of the plateau of action potentials accompanied by aberrant Ca2+ releases and EADs, which were abolished by inhibition of CaMKII. Computer simulations showed that late aberrant Ca2+ releases caused by RyR hyperactivity promote EADs and underlie the enhanced triggered activity through increased forward mode of NCX1. Conclusions Hyperactive, hyperphosphorylated RyRs due to reduced local phosphatase activity enhance triggered activity in LQT2 syndrome. EADs are promoted by aberrant RyR-mediated Ca2+ releases that are present despite a reduction of sarcoplasmic reticulum (SR) content. Those releases increase forward mode NCX1, thereby slowing repolarization and enabling L-type Ca2+ current reactivation. PMID:25249569

  12. Characteristics of divertor detachment for ITER conditions

    NASA Astrophysics Data System (ADS)

    Kukushkin, A. S.; Pacher, H. D.; Pitts, R. A.

    2015-08-01

    The relative role of particle balance vs. momentum balance in the phenomenon of divertor plasma detachment in tokamaks is re-assessed. Ion removal from the plasma flow by volumetric recombination and/or cross-field transport is identified as the key element in the formation of the rollover of the ion saturation current on the targets, whereas "momentum removal" (friction) is responsible for maintaining high plasma pressure upstream. The deterioration of neutral particle confinement in the divertor as particle throughput increases is the primary cause of the solution collapse typically seen when deep detachment is modelled for present day experiments.

  13. Evaluation and management of pediatric rhegmatogenous retinal detachment

    PubMed Central

    Wenick, Adam S.; Barañano, David E.

    2012-01-01

    Pediatric rhegmatogenous retinal detachments are rare, accounting for less than ten percent of all rhegmatogenous retinal detachments. While most retinal detachments in the adult population are related to posterior vitreous detachment, pediatric retinal detachment are often related to trauma or an underlying congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the often late presentation of the disease, and the high incidence of bilateral pathology in children all pose significant challenges in the management of these patients. We discuss the epidemiology of pediatric rhegmatogenous retinal detachment, review the genetic syndromes associated with a high incidence of retinal detachment, and examine other common causes of retinal detachment in this age group. We then outline an approach to evaluation and management and describe the expected outcomes of repair of retinal detachment in the pediatric population. PMID:23961003

  14. Jules Gonin. Pioneer of retinal detachment surgery.

    PubMed

    Wolfensberger, Thomas J

    2003-12-01

    Before the turn of the 20th century, eyes with a retinal detachment were considered doomed. Contrary to other branches of ophthalmology, such as cataract extraction, the surgical treatment of retinal detachment was still in its infancy, and the surgical success rates were less than five percent. From 1902 to 1921 Jules Gonin almost single handedly changed the landscape of retinal detachment surgery forever. He recognised that the retinal break was the cause--and not the consequence as it was largely believed at the time--of the retinal detachment, and that the treatment had at all costs to comprise the closure of the break by cauterisation. He named the procedure ignipuncture, as he cauterised the retina through the sclera with a very hot pointed instrument. Despite rigorously detailed clinical observations and increasing success rates, his discovery was not readily accepted and sometimes openly opposed by a large part of the ophthalmic establishment. It was not until 1929 that he received worldwide acclaim at the International Ophthalmological Congress in Amsterdam for his surgical technique. His legacy lives on in the eye hospital in Lausanne that bears his name, in the Gonin Medal awarded by the International Council of Ophthalmology every four years for the highest achievement in ophthalmology, and in a street named after him, the very street that he used to walk from his home to the hospital every day. PMID:14750617

  15. Electrically induced drop detachment and ejection

    NASA Astrophysics Data System (ADS)

    Cavalli, Andrea; Preston, Daniel J.; Tio, Evelyn; Martin, David W.; Miljkovic, Nenad; Wang, Evelyn N.; Blanchette, Francois; Bush, John W. M.

    2016-02-01

    A deformed droplet may leap from a solid substrate, impelled to detach through the conversion of surface energy into kinetic energy that arises as it relaxes to a sphere. Electrowetting provides a means of preparing a droplet on a substrate for lift-off. When a voltage is applied between a water droplet and a dielectric-coated electrode, the wettability of the substrate increases in a controlled way, leading to the spreading of the droplet. Once the voltage is released, the droplet recoils, due to a sudden excess in surface energy, and droplet detachment may follow. The process of drop detachment and lift-off, prevalent in both biology and micro-engineering, has to date been considered primarily in terms of qualitative scaling arguments for idealized superhydrophobic substrates. We here consider the eletrically-induced ejection of droplets from substrates of finite wettability and analyze the process quantitatively. We compare experiments to numerical simulations and analyze how the energy conversion efficiency is affected by the applied voltage and the intrinsic contact angle of the droplet on the substrate. Our results indicate that the finite wettability of the substrate significantly affects the detachment dynamics, and so provide new rationale for the previously reported large critical radius for drop ejection from micro-textured substrates.

  16. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer's Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation.

    PubMed

    Tyagi, Ethika; Fiorelli, Tina; Norden, Michelle; Padmanabhan, Jaya

    2013-01-01

    The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer's disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1 β (IL-1 β ) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes. It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1 β injection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK). We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation. These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD. PMID:24175110

  17. The role of CDK5 and GSK3B kinases in hyperphosphorylation of microtubule associated protein tau (MAPT) in Alzheimer's disease

    PubMed Central

    Jayapalan, Saranya; Natarajan, Jeyakumar

    2013-01-01

    Alzheimer's disease is the most common form of dementia. Abnormal hyperphosphorylation of Microtubule associated protein tau (MAPT) is one of the hallmarks of Alzheimer's disease and related tau pathies. CDK5 and GSK3B are the two main protein kinases that have an important role in the abnormal hyperphosphorylation of MAPT which leads to Alzheimer's disease. Structural information for both MAPT-CDK5 and MAPT-GSK3B complexes being absent, we resorted to molecular modeling for gaining insight into the mechanism of implication of hyperphosphorylation of MAPT by both enzymes. First the tertiary structure of MAPT was modeled and its active regions were defined. This was followed by molecular docking and interaction studies of MAPT with CDK5 and GSK3B kinases to infer the role of these kinases in abnormal hyperphosphorylation of MAPT protein. In addition, we have investigated the characteristic features such as phosphorylation sites and ATP binding sites of MAPT and two kinases. Further we computed the stabilization centers and stabilization residues of the MAPT protein and two kinases before and after docking process. The overall results portray that CDK5 is strongly involved in the hyperphosphorylation of MAPT when compared to GSK3B. PMID:24497730

  18. Vinexin β Interacts with Hepatitis C Virus NS5A, Modulating Its Hyperphosphorylation To Regulate Viral Propagation

    PubMed Central

    Xiong, Wei; Yang, Jie; Wang, Mingzhen; Wang, Hailong; Rao, Zhipeng; Zhong, Cheng; Xin, Xiu; Mo, Lin; Yu, Shujuan

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is essential for HCV genome replication and virion production and is involved in the regulation of multiple host signaling pathways. As a proline-rich protein, NS5A is capable of interacting with various host proteins containing Src homology 3 (SH3) domains. Previous studies have suggested that vinexin, a member of the sorbin homology (SoHo) adaptor family, might be a potential binding partner of NS5A by yeast two-hybrid screening. However, firm evidence for this interaction is lacking, and the significance of vinexin in the HCV life cycle remains unclear. In this study, we demonstrated that endogenously and exogenously expressed vinexin β coimmunoprecipitated with NS5A derived from different HCV genotypes. Two residues, tryptophan (W307) and tyrosine (Y325), in the third SH3 domain of vinexin β and conserved Pro-X-X-Pro-X-Arg motifs at the C terminus of NS5A were indispensable for the vinexin-NS5A interaction. Furthermore, downregulation of endogenous vinexin β significantly suppressed NS5A hyperphosphorylation and decreased HCV replication, which could be rescued by expressing a vinexin β short hairpin RNA-resistant mutant. We also found that vinexin β modulated the hyperphosphorylation of NS5A in a casein kinase 1α-dependent on manner. Taken together, our findings suggest that vinexin β modulates NS5A phosphorylation via its interaction with NS5A, thereby regulating HCV replication, implicating vinexin β in the viral life cycle. IMPORTANCE Hepatitis C virus (HCV) nonstructural protein NS5A is a phosphoprotein, and its phosphorylation states are usually modulated by host kinases and other viral nonstructural elements. Additionally, cellular factors containing Src homology 3 (SH3) domains have been reported to interact with proline-rich regions of NS5A. However, it is unclear whether there are any relationships between NS5A phosphorylation and the NS5A-SH3 interaction, and little is known

  19. Syneresis and delayed detachment in agar plates.

    PubMed

    Divoux, Thibaut; Mao, Bosi; Snabre, Patrick

    2015-05-14

    Biogels made of crosslinked polymers such as proteins or polysaccharides behave as porous soft solids and store large amounts of solvent. These gels undergo spontaneous aging, called syneresis, which consists of the shrinkage of the gel matrix and the progressive expulsion of solvent. As a result, a biogel originally casted in a container often loses contact with the container sidewalls, and the detachment time is difficult to anticipate a priori, since it may occur over variable time spans (from hours to days). Here we report on syneresis phenomena in agar plates, which consist of Petri dishes filled with a gel mainly composed of agar. Direct observations and speckle pattern correlation analysis allow us to rationalize the delayed detachment of the gel from the sidewall of the Petri dish. The detachment time t* is surprisingly not controlled by the mass loss as one would intuitively expect. Instead, t* is strongly correlated to the gel minimum thickness emin measured along the sidewall of the plate, and increases as a robust function of emin, independently of the prior mass-loss history. Time-resolved correlation spectroscopy atypically applied to such weakly diffusive media gives access to the local thinning rate of the gel. This technique also allows us to detect the gel micro-displacements that are triggered by water evaporation prior to the detachment, and even to anticipate the latter from a few hours. Our work provides observables to predict the detachment time of agar gels in dishes, and highlights the relevance of speckle pattern correlation analysis for the quantitative investigation of the syneresis dynamics in biopolymer gels. PMID:25812667

  20. Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients

    PubMed Central

    Gu, Yong-Hao; Ke, Gen-Jie; Wang, Lin; Gu, Qi-Hong; Zhou, En-Liang; Pan, Hong-Biao; Wang, Shi-Ying

    2016-01-01

    AIM To comprehensively analyze the risk factors of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope (UBM). Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60±3.62 vs 12.96±3.55, P<0.001), best-corrected visual acuity was worse [3.00 (2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and larger extent of retinal detachment (P<0.001) were significant and independent risk factors for developing CD. CONCLUSION For CD in RRD, related factors include BCVA, IOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low IOP are significant and independent risk factors. PMID:27500106

  1. Modeling of detached and unsteady eutectic solidification

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri I.

    Detached solidification provides a new possibility to grow crystals with improved quality. However, it has not been reproducible. The first part of this dissertation is dedicated to discussion of the mechanisms and conditions that would help to bring detached solidification from a space laboratory to a terrestrial factory. The possibility of a steady-state gap during detached solidification was proved by solving the mass transport and Navier-Stokes equations. A high contact angle of the melt with the ampoule wall, appreciable gas atmosphere, and a low freezing rate are needed to obtain detachment. Stability analysis showed that mass transfer of volatile species from the melt into the gap and heat transfer stabilize detached configuration. In vertical solidification on earth, a convex freezing interface was shown to provide enhanced transport of volatile species towards the gap, and, therefore, supports detachment. The influence of convection on eutectic microstructure selection has been a question for many years. Both experiment and theory have shown that buoyancy-driven convection alone is not enough to explain the difference in microstructure of earth- and space-grown eutectics. The second part of this dissertation is devoted to a study of the influence of temperature oscillations on microstructure selection. Two different models were chosen. The first, a sharp-interface model, was able to give a solution for the excess compositional undercooling for different leading conditions of both lamellar and rod eutectics. The limitation of this model is that it's not able to set the conditions for catastrophic morphological changes. Application of the principle of minimum entropy production to stationary eutectic growth predicts a decrease in eutectic spacing due to freezing rate oscillations. The second, a phase-field model, was developed for the evolution of the microstructure. This phase-field model correctly describes unsteady eutectic solidification, as well as

  2. Overactivation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion.

    PubMed

    Xu, Cheng-Shi; Liu, An-Chun; Chen, Juan; Pan, Zhi-Yong; Wan, Qi; Li, Zhi-Qiang; Wang, Ze-Fen

    2015-08-01

    Middle cerebral artery occlusion (MCAO) induces secondary damages in the hippocampus that is remote from primary ischemic regions. Tau hyperphosphorylation is an important risk for neurodegenerative diseases. Increased tau phosphorylation has been identified in ischemic cortex, but little is known regarding the changes in the hippocampus. We showed that unilateral transient MCAO induced accumulation of hyperphosphorylated tau and concurrent dephosphorylation of glycogen synthase kinase-3β at Ser 9 in the ipsilateral hippocampus. These MCAO-induced changes were not reproduced when glutamatergic inputs from the entorhinal cortex to the hippocampus were transected; however, the changes were mimicked by intrahippocampal N-methyl-d-aspartate (NMDA) administration. Inhibition of NMDA receptor (NMDAR) subunit NR2B, but not NR2A activity in the hippocampus attenuated the accumulation of hyperphosphorylated tau and spatial cognitive impairment in MCAO rats. Together, our data suggest that overactivation of NR2B-containing NMDARs through entorhinal-hippocampal connection plays an important role in the accumulation of hyperphosphorylated tau in the hippocampus following MCAO. Glycogen synthase kinase-3β is an important protein kinase involved in NMDARs-mediated tau hyperphosphorylation. This study indicates that early inhibition of NR2B-containing NMDARs may represent a potential strategy to prevent or delay the occurrence of post-stroke dementia. Middle cerebral artery occlusion induces secondary damage in the hippocampus that is remote from primary ischemic regions. We propose that excessive activation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiated the accumulation of hyperphosphorylated tau in the hippocampus, which subsequently induced cognitive deficit. This study provides new insights into the prospects of NR2B inhibition in stoke therapy. PMID:25903928

  3. Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau.

    PubMed

    Liu, Shi-Jie; Zheng, Ping; Wright, David K; Dezsi, Gabi; Braine, Emma; Nguyen, Thanh; Corcoran, Niall M; Johnston, Leigh A; Hovens, Christopher M; Mayo, Jamie N; Hudson, Matthew; Shultz, Sandy R; Jones, Nigel C; O'Brien, Terence J

    2016-07-01

    There are no treatments in clinical practice known to mitigate the neurobiological processes that convert a healthy brain into an epileptic one, a phenomenon known as epileptogenesis. Downregulation of protein phosphatase 2A, a protein that causes the hyperphosphorylation of tau, is implicated in neurodegenerative diseases commonly associated with epilepsy, such as Alzheimer's disease and traumatic brain injury. Here we used the protein phosphatase 2A activator sodium selenate to investigate the role of protein phosphatase 2A in three different rat models of epileptogenesis: amygdala kindling, post-kainic acid status epilepticus, and post-traumatic epilepsy. Protein phosphatase 2A activity was decreased, and tau phosphorylation increased, in epileptogenic brain regions in all three models. Continuous sodium selenate treatment mitigated epileptogenesis and prevented the biochemical abnormalities, effects which persisted after drug withdrawal. Our studies indicate that limbic epileptogenesis is associated with downregulation of protein phosphatase 2A and the hyperphosphorylation of tau, and that targeting this mechanism with sodium selenate is a potential anti-epileptogenic therapy. PMID:27289302

  4. Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer's Disease.

    PubMed

    Jiang, Teng; Zhang, Ying-Dong; Zhou, Jun-Shan; Zhu, Xi-Chen; Tian, You-Yong; Zhao, Hong-Dong; Lu, Huan; Gao, Qing; Tan, Lan; Yu, Jin-Tai

    2016-05-01

    As a recently identified bioactive peptide of brain renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)] along with its metabolic enzyme angiotensin-converting enzyme (ACE) 2 and its receptor Mas forms ACE2/Ang-(1-7)/Mas axis. Accumulating evidence suggests an essential role of ACE2/Ang-(1-7)/Mas axis in maintaining normal cognitive functions in both animals and human subjects, and dysregulation of this axis contributed to the pathogenesis of several neurodegenerative diseases such as hypertension-induced neurodegeneration and vascular dementia. To date, whether this axis was associated with the etiology and progression of Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, remains unclear. In the current study, by using senescence-accelerated mouse prone 8 (SAMP8) mice, an animal model of sporadic AD, we showed for the first time that the level of Ang-(1-7) in the brain was significantly reduced during disease progression. More importantly, an inverse correlation was found between Ang-(1-7) level and tau hyperphosphorylation, a pathological hallmark of AD, in cerebral cortex and hippocampus of SAMP8 mice. Meanwhile, this has been further confirmed in P301S mice, an animal model of pure tauopathy. All these findings suggested that Ang-(1-7), the main effector of brain ACE2/Ang-(1-7)/Mas axis, might be implicated in the etiology and progression of AD, possibly via modulation of tau hyperphosphorylation. PMID:26044748

  5. Citalopram attenuates tau hyperphosphorylation and spatial memory deficit induced by social isolation rearing in middle-aged rats.

    PubMed

    Ren, Qing-Guo; Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Qi-Da; Zhang, Zhi-Jun

    2015-05-01

    Social isolation (SI) is considered as a chronic stress. Here, middle-aged rats (8 months) were group or isolation reared for 6 weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Changes in recognition memory, depression and anxiety-like behavior, and phosphorylated tau were investigated. We found that SI did not lead to obvious depression/anxiety-like behavior in middle-aged rats. Memory deficits and increased tau hyperphosphorylation at Tau-1, Ser396 episodes could be almost reversed by citalopram. The level of Ser9-phosphorylated GSK-3β (inactive form) was significantly decreased in the SI group which also could be almost reversed by citalopram, suggesting that the citalopram could prevent GSK-3β from SI-induced overactivation. The melatonin level was decreased in SI group compared with group housed (GH) group, and citalopram could partly restore the level of melatonin. We also found that citalopram could increase MT1 and MT2 in mRNA level. Our results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and spatial memory deficit induced by SI in middle-aged rats. Suggesting that SI might constitute a risk factor for Alzheimer's disease (AD), and citalopram may represent a therapeutic strategy for the treatment of AD. PMID:25476250

  6. Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine.

    PubMed

    Chohan, Muhammad Omar; Khatoon, Sabiha; Iqbal, Inge-Grundke; Iqbal, Khalid

    2006-07-10

    The activity of protein phosphatase (PP)-2A, which regulates tau phosphorylation, is compromised in Alzheimer disease brain. Here we show that the transient transfection of PC12 cells with inhibitor-2 (I2PP2A) of PP2A causes abnormal hyperphosphorylation of tau at Ser396/Ser404 and Ser262/Ser356. This hyperphosphorylation of tau is observed only when a sub-cellular shift of I2PP2A takes place from the nucleus to the cytoplasm and is accompanied by cleavage of I2PP2A into a 20 kDa fragment. Memantine, an un-competitive inhibitor of N-methyl-D-aspartate receptors, inhibits this abnormal phosphorylation of tau and cell death and prevents the I2PP2A-induced inhibition of PP2A activity in vitro. These findings demonstrate novel mechanisms by which I2PP2A regulates the intracellular activity of PP2A and phosphorylation of tau, and by which Memantine modulates PP2A signaling and inhibits neurofibrillary degeneration. PMID:16806196

  7. Folate/vitamin-B12 prevents chronic hyperhomocysteinemia-induced tau hyperphosphorylation and memory deficits in aged rats.

    PubMed

    Wei, Wei; Liu, Ying-Hua; Zhang, Chang-E; Wang, Qun; Wei, Zelan; Mousseau, Darrell D; Wang, Jian-Zhi; Tian, Qing; Liu, Gong-Ping

    2011-01-01

    Hyperhomocysteinemia is associated with an increased risk of Alzheimer's disease (AD). Our previous work has demonstrated that combined folate and vitamin B12 (vit-B12) supplementation prevents tau hyperphosphorylation and memory deficits induced by acute administration of homocysteine in young rats. Here, we further investigated whether folate/vit-B12 supplementation is also effective in aged rats with a chronically high level of homocysteine. 18-month-old rats were injected with homocysteine via the vena caudalis with or without a concurrent folate/vit-B12 supplementation for 28 weeks. We found that hyperhomocysteinemia induced tau hyperphosphorylation and accumulation in hippocampus and cortex. Concurrent signaling changes included the activation of glycogen synthase kinases-3β, cyclin-dependent kinase-5, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38MAPK, and inhibition of protein phosphatase 2A. Although the ability to learn was not affected, the aged rats exhibited significant memory deficits. Folate/vit-B12 supplementation attenuated these biochemical and behavioral correlates. These data demonstrate that folate/vit-B12 supplementation is also effective in a chronic hyperhomocysteinemia model in reversing the AD-like tau pathologies and memory deficits. PMID:21860088

  8. Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress

    PubMed Central

    AbdAlla, Said; el Hakim, Ahmed; Abdelbaset, Ahmed; Elfaramawy, Yasser; Quitterer, Ursula

    2015-01-01

    With increasing life expectancy, Alzheimer's disease (AD) and other types of age-associated dementia are on the rise worldwide. Treatment approaches for dementia are insufficient and novel therapies are not readily available. In this context repurposing of established drugs appears attractive. A well-established class of cardiovascular drugs, which targets the angiotensin II system, is such a candidate, which currently undergoes a paradigm shift with regard to the potential benefit for treatment of neurodegenerative symptoms. In search for additional evidence, we subjected aged rats to chronic unpredictable mild stress, which is known to enhance the development of AD-related neuropathological features. We report here that four weeks of chronic mild stress induced a strong upregulation of the hippocampal angiotensin-converting enzyme (Ace) at gene expression and protein level. Concomitantly, tau protein hyperphosphorylation developed. Signs of neurodegeneration were detected by the significant downregulation of neuronal structure proteins such as microtubule-associated protein 2 (Map2) and synuclein-gamma (Sncg). Ace was involved in neurodegenerative symptoms because treatment with the brain-penetrating ACE inhibitor, captopril, retarded tau hyperphosphorylation and signs of neurodegeneration. Moreover, ACE inhibitor treatment could counteract glutamate neurotoxicity by preventing the downregulation of glutamate decarboxylase 2 (Gad2). Taken together, ACE inhibition targets neurodegeneration triggered by environmental stress. PMID:26697495

  9. On Transients in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Mazuruk, K.; Volz, M. P.

    2011-01-01

    In detached Bridgman growth, a gap exists between the growing crystal and the crucible wall. According to crystal shape stability theory, only specific gap widths will be dynamically stable. Beginning with a crystal diameter that differs from stable conditions, the transient crystal growth process is analyzed. The transient shapes are calculated assuming that the growth angle is constant. Anisotropy and dynamic contact angle effects are considered. In microgravity, dynamic stability depends only on capillary effects and is decoupled from heat transfer. However, heat transfer will influence the crystal-melt interface shape. The local angles and the crystal-melt-vapor triple junction are analyzed and the applicability of the Herring formula is discussed. A potential microgravity experiment is proposed which would enhance our understanding of the detached growth dynamic stability problem.

  10. Retinoschisis transposition following a retinal detachment repair

    PubMed Central

    McVeigh, Katherine; Keller, Johannes; Haynes, Richard J.

    2015-01-01

    Objective: The authors have observed this phenomenon of translocation of the schisis cavity in a few previous cases and aim to report this unusual finding. Method: A patient with known superotemporal retinoschisis developed a distinctly separate inferotemporal retinal detachment in his left eye. This was repaired with a vitrectomy, cryotherapy and C2F6 tamponade under local anaesthetic. Following surgery, the retinoschisis was found in the inferonasal quadrant of the eye and remained stable as the gas dispersed. Result: We hypothesise that the tamponading agent compressed the viscous fluid within the area of schisis, displacing the area of schisis circumferentially. Conclusion: This case emphasises that as long as the retinal breaks are properly sealed, no intervention is required with the schisis during rhegmatogenous retinal detachment surgery.

  11. High and Low Temperature Oceanic Detachment Faults

    NASA Astrophysics Data System (ADS)

    Titarenko, Sofya; McCaig, Andrew

    2013-04-01

    One of the most important discoveries in Plate Tectonics in the last ten years is a "detachment mode" of seafloor spreading. Up to 50% of the Atlantic seafloor has formed by a combination of magmatism and slip on long-lived, convex-up detachment faults, forming oceanic core complexes (OCC). Two end-member types of OCC can be defined: The Atlantis Bank on the Southwest Indian Ridge is a high temperature OCC sampled by ODP Hole 735b. Deformation was dominated by crystal-plastic flow both above and below the solidus at 800-950 °C, over a period of around 200 ka. In contrast, the Atlantis Massif at 30 °N in the Atlantic, sampled by IODP Hole 1309D, is a low temperature OCC in which crystal plastic deformation of gabbro is very rare and greenschist facies deformation was localised onto talc-tremolite-chlorite schists in serpentinite, and breccia zones in gabbro and diabase. The upper 100m of Hole 1309D contains about 43% diabase intruded into hydrated fault breccias. This detachment fault zone can be interpreted as a dyke-gabbro transition, which was originally (before flexural unroofing) a lateral boundary between active hydrothermal circulation in the fault zone and hangingwall, and intrusion of gabbroic magma in the footwall. Thus a major difference between high and low temperature detachment faults may be cooling of the latter by active hydrothermal circulation. 2-D thermal modelling suggests that if a detachment fault is formed in a magmatically robust segment of a slow spreading ridge, high temperature mylonites can be formed for 1-2 ka provided there is no significant hydrothermal cooling of the fault zone. In contrast, if the fault zone is held at temperatures of 400 °C by fluid circulation, cooling of the upper 1 km of the fault footwall occurs far too rapidly for extensive mylonites to form. Our models are consistent with published cooling rate data from geospeedometry and isotopic closure temperatures. The control on this process is likely a combination of

  12. Detached Growth of Germanium by Directional Solidification

    NASA Technical Reports Server (NTRS)

    Palosz, W.; Volz, M.; Cobb, S.; Motakef, S.; Szofran, F. R.

    2004-01-01

    Detached crystal growth technique (dewetting) offers improvement in the quality of the grown crystals by preventing sticking to the walls of the crucible and thus reducing the possibility of parasitic nucleation and formation of lattice defects upon cooling. One of the factors relevant for the phenomena is the pressure differential across the meniscus at the crystal-melt interface. We investigated this effect experimentally. The growth took place in closed ampoules under the pressure of an inert gas (forming gas: 96% Ar + 4% H2). The pressure above the melt was adjustable and allowed for a control of the pressure difference between the top and bottom menisci. The crystals were characterized, particularly by taking profilometer measurements along the grown crystals surface. The effects of the experimental conditions on the detachment were compared with those predicted based on the theory of Duffar et al.

  13. Mechanism of bubble detachment from vibrating walls

    SciTech Connect

    Kim, Dongjun; Park, Jun Kwon Kang, Kwan Hyoung; Kang, In Seok

    2013-11-15

    We discovered a previously unobserved mechanism by which air bubbles detach from vibrating walls in glasses containing water. Chaotic oscillation and subsequent water jets appeared when a wall vibrated at greater than a critical level. Wave forms were developed at water-air interface of the bubble by the wall vibration, and water jets were formed when sufficiently grown wave-curvatures were collapsing. Droplets were pinched off from the tip of jets and fell to the surface of the glass. When the solid-air interface at the bubble-wall attachment point was completely covered with water, the bubble detached from the wall. The water jets were mainly generated by subharmonic waves and were generated most vigorously when the wall vibrated at the volume resonant frequency of the bubble. Bubbles of specific size can be removed by adjusting the frequency of the wall's vibration.

  14. Detached Growth of Germanium and Germaniumsilicon

    NASA Technical Reports Server (NTRS)

    Dold, P.; Schweizer, M.; Szofran, F.; Benz, K. W.

    1999-01-01

    Up to now, detached growth was observed mainly under microgravity, i.e. under the absence of hydrostatic pressure that hinders the formation of a free melt meniscus. the detached growth of germanium doped with gallium was obtained under 1 g conditions, the growth was performed in quartz-glass ampoule. Part of the crystal grew without wall contact, the detached growth was observed in-situ with a CCD-camera as well as after the growth process in form of growth lines and the formation of <111> facets on the crystal surface. GeSi crystal (oriientation: <111>, maximum silicon content: 4 at%, seed material: Ge) was grown in a pBN crucible (excluding the possibility of in-situ monitoring of the growth process). The grown crystal exhibits three growth facets, indicating also wall free growth. Surface analysis of the crystals (NDIC, SEM) and characterization of crystal segregation (EDAX, resistivity measurement) and defect structure (EPD, x-ray diffraction measurements) will be presented.

  15. Optimizing the treatment of rhegmatogenous retinal detachment.

    PubMed

    Hajari, Javad Nouri

    2016-03-01

    Surgical approaches for rhegmatogenous retinal detachment (RRD) have evolved rapidly in the past century. This has resulted in an increase in the anatomical success rate from zero per cent in the beginning of the 1900s to now almost 100 per cent. Rhegmatogenous retinal detachment is regarded as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first paper, data on the incidence of RRD in Denmark are presented based on data from a nation register the National Patient Registry (NPR). It was discovered that the incidence of RRD in Denmark is similar to previous reported numbers and that the incidence has been increasing due to increasing numbers of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure that the patients are also treated in the most optimal way. To ensure this, an indicator is needed to monitor the quality at the different centres. This indicator presented in the second paper is based in the occurrence of redetachment. We define a detachment to be caused by poor surgery if the retina detaches within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery be performed to attain the most optimal result? In the third paper, we evaluated the progression of posterior RRD with an optical coherence tomography to make an objective assessment of

  16. Improved Crystal Quality by Detached Solidification in Microgravity

    NASA Technical Reports Server (NTRS)

    Regel, Liya L.; Wilcox, William R.

    2003-01-01

    The goals of our work on detached solidification have been to: 1) Develop a complete understanding of all of the phenomena of detached solidification; 2) Make it possible to achieve detached solidification reproducibly; and 3) Increase crystallographic perfection through detached solidification. Specifically, we aimed in this project to: 1) Identify a system and develop methods that would allow viewing of the melt surface and convection in the melt during detached solidification in microgravity; 2) Improve understanding of the origination and evolution of detachment through experiments and theoretical treatments; and 3) Achieve detachment on earth. The project resulted in 14 publications, 15 presentations, completion of 2 Ph.D. theses, and completion of 2 M.S. theses. Two additional papers are currently being reviewed for publication. Copies of most of the papers are included as appendices.

  17. Psychological Detachment in the Relationship between Job Stressors and Strain

    PubMed Central

    Safstrom, My; Hartig, Terry

    2013-01-01

    We investigated the mediating versus moderating role of psychological detachment in the relationship between job stressors and psychological strain. Our sample consisted of 173 university students invested in challenging programs of advanced professional studies, who could find it difficult to detach from work. Hierarchical regression analyses of cross-sectional survey data affirmed the role of psychological detachment as a mediator in the relationship between job demands and perceived stress. Detachment also mediated the relationship between job demands and satisfaction with life, although the association disappeared when controlling for negative affectivity. Detachment did not mediate relationships between job demands and cognitive failures. Psychological detachment did not moderate any of the investigated relationships. The study contributes to a view of psychological detachment as less subject to individual differences than to the imposition of stressors in the given context. PMID:25379246

  18. Numerical computational of fluid flow through a detached retina

    NASA Astrophysics Data System (ADS)

    Jiann, Lim Yeou; Ismail, Zuhaila; Shafie, Sharidan; Fitt, Alistair

    2015-02-01

    In this paper, a phenomenon of fluid flow through a detached retina is studied. Rhegmatogeneous retinal detachment happens when vitreous humour flow through a detached retina. The exact mechanism of Rhegmatogeneous retinal detachment is complex and remains incomplete. To understand the fluid flow, a paradigm mathematical model is developed and is approximated by the lubrication theory. The numerical results of the velocity profile and pressure distribution are computed by using Finite Element Method. The effects of fluid mechanical on the retinal detachment is discussed and analyzed. Based on the analysis, it is found that the retinal detachment deformation affects the pressure distribution. It is important to comprehend the development of the retinal detachment so that a new treatment method can be developed.

  19. Two-Dimensional Island Shape Determined by Detachment

    NASA Astrophysics Data System (ADS)

    Saito, Yukio; Kawasaki, Ryo

    2007-07-01

    Effect of an anisotropic detachment on a heteroepitaxial island shape is studied by means of a kinetic Monte Carlo simulation of a square lattice gas model. Only with molecular deposition followed by surface diffusion, islands grow in a ramified dendritic shape, similar to diffusion-limited aggregate (DLA). Introduction of molecular detachment from edges makes islands compact. To understand an anisotropic island shape observed in the experiment of pentacene growth on a hydrogen-terminated Si(111) vicinal surface, asymmetry in detachment around the substrate step is assumed. Edge molecules detach more to the higher terrace than to the lower terrace. The island edge from which molecules are easy to detach is smooth and the one hard to detach is dendritic. If islands are close to each other, islands tend to align in a line, since detached molecules from the smooth edge of the right island are fed to the dendritic and fast growing edge of the left island.

  20. Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

    PubMed

    Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

    2016-09-01

    SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and

  1. Sex hormone-related neurosteroids differentially rescue bioenergetic deficits induced by amyloid-β or hyperphosphorylated tau protein.

    PubMed

    Grimm, Amandine; Biliouris, Emily E; Lang, Undine E; Götz, Jürgen; Mensah-Nyagan, Ayikoe Guy; Eckert, Anne

    2016-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease marked by a progressive cognitive decline. Metabolic impairments are common hallmarks of AD, and amyloid-β (Aβ) peptide and hyperphosphorylated tau protein--the two foremost histopathological signs of AD--have been implicated in mitochondrial dysfunction. Neurosteroids have recently shown promise in alleviating cognitive and neuronal sequelae of AD. The present study evaluates the impact of neurosteroids belonging to the sex hormone family (progesterone, estradiol, estrone, testosterone, 3α-androstanediol) on mitochondrial dysfunction in cellular models of AD: human neuroblastoma cells (SH-SY5Y) stably transfected with constructs encoding (1) the human amyloid precursor protein (APP) resulting in overexpression of APP and Aβ, (2) wild-type tau (wtTau), and (3) mutant tau (P301L), that induces abnormal tau hyperphosphorylation. We show that while APP and P301L cells both display a drop in ATP levels, they present distinct mitochondrial impairments with regard to their bioenergetic profiles. The P301L cells presented a decreased maximal respiration and spare respiratory capacity, while APP cells exhibited, in addition, a decrease in basal respiration, ATP turnover, and glycolytic reserve. All neurosteroids showed beneficial effects on ATP production and mitochondrial membrane potential in APP/Aβ overexpressing cells while only progesterone and estradiol increased ATP levels in mutant tau cells. Of note, testosterone was more efficient in alleviating Aβ-induced mitochondrial deficits, while progesterone and estrogen were the most effective neurosteroids in our model of AD-related tauopathy. Our findings lend further support to the neuroprotective effects of neurosteroids in AD and may open new avenues for the development of gender-specific therapeutic approaches in AD. PMID:26198711

  2. Kinematic evidence for downdip movement on the Mormon Peak detachment

    NASA Astrophysics Data System (ADS)

    Walker, Christopher D.; Anders, Mark H.; Christie-Blick, Nicholas

    2007-03-01

    The Mormon Peak detachment is considered to be one of the best examples of a rooted upper crustal detachment fault that propagated through the brittle crust at a low angle. The hanging wall of the detachment today consists of a number of isolated blocks that have been interpreted as remnants of a once-contiguous extensional allochthon. Here we present the results of a new study of directional indicators from the basal surfaces beneath these blocks. These measurements do not agree with the long-standing interpretation of a S75°W movement direction for the detachment hanging wall. Instead, the most recent movement on each section of the detachment took place approximately parallel to the present downdip direction. We conclude that the Mormon Peak detachment is best explained as the basal surfaces to a series of rootless gravity slides.

  3. Detachment of multi species biofilm in circulating fluidized bed bioreactor.

    PubMed

    Patel, Ajay; Nakhla, George; Zhu, Jingxu

    2005-11-20

    In this study, the detachment rates of various microbial species from the aerobic and anoxic biofilms in a circulating fluidized bed bioreactor (CFBB) with two entirely separate aerobic and anoxic beds were investigated. Overall detachment rate coefficients for biomass, determined on the basis of volatile suspended solids (VSS), glucose and protein as well as for specific microbial groups, i.e., for nitrifiers, denitrifiers, and phosphorous accumulating organisms (PAOs), were established. Biomass detachment rates were found to increase with biomass attachment on carrier media in both beds. The detachment rate coefficients based on VSS were significantly affected by shear stress, whereas for protein, glucose and specific microbial groups, no significant effect of shear stress was observed. High detachment rates were observed for the more porous biofilm structure. The presence of nitrifiers in the anoxic biofilm and denitrifiers in the aerobic biofilm was established by the specific activity measurements. Detachment rates of PAOs in aerobic and anoxic biofilms were evaluated. PMID:16028296

  4. Meniscus Shapes in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K

    2010-01-01

    In detached Bridgman crystal growth, most of the melt is in contact with the ampoule wall, but the crystal is separated from the wall by a small gap, typically 1-100 micrometers. A liquid free surface, or meniscus, bridges across this gap at the position of the melt-crystal interface. Meniscus shapes have been calculated for the case of detached Bridgman growth in cylindrical ampoules by solving the Young-Laplace equation. Key parameters affecting meniscus shapes are the growth angle, contact angle of the meniscus to the ampoule wall, the pressure differential across the meniscus, and the Bond number, a measure of the ratio of gravitational to capillary forces. In general, for specified values of growth and contact angles, solutions exist only over a finite range of pressure differentials. For intermediate values of the Bond number, there are multiple solutions to the Young-Laplace equations. There are also cases where, as a function of pressure differential, existence intervals alternate with intervals where no solutions exist. The implications of the meniscus shape calculations on meniscus stability are discussed.

  5. Detection of detachments and inhomogeneities in frescos by Compton scattering

    NASA Astrophysics Data System (ADS)

    Castellano, A.; Cesareo, R.; Buccolieri, G.; Donativi, M.; Palamà, F.; Quarta, S.; De Nunzio, G.; Brunetti, A.; Marabelli, M.; Santamaria, U.

    2005-07-01

    A mobile instrument has been developed for the detection and mapping of detachments in frescos by using Compton back scattered photons. The instrument is mainly composed of a high energy X-ray tube, an X-ray detection system and a translation table. The instrument was first applied to samples simulating various detachment situations, and then transferred to the Vatican Museum to detect detachments and inhomogeneities in the stanza di Eliodoro, one of the "Raphael's stanze".

  6. Detachment faults at Mid-Ocean Ridges garner interest

    NASA Astrophysics Data System (ADS)

    Mitchell, Neil; Escartin, Jaview; Allerton, Simon

    The recent discovery of low-angle faults known as detachments on the Mid-Atlantic Ridge requires a major reevaluation of how the oceanic crust forms at slow spreading ridges. Detachment faults can expose large areas of plutonic and ultramafic rocks on the seafloor, without an overlying volcanic carapace. They could profoundly influence the thermal structure, rheology, composition, and style of magmatic accretion at ridges. Oceanic detachments have many parallels with continental detachment faults, with the added advantage that the morphology of the fault surface is pristine, unaffected by subareal erosion.

  7. Changes in spectral properties of detached leaves

    NASA Technical Reports Server (NTRS)

    Daughtry, C. S. T.; Biehl, L. L.

    1984-01-01

    If leaf senescence can be delayed for several days without significant changes in spectral properties, then samples of leaves at remote test sites could be prepared and shipped to laboratories to measure spectral properties. The changes in spectral properties of detached leaves were determined. Leaves from red birch and red pine were immersed in water or 0.001 M benzylaminopurine (BAP) and stored in plastic bags in the dark at either 5 or 25 C. Total directional-hemispherical reflectance and transmittance of the adaxial surface of birch leaves were measured over the 400 to 1100 nm wavelength region with a spectroradiometer and integrating sphere. Pine needles were taped together and reflectance of the mat of needles was measured. Spectral properties changed less than 5% of initial values during the first week when leaves were stored at 5 C. Storage at 25 C promoted rapid senescence and large changes in spectral properties. BAP delayed, but did not stop, senescence at 25 C.

  8. Crystal Shape Evolution in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.

    2013-01-01

    Detached (or dewetted) Bridgman crystal growth defines that process in which a gap exists between a growing crystal and the crucible wall. Existence of the gap provides several advantages, including no sticking of the crystal to the crucible wall, reduced thermal and mechanical stresses, reduced dislocations, and no heterogeneous nucleation by the crucible. Numerical calculations are used to determine the conditions in which a gap can exist. According to crystal shape stability theory, only some of these gap widths will be dynamically stable. Beginning with a crystal diameter that differs from stable conditions, the transient crystal growth process is analyzed. In microgravity, dynamic stability depends only on capillary effects and is decoupled from heat transfer. Depending on the initial conditions and growth parameters, the crystal shape will evolve towards the crucible wall, towards a stable gap width, or towards the center of the crucible, collapsing the meniscus. The effect of a tapered crucible on dynamic stability is also described.

  9. Crystal Shape Evolution in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.

    2013-01-01

    Detached (or dewetted) Bridgman crystal growth defines that process in which a gap exists between a growing crystal and the crucible wall. Existence of the gap provides several advantages, including no sticking of the crystal to the crucible wall, reduced thermal and mechanical stresses, reduced dislocations, and no heterogeneous nucleation by the crucible. Numerical calculations are used to determine the conditions in which a gap can exist. According to crystal shape stability theory, only some of these gap widths will be dynamically stable. Beginning with a crystal diameter that differs from stable conditions, the transient crystal growth process is analyzed. In microgravity, dynamic stability depends only on capillary effects and is decoupled from heat transfer. Depending on the initial conditions and growth parameters, the crystal shape will evolve towards the crucible wall, towards a stable gap width, or towards the center of the crucible, collapsing the meniscus. The effect of a tapered crucible on dynamic stability is also described

  10. Biofilm Growth and Detachment of Actinobacillus actinomycetemcomitans

    PubMed Central

    Kaplan, Jeffrey B.; Meyenhofer, Markus F.; Fine, Daniel H.

    2003-01-01

    The gram-negative, oral bacterium Actinobacillus actinomycetemcomitans has been implicated as the causative agent of several forms of periodontal disease in humans. When cultured in broth, fresh clinical isolates of A. actinomycetemcomitans form tenacious biofilms on surfaces such as glass, plastic, and saliva-coated hydroxyapatite, a property that probably plays an important role in the ability of this bacterium to colonize the oral cavity and cause disease. We examined the morphology of A. actinomycetemcomitans biofilm colonies grown on glass slides and in polystyrene petri dishes by using light microscopy and scanning and transmission electron microscopy. We found that A. actinomycetemcomitans developed asymmetric, lobed biofilm colonies that displayed complex architectural features, including a layer of densely packed cells on the outside of the colony and nonaggregated cells and large, transparent cavities on the inside of the colony. Mature biofilm colonies released single cells or small clusters of cells into the medium. These released cells adhered to the surface of the culture vessel and formed new colonies, enabling the biofilm to spread. We isolated three transposon insertion mutants which produced biofilm colonies that lacked internal, nonaggregated cells and were unable to release cells into the medium. All three transposon insertions mapped to genes required for the synthesis of the O polysaccharide (O-PS) component of lipopolysaccharide. Plasmids carrying the complementary wild-type genes restored the ability of mutant strains to synthesize O-PS and release cells into the medium. Our findings suggest that A. actinomycetemcomitans biofilm growth and detachment are discrete processes and that biofilm cell detachment evidently involves the formation of nonaggregated cells inside the biofilm colony that are destined for release from the colony. PMID:12562811

  11. The Oman Ophiolite from Detachment to Obduction

    NASA Astrophysics Data System (ADS)

    Boudier, F. I.

    2014-12-01

    An overview model is presented accounting for older and up-dated published data. Detachment of the Oman ophiolite exhumed a 20 km thick fragment of oceanic lithosphere 500 x 100 km2 in extension. This detachment occurred at margin of a fast spreading NeoTethyan Ocean, at P/T conditions ~900°C-200 MPa, 95-95.5 Ma ago. The Hawasinah nappes underlying the ophiolite at present, represent the stacking of the sedimentary cover deposited on the Arabian continental margin, thinned and rifted since Permian time, and extending more than 300 km north from the present shore. The sedimentary record points to the collapse of the continental basement at Jurassic-Cretaceous boundary, 140 Ma ago. Subduction of the rifted continental margin is inferred, as recorded in the Saih Hatat high-pressure rocks whose metamorphic age 80-140 Ma is discussed, as well as the vergence of related subduction. Late Cretaceous time 85-70 Ma marks the emplacement of the Oman ophiolite in the Muti Basin, to its present position inland the Permo-Triassic continental margin. These episodes are not similarly recorded in the northern part of the Oman Mountains, that do not expose any HP metamorphic belt, but granulitic crustal rocks and large development of syn-obduction non-MORB magmatism in the ophiolite crustal section. Collision is achieved at the northern tip, the Musandam area, linked to the opening of the Gulf of Aden 25 Ma ago, and northward drift of the Arabian Plate.

  12. Recurrent Annular Peripheral Choroidal Detachment after Trabeculectomy

    PubMed Central

    Liu, Shaohui; Sun, Lisa L.; Kavanaugh, A. Scott; Langford, Marlyn P.; Liang, Chanping

    2013-01-01

    We report a challenging case of recurrent flat anterior chamber without hypotony after trabeculectomy in a 54-year-old Black male with a remote history of steroid-treated polymyositis, cataract surgery, and uncontrolled open angle glaucoma. The patient presented with a flat chamber on postoperative day 11, but had a normal fundus exam and intraocular pressure (IOP). Flat chamber persisted despite treatment with cycloplegics, steroids, and a Healon injection into the anterior chamber. A transverse B-scan of the peripheral fundus revealed a shallow annular peripheral choroidal detachment. The suprachoroidal fluid was drained. The patient presented 3 days later with a recurrent flat chamber and an annular peripheral choroidal effusion. The fluid was removed and reinforcement of the scleral flap was performed with the resolution of the flat anterior chamber. A large corneal epithelial defect developed after the second drainage. The oral prednisone was tapered quickly and the topical steroid was decreased. One week later, his vision decreased to count fingers with severe corneal stromal edema and Descemet's membrane folds that improved to 20/50 within 24 h of resumption of the oral steroid and frequent topical steroid. The patient's visual acuity improved to 20/20 following a slow withdrawal of the oral and topical steroid. Eight months after surgery, the IOP was 15 mm Hg without glaucoma medication. The detection of a shallow anterior choroidal detachment by transverse B-scan is critical to making the correct diagnosis. Severe cornea edema can occur if the steroid is withdrawn too quickly. Thus, steroids should be tapered cautiously in steroid-dependent patients. PMID:24348402

  13. Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3{zeta} protein

    SciTech Connect

    Sadik, Golam; Tanaka, Toshihisa; Kato, Kiyoko; Yanagi, Kentaro; Kudo, Takashi; Takeda, Masatoshi

    2009-05-22

    Tau isoforms, 3-repeat (3R) and 4-repeat tau (4R), are differentially involved in neuronal development and in several tauopathies. 14-3-3 protein binds to tau and 14-3-3/tau association has been found both in the development and in tauopathies. To understand the role of 14-3-3 in the differential regulation of tau isoforms, we have performed studies on the interaction and aggregation of 3R-tau and 4R-tau, either phosphorylated or unphosphorylated, with 14-3-3{zeta}. We show by surface plasmon resonance studies that the interaction between unphosphorylated 3R-tau and 14-3-3{zeta} is {approx}3-folds higher than that between unphosphorylated 4R-tau and 14-3-3{zeta}. Phosphorylation of tau by protein kinase A (PKA) increases the affinity of both 3R- and 4R-tau for 14-3-3{zeta} to a similar level. An in vitro aggregation assay employing both transmission electron microscopy and fluorescence spectroscopy revealed the aggregation of unphosphorylated 4R-tau to be significantly higher than that of unphosphorylated 3R-tau following the induction of 14-3-3{zeta}. The filaments formed from 3R- and 4R-tau were almost similar in morphology. In contrast, the aggregation of both 3R- and 4R-tau was reduced to a similar low level after phosphorylation with PKA. Taken together, these results suggest that 14-3-3{zeta} exhibits a similar role for tau isoforms after PKA-phosphorylation, but a differential role for unphosphorylated tau. The significant aggregation of 4R-tau by 14-3-3{zeta} suggests that 14-3-3 may act as an inducer in the generation of 4R-tau-predominant neurofibrillary tangles in tauopathies.

  14. Structural Recovery of the Detached Macula after Retinal Detachment Repair as Assessed by Optical Coherence Tomography

    PubMed Central

    Joe, Soo Geun; Kim, Yoon Jeon; Chae, Ju Byung; Yang, Sung Jae; Lee, Joo Yong; Kim, June-Gone

    2013-01-01

    Purpose To investigate correlations between preoperative and postoperative foveal microstructures in patients with macula-off rhegmatogenous retinal detachment (RRD). Methods We reviewed the records of 31 eyes from 31 patients with macula-off RRD who had undergone successful re-attachment surgery. We analyzed data obtained from complete ophthalmologic examinations and optical coherence tomography (OCT) before and 9 to 12 months after surgery. All postoperative OCT measurements were taken with spectral-domain OCT, but a subset of preoperative OCT measurements were taken with time-domain OCT. Results The mean duration of macular detachment was 15.5 ± 15.2 days, and mean preoperative best-corrected visual acuity (BCVA, logarithm of the minimum angle of resolution) was 1.03 ± 0.68. Preoperative visual acuity was correlated with retinal detachment height (p < 0.001) and the existence of intraretinal separation (IRS) along with outer layer undulation (OLU) (p = 0.022), but not with macula-off duration. The final BCVA was significantly correlated with integrity of the junction between the photoreceptor inner and outer segments (IS/OS) combined with the continuity of external limiting membrane (ELM) (p = 0.025). The presence of IRS and OLU on a detached macula were highly correlated with the final postoperative integrity of the IS/OS junction and the ELM (p = 0.017). Conclusions Eyes preoperatively exhibiting IRS and OLU showed a higher incidence of disruption to the photoreceptor IS/OS junction and the ELM at final follow-up. Such a close correlation between preoperative and postoperative structural changes may explain why ultimate visual recovery in such eyes is poor. PMID:23730110

  15. von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination.

    PubMed

    Kuznetsova, Anna V; Meller, Jaroslaw; Schnell, Phillip O; Nash, James A; Ignacak, Monika L; Sanchez, Yolanda; Conaway, Joan W; Conaway, Ronald C; Czyzyk-Krzeska, Maria F

    2003-03-01

    The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-alpha and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylation-dependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation. PMID:12604794

  16. von Hippel–Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination

    PubMed Central

    Kuznetsova, Anna V.; Meller, Jaroslaw; Schnell, Phillip O.; Nash, James A.; Ignacak, Monika L.; Sanchez, Yolanda; Conaway, Joan W.; Conaway, Ronald C.; Czyzyk-Krzeska, Maria F.

    2003-01-01

    The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1α (HIF-1α) that binds von Hippel–Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-α and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylation-dependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation. PMID:12604794

  17. Fibrinogen and rhegmatogenous retinal detachment: a pilot prospective study

    PubMed Central

    Theocharis, IP

    2010-01-01

    Purpose: To examine the correlation, if any, between fibrinogen plasma levels (FPL) and the clinical features of rhegmatogenous retinal detachment (RRD). Methods: FPL were measured preoperatively in 33 patients with primary RRD. Patient characteristics and detachment features such as the numbers of breaks and the extent of the detachment were recorded; Results: No statistically significant correlation was found between FPL and the number of breaks. A statistically significant correlation was found between FPL and the extent of the RRD, even if the influence of the number of breaks was excluded. Conclusions: FPL correlate with retinal detachment extent, which implicates an acute inflammatory response to detachment traumatic phenomenon or a role of the fibrinogen molecule in retinal adhesiveness. PMID:20186280

  18. Spontaneous Solitaire™ AB Thrombectomy Stent Detachment During Stroke Treatment

    SciTech Connect

    Akpinar, Suha Yilmaz, Guliz

    2015-04-15

    Spontaneous Solitaire™ stent retriever detachment is a rarely defined entity seen during stroke treatment, which can result in a disastrous clinical outcome if it cannot be solved within a critical stroke treatment time window. Two solutions to this problem are presented in the literature. The first is to leave the stent in place and apply angioplasty to the detached stent, while the second involves surgically removing the stent from the location at which it detached. Here, we present a case of inadvertent stent detachment during stroke treatment for a middle cerebral artery M1 occlusion resulting in progressive thrombosis. The detached stent was removed endovascularly by another Solitaire stent, resulting in the recanalization of the occluded middle cerebral artery.

  19. Three-dimensional necking during viscous slab detachment

    NASA Astrophysics Data System (ADS)

    Tscharner, M.; Schmalholz, S. M.; Duretz, T.

    2014-06-01

    We study the three-dimensional (3-D) deformation during detachment of a lithospheric slab with simple numerical models using the finite element method. An initially vertical layer of power law viscous fluid mimics the slab and is surrounded by a linear or power law viscous fluid representing asthenospheric mantle. We quantify the impact of slab size and shape (symmetric/asymmetric) on slab detachment and identify two processes that control the lateral (i.e., along-trench) slab deformation: (1) the horizontal deflection of the lateral, vertical slab sides (> 100 km with velocities up to 16 mm/yr) and (2) the propagation of localized thinning (necking) inside the slab (with velocities >9 cm/yr). The lateral propagation velocity is approximately constant during slab detachment. Larger slabs (here wider than approximately 300 km) detach with rates similar to those predicted by 2-D models, whereas smaller slabs detach slower. Implications for geodynamic processes and interpretations of seismic tomography are discussed.

  20. Dissociative detachment relates to psychotic symptoms and personality decompensation.

    PubMed

    Allen, J G; Coyne, L; Console, D A

    1997-01-01

    Previous studies have addressed the prominence of psychotic symptoms in conjunction with multiple personality disorder (now dissociative identity disorder). The present study examines the relation between psychotic symptoms and a more pervasive form of dissociative disturbance, namely dissociative detachment. Two hundred sixty-six women in inpatient treatment for severe trauma-related disorders completed the Dissociative Experiences Scale (DES), and 102 of these patients also completed the Millon Clinical Multiaxial Inventory (MCMI-III). A factor analysis of the DES yielded two dimensions of dissociative detachment: detachment from one's own actions and detachment from the self and the environment. Each of these DES dimensions relates strongly to the thought disorder and schizotypal personality disorder scales of the MCMI-III. We propose that severe dissociative detachment, by virtue of loosening the moorings in inner and outer reality, is conducive to psychotic symptoms and personality decompensation. PMID:9406738

  1. Detachment of Sessile Droplets in Immiscible Fluids Using Electrowetting

    NASA Astrophysics Data System (ADS)

    Hong, Jiwoo; Lee, Sang Joon

    2014-11-01

    The detachment (or removal) of droplets from a solid surface is an indispensable process in numerous practical applications. Here we firstly detach sessile droplets in immiscible fluids from a hydrophobic surface by electrowetting. The critical conditions for droplet detachment are determined by exploring the retracting dynamics for a wide range of driving voltages and physical properties of fluids. The relationships between physical parameters and dynamic characteristics of retracting and jumping droplets, such as contact time and jumping height, are also established. The threshold voltage for droplet detachment in oil with high viscosity is largely reduced by electrowetting actuations with a square pulse. Finally, by using DC and AC electrowetting actuations, we demonstrate the detachment of oil droplets with very low contact angle on a hydrophobic surface in water.

  2. Cytoplasmic Retention of Protein Phosphatase 2A Inhibitor 2 (I2PP2A) Induces Alzheimer-like Abnormal Hyperphosphorylation of Tau*

    PubMed Central

    Arif, Mohammad; Wei, Jianshe; Zhang, Qi; Liu, Fei; Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Iqbal, Khalid

    2014-01-01

    Abnormal hyperphosphorylation of Tau leads to the formation of neurofibrillary tangles, a hallmark of Alzheimer disease (AD), and related tauopathies. The phosphorylation of Tau is regulated by protein phosphatase 2A (PP2A), which in turn is modulated by endogenous inhibitor 2 (I2PP2A). In AD brain, I2PP2A is translocated from neuronal nucleus to cytoplasm, where it inhibits PP2A activity and promotes abnormal phosphorylation of Tau. Here we describe the identification of a potential nuclear localization signal (NLS) in the C-terminal region of I2PP2A containing a conserved basic motif, 179RKR181, which is sufficient for directing its nuclear localization. The current study further presents an inducible cell model (Tet-Off system) of AD-type abnormal hyperphosphorylation of Tau by expressing I2PP2A in which the NLS was inactivated by 179RKR181 → AAA along with 168KR169 → AA mutations. In this model, the mutant NLS (mNLS)-I2PP2A (I2PP2AAA-AAA) was retained in the cell cytoplasm, where it physically interacted with PP2A and inhibited its activity. Inhibition of PP2A was associated with the abnormal hyperphosphorylation of Tau, which resulted in microtubule network instability and neurite outgrowth impairment. Expression of mNLS-I2PP2A activated CAMKII and GSK-3β, which are Tau kinases regulated by PP2A. The immunoprecipitation experiments showed the direct interaction of I2PP2A with PP2A and GSK-3β but not with CAMKII. Thus, the cell model provides insights into the nature of the potential NLS and the mechanistic relationship between I2PP2A-induced inhibition of PP2A and hyperphosphorylation of Tau that can be utilized to develop drugs preventing Tau pathology. PMID:25128526

  3. Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model.

    PubMed

    Guo, Weirui; Ceolin, Laura; Collins, Katie A; Perroy, Julie; Huber, Kimberly M

    2015-12-15

    Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder. PMID:26670047

  4. Stress-induced recruitment of epiplakin to keratin networks increases their resistance to hyperphosphorylation-induced disruption.

    PubMed

    Spazierer, Daniel; Raberger, Julia; Gross, Karin; Fuchs, Peter; Wiche, Gerhard

    2008-03-15

    Epiplakin is a large (>725 kDa) cytoskeletal protein exclusively expressed in epithelial tissues. It has a unique structure, consisting entirely of plakin repeat domains (PRDs), one of the hallmarks of spectraplakin protein family members. Previous studies, including the phenotypic analyses of knockout mice, failed to reveal the biological function of epiplakin. Using in vitro binding assays, we show here that all but one of the 16 PRDs of mouse epiplakin bind to keratins of basal keratinocytes. Nevertheless, in primary keratinocyte cell cultures, epiplakin only partially colocalized with keratin intermediate filament networks. However, upon application of cellular stress in the form of keratin hyperphosphorylation, osmotic shock or UV irradiation, the entire cytoplasmic epiplakin pool became associated with keratin. In response to such types of stress, epiplakin initially translocated to the still-intact keratin filament network and remained associated with keratin after its disruption and transformation into granular aggregates. Time-course experiments revealed that serine/threonine (okadaic acid) and tyrosine (orthovanadate) phosphatase inhibitor-induced filament disruption in differentiated keratinocytes proceeded faster in epiplakin-deficient cells compared with wild-type cells. Our data suggest that epiplakin plays a role in keratin filament reorganization in response to stress, probably by protecting keratin filaments against disruption in a chaperone-like fashion. PMID:18285451

  5. Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes.

    PubMed

    Tan, Xin L; Wright, David K; Liu, Shijie; Hovens, Christopher; O'Brien, Terence J; Shultz, Sandy R

    2016-09-01

    Mild traumatic brain injuries may result in cumulative brain damage and neurodegenerative disease. To date, there is no pharmaceutical intervention known to prevent these consequences. Hyperphosphorylated tau has been associated in this process, and protein phosphatase 2A 55 kDa regulatory B subunit (PP2A/PR55) - the major tau phosphatase - is decreased after a brain insult. Sodium selenate up-regulates PP2A/PR55 and dephosphorylates tau, and may hold promise as a treatment in the mild brain injury setting. Here we investigated sodium selenate treatment in rats given repeated mild traumatic brain injuries. Rats were given three mild fluid percussion injuries or three sham-injuries, and treated with sodium selenate (1 mg/kg/day) or saline-vehicle for three months before undergoing behavioral testing, MRI, and post-mortem analysis of brain tissue. Repeated mild traumatic brain injuries increased the phosphorylation of tau and decreased PP2A/PR55, whilst inducing brain atrophy and cognitive and sensorimotor deficits. Sodium selenate treatment increased PP2A/PR55, and decreased tau phosphorylation, brain damage, and cognitive and motor impairments in rats given repeated mild traumatic brain injuries. Our findings implicate PP2A/PR55 and tau as important mechanisms in the pathophysiological aftermath of repeated mild brain traumas, and support sodium selenate as a novel and translatable treatment for these common injuries. PMID:27163189

  6. Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice.

    PubMed

    Yu, Yang; Li, Xiaojing; Blanchard, Julie; Li, Yi; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2015-04-01

    Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by progressive neurodegeneration. Decreased brain energy and glucose metabolism occurs before the appearance of AD symptoms and worsens while the disease progresses. Deregulated brain insulin signaling has also been found in AD recently. To restore brain insulin sensitivity and glucose metabolism, pioglitazone and rosiglitazone, two insulin sensitizers commonly used for treating type 2 diabetes, have been studied and shown to have some beneficial effects in AD mouse models. However, the molecular mechanisms of the beneficial effects remain elusive. In the present study, we treated the 3xTg-AD mice, a widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months and studied the effects of the treatments on cognitive performance and AD-related brain alterations. We found that the chronic treatment improved spatial learning, enhanced AKT signaling, and attenuated tau hyperphosphorylation and neuroinflammation. These findings shed new light on the possible mechanisms by which these two insulin sensitizers might be useful for treating AD and support further clinical trials evaluating the efficacy of these drugs. PMID:25113171

  7. Biochemical properties of the stimulatory activity of DNA polymerase alpha by the hyper-phosphorylated retinoblastoma protein.

    PubMed

    Takemura, Masaharu

    2002-06-01

    Previously, my colleagues and I have reported that the immunopurified hyper-phosphorylated retinoblastoma protein (ppRb) stimulates the activity of DNA polymerase alpha. I describe here the biochemical characteristics of this stimulatory activity. DNA polymerase alpha-stimulatory activity of ppRb was most remarkable when using activated DNA as a template-primer, rather than using poly(dT)-(rA)(10), poly(dA)-(dT)(12-18), and so on. Kinetic analysis showed that there was no significant difference in K(m) value for deoxyribonucleotides of DNA polymerase alpha in the presence of ppRb. Adding ppRb resulted in the overcoming pause site on the template, but did not affect the rate of misincorporation of incorrect deoxyribonucleotides. By adding ppRb, the optimal concentration of template-primer was shifted to a higher region, but not using M13 singly primed DNA. The ppRb seemed to assist the process that DNA polymerase alpha changed its conformation resulting in appropriate enzyme activity. These results suggest that ppRb affects both template-primer and DNA polymerase alpha and makes appropriate circumstances for the enzyme reaction. PMID:12049795

  8. Loss of the m-AAA protease subunit AFG₃L₂ causes mitochondrial transport defects and tau hyperphosphorylation.

    PubMed

    Kondadi, Arun Kumar; Wang, Shuaiyu; Montagner, Sara; Kladt, Nikolay; Korwitz, Anne; Martinelli, Paola; Herholz, David; Baker, Michael J; Schauss, Astrid C; Langer, Thomas; Rugarli, Elena I

    2014-05-01

    The m-AAA protease subunit AFG₃L₂ is involved in degradation and processing of substrates in the inner mitochondrial membrane. Mutations in AFG₃L₂ are associated with spinocerebellar ataxia SCA28 in humans and impair axonal development and neuronal survival in mice. The loss of AFG₃L₂ causes fragmentation of the mitochondrial network. However, the pathogenic mechanism of neurodegeneration in the absence of AFG₃L₂ is still unclear. Here, we show that depletion of AFG₃L₂ leads to a specific defect of anterograde transport of mitochondria in murine cortical neurons. We observe similar transport deficiencies upon loss of AFG₃L₂ in OMA1-deficient neurons, indicating that they are not caused by OMA1-mediated degradation of the dynamin-like GTPase OPA1 and inhibition of mitochondrial fusion. Treatment of neurons with antioxidants, such as N-acetylcysteine or vitamin E, or decreasing tau levels in axons restored mitochondrial transport in AFG₃L₂-depleted neurons. Consistently, tau hyperphosphorylation and activation of ERK kinases are detected in mouse neurons postnatally deleted for Afg3l2. We propose that reactive oxygen species signaling leads to cytoskeletal modifications that impair mitochondrial transport in neurons lacking AFG₃L₂. PMID:24681487

  9. Effect of sodium fluoride, ampicillin, and chlorhexidine on Streptococcus mutans biofilm detachment.

    PubMed

    Liu, Jia; Ling, Jun-Qi; Zhang, Kai; Huo, Li-Jun; Ning, Yang

    2012-08-01

    We examined the effect of three clinically used antimicrobials on Streptococcus mutans UA159 biofilm detachment under flow conditions. Sodium fluoride (NaF) and chlorhexidine at MIC levels promoted biofilm detachment and inhibited detachment when concentrations were higher than the MIC and reduced detached-cell viability only at high concentrations. Ampicillin at all concentrations tested inhibited detachment and reduced the percentage of viable biofilm-detached cells. All the three antimicrobial treatments reduced biofilm live/dead cell ratios. PMID:22664966

  10. Effect of Sodium Fluoride, Ampicillin, and Chlorhexidine on Streptococcus mutans Biofilm Detachment

    PubMed Central

    Liu, Jia; Zhang, Kai; Huo, Li-Jun; Ning, Yang

    2012-01-01

    We examined the effect of three clinically used antimicrobials on Streptococcus mutans UA159 biofilm detachment under flow conditions. Sodium fluoride (NaF) and chlorhexidine at MIC levels promoted biofilm detachment and inhibited detachment when concentrations were higher than the MIC and reduced detached-cell viability only at high concentrations. Ampicillin at all concentrations tested inhibited detachment and reduced the percentage of viable biofilm-detached cells. All the three antimicrobial treatments reduced biofilm live/dead cell ratios. PMID:22664966

  11. Stability of Menisci in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Mazuruk, Konstantin; Volz, Martin P.

    2013-01-01

    Detached growth, also referred to as dewetted growth, is a Bridgman crystal growth process in which the melt is in contact with the crucible wall but the crystal is not. A meniscus bridges the gap between the top of the crystal and the crucible wall. The meniscus shape depends on the contact angle of the melt with the crucible wall, the growth angle of the melt with respect to the solidifying crystal, the gas pressure differential, the Weber number describing the rotation rate of the crucible, and the Bond number. Only some of the meniscus shapes are stable and the stability criterion is the sign of the second variation of the potential energy upon admissible meniscus shape perturbations. The effects of confined gas volumes above and below the melt and crucible rotation are evaluated. The analysis is applicable to the non-stationary case where the crystal radius changes during growth. Static stability maps (crystal radius versus pressure differential) are obtained for a series of Bond numbers, growth angles and Weber numbers. Also, the specific cases of Ge and InSb, in both terrestrial and microgravity conditions, are analyzed. Stability was found to depend significantly on whether the interior surface was considered to be microscopically rough or smooth, corresponding to pinned or unpinned states. It was also found that all meniscus shapes are statically stable in a microgravity environment.

  12. Magnetic Nozzle and Plasma Detachment Experiment

    NASA Technical Reports Server (NTRS)

    Chavers, Gregory; Dobson, Chris; Jones, Jonathan; Martin, Adam; Bengtson, Roger D.; Briezman, Boris; Arefiev, Alexey; Cassibry, Jason; Shuttpelz, Branwen; Deline, Christopher

    2006-01-01

    High power plasma propulsion can move large payloads for orbit transfer (such as the ISS), lunar missions, and beyond with large savings in fuel consumption owing to the high specific impulse. At high power, lifetime of the thruster becomes an issue. Electrodeless devices with magnetically guided plasma offer the advantage of long life since magnetic fields confine the plasma radially and keep it from impacting the material surfaces. For decades, concerns have been raised about the plasma remaining attached to the magnetic field and returning to the vehicle along the closed magnetic field lines. Recent analysis suggests that this may not be an issue of the magnetic field is properly shaped in the nozzle region and the plasma has sufficient energy density to stretch the magnetic field downstream. An experiment was performed to test the theory regarding the Magneto-hydrodynamic (MHD) detachment scenario. Data from this experiment will be presented. The Variable Specific Impulse Magnetoplasma Rocket (VASIMR) being developed by the Ad Astra Rocket Company uses a magnetic nozzle as described above. The VASIMR is also a leading candidate for exploiting an electric propulsion test platform being considered for the ISS.

  13. Descemet's Membrane Detachment Management Following Trabeculectomy

    PubMed Central

    Sharifipour, Farideh; Nassiri, Saman; Idan, Aida

    2016-01-01

    Purpose: To present a case of total Descemet's membrane detachment (DMD) after trabeculectomy and its surgical management. Case Report: A 68-year-old woman presented with large DMD and corneal edema one day after trabeculectomy. Intracameral air injection on day 3 was not effective. Choroidal effusion complicated the clinical picture with Descemet's membrane (DM) touching the lens. Choroidal tap with air injection on day 6 resulted in DM attachment and totally clear cornea on the next day. However, on day 12 the same scenario was repeated with choroidal effusion, shallow anterior chamber (AC), and DM touching the lens. The third surgery included transconjunctival closure of the scleral flap with 10/0 nylon sutures, choroidal tap, and intracameral injection of 20% sulfur hexafluoride. After the third surgery, DM remained attached with clear cornea. Suture removal and needling bleb revision preserved bleb function. Lens opacity progressed, and the patient underwent uneventful cataract surgery 4 months later. Conclusion: Scleral flap closure using transconjunctival sutures can be used for DMD after trabeculectomy to make the eye a closed system. Surgical drainage of choroidal effusions should be considered to increase the AC depth. PMID:27621793

  14. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    PubMed Central

    Rantakari, Pia; Auvinen, Kaisa; Karikoski, Marika; Mattila, Elina; Potter, Christopher; Sundberg, John P.; Hogg, Nancy; Gahmberg, Carl G.

    2013-01-01

    SUMMARY Sharpin-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and human chemokine-activated lymphocytes migrating on ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration and uropod defects in SHARPIN deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically we show that SHARPIN interacts directly with LFA-1, a leukocyte counter-receptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells. PMID:24210817

  15. Balancing engagement/detachment in AIDS-related multiple losses.

    PubMed

    Carmack, B J

    1992-01-01

    The process gay persons use to manage the multiple losses and cumulative grief from losing lovers, friends, colleagues and clients to AIDS was explored. Interviews with gay individuals (n = 19) in a large urban area in the West provided data for conceptual coding and comparative analysis. Balancing engagement and detachment was identified as the basic social-psychological process that described how gay individuals struggled to reach an optimal balance in their involvement in the needs of individuals and the community. Four conceptual categories were identified: dysfunctional engagement, functional engagement, functional detachment and dysfunctional detachment. These four categories occur within the contexts of previous life style and redefinition of personal values. PMID:1541482

  16. Shape Evolution of Detached Bridgman Crystals Grown in Microgravity

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.

    2015-01-01

    A theory describing the shape evolution of detached Bridgman crystals in microgravity has been developed. A starting crystal of initial radius r0 will evolve to one of the following states: Stable detached gap; Attachment to the crucible wall; Meniscus collapse. Only crystals where alpha plus omega is great than 180 degrees will achieve stable detached growth in microgravity. Results of the crystal shape evolution theory are consistent with predictions of the dynamic stability of crystallization (Tatarchenko, Shaped Crystal Growth, Kluwer, 1993). Tests of transient crystal evolution are planned for ICESAGE, a series of Ge and GeSi crystal growth experiments planned to be conducted on the International Space Station (ISS).

  17. Sensitivity of detachment extent to magnetic configuration and external parameters

    NASA Astrophysics Data System (ADS)

    Lipschultz, Bruce; Parra, Felix I.; Hutchinson, Ian H.

    2016-05-01

    Divertor detachment may be essential to reduce heat loads to magnetic fusion tokamak reactor divertor surfaces. Yet in experiments it is difficult to control the extent of the detached, low pressure, plasma region. At maximum extent the front edge of the detached region reaches the X-point and can lead to degradation of core plasma properties. We define the ‘detachment window’ in a given position control variable C (for example, the upstream plasma density) as the range in C within which the front location can be stably held at any position from the target to the X-point; increased detachment window corresponds to better control. We extend a 1D analytic model [1] to determine the detachment window for the following control variables: the upstream plasma density, the impurity concentration and the power entering the scrape-off layer (SOL). We find that variations in magnetic configuration can have strong effects; increasing the ratio of the total magnetic field at the X-point to that at the target, {{B}×}/{{B}t} , (total flux expansion, as in the super-x divertor configuration) strongly increases the detachment window for all control variables studied, thus strongly improving detachment front control and the capability of the divertor plasma to passively accommodate transients while still staying detached. Increasing flux tube length and thus volume in the divertor, through poloidal flux expansion (as in the snowflake or x-divertor configurations) or length of the divertor, also increases the detachment window, but less than the total flux expansion does. The sensitivity of the detachment front location, z h , to each control variable, C, defined as \\partial {{z}h}/\\partial C , depends on the magnetic configuration. The size of the radiating volume and the total divertor radiation increase \\propto {{≤ft({{B}×}/{{B}t}\\right)}2} and \\propto {{B}×}/{{B}t} , respectively, but not by increasing divertor poloidal flux expansion or field line length. We

  18. Neutral beam heating of detached plasmas in TFTR

    SciTech Connect

    Bush, C.E.; Strachan, J.D.; Schivell, J.; Mansfield, D.K.; Taylor, G.; Grek, B.; Budny, R.; McNeill, D.H.; Bell, M.G.; Boody, F.P.

    1989-05-01

    Detached plasmas on TFTR have been heated with neutral beam auxiliary power for the first time. At beam powers above 2 MW the detached plasmas in TFTR expand and reattach to the limiters. Deuterium and/or impurity gas puffing can be used to maintain plasmas in the detached state at powers of over 5 MW. Transient events were observed in a number of these plasmas, including a confinement-related delay in evolution of the edge emissivity and some phenomena which appear similar to those seen in the H-mode. 16 refs., 5 figs.

  19. Improved Crystal Quality by Detached Solidification in Microgravity

    NASA Technical Reports Server (NTRS)

    Regel, Liya L.; Wilcox, William R.

    1999-01-01

    Directional solidification in microgravity has often led to ingots that grew with little or no contact with the ampoule wall. When this occurred, crystallographic perfection was usually greatly improved -- often by several orders of magnitude. Unfortunately, until recently the true mechanisms underlying detached solidification were unknown. As a consequence, flight experiments yielded erratic results. Within the past four years, we have developed a new theoretical model that explains many of the flight results. This model gives rise to predictions of the conditions required to yield detached solidification, both in microgravity and on earth. A discussion of models of detachment, the meniscus models and results of theoretical modeling, and future plans are presented.

  20. Vitrectomy, lensectomy and silicone oil tamponade in the management of retinal detachment associated with choroidal detachment

    PubMed Central

    Gui, Jun-Min; Jia, Li; Liu, Lei; Liu, Jian-Di

    2013-01-01

    AIM To report the results of combined vitrectomy, lensectomy and silicone oil (SO) tamponade in treating primary rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS A retrospective, consecutive and case series study of 21 subjects with concurrent RRD associated with CD was conducted. All subjects underwent a standard three-port 20G pars plana vitrectomy (PPV) with lensectomy and silicone oil tamponade. Mean follow-up time was 8 months (rang from 4 to 19 months). The primary and final anatomic success rate, visual acuity and final intraocular pressure(IOP) were recorded and analyzed. RESULTS Of 21 subjects, 8 were women and 13 were men. Age at presentation ranged from 22 to 75 years (mean 57.4 years). The presenting vision ranged from light perception to 0.15. The initial IOP ranged from 3mmHg to 12mmHg (mean 6.2mmHg). All eyes were phakic except one pseudophakic. No intraocular lens was implanted during the primary surgical intervention. Fifteen of 21 (71.4%) eyes had retina reattached after one operation. Six eyes had recurrent inferior retinal detachment due to proliferation. Five of them were successfully reattached after one or more additional operations. Mean IOP at final follow-up was 15.2mmHg (range from 8mmHg to 20mmHg). One case declined for further operation. The final reattachment rate was 95.2%. Visual acuity improved in 19 (90.5%) eyes, was unchanged in 1 (4.8%) eye and decreased in 1 (4.8%) eye. CONCLUSION Combination of vitrectomy, lensectomy and silicone tamponade is an effective method in treating RRD associated with CD, reducing the incidence of postoperative hypotony. PMID:23826529

  1. Advantages of diabetic tractional retinal detachment repair

    PubMed Central

    Sternfeld, Amir; Axer-Siegel, Ruth; Stiebel-Kalish, Hadas; Weinberger, Dov; Ehrlich, Rita

    2015-01-01

    Purpose To evaluate the outcomes and complications of patients with diabetic tractional retinal detachment (TRD) treated with pars plana vitrectomy (PPV). Patients and methods We retrospectively studied a case series of 24 eyes of 21 patients at a single tertiary, university-affiliated medical center. A review was carried out on patients who underwent PPV for the management of TRD due to proliferative diabetic retinopathy from October 2011 to November 2013. Preoperative and final visual outcomes, intraoperative and postoperative complications, and medical background were evaluated. Results A 23 G instrumentation was used in 23 eyes (95.8%), and a 25 G instrumentation in one (4.2%). Mean postoperative follow-up time was 13.3 months (4–30 months). Visual acuity significantly improved from logarithm of the minimum angle of resolution (LogMAR) 1.48 to LogMAR 1.05 (P<0.05). Visual acuity improved by ≥3 lines in 75% of patients. Intraoperative complications included iatrogenic retinal breaks in seven eyes (22.9%) and vitreal hemorrhage in nine eyes (37.5%). In two eyes, one sclerotomy was enlarged to 20 G (8.3%). Postoperative complications included reoperation in five eyes (20.8%) due to persistent subretinal fluid (n=3), vitreous hemorrhage (n=1), and dislocated intraocular lens (n=1). Thirteen patients (54.2%) had postoperative vitreous hemorrhage that cleared spontaneously, five patients (20.8%) required antiglaucoma medications for increased intraocular pressure, seven patients (29.2%) developed an epiretinal membrane, and two patients (8.3%) developed a macular hole. Conclusion Patients with diabetic TRD can benefit from PPV surgery. Intraoperative and postoperative complications can be attributed to the complexity of this disease. PMID:26604667

  2. The detached eclipsing binary TX Her revisited

    NASA Astrophysics Data System (ADS)

    Erdem, A.; Aliçavuş, F.; Soydugan, F.; Doğru, S. S.; Soydugan, E.; Çiçek, C.; Demircan, O.

    2011-12-01

    This paper presents new CCD Bessell BVRI light curves and photometric analysis of the Algol-type binary star TX Her. The CCD observations were carried out at Çanakkale Onsekiz Mart University Observatory in 2010. New BVRI light curves from this study and radial velocity curves from Popper (1970) were solved simultaneously using modern light and radial velocity curves synthesis methods. The general results show that TX Her is a well-detached eclipsing binary, however, both component stars fill at least half of their Roche lobes. A significant third light contribution to the total light of the system could not be determined. Using O- C residuals formed by the updated minima times, an orbital period study of the system was performed. It was confirmed that the tilted sinusoidal O- C variation corresponds to an apparent period variation caused by the light travel time effect due to an unseen third body. The following absolute parameters of the components were derived: M1 = 1.62 ± 0.04 M ⊙, M2 = 1.45 ± 0.03 M ⊙, R1 = 1.69 ± 0.03 R ⊙, R2 = 1.43 ± 0.03 R ⊙, L1 = 8.21 ± 0.90 L ⊙ and L2 = 3.64 ± 0.60 L ⊙. The distance to TX Her was calculated as 155 ± 10 pc, taking into account interstellar extinction. The position of the components of TX Her in the HR diagram are also discussed. The components are young stars with an age of ˜500 Myr.

  3. A detachable mobile and adjustable telemetry system

    PubMed Central

    Parker, Tommy S; Persons, William E; Bradley, Joseph G; Gregg, Margaret; Gonzales, Shinelle K; Helton, Jesse S

    2013-01-01

    Many traditional mobile telemetry systems require permanently mounting a rod through the cabin of a vehicle to serve as the mast for a directional antenna. In this article we present an alternative to this configuration by providing a platform that can be placed atop the vehicle in which the antenna mast can be mounted and controlled from the cabin of the vehicle. Thereby making this design a viable option for researchers who share vehicles with others that may not approve of permanent vehicle modifications such as placing a hole in the roof of the vehicle as required by traditional mobile configurations. We tested the precision and accuracy of detachable mobile and adjustable telemetry system (DMATS) in an urban park with varying terrain, tree stands, overhead wires, and other structures that can contribute to signal deflection. We placed three radiocollars 50 m apart and 1.2 m above the ground then established three testing stations ∼280 m from the location of the radiocollars. The DMATS platform required 12 h for completion and cost $1059 USD. Four technicians were randomly assigned radio collars to triangulate using DMATS and a handheld telemetry system. We used a one-way analysis of variance (ANOVA) with a Scheffe post hoc test to compare error ellipses between azimuths taken using DMATS and the hand held system. Average error ellipses for all testers was 1.96 ± 1.22 ha. No significant differences were found between error ellipses of testers (P = 0.292). Our design, the DMATS, does not require any vehicle modification; thereby, making this a viable option for researchers sharing vehicles with others that may not approve of permanent vehicle alterations. PMID:23919133

  4. A detachable mobile and adjustable telemetry system.

    PubMed

    Parker, Tommy S; Persons, William E; Bradley, Joseph G; Gregg, Margaret; Gonzales, Shinelle K; Helton, Jesse S

    2013-07-01

    Many traditional mobile telemetry systems require permanently mounting a rod through the cabin of a vehicle to serve as the mast for a directional antenna. In this article we present an alternative to this configuration by providing a platform that can be placed atop the vehicle in which the antenna mast can be mounted and controlled from the cabin of the vehicle. Thereby making this design a viable option for researchers who share vehicles with others that may not approve of permanent vehicle modifications such as placing a hole in the roof of the vehicle as required by traditional mobile configurations. We tested the precision and accuracy of detachable mobile and adjustable telemetry system (DMATS) in an urban park with varying terrain, tree stands, overhead wires, and other structures that can contribute to signal deflection. We placed three radiocollars 50 m apart and 1.2 m above the ground then established three testing stations ∼280 m from the location of the radiocollars. The DMATS platform required 12 h for completion and cost $1059 USD. Four technicians were randomly assigned radio collars to triangulate using DMATS and a handheld telemetry system. We used a one-way analysis of variance (ANOVA) with a Scheffe post hoc test to compare error ellipses between azimuths taken using DMATS and the hand held system. Average error ellipses for all testers was 1.96 ± 1.22 ha. No significant differences were found between error ellipses of testers (P = 0.292). Our design, the DMATS, does not require any vehicle modification; thereby, making this a viable option for researchers sharing vehicles with others that may not approve of permanent vehicle alterations. PMID:23919133

  5. On Favorable Thermal Fields for Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Stelian, Carmen; Volz, Martin P.; Derby, Jeffrey J.

    2009-01-01

    The thermal fields of two Bridgman-like configurations, representative of real systems used in prior experiments for the detached growth of CdTe and Ge crystals, are studied. These detailed heat transfer computations are performed using the CrysMAS code and expand upon our previous analyses [14] that posited a new mechanism involving the thermal field and meniscus position to explain stable conditions for dewetted Bridgman growth. Computational results indicate that heat transfer conditions that led to successful detached growth in both of these systems are in accordance with our prior assertion, namely that the prevention of crystal reattachment to the crucible wall requires the avoidance of any undercooling of the melt meniscus during the growth run. Significantly, relatively simple process modifications that promote favorable thermal conditions for detached growth may overcome detrimental factors associated with meniscus shape and crucible wetting. Thus, these ideas may be important to advance the practice of detached growth for many materials.

  6. Serous retinal detachment after trabeculectomy in angle recession glaucoma

    PubMed Central

    Roy, Avik Kumar; Padhy, Debananda

    2015-01-01

    An 18-year-old male with 360 degree angle recession after blunt trauma in his right eye developed uncontrolled intraocular pressure (IOP) despite four antiglaucoma medications (AGM) with advancing disc damage. He underwent trabeculectomy with intraoperative mitomycin-c (MMC) application. There was an intraoperative vitreous prolapse which was managed accordingly. On post-surgery day 1, he had shallow choroidal detachment superiorly with non-recordable IOP. This was deteriorated 1 week postoperatively as choroidal detachment proceeded to serous retinal detachment. He was started with systemic steroid in addition to topical route. The serous effusions subsided within 2 weeks time. At the last follow up at 3 months, he was enjoying good visual acuity, deep anterior chamber, diffuse bleb, an IOP in low teens off any AGM and attached retina. This case highlights the rare occurrence of serous retinal detachment after surgical management of angle recession glaucoma.

  7. One- and two-photon detachment of O-

    NASA Astrophysics Data System (ADS)

    Génévriez, Matthieu; Urbain, Xavier; Dochain, Arnaud; Cyr, Alain; Dunseath, Kevin M.; Terao-Dunseath, Mariko

    2016-08-01

    Cross sections for one- and two-photon detachment of O-(1 s22 s22 p5P2o) have been determined in a joint experimental and theoretical study. The absolute measurement is based on the animated-crossed-beam technique, which is extended to the case of pulsed lasers, pulsed ion beams, and multiphoton detachment. The ab initio calculations employ R -matrix Floquet theory, with simple descriptions of the initial bound state and the residual oxygen atom which reproduce well the electron affinity and ground-state polarizability. For one-photon detachment, the measured and computed cross sections are in good mutual agreement, departing significantly from previous reference experiments and calculations. The generalized two-photon detachment cross section, measured at the Nd:YAG laser wavelength, is in good agreement with the R -matrix Floquet calculations. Long-standing discrepancies between theory and experiment are thus resolved.

  8. O1 DETACHED GARAGE FRONT ELEVATION. Naval Magazine Lualualei, Headquarters ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    O-1 DETACHED GARAGE FRONT ELEVATION. - Naval Magazine Lualualei, Headquarters Branch, Garage for Building O, Sixty-sixth Street between Constitution & Amberjack Streets, behind Building O, Pearl City, Honolulu County, HI

  9. O1 DETACHED GARAGE FRONT AND SIDE VIEW. Naval Magazine ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    O-1 DETACHED GARAGE FRONT AND SIDE VIEW. - Naval Magazine Lualualei, Headquarters Branch, Garage for Building O, Sixty-sixth Street between Constitution & Amberjack Streets, behind Building O, Pearl City, Honolulu County, HI

  10. Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation

    PubMed Central

    Selenica, M-L; Jensen, H S; Larsen, A K; Pedersen, M L; Helboe, L; Leist, M; Lotharius, J

    2007-01-01

    Background and purpose: Glycogen synthase kinase-3 (GSK-3) affects neuropathological events associated with Alzheimeŕs disease (AD) such as hyperphosphorylation of the protein, tau. GSK-3β expression, enzyme activity and tau phosphorylated at AD-relevant epitopes are elevated in juvenile rodent brains. Here, we assess five GSK-3β inhibitors and lithium in lowering phosphorylated tau (p-tau) and GSK-3β enzyme activity levels in 12-day old postnatal rats. Experimental approach: Brain levels of inhibitors following treatment in vivo were optimized based on pharmacokinetic data. At optimal doses, p-tau (Ser396) levels in brain tissue was measured by immunoblotting and correlated with GSK-3β enzyme activities in the same tissues. Effects of GSK inhibitors on p-tau, GSK-3β activities and cell death were measured in a human neuronal cell line (LUHMES). Key results: Lithium and CHIR98014 reduced tau phosphorylation (Ser396) in the cortex and hippocampus of postnatal rats, while Alsterpaullone and SB216763 were effective only in hippocampus. AR-A014418 and Indirubin-3′-monoxime were ineffective in either brain region. Inhibition of p-tau in brain required several-fold higher levels of GSK inhibitors than the IC50 values obtained in recombinant or cell-based GSK-3β enzyme activity assays. The inhibitory effect on GSK-3β activity ex vivo correlated with protection against cell death and decrease of p-tau- in LUHMES cells, using low μM inhibitor concentrations. Conclusions and Implications: Selective small-molecule inhibitors of GSK-3 reduce tau phosphorylation in vivo. These findings corroborate earlier suggestions that GSK-3β may be an attractive target for disease-modification in AD and related conditions where tau phosphorylation is believed to contribute to disease pathogenesis. PMID:17906685

  11. Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau.

    PubMed Central

    Askanas, V.; Engel, W. K.; Bilak, M.; Alvarez, R. B.; Selkoe, D. J.

    1994-01-01

    We immunostained muscle biopsies of 8 patients with sporadic inclusion body myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body myopathy (H-IBM) (both diseases being characterized by similar muscle fiber vacuoles containing inclusions), and 11 normal and disease controls. We used the following well-characterized antibodies against tau protein: Tau-1, Alz-50, and anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and beta-amyloid protein also contained inclusions immunoreactive with Alz-50 and anti-PHF antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles was obtained only after dephosphorylation of muscle sections. By electronmicroscopy, all three antibodies immunodecorated exclusively cytoplasmic twisted tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and beta-amyloid-positive muscle fiber vacuoles contained inclusions immunoreactive with anti-PHF antiserum, but in only 40% of those fibers were the inclusions immunoreactive with Alz-50. In six H-IBM patients there were no tau-1 immunoreactive inclusions in any of their vacuolated muscle fibers; in one patient, 24% of the vacuolated fibers had tau-1 immunoreactivity. By demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer brain PHFs, is a component of S-IBM-muscle TTFs (which are also ultrastructurally similar to PHFs), our study: 1) provides the first demonstration of abnormally accumulated tau in nonneural tissue and 2) suggests that the cytopathogenesis in Alzheimer brain and S-IBM muscle may share some similar mechanisms. Whether the difference in tau immunoreactivity between S-IBM and most of the H-IBM patients reflects a difference in genetically determined transcriptional or posttranslational modifications of tau protein or other factors remains to be determined. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8291607

  12. Detection of hyperphosphorylated tau protein and α-synuclein in spinal cord of patients with Alzheimer’s disease

    PubMed Central

    Guo, Yanjun; Wang, Luning; Zhu, Mingwei; Zhang, Honghong; Hu, Yazhuo; Han, Zhitao; Liu, Jia; Zhao, Weiqin; Wang, Dexin

    2016-01-01

    The aim of this study was to investigate the neuropathological features of the spinal cord in patients suffering with Alzheimer’s disease (AD). Spinal cord tissue collected from three AD patients and eight controls was selected for the study. Data were collected at T2, T8, T10, L4, and S2 spinal levels. The sections were subjected to hematoxylin and eosin and Gallyas–Braak staining methods and then were immunostained with antibodies such as phosphorylated tau protein (AT8), α-synuclein, Aβ, amyloid precursor protein, ubiquitin, and TDP-43. Pathological changes exhibited by the biomarkers were detected by microscopy. Neurofibrillary tangles (NFTs) were detectable in spinal anterior horn motor neurons in two of the three AD patients. AT8-positive axons or axon-like structures and AT8 expression in glial cells were detected in all three AD cases. Hyperphosphorylation of tau protein was detected in spinal anterior horn cells, glial cells, and axons, and its severity was associated with NFTs in the brain tissue. α-Synuclein-positive Lewy bodies and scattered Lewy-like neuritis were detected in the medial horn of the thoracic spinal cord and ventral sacral gray matter, respectively, in one patient who had AD with Lewy bodies. Neither amyloid deposition nor amyloid precursor protein and TDP-43 expression was detected in the spinal cord of AD patients. Spinal cord of AD patients was observed to contain phosphorylated tau protein and α-synuclein immunoreactive structures, which may play a role in dyskinesia and autonomic dysfunction in advanced AD. PMID:27013875

  13. Pattern of tau hyperphosphorylation and neurotransmitter markers in the brainstem of senescent tau filament forming transgenic mice.

    PubMed

    Morcinek, Kerstin; Köhler, Christoph; Götz, Jürgen; Schröder, Hannsjörg

    2013-02-25

    The early occurrence of brainstem-related symptoms, e.g. gait and balance impairment, apathy and depression in Alzheimer's disease patients suggests brainstem involvement in the initial pathogenesis. To address the question whether tau filament forming mice expressing mutated human tau mirror histopathological changes observed in Alzheimer brainstem, the degree and distribution of neurofibrillary lesions as well as the pattern of cholinergic and monoaminergic neurons were investigated. The expression of the human tau transgene was observed in multiple brainstem nuclei, particularly in the magnocellular reticular formation, vestibular nuclei, cranial nerve motor nuclei, sensory trigeminal nerve nuclei, inferior and superior colliculi, periaqueductal and pontine gray matter, and the red nucleus. Most of the human tau-immunoreactive cell groups also showed tau hyperphosphorylation at the epitopes Thr231/Ser235 and Ser202/Thr205, while abnormal tau phosphorylation at the epitope Ser422 or silver stained structures were almost totally lacking. We found no obvious differences in distribution and density of cholinergic and monoaminergic neurons between tau-transgenic and wild type mice. Although numerous brainstem nuclei in our model expressed human tau protein, the development of neurofibrillary tangles, neuropil threads and ghost tangles was rare and likewise its distribution differed largely from Alzheimer's disease pattern. The number of monoaminergic neurons remained unchanged in the transgenic mice, while monoaminergic nuclei in Alzheimer brainstem showed a distinct neuronal loss. However, the distribution of pretangle-affected neurons in the tau-transgenic mice partly resembled those seen in progressive supranuclear palsy, presenting these animals as a model to examine brainstem pathogenesis of progressive supranuclear palsy. PMID:23261664

  14. Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.

    PubMed

    Yu, Lixia; Chen, Yuan; Wang, Weiguang; Xiao, Zhonghai; Hong, Yan

    2016-08-01

    Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia. PMID:27497480

  15. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation

    PubMed Central

    Boscolo, Elisa; Coma, Silvia; Luks, Valerie L.; Greene, Arin; Klagsbrun, Michael; Warman, Matthew L.; Bischoff, Joyce

    2014-01-01

    Lymphatic malformations (LM) are characterized by abnormal formation of lymphatic vessels and tissue overgrowth. The lymphatic vessels present in LM lesions may become blocked and enlarged as lymphatic fluid collects, forming a mass or cyst. Lesions are typically diagnosed during childhood, and are often disfiguring and life threatening. Available treatments consist of sclerotherapy, surgical removal and therapies to diminish complications. We isolated lymphatic endothelial cells (LM-LEC) from a surgically removed microcystic LM lesion. LM-LEC and normal human dermal-LEC (HD-LEC) expressed endothelial (CD31, VE-Cadherin) as well as lymphatic endothelial (Podoplanin, PROX1, LYVE1)-specific markers. Targeted gene sequencing analysis in patient-derived LM-LEC revealed the presence of two mutations in class I phosphoinositide 3-kinases (PI3K) genes. One is an inherited, premature stop codon in the PI3K regulatory subunit PIK3R3. The second is a somatic missense mutation in the PI3K catalytic subunit PIK3CA; this mutation has been found in association with overgrowth syndromes and cancer growth. LM-LEC exhibited angiogenic properties: both cellular proliferation and sprouting in collagen were significantly increased compared to HD-LEC. AKT-Thr308 was constitutively hyper-phosphorylated in LM-LEC. Treatment of LM-LEC with PI3-Kinase inhibitors Wortmannin and LY294 decreased cellular proliferation and prevented the phosphorylation of AKT-Thr308 in both HD-LEC and LM-LEC. Treatment with the mTOR inhibitor rapamycin also diminished cellular proliferation, sprouting and AKT phosphorylation, but only in LM-LEC. Our results implicate disrupted PI3K-AKT signaling in LEC isolated from a human lymphatic malformation lesion. PMID:25424831

  16. Atorvastatin ameliorates cognitive impairment, Aβ1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice.

    PubMed

    Zhou, Dongsheng; Liu, Huaxia; Li, Chenli; Wang, Fangyan; Shi, Yaosheng; Liu, Lingjiang; Zhao, Xin; Liu, Aiming; Zhang, Junfang; Wang, Chuang; Chen, Zhongming

    2016-06-01

    Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Aβ and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3β signaling and contributes to subsequent down-regulation of Aβ1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3β signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Aβ1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3β activity by increasing phosphorylation of GSK3β (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3β signaling which may contribute to down-regulation of Aβ1-42 and tau hyperphosphorylation. PMID:26883430

  17. Retinal detachment in the Morning Glory syndrome. Pathogenesis and management.

    PubMed

    von Fricken, M A; Dhungel, R

    1984-01-01

    A case of bilateral Morning Glory syndrome is presented, unusual because of a rhegmatogenous posterior pole retinal detachment in the left eye. Posterior pole retinal detachments have been described in association with this syndrome. This case report is the first presentation of a retinal tear located within the excavation surrounding the optic nerve. A surgical management approach is presented wherein vitrectomy and internal gas tamponade are utilized to reattach the retina. PMID:6463401

  18. Scleral buckling for retinal detachment in patients with retinoblastoma

    SciTech Connect

    Buzney, S.M.; Pruett, R.C.; Regan, C.D.; Walton, D.S.; Smith, T.R.

    1984-10-15

    Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years.

  19. Simulating Biofilm Deformation and Detachment with the Immersed Boundary Method

    NASA Astrophysics Data System (ADS)

    Sudarsan, Rangarajan; Ghosh, Sudeshna; Stockie, John M.; Eberl, Hermann J.

    2016-03-01

    We apply the immersed boundary (or IB) method to simulate deformation and detachment of a periodic array of wall-bounded biofilm colonies in response to a linear shear flow. The biofilm material is represented as a network of Hookean springs that are placed along the edges of a triangulation of the biofilm region. The interfacial shear stress, lift and drag forces acting on the biofilm colony are computed by using fluid stress jump method developed by Williams, Fauci and Gaver [Disc. Contin. Dyn. Sys. B 11(2):519-540, 2009], with a modified version of their exclusion filter. Our detachment criterion is based on the novel concept of an averaged equivalent continuum stress tensor defined at each IB point in the biofilm which is then used to determine a corresponding von Mises yield stress; wherever this yield stress exceeds a given critical threshold the connections to that node are severed, thereby signalling the onset of a detachment event. In order to capture the deformation and detachment behaviour of a biofilm colony at different stages of growth, we consider a family of four biofilm shapes with varying aspect ratio. Our numerical simulations focus on the behaviour of weak biofilms (with relatively low yield stress threshold) and investigate features of the fluid-structure interaction such as locations of maximum shear and increased drag. The most important conclusion of this work is that the commonly employed detachment strategy in biofilm models based only on interfacial shear stress can lead to incorrect or inaccurate results when applied to the study of shear induced detachment of weak biofilms. Our detachment strategy based on equivalent continuum stresses provides a unified and consistent IB framework that handles both sloughing and erosion modes of biofilm detachment, and is consistent with strategies employed in many other continuum based biofilm models.

  20. Retinal Detachment due to CrossFit Training Injury.

    PubMed

    Joondeph, Stephanie A; Joondeph, Brian C

    2013-01-01

    The purpose of this paper is to describe a traumatic retinal detachment occurring as a result of CrossFit training using an elastic exercise band. The patient sustained an ocular injury from an elastic band during CrossFit training, resulting in a giant retinal dialysis and retinal detachment, which were successfully repaired. Trainers and athletes need to be aware of the potential for ocular injury from elastic exercise bands and take appropriate precautions. PMID:24106626

  1. Retinal Detachment due to CrossFit Training Injury

    PubMed Central

    Joondeph, Stephanie A.; Joondeph, Brian C.

    2013-01-01

    The purpose of this paper is to describe a traumatic retinal detachment occurring as a result of CrossFit training using an elastic exercise band. The patient sustained an ocular injury from an elastic band during CrossFit training, resulting in a giant retinal dialysis and retinal detachment, which were successfully repaired. Trainers and athletes need to be aware of the potential for ocular injury from elastic exercise bands and take appropriate precautions. PMID:24106626

  2. 1. Streetscape with south sides of Medical Detachment Barracks on ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Streetscape with south sides of Medical Detachment Barracks on Ramp No. 5. Part of Building No. 9962-A with door is on far right. Also shown are the south A-sides of Buildings Nos. 9963, 9964, 9965, 9966, 9967 and 9968. The new Madigan Army Medical Center, which opened in 1992, is in far distance on right. - Madigan Hospital, Medical Detachment Barracks, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, Tacoma, Pierce County, WA

  3. Tracing detached and attached care practices in nursing education.

    PubMed

    Soffer, Ann Katrine B

    2014-07-01

    The implementation of skills labs in Danish nursing education can, in itself, be viewed as a complexity. The students are expected to eventually carry out their work in a situated hospital practice, but they learn their professional skills in a different space altogether, detached and removed from the hospitals and practising on plastic dummies. Despite the apparent artificiality of the skills lab, this article will show that it is possible to analyse some of the fundamental aspects of care in nursing by ethnographically following this phenomenon of simulation-based training. These particular aspects of care are not explicated in the curriculum or textbooks; however, they surfaced once this crooked approach to studying care in a simulated practice was applied. The article start from the assertion that detached engagements are not recognized within the field of nursing education as an equal component to attachments. Yet empirical cases from the skills lab and hospitals illustrate how students sometimes felt emotionally attached to plastic dummies and how experienced nurses sometimes practised a degree of detachment in relation to human patients. Detached engagements will therefore be presented as part of care practices of nurses - rendering the ability to detach in engagement with patients a professional skill that students also need to learn. In the analysis to follow, attached and detached engagements are located on an equal plane by integrating both into the same conceptual framework, rather than imposing a priori notions about their dialectic relation. The analysis shows that it is the particular intertwinement of attachment and detachment that gives care its fundamental meaning. In conclusion, the need for a conceptual shift from a strong emphasis on attached engagement to a more balanced analytical approach to care work, as involving both attached and detached engagement within Danish nursing education, is advocated. PMID:24528597

  4. Method for the detachment of culturable bacteria from wetland gravel.

    PubMed

    Weber, Kela P; Legge, Raymond L

    2010-03-01

    The study of bacterial communities in microbially-mediated water treatment systems is becoming increasingly popular. Aquatic bacterial communities are often found in fixed-film environments, residing within a matrix of extracellular polymeric substances commonly referred to as a biofilm. A method for detaching the biofilm is required to either enumerate or characterize these bacterial communities. There are a variety of detachment methods including scraping, swabbing, shaking, sonication, blending, and digestion. The objective of this work was to develop an agitation-based protocol for detachment of culturable bacterial communities from the biofilm surrounding pea gravel from constructed wetland mesocosms. Three different protocol factors were systematically investigated using a triplicated 2(3) factorial design to determine the most effective detachment protocol. Factors studied included: the use of either tap water or phosphate buffer as the shaking/detachment solution; the use of either manual-shaking at room temperature or mechanical shaking at 30 degrees C; and the presence or absence of an enzyme cocktail consisting of lipase, beta-galactosidase and alpha-glucosidase. The resulting suspensions were evaluated for organics, inorganics, culturable bacteria, community level physiological profile (CLPP) and several BIOLOG ECO plate substrate related diversity indices. Using these metrics, the most effective shaking/detachment protocol was identified as mechanical shaking for 3h at 30 degrees C using a phosphate buffer with an enzyme cocktail. PMID:20079767

  5. Defect Density Characterization of Detached-Grown Germanium Crystals

    NASA Technical Reports Server (NTRS)

    Schweizer, M.; Cobb, S. D.; Volz, M. P.; Szoke, J.; Szofran, F. R.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Several (111)-oriented, Ga-doped germanium crystals were grown in pyrolytic boron nitride (pBN) containers by the Bridgman and the detached Bridgman growth techniques. Growth experiments in closed-bottom pBN containers resulted in nearly completely detached-grown crystals, because the gas pressure below the melt can build up to a higher pressure than above the melt. With open-bottom tubes the gas pressure above and below the melt is balanced during the experiment, and thus no additional force supports the detachment. In this case the crystals grew attached to the wall. Etch pit density (EPD) measurements along the axial growth direction indicated a strong improvement of the crystal quality of the detached-grown samples compared to the attached samples. Starting in the seed with an EPD of 6-8 x 10(exp 3)/square cm it decreased in the detached-grown crystals continuously to about 200-500/square cm . No significant radial difference between the EPD on the edge and the middle of the crystal exists. In the attached grown samples the EPD increases up to a value of about 2-4 x 10(exp 4)/square cm (near the edge) and up to 1 x 10(exp 4)/square cm in the middle of the sample. Thus the difference between the detached- and the attached-grown crystals with respect to the EPD is approximately two orders of magnitude.

  6. Unilateral, recurrent exudative retinal detachment in association with pansinusitis

    PubMed Central

    Osman Saatci, Ali; Ozbek Soylemezoglu, Zeynep; Barut Selver, Ozlem; Cenk Ecevit, M.; Ada, Emel

    2012-01-01

    Aim: To report a patient with unilateral exudative retinal detachment due to pansinusitis. Methods: Case report. Results: A 65-year-old woman with a two-month history of blurred vision, red eye and lid swelling in her left eye was referred to us. Her best-corrected visual acuity was 20/20 in the right eye and 20/200 in the left. Conjunctival vessels were engorged in the OS. Funduscopy revealed a 360° exudative detachment in OS and computerized tomography (CT) imaging revealed pansinusitis. Systemic antibiotic treatment was employed and exudative detachment regressed. However, exudative detachment remitted as soon as antibiotic treatment ceased. Finally she underwent sinus surgery and decompression of the orbita. Her visual acuity improved to 20/100 just two days after the surgery, stabilized at 20/30 and no further recurrences occured during the follow-up of 10 months. Conclusion: Since exudative retinal detachment usually accompanies systemic inflammatory or neoplastic diseases, systemic screening and collaboration with other disciplines are mandatory. To the best of our knowledge, this is the first report of a case that developed exudative retinal detachment due to pansinusitis and only recovered after decompression surgery.

  7. Growth and Detachment of 5 Helix DNA Ribbons.

    PubMed

    Bashar, Saima; Hwang, Si Un; Lee, Junwye; Amin, Rashid; Dugasani, Sreekantha Reddy; Ha, Tai Hwan; Park, Sung Ha

    2016-04-01

    We report on the concentration-dependent surface-assisted growth and time-temperature-dependent detachment of one-dimensional 5 helix DNA ribbons (5HR) on a mica substrate. The growth coverage ratio was determined by varying the concentration of the 5HR strands in a test tube, and the detachment rate of 5HR on mica was determined by varying the incubation time at a fixed temperature on a heat block. The topological changes in the concentration-dependent attachment and the time-temperature-dependent detachment for 5HR on mica were observed via atomic force microscopy. The observations indicate that 5HR started to grow on mica at ~10 nM and provided full coverage at ~50 nM. In contrast, 5HR at 65 °C started to detach from mica after 5 min and was completely removed after 10 min. The growth and detachment coverage show a sinusoidal variation in the growth ratio and a linear variation with a rate of detachment of 20%/min, respectively. The physical parameters that control the stability of the DNA structures on a given substrate should be studied to successfully integrate DNA structures for physical and chemical applications. PMID:27451775

  8. Improved Crystal Quality By Detached Solidification in Microgravity

    NASA Technical Reports Server (NTRS)

    Regel, Liya L.; Wilcox, William R.; Wang, Yaz-Hen; Wang, Jian-Bin

    2003-01-01

    Many microgravity directional solidification experiments yielded ingots with portions that grew without contacting the ampoule wall, leading to greatly improved crystallographic perfection. Our long term goals have been: (1) To develop a complete understanding of all of the phenomena of detached solidification.; (2) To make it possible to achieve detached solidification reproducibly; (3) To increase crystallographic perfection through detached solidification. We have three major achievements to report here: (1) We obtained a new material balance solution for the Moving Meniscus Model of detached solidification. This solution greatly clarifies the physics as well as the roles of the parameters in the system; (2) We achieved detached solidification of InSb growing on earth in BN-coated ampoules; (3) We performed an extensive series of experiments on freezing water that showed how to form multiple gas bubbles or tubes on the ampoule wall. However, these did not propagate around the wall and lead to fully detached solidification unless the ampoule wall was extremely rough and non-wetted.

  9. A 24-Residue Peptide (p5), Derived from p35, the Cdk5 Neuronal Activator, Specifically Inhibits Cdk5-p25 Hyperactivity and Tau Hyperphosphorylation*

    PubMed Central

    Zheng, Ya-Li; Amin, Niranjana D.; Hu, Ya-Fang; Rudrabhatla, Parvathi; Shukla, Varsha; Kanungo, Jyotshnabala; Kesavapany, Sashi; Grant, Philip; Albers, Wayne; Pant, Harish C.

    2010-01-01

    The activity of Cdk5-p35 is tightly regulated in the developing and mature nervous system. Stress-induced cleavage of the activator p35 to p25 and a p10 N-terminal domain induces deregulated Cdk5 hyperactivity and perikaryal aggregations of hyperphosphorylated Tau and neurofilaments, pathogenic hallmarks in neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis, respectively. Previously, we identified a 125-residue truncated fragment of p35 called CIP that effectively and specifically inhibited Cdk5-p25 activity and Tau hyperphosphorylation induced by Aβ peptides in vitro, in HEK293 cells, and in neuronal cells. Although these results offer a possible therapeutic approach to those neurodegenerative diseases assumed to derive from Cdk5-p25 hyperactivity and/or Aβ induced pathology, CIP is too large for successful therapeutic regimens. To identify a smaller, more effective peptide, in this study we prepared a 24-residue peptide, p5, spanning CIP residues Lys245–Ala277. p5 more effectively inhibited Cdk5-p25 activity than did CIP in vitro. In neuron cells, p5 inhibited deregulated Cdk5-p25 activity but had no effect on the activity of endogenous Cdk5-p35 or on any related endogenous cyclin-dependent kinases in HEK293 cells. Specificity of p5 inhibition in cortical neurons may depend on the p10 domain in p35, which is absent in p25. Furthermore, we have demonstrated that p5 reduced Aβ(1–42)-induced Tau hyperphosphorylation and apoptosis in cortical neurons. These results suggest that p5 peptide may be a unique and useful candidate for therapeutic studies of certain neurodegenerative diseases. PMID:20720012

  10. Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice.

    PubMed

    Hu, Yu; Lai, Jinsheng; Wan, Baoquan; Liu, Xingfa; Zhang, Yemao; Zhang, Jiangong; Sun, Dongsheng; Ruan, Guoran; Liu, Enjie; Liu, Gong-Ping; Chen, Chen; Wang, Dao Wen

    2016-03-01

    Although numerous studies have reported the influence of extremely low frequency magnetic field (ELF-MF) exposure on human health, its effects on cognitive deficits in Alzheimer's disease (AD) have remained under debate. Moreover, the influence of ELF-MF on hyperphosphorylated tau, which is one of the most common pathological hallmarks of AD, has not been reported to date. Therefore, transgenic mice (3xTg) were used in the present study. 3xTg mice, which express an APP/PS1 mutation combined with a tau (P301L) mutation and that develop cognitive deficits at 6 months of age, were subjected to ELF-MF (50Hz, 500μT) exposure or sham exposure daily for 3 months. We discovered that ELF-MF exposure ameliorated cognitive deficits and increased synaptic proteins in 3xTg mice. The protective effects of ELF-MF exposure may have also been caused by the inhibition of apoptosis and/or decreased oxidative stress levels that were observed in the hippocampus tissues of treated mice. Furthermore, tau hyperphosphorylation was decreased in vivo because of ELF-MF exposure, and this decrease was induced by the inhibition of GSK3β and CDK5 activities and activation of PP2Ac. We are the first to report that exposure to ELF-MF can attenuate tau phosphorylation. These findings suggest that ELF-MF exposure could act as a valid therapeutic strategy for ameliorating cognitive deficits and attenuating tau hyperphosphorylation in AD. PMID:26945731

  11. Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation.

    PubMed

    Xian, Yan-Fang; Mao, Qing-Qiu; Wu, Justin C Y; Su, Zi-Ren; Chen, Jian-Nan; Lai, Xiao-Ping; Ip, Siu-Po; Lin, Zhi-Xiu

    2014-01-01

    The progressive accumulation of amyloid-β (Aβ) in the form of senile plaques has been recognized as a key causative factor leading to the cognitive deficits seen in Alzheimer's disease (AD). Recent evidence indicates that Aβ induces neurotoxicity in the primary neuronal cultures as well as in the brain. Previously, we have demonstrated that isorhynchophylline (IRN), the major chemical ingredient of Uncaria rhynchophylla, possessed potent neuroprotective effects. In the present study, we aimed to investigate the effect of IRN on cognitive function, neuronal apoptosis, and tau protein hyperphosphorylation in the hippocampus of the Aβ25-35-treated rats and to elucidate its action mechanisms. We showed that Aβ25-35 injection caused spatial memory impairment, neuronal apoptosis, and tau protein hyperphosphorylation. Treatment with IRN (20 or 40 mg/kg) for 21 days could significantly ameliorate the cognitive deficits induced by Aβ25-35 in the rats. In addition, IRN attenuated the Aβ25-35-induced neuronal apoptosis in hippocampus by down-regulating the protein and mRNA levels of the ratio of Bcl-2/Bax, cleaved caspase-3 and caspase-9, as well as suppressing the tau protein hyperphosphorylation at the Ser396, Ser404, and Thr205 sites. Mechanistic study showed that IRN could inhibit the glycogen synthase kinase 3β (GSK-3β) activity, and activate the phosphorylation of phosphatidylinositol 3-kinase (PI3K) substrate Akt. These results indicate that down-regulation of GSK-3β activity and activation of PI3K/Akt signaling pathway are intimately involved in the neuroprotection of IRN. The experimental findings provide further evidence to affirm the potential of IRN as a worthy candidate for further development into a therapeutic agent for AD and other tau pathology-related neurodegenerative diseases. PMID:24164737

  12. Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice

    PubMed Central

    Kang, Eun-Bum; Cho, Joon-Yong

    2015-01-01

    Purpose Neurofibrillary tangles, one of pathological features of Alzheimer’s disease, are produced by the hyperphosphorylation and aggregation of tau protein. This study aimed to investigate the effects of treadmill exercise on PI3K/AKT/mTOR signal transmission, autophagy, and cognitive ability that are involved in the hyperphosphorylation and aggregation of tau protein. Methods Experimental animals (NSE/htau23 mice) were divided into non-transgenic control group (Non-Tg-Control; CON; n = 7), transgenic control group (Tg-CON; n = 7), and transgenic exercise group (Tg-Treadmill Exercise; TE; n = 7). The Tg-TE group was subjected to treadmill exercise for 12 weeks. After the treadmill exercise was completed, the cognitive ability was determined by conducting underwater maze tests. Western blot was conducted to determine the phosphorylation status of PI3K/AKT/mTOR proteins and autophagy-related proteins (Beclin-1, p62, LC3-B); hyperphosphorylation and aggregation of tau protein (Ser199/202, Ser404, Thr231, PHF-1); and phosphorylation of GSK-3β, which is involved in the phosphorylation of tau protein in the cerebral cortex of experimental animals. Results In the Tg-TE group that was subjected to treadmill exercise for 12 weeks, abnormal mTOR phosphorylation of PI3K/AKT proteins was improved via increased phosphorylation and its activity was inhibited by increased GSK-3β phosphorylation compared with those in the Tg-CON group, which was used as the control group. In addition, the expression of Beclin-1 protein involved in autophagosome formation was increased in the Tg-TE group compared with that in the Tg-CON group, whereas that of p62 protein was reduced in the Tg-TE group compared with that in the Tg-CON group. Autophagy was activated owing to the increased expression of LC3-B that controls the completion of autophagosome formation. The hyperphosphorylation and aggregation (Ser199/202, Ser404, Thr231, PHF-1) of tau protein was found to be reduced in the Tg

  13. A Chick Model of Retinal Detachment: Cone Rich and Novel

    PubMed Central

    Cebulla, Colleen M.; Zelinka, Chris P.; Scott, Melissa A.; Lubow, Martin; Bingham, Amanda; Rasiah, Stephen; Mahmoud, Ashraf M.; Fischer, Andy J.

    2012-01-01

    Background Development of retinal detachment models in small animals can be difficult and expensive. Here we create and characterize a novel, cone-rich retinal detachment (RD) model in the chick. Methodology/Principal Findings Retinal detachments were created in chicks between postnatal days 7 and 21 by subretinal injections of either saline (SA) or hyaluronic acid (HA). Injections were performed through a dilated pupil with observation via surgical microscope, using the fellow eye as a control. Immunohistochemical analyses were performed at days 1, 3, 7, 10 and 14 after retinal detachment to evaluate the cellular responses of photoreceptors, Müller glia, microglia and nonastrocytic inner retinal glia (NIRG). Cell proliferation was detected with bromodeoxyuridine (BrdU)-incorporation and by the expression of proliferating cell nuclear antigen (PCNA). Cell death was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). As in mammalian models of RD, there is shortening of photoreceptor outer segments and mis-trafficking of photoreceptor opsins in areas of RD. Photoreceptor cell death was maximal 1 day after RD, but continued until 14 days after RD. Müller glia up-regulated glial fibriliary acidic protein (GFAP), proliferated, showed interkinetic nuclear migration, and migrated to the subretinal space in areas of detachment. Microglia became reactive; they up-regulated CD45, acquired amoeboid morphology, and migrated toward outer retina in areas of RD. Reactive NIRG cells accumulated in detached areas. Conclusions/Significance Subretinal injections of SA or HA in the chick eye successfully produced retinal detachments and cellular responses similar to those seen in standard mammalian models. Given the relatively large eye size, and considering the low cost, the chick model of RD offers advantages for high-throughput studies. PMID:22970190

  14. Origin of metamorphic core complexes and detachment faults

    NASA Astrophysics Data System (ADS)

    Wu, G.; Lavier, L. L.

    2013-12-01

    Origin of metamorphic core complexes and detachment faults Guangliang Wu1,2, Luc L. Lavier1,2 1 Institute for Geophysics, University of Texas at Austin, TX 78758, USA 2 Department of Geological Sciences, University of Texas at Austin, TX 78712, USA Metamorphic core complexes (MCCs) and detachment faults are widely observed in collapsing orogens, such as Western US Cordillera, the Aegean and Papua New Guinea. A theory for the origin of MCCs has to provide: i) a viable mechanism to bring deeper crustal material to the surface, ii) a scenario that allows slip on low-angle detachment faults, and iii) a viable mechanism to form a flat Moho at a certain stage of evolution. However, previous models ignored at least one of these three requirements. Using thermo-mechanical models constrained by geological and geophysical observation, we simulated MCCs and detachment faults in the context of collapsing orogens with preexisting shear zones and middle crust of variable strength. We found that MCCs and detachment faults are natural products of gravity driven middle crustal extrusion and exhumation and strong crustal decoupling along the preexisting shear zones in a favorable state of stress in collapsing orogens. Based on previous geological and geophysical observations and our numerical simulations, we categorized MCCs into four types: i) massifs, such as Menderes massif and SW Rhodope massif, ii) single large asymmetric MCC (classic MCC), such as Whipple mountains and Snake Range Mountains, Western US Cordillera and Crete and Cyclades, the Aegean, iii) multiple less evolved MCCs, such as Black Mountains turtlebacks, and iv) subsurface ';MCC', such as interpreted at the Adriatic coast. We also recognized two types of detachment faults: one being listric fault transitioning to a convex upward shear zone at greater depth and the other a shallow exhumed upward convex shear zone. Our new models successfully predict many MCCs and detachment faults known to date.

  15. Mesospheric electron detachment and LORE recovery times

    NASA Astrophysics Data System (ADS)

    Gordillo-Vazquez, Francisco J.; Haldoupis, Christos; Luque, Alejandro

    2015-04-01

    We present new results concerning the recovery times (> 10 minutes) of LOng Recovery Early VLF events (LORE) in the upper mesosphere connected to electromagnetic pulses (EMP) of large (> 250 kA km) charge moment change (CMC) ± CG (cloud to ground) lightning capable of producing elves or elve-sprite pairs (in the case of +CG parent lightning) [1], [2]. We have modeled two possible scenarios considering first the relaxation of slightly perturbed ambient electron densities (ne0 + Δne) without an impulsive ionization source and another scenario where the ambient electron density is considerably enhanced due to an impulsive ionization source (the lightning EMP). The full non-equilibrium kinetic and 2D EMP modelling of the perturbed mesosphere in the 76 km - 92 km range during LORE occurring conditions indicates that the electron density relaxation time (defined as the time the perturbed electron density, Δne, takes to decay a factor 1/e of the way to the ambient electron density (ne0)) is critically controlled at each altitude by the relative importance of associative detachment (of O- by, respectively, O and CO and of O2- by O) with respect to electron loss mechanisms (mainly 3-body, 2-body attachment and electron-ion recombination at the highest altitudes). We found that the maximum electron density relaxation time (> 15000 s) occur between 80 km and 82 km while it decreases with increasing altitudes to 12000 s (at 85 km) and about 2000 s (at 92 km). However, LORES are presumably due to VLF scattering from electron density enhancements caused by lightning-induced EMPs in the uppermost D region ionosphere (85 - 92 km). Thus the observed VLF signal recoveries (LORE recovery times) should associate with the relaxation of the maximum enhanced electron densities produced by elves between 85 km and 92 km [3]. Finally, our results for the lowest altitudes considered (76 km and 77 km) are in good agreement with the recovery times (between 20 s and 120 s) of the typical

  16. Numerical Investigation of Plasma Detachment in Magnetic Nozzle Experiments

    NASA Technical Reports Server (NTRS)

    Sankaran, Kamesh; Polzin, Kurt A.

    2008-01-01

    At present there exists no generally accepted theoretical model that provides a consistent physical explanation of plasma detachment from an externally-imposed magnetic nozzle. To make progress towards that end, simulation of plasma flow in the magnetic nozzle of an arcjet experiment is performed using a multidimensional numerical simulation tool that includes theoretical models of the various dispersive and dissipative processes present in the plasma. This is an extension of the simulation tool employed in previous work by Sankaran et al. The aim is to compare the computational results with various proposed magnetic nozzle detachment theories to develop an understanding of the physical mechanisms that cause detachment. An applied magnetic field topology is obtained using a magnetostatic field solver (see Fig. I), and this field is superimposed on the time-dependent magnetic field induced in the plasma to provide a self-consistent field description. The applied magnetic field and model geometry match those found in experiments by Kuriki and Okada. This geometry is modeled because there is a substantial amount of experimental data that can be compared to the computational results, allowing for validation of the model. In addition, comparison of the simulation results with the experimentally obtained plasma parameters will provide insight into the mechanisms that lead to plasma detachment, revealing how they scale with different input parameters. Further studies will focus on modeling literature experiments both for the purpose of additional code validation and to extract physical insight regarding the mechanisms driving detachment.

  17. Adhesion and detachment of a capsule in axisymmetric flow

    NASA Astrophysics Data System (ADS)

    Keh, M. P.; Leal, L. G.

    2016-05-01

    The adhesion and detachment of a capsule on a solid boundary surface is studied via a combination of scaling theory and numerical simulation and the behavior is compared and contrasted with a vesicle. It is shown that the dominant physical property for both capsules and vesicles is the area dilation modulus Ks of the membrane. The nonzero shear modulus Gs for capsules increases the resistance to deformation and thus decreases slightly the equilibrium contact radius for an adhered capsule compared to an adhered vesicle. The detachment process in this study is due to an external axisymmetric flow. Unlike a rigid body that must be pulled away without change of shape, capsules (and vesicles) almost always detach dominantly by peeling in which the contact radius decreases but the minimum separation distance does not change until the final moments of detachment. Compared to a vesicle with the same Ks, a capsule maintains a more compact shape and is harder to elongate under a given external flow. Hence, the detachment process is slower for capsules compared to vesicles with the same Ks.

  18. Laser induced detachment and re-orientation of cells

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Ingle, Ninad; Mohanty, Samarendra K.

    2011-03-01

    Re-orientation of adhering cell(s) with respect to other cell(s) has not been yet possible, thus limiting study of controlled interaction between cells. Here, we report cell detachment upon irradiation with a focused near-infrared laser beam, and reorientation of adherent cells. The cell gets detached after irradiation for few seconds, followed by vertical orientation. The detached cell was transported along axial direction by scattering force and trapped at a higher plane inside the media using the same laser beam by Gravito-optical trap. The trapped cell could then be repositioned by movement of the sample stage and reoriented by rotation of the astigmatic trapping beam. The height at which the cell was stably held was found to depend on the laser beam power. The cell could be brought back to the substrate by reducing the laser beam power using a polarizer or blocking the laser beam. Viability of the detached and manipulated cell was found not to be compromised as confirmed by PI fluorescence exclusion assay. The re-oriented cell was allowed to re-attach to the substrate at a controlled distance and orientation with respect to other cells. Further, the cell was found to retain its shape even after multiple detachments and manipulation using the laser beam. This technique opens up new avenues for non-contact modification of cellular orientations that will enable study of inter-cellular interactions and design of engineered tissue.

  19. Miocene detachment faulting predating EPR propagation: Southern Baja California

    NASA Astrophysics Data System (ADS)

    Bot, Anna; Geoffroy, Laurent; Authemayou, Christine; Bellon, Hervé; Graindorge, David; Pik, Raphaël.

    2016-05-01

    At the southern tip of the Baja California peninsula, we characterize the onshore structures and kinematics associated with crustal necking leading up to the Pliocene breakup and early East Pacific Rise seafloor spreading. From a combination of tectonic field investigations, K-Ar and cosmogenic isotope dating and geomorphology, we propose that the Los Cabos block represents the exhumed footwall of a major detachment fault. This north trending detachment fault is marked by a conspicuous low-dipping brittle-ductile shear zone showing a finite displacement with top to the SE ending to the ESE. This major feature is associated with fluid circulations which led to rejuvenation of the deformed Cretaceous magmatic rocks at a maximum of 17.5 Ma. The detachment footwall displays kilometer-scale corrugations controlling the present-day drainage pattern. This major detachment is synchronous with the development of the San José del Cabo Basin where syntectonic sedimentation took place from the middle Miocene to probably the early Pliocene. We propose that this seaward dipping detachment fault accommodates the proximal crustal necking of the Baja California passive margin, which predates the onset of formation of the East Pacific Rise spreading axis in the Cabo-Puerto Vallarta segment. Our data illustrate an apparent anticlockwise rotation of the stretching direction in Baja California Sur from ~17 Ma to the Pliocene.

  20. Analytical calculations for impurity seeded partially detached divertor conditions

    NASA Astrophysics Data System (ADS)

    Kallenbach, A.; Bernert, M.; Dux, R.; Reimold, F.; Wischmeier, M.; ASDEX Upgrade Team

    2016-04-01

    A simple analytical formula for the impurity seeded partially detached divertor operational point has been developed using 1D modelling. The inclusion of charge exchange momentum loss terms improves the 1D modelling for ASDEX Upgrade conditions and its extrapolation to larger devices. The investigations are concentrated around a partially detached divertor working point of low heat flux and an electron temperature around 2.5 eV at the target which are required to maintain low sputtering rates at a tungsten target plate. An experimental formula for the onset of detachment by nitrogen seeding in ASDEX Upgrade is well reproduced, and predictions are given for N, Ne and Ar seeding for variable device size. Moderate deviations from a linear {{P}\\text{sep}}/R size dependence of the detachment threshold are seen in the modelling caused by upstream radiation at longer field line lengths. The presented formula allows the prediction of the neutral gas or seed impurity pressure which is required to achieve partial detachment for a given {{P}\\text{sep}} in devices with a closed divertor similar to the geometry in ASDEX Upgrade.

  1. Magnetohydrodynamic scenario of plasma detachment in a magnetic nozzle

    SciTech Connect

    Arefiev, Alexey V.; Breizman, Boris N.

    2005-04-15

    Some plasma propulsion concepts rely on a strong magnetic field to guide the plasma flow through the thruster nozzle. The question then arises of how the magnetically confined plasma can detach from the spacecraft. This work presents a magnetohydrodynamic (MHD) detachment scenario in which the plasma flow stretches the magnetic field lines to infinity. Detachment takes place after the energy density of the expanding magnetic field drops below the kinetic energy density of the plasma. As plasma flows along the magnetic field lines, the originally sub-Alfvenic flow becomes super-Alfvenic; this transition is similar to what occurs in the solar wind. In order to describe the detachment quantitatively, the ideal MHD equations have been solved for a cold plasma flow in a slowly diverging nozzle. The solution exhibits a well-behaved transition from sub- to super-Alfvenic flow inside the nozzle and a rarefaction wave at the edge of the outgoing flow. It is shown that efficient detachment is feasible if the nozzle is sufficiently long.

  2. Detached tip of a transseptal sheath during left atrial ablation.

    PubMed

    El-Damaty, Ahmed; Love, Michael; Parkash, Ratika

    2012-02-15

    Left atrial ablation has become more commonplace with the advent of catheter ablation for atrial fibrillation. A number of transseptal sheaths have been produced to enhance safe and efficient catheter manipulation in the left atrium (LA) for these procedures. Some of the sheaths have been subject to recall due to partial or complete detachment of its radiopaque tip. We report a case of a 46 year-old female diagnosed with idiopathic dilated cardiomyopathy that presented with atypical left atrial flutter. During electrophysiologic study, a Swartz braided SL1 (SL-1) transseptal sheath was used to introduce the ablation catheter to the left atrium. During left atrial mapping, the radiopaque tip of the sheath detached from the rest of the sheath and was seen floating in the LA. After exchanging the SL-1 sheath with a deflectable sheath, the detached segment was retrieved out of the LA and eventually out of the vascular system using an angioplasty balloon advanced over a wire and inflated distal to the lumen of the detached tip. The root cause of this malfunction was found to be lack of a secondary bonding process that these sheaths generally undergo during the manufacturing process. We describe the case of a left atrial ablation procedure where a novel percutaneous method was able to successfully retrieve the detached tip of a transseptal sheath from the vascular system, thereby avoiding a potential catastrophic complication or thoracotomy. This method may be useful in other cases where similar circumstances may present. PMID:22162088

  3. The Neuroprotective Effects of Justicidin A on Amyloid Beta25-35-Induced Neuronal Cell Death Through Inhibition of Tau Hyperphosphorylation and Induction of Autophagy in SH-SY5Y Cells.

    PubMed

    Gu, Ming-Yao; Kim, Joonki; Yang, Hyun Ok

    2016-06-01

    Justicidin A is a structurally defined arylnaphthalide lignan, which has been shown anti-cancer activity; however, the neuroprotective effect of justicidin A is still untested. In this study, we investigated the action of justicidin A on amyloid beta (Aβ)25-35-induced neuronal cell death via inhibition of the hyperphosphorylation of tau and induction of autophagy in SH-SY5Y cells. Pretreatment with justicidin A significantly elevated cell viability in cells treated with Aβ25-35. Western blot data demonstrated that justicidin A inhibited the Aβ25-35-induced up-regulation the levels of hyperphosphorylation of tau in SH-SY5Y cells. In addition, treatment with justicidin A significantly induced autophagy as measured by the increasing LC3 II/I ratio, an important autophagy marker. These studies showed that justicidin A inhibited activity of glycogen synthase kinase-3beta (GSK-3β), which is an important kinase in up-stream signaling pathways; inhibited hyperphosphorylation of tau in AD; and enhanced activity of AMP-activated protein kinase (AMPK), which is the key molecule for both hyperphosphorylation of tau and induction of autophagy. These data provide the first evidence that justicidin A protects SH-SY5Y cells from Aβ25-35-induced neuronal cell death through inhibition of hyperphosphorylation of tau and induction of autophagy via regulation the activity of GSK-3β and AMPK, and they also provide some insights into the relationship between tau protein hyperphosphorylation and autophagy. Thus, we conclude that justicidin A may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for AD. PMID:26887582

  4. Shape of heteroepitaxial island determined by asymmetric detachment

    NASA Astrophysics Data System (ADS)

    Saito, Yukio; Kawasaki, Ryo

    2008-02-01

    Square lattice gas models for heteroepitaxial growth are studied by means of kinetic Monte Carlo simulations, in order to find a possible origin of anisotropic island shape observed in growth experiments of long organic molecules. When deposited molecules form clusters irreversibly at their encounter during surface diffusion, islands grow in a ramified dendritic shape, similar to DLA. Introduction of molecular detachment from edges makes islands compact with smooth edges. Tilting of adsorbed long molecules or steps in a vicinal substrate may induce orientation dependence in the detachment rate of edge molecules from an island. In simulations with orientation-dependent detachment rates, a clear anisotropy in an island shape is observed. Shape anisotropy on a vicinal substrate is enhanced as steps get dense, in agreement to the experimental observation.

  5. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    PubMed Central

    Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were also areas of white without pressure, chorioretinal scarring and retinal breaks. All the changes were limited to beyond the equator but were found to span 360 degrees. She was treated with barrage laser all around to prevent extension of the retinal detachment posteriorly. She remained stable till her latest follow-up two years after the barrage laser. This case is reported for its rarity with a discussion of the probable differential diagnoses. To the best of our knowledge, this is the first report of such findings in lattice degeneration.

  6. Streetscape showing north sides of five of eight Medical Detachment ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Streetscape showing north sides of five of eight Medical Detachment Barracks on Ramp No. 5. Note that Building No. 9966-B on right has a wooden frame sun porch. This Standard Ward construction is different than most of the other Medical Detachment Barracks, which are all- brick. On the opposite side of this building, the construction is all-brick (Building No. 9966-A, not shown). Buildings No. 9967-B and 9968-B (not shown) also have wooden frame sun porches. Other buildings in photo are, on right, the north B-sides of Buildings Nos. 9965, 9964, 9963 and 9962. On left is Building No. 9971-A on Ramp No. 6. Corridor A is visible in far distance. - Madigan Hospital, Medical Detachment Barracks, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, Tacoma, Pierce County, WA

  7. Gavage of D-Ribose induces Aβ-like deposits, Tau hyperphosphorylation as well as memory loss and anxiety-like behavior in mice

    PubMed Central

    Wang, Yujing; Su, Tao; Zhou, Lei; Liu, Ying; He, Rongqiao

    2015-01-01

    In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. Aβ-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates Aβ-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for age-related cognitive impairment and diabetic encephalopathy. PMID:26452037

  8. Protein interaction module-assisted function X (PIMAX) approach to producing challenging proteins including hyperphosphorylated tau and active CDK5/p25 kinase complex.

    PubMed

    Sui, Dexin; Xu, Xinjing; Ye, Xuemei; Liu, Mengyu; Mianecki, Maxwell; Rattanasinchai, Chotirat; Buehl, Christopher; Deng, Xiexiong; Kuo, Min-Hao

    2015-01-01

    Many biomedically critical proteins are underrepresented in proteomics and biochemical studies because of the difficulty of their production in Escherichia coli. These proteins might possess posttranslational modifications vital to their functions, tend to misfold and be partitioned into bacterial inclusion bodies, or act only in a stoichiometric dimeric complex. Successful production of these proteins requires efficient interaction between these proteins and a specific "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a natural physical partner within the dimeric complex. Here we report the design and application of a protein interaction module-assisted function X (PIMAX) system that effectively overcomes these hurdles. By fusing two proteins of interest to a pair of well-studied protein-protein interaction modules, we were able to potentiate the association of these two proteins, resulting in successful production of an enzymatically active cyclin-dependent kinase complex and hyperphosphorylated tau protein, which is intimately linked to Alzheimer disease. Furthermore, using tau isoforms quantitatively phosphorylated by GSK-3β and CDK5 kinases via PIMAX, we demonstrated the hyperphosphorylation-stimulated tau oligomerization in vitro, paving the way for new Alzheimer disease drug discoveries. Vectors for PIMAX can be easily modified to meet the needs of different applications. This approach thus provides a convenient and modular suite with broad implications for proteomics and biomedical research. PMID:25385071

  9. Detached Solidification of Germanium-Silicon Crystals on the ISS

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.; Croell, A.

    2016-01-01

    A series of Ge(sub 1-x) Si(sub x) crystal growth experiments are planned to be conducted in the Low Gradient Furnace (LGF) onboard the International Space Station. The primary objective of the research is to determine the influence of containment on the processing-induced defects and impurity incorporation in germanium-silicon alloy crystals. A comparison will be made between crystals grown by the normal and "detached" Bridgman methods and the ground-based float zone technique. Crystals grown without being in contact with a container have superior quality to otherwise similar crystals grown in direct contact with a container, especially with respect to impurity incorporation, formation of dislocations, and residual stress in crystals. "Detached" or "dewetted" Bridgman growth is similar to regular Bridgman growth in that most of the melt is in contact with the crucible wall, but the crystal is separated from the wall by a small gap, typically of the order of 10-100 microns. Long duration reduced gravity is essential to test the proposed theory of detached growth. Detached growth requires the establishment of a meniscus between the crystal and the ampoule wall. The existence of this meniscus depends on the ratio of the strength of gravity to capillary forces. On Earth, this ratio is large and stable detached growth can only be obtained over limited conditions. Crystals grown detached on the ground exhibited superior structural quality as evidenced by measurements of etch pit density, synchrotron white beam X-ray topography and double axis X-ray diffraction.

  10. Numerical Optimization of the Thermal Field in Bridgman Detached Growth

    NASA Technical Reports Server (NTRS)

    Stelian, C.; Volz, M. P.; Derby, J. J.

    2009-01-01

    The global modeling of the thermal field in two vertical Bridgman-like crystal growth configurations, has been performed to get optimal thermal conditions for a successful detached growth of Ge and CdTe crystals. These computations are performed using the CrysMAS code and expand upon our previous analysis [1] that propose a new mechanism involving the thermal field and meniscus position to explain stable conditions for dewetted Bridgman growth. The analysis of the vertical Bridgman configuration with two heaters, used by Palosz et al. for the detached growth of Ge, shows, consistent with their results, that the large wetting angle of germanium on boron nitride surfaces was an important factor to promote a successful detached growth. Our computations predict that by initiating growth much higher into the hot zone of the furnace, the thermal conditions will be favorable for continued detachment even for systems that did not exhibit high contact angles. The computations performed for a vertical gradient freeze configuration with three heaters representative of that used for the detached growth of CdTe, show favorable thermal conditions for dewetting during the entirely growth run described. Improved thermal conditions are also predicted for coated silica crucibles when the solid-liquid interface advances higher into the hot zone during the solidification process. The second set of experiments on CdTe growth described elsewhere has shown the reattachment of the crystal to the crucible after few centimeters of dewetted growth. The thermal modeling of this configuration shows a second solidification front appearing at the top of the sample and approaching the middle line across the third heater. In these conditions, the crystal grows detached from the bottom, but will be attached to the crucible in the upper part because of the solidification without gap in this region. The solidification with two interfaces can be avoided when the top of the sample is positioned below

  11. Magnetic Detachment and Plume Control in Escaping Magnetized Plasma

    SciTech Connect

    P. F. Schmit and N. J. Fisch

    2008-11-05

    The model of two-fluid, axisymmetric, ambipolar magnetized plasma detachment from thruster guide fields is extended to include plasmas with non-zero injection angular velocity profiles. Certain plasma injection angular velocity profiles are shown to narrow the plasma plume, thereby increasing exhaust efficiency. As an example, we consider a magnetic guide field arising from a simple current ring and demonstrate plasma injection schemes that more than double the fraction of useful exhaust aperture area, more than halve the exhaust plume angle, and enhance magnetized plasma detachment.

  12. DUAL ORIGIN OF AEROSOLS IN TITAN'S DETACHED HAZE LAYER

    SciTech Connect

    Cours, T.; Burgalat, J.; Rannou, P.; Rodriguez, S.; Brahic, A.

    2011-11-10

    We have analyzed scattered light profiles from the Cassini Imaging Science Subsystem, taken at the limb and at several large phase angles. We also used results from an occultation observed by Ultraviolet Imaging Spectrograph in the ultraviolet. We found that particles responsible for the scattering in the detached haze have an effective radius around 0.15 {mu}m and the aerosol size distribution follows a power law (exponent about -4.5). We discuss these results along with microphysical constraints and thermal equilibrium of the detached haze, and we conclude that only a strong interaction with atmospheric dynamics can explain such a structure.

  13. Bilateral Simultaneous Rhegmatogenous Retinal Detachment following Laser in situ Keratomileusis.

    PubMed

    Yumusak, Erhan; Ornek, Kemal; Ozkal, Fatma

    2016-01-01

    A 21-year-old woman developed simultaneous rhegmatogenous retinal detachment after laser in situ keratomileusis (LASIK) in both eyes. She underwent pars plana vitrectomy surgery combined with endolaser photocoagulation and silicone oil tamponade in the right eye. A week later, pneumatic retinopexy was done in the left eye. As the retinal tear did not seal, 360° scleral buckling surgery was performed and retina was attached. Bilateral simultaneous rhegmatogenous retinal detachment after LASIK for correction of myopia can be a serious complication. Patients should be informed about the possibility of this complication. PMID:27462264

  14. Mutual electron detachment in collisions between negative ions

    NASA Astrophysics Data System (ADS)

    Schulze, R.; Melchert, F.; Krüdener, S.; Meuser, S.; Petri, S.; Benner, M.; Salzborn, E.

    1992-10-01

    Employing the crossed-beams technique, we have measured absolute cross sections for mutual electron detachment in collisions between two negative ions H-+X-→H0+X0+2e-(X-:B-, H-,Cu-,O-,Au-,F-) in the CM-energy range between a few keV and about 100 keV. The results obtained appear not to obey a simple scaling with negative ion binding energies. For H-+H--collisions also the single detachment reaction H-+H-→H0+... has been investigated.

  15. Subduction and slab detachment in the Mediterranean-Carpathian region.

    PubMed

    Wortel, M J; Spakman, W

    2000-12-01

    Seismic tomography models of the three-dimensional upper mantle velocity structure of the Mediterranean-Carpathian region provide a better understanding of the lithospheric processes governing its geodynamical evolution. Slab detachment, in particular lateral migration of this process along the plate boundary, is a key element in the lithospheric dynamics of the region during the last 20 to 30 million years. It strongly affects arc and trench migration, and causes along-strike variations in vertical motions, stress fields, and magmatism. In a terminal-stage subduction zone, involving collision and suturing, slab detachment is the natural last stage in the gravitational settling of subducted lithosphere. PMID:11110653

  16. Bilateral Simultaneous Rhegmatogenous Retinal Detachment following Laser in situ Keratomileusis

    PubMed Central

    Yumusak, Erhan; Ornek, Kemal; Ozkal, Fatma

    2016-01-01

    A 21-year-old woman developed simultaneous rhegmatogenous retinal detachment after laser in situ keratomileusis (LASIK) in both eyes. She underwent pars plana vitrectomy surgery combined with endolaser photocoagulation and silicone oil tamponade in the right eye. A week later, pneumatic retinopexy was done in the left eye. As the retinal tear did not seal, 360° scleral buckling surgery was performed and retina was attached. Bilateral simultaneous rhegmatogenous retinal detachment after LASIK for correction of myopia can be a serious complication. Patients should be informed about the possibility of this complication. PMID:27462264

  17. Analytic formulas for above threshold ionization or detachment plateau spectra

    NASA Astrophysics Data System (ADS)

    Frolov, M. V.; Manakov, N. L.; Starace, Anthony F.

    2009-11-01

    Closed form analytic formulas are derived in the tunneling limit for both above threshold detachment (ATD) of negative ions and above threshold ionization (ATI) of neutral atoms. These formulas provide a fully quantum justification of the well-known classical three-step scenario for strong field ionization and detachment spectra in the high energy region of the ATI or ATD plateau and also provide analytical insight into how the ATI/ATD rates may be controlled by varying the laser field parameters or by varying the atomic species.

  18. Evaluation of bacterial detachment rates in porous media

    SciTech Connect

    Peyton, B.M.; Hooker, B.S.; Skeen, R.S.; Cunningham, A.B.; Lundman, R.W.

    1994-05-01

    The ability of published biomass detachment rate expressions to describe experimental data obtained from porous media reactors using Pseudomonas aeruginosa grown aerobically on glucose was evaluated. A first-order rate expression on attached biomass concentration best reflected effluent substrate concentration for combined data sets. Detachment rate coefficient k{sub d1} was dependent on initial substrate concentration. Simulation of porous media reactor experiments indicated that responses using higher influent substrate concentrations possessed greater sensitivity to variations in k{sub d1}. Simulations of field bioremediation systems suggest the use of accurate biofilm development kinetics is important in the prediction of well bore biofouling.

  19. Detached Shells of Dust and Gas around Carbon Stars

    NASA Astrophysics Data System (ADS)

    Maercker, M.; Olofsson, H.; Eriksson, K.; Gustafsson, B.; Schöier, F. L.

    2011-09-01

    We present observations of dust-scattered light of the carbon stars U Ant, R Scl, and U Cam taken with the EFOSC2 camera on the ESO 3.6-m telescope and the ACS on the Hubble Space Telescope. The observations show the detached shells around these stars in unprecedented detail, revealing a distinctively clumpy structure in the HST images of R Scl, and a separation of the dust and gas in the ground-based data for U Ant. This allows us to investigate the detached shells and their origin with exceptional precision.

  20. Two-dimensional simulations of surface deformation caused by slab detachment

    NASA Astrophysics Data System (ADS)

    Buiter, Susanne J. H.; Govers, Rob; Wortel, M. J. R.

    2002-09-01

    Detachment of the deeper part of subducted lithosphere causes changes in a subduction zone system which may be observed on the Earth's surface. Constraints on the expected magnitudes of these surface effects can aid in the interpretation of geological observations near convergent plate margins where detachment is expected. In this study, we quantify surface deformation caused by detachment of subducted lithosphere. We determine the range of displacement magnitudes which can be associated with slab detachment using numerical models. The lithospheric plates in our models have an effective elastic thickness, which provides an upper bound for rapid processes, like slab detachment, to the surface deformation of lithosphere with a more realistic rheology. The surface topography which develops during subduction is compared with the topography shortly after detachment is imposed. Subduction with a non-migrating trench system followed by detachment leads to a maximum surface uplift of 2-6 km, while this may be higher for the case of roll-back preceding detachment. In the latter situation, the back-arc basin may experience a phase of compression after detachment. Within the context of our elastic model, the surface uplift resulting from slab detachment is sensitive to the depth of detachment, a change in friction on the subduction fault during detachment and viscous stresses generated by sinking of the detached part of the slab. Overall, surface uplift of these magnitudes is not diagnostic of slab detachment since variations during ongoing subduction may result in similar vertical surface displacements.

  1. Liquid Droplet Detachment and Entrainment in Microscale Flows

    NASA Astrophysics Data System (ADS)

    Hidrovo, Carlos

    2005-11-01

    In this talk we will present a first order study of liquid water detachment and entrainment into air flows in hydrophobic microchannels. Silicon based microstructures consisting of 23 mm long U-shaped channels of different geometry were used for this purpose. The structures are treated with a Molecular Vapor Deposition (MVD) process that renders them hydrophobic. Liquid water is injected through a side slot located 2/3 of the way downstream from the air channel inlet. The water entering the air channel beads up into slugs or droplets that grow in size at this injection location until they fill and flood the channel or are carried away by the air flow. The slugs/droplets dimensions at detachment are correlated against superficial gas velocity and proper dimensionless parameters are postulated and examined to compare hydrodynamic forces against surface tension. It is found that slug/droplet detachment is dominated by two main forces: pressure gradient drag, arising from confinement of a viscous flow in the channel, and inertial drag, arising from the stagnation of the air due to obstruction by the slugs/droplets. A detachment regime map is postulated based on the relative importance of these forces under different flow conditions.

  2. On favorable thermal fields for detached Bridgman growth

    NASA Astrophysics Data System (ADS)

    Stelian, Carmen; Volz, Martin P.; Derby, Jeffrey J.

    2009-06-01

    The thermal fields of two Bridgman-like configurations, representative of real systems used in prior experiments for the detached growth of CdTe and Ge crystals, are studied. These detailed heat transfer computations are performed using the CrysMAS code and expand upon our previous analysis [C. Stelian, A. Yeckel, J.J. Derby, Influence of thermal phenomena on crystal reattachment during the dewetted Bridgman growth, J. Cryst. Growth, in press] that posited a new mechanism involving the thermal field and meniscus position to explain stable conditions for dewetted Bridgman growth. Computational results indicate that heat transfer conditions that led to successful detached growth in both of these systems are in accordance with our prior assertion, namely that the prevention of crystal reattachment to the crucible wall requires the avoidance of any undercooling of the melt meniscus during the growth run. Significantly, relatively simple process modifications that promote favorable thermal conditions for detached growth may overcome detrimental factors associated with meniscus shape and crucible wetting. Thus, these ideas may be important to advance the practice of detached growth for many materials.

  3. Bilateral Rhegmatogenous Retinal Detachment during External Beam Radiotherapy

    PubMed Central

    Hidaka, Takako; Chuman, Hideki; Nao-i, Nobuhisa

    2016-01-01

    Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD. PMID:27462261

  4. Existence and Stability of Menisci in Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.

    2011-01-01

    Detached growth, also referred to as dewetted growth, is a Bridgman crystal growth process in which the melt is in contact with the crucible wall but the crystal is not. A meniscus bridges the gap between the top of the crystal and the crucible wall. The Young-Laplace capillary equation was used to calculate the crystal radii of detached states as a function of the pressure differential across the meniscus. The detached states depend on the contact angle of the melt with the crucible wall, the growth angle of the melt with respect to the solidifying crystal, and the Bond number. A static stability analysis was performed on the calculated detached states. The stability criterion was the sign of the second variation of the potential energy upon admissible meniscus shape perturbations. The conditions considered corresponded to the growth of Ge and InSb, in both terrestrial and microgravity conditions. Stability was found to depend significantly on whether the interior surface was considered to be microscopically rough or smooth, corresponding to pinned or unpinned states. It was also found that all meniscus shapes which are single-valued functions of the radius are statically stable in a microgravity environment.

  5. Sampling device with a capped body and detachable handle

    DOEpatents

    Jezek, Gerd-Rainer

    2000-01-01

    The apparatus is a sampling device having a pad for sample collection, a body which supports the pad, a detachable handle connected to the body and a cap which encloses and retains the pad and body to protect the integrity of the sample.

  6. Bilateral Rhegmatogenous Retinal Detachment during External Beam Radiotherapy.

    PubMed

    Hidaka, Takako; Chuman, Hideki; Nao-I, Nobuhisa

    2016-01-01

    Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD. PMID:27462261

  7. OEDGE Modeling of Detachment Threshold Experiments on DIII-D

    NASA Astrophysics Data System (ADS)

    Elder, J. D.; Stangeby, P. C.; McLean, A. G.; Leonard, A. W.; Watkins, J. G.

    2015-11-01

    A detachment threshold experiment was performed on DIII-D in which the divertor plasma transitioned from attached to weakly detached at the strike point with minimal changes in upstream parameters. The value of Te at the outer strike point measured by Thompson scattering decreased from ~ 10eV (attached) to ~ 2 eV (weakly detached). Both the Langmuir probes and the divertor Thomson diagnostics recorded increases in the particle flux on the order of a factor of two between these divertor conditions. OEDGE is used to model both of these plasma regimes for both L-mode and H-mode discharges. The behaviour of molecular hydrogen is assessed using OEDGE and possible roles of hydrogen molecules in the detachment process are examined. Work supported by the US Department of Energy under DE-FC02-04ER54698, DE-FG02-04ER54578, DE-AC04-94AL85000, DE-AC05-00OR22725, and DE-AC52-07NA27344.

  8. Detachment faults: Evidence for a low-angle origin

    SciTech Connect

    Scott, R.J.; Lister, G.S. )

    1992-09-01

    The origin of low-angle normal faults or detachment faults mantling metamorphic core complexes in the southwestern United States remains controversial. If [sigma][sub 1] is vertical during extension, the formation of, or even slip along, such low-angle normal faults is mechanically implausible. No records exist of earthquakes on low-angle normal faults in areas currently undergoing continental extension, except from an area of actively forming core complexes in the Solomon Sea, Papua New Guinea. In light of such geophysical and mechanical arguments, W.R. Buck and B. Wernicke and G.J. Axen proposed models in which detachment faults originate as high-angle normal faults, but rotate to low angles and become inactive as extension proceeds. These models are inconsistent with critical field relations in several core complexes. The Rawhide fault, an areally extensive detachment fault in western Arizona, propagated at close to its present subhorizontal orientation late in the Tertiary extension of the region. Neither the Wernicke and Axen nor Buck models predict such behavior; in fact, both models preclude the operation of low-angle normal faults. The authors recommend that alternative explanations or modifications of existing models are needed to explain the evidence that detachment faults form and operate with gentle dips.

  9. Turbulent Simulations of Divertor Detachment Based On BOUT + + Framework

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Xu, Xueqiao; Xia, Tianyang; Ye, Minyou

    2015-11-01

    China Fusion Engineering Testing Reactor is under conceptual design, acting as a bridge between ITER and DEMO. The detached divertor operation offers great promise for a reduction of heat flux onto divertor target plates for acceptable erosion. Therefore, a density scan is performed via an increase of D2 gas puffing rates in the range of 0 . 0 ~ 5 . 0 ×1023s-1 by using the B2-Eirene/SOLPS 5.0 code package to study the heat flux control and impurity screening property. As the density increases, it shows a gradually change of the divertor operation status, from low-recycling regime to high-recycling regime and finally to detachment. Significant radiation loss inside the confined plasma in the divertor region during detachment leads to strong parallel density and temperature gradients. Based on the SOLPS simulations, BOUT + + simulations will be presented to investigate the stability and turbulent transport under divertor plasma detachment, particularly the strong parallel gradient driven instabilities and enhanced plasma turbulence to spread heat flux over larger surface areas. The correlation between outer mid-plane and divertor turbulence and the related transport will be analyzed. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-675075.

  10. Experimental Characterization of Plasma Detachment from Magnetic Nozzles

    NASA Astrophysics Data System (ADS)

    Olsen, Christopher Scott

    Magnetic nozzles, like Laval nozzles, are observed in several natural systems and have application in areas such as electric propulsion and plasma processing. Plasma flowing through these nozzles is inherently tied to the field lines and must separate for momentum redirection or particle transport to occur. Plasma detachment and associated mechanisms from a magnetic nozzle are investigated. Experimental results are presented from the plume of the VASIMRRTM VX-200 device flowing along an axisymmetric magnetic nozzle and operated at two ion energies to explore momentum dependent detachment. The argon plume expanded into a 150m3 vacuum chamber where the background pressure was low enough that charge-exchange mean-free-paths were longer than experiment scale lengths. This magnetic nozzle system is demonstrated to hydrodynamically scale up to astrophysical plasmas, particularly the solar chromosphere, implying general relevance to many systems. Plasma parameters were mapped over a large spatial range using measurements from multiple plasma diagnostics. The data show that the plume does not follow the magnetic field lines. A mapped integration of the ion flux shows the plume may be divided into three regions where 1) the plume briefly follows the magnetic flux, 2) diverges quadratically before 3) expanding with linear trajectories. Transitioning from region 1→2, the ion flux departs from the magnetic flux suggesting ion detachment. An instability forms in region 2 driving an oscillating electric field that causes ions to expand before enhancing electron cross-field transport through anomalous resistivity. Transitioning from region 2→3 the electric field dissipates, the trajectories linearize, and the plume effectively detaches. A delineation of sub-to-super Alfvenic flow aligns well with the inflection points of the linearization without a change in magnetic topology. The detachment process is best described as a two part process: First, ions detach by a breakdown of

  11. Seismic Slip on an Oblique Detachment Fault at Low Angles

    NASA Astrophysics Data System (ADS)

    Janecke, S. U.; Steely, A. N.; Evans, J. P.

    2008-12-01

    Pseudotachylytes are one of the few accepted indicators of seismic slip along ancient faults. Low-angle normal faults have produced few large earthquakes in historic times and low-angle normal faults (detachment faults) are typically severely misoriented relative to a vertical maximum compressive stress. As a result many geoscientists question whether low-angle normal faults produce earthquakes at low angles. Relationships in southern California show that a major low-angle normal-oblique fault slipped at low angles and produced large earthquakes. The exhumed Late Cenozoic West Salton detachment fault preserves spectacular fault- related pseudotachylytes along its fault plane and injected into its hanging wall and footwall. Composite pseudotachylyte zones are up to 1.25 m thick and persists over lateral distances of at least 10's of meters. Pseudotachylyte is common in most thin sections of damaged fault rocks with more than 20% (by volume) of cataclasite. We recognized the presence of original melt using numerous criteria: abundant spherulites in thin sections, injection structures at both the thin-section and outcrop scale, black aphanitic textures, quenched vein margins, variations in microcrystallite textures and/or size with respect to the vein margin, and glassy textures in hand sample. Multiple earthquakes are inferred to produce the layered "stratigraphy" in some exposures of pseudotachylytes. We infer that the West Salton detachment fault formed and slipped at low angles because it nearly perfectly reactivates a Cretaceous ductile thrust system at the half km scale and dips between 10 and 45 degrees. The about 30 degree NNE dip of the detachment fault on the north side of Yaqui Ridge is likely steeper than its dip during detachment slip because there is local steepening on the flanks of the Yaqui Ridge antiform in a contractional stepover of a crosscutting Quaternary San Felipe dextral fault zone. These relationships indicate a low dip on the detachment

  12. Bacterial detachment from salivary conditioning films by dentifrice supernates.

    PubMed

    van der Mei, Henny C; White, Donald J; Cox, Ed R; Geertsema-Doornbusch, Gesinda I; Busscher, Henk J

    2002-01-01

    This study compared the detachment by supernates of nine different dentifrices of four oral bacterial strains adhering to a salivary pellicle in a parallel plate flow chamber. Ultra-thin bovine enamel slabs were coated for 1.5 h with human whole saliva. Following buffer rinsing, a bacterial suspension of Streptococcus oralis, Streptococcus sanguis, Streptococcus mutans or Actinomyces naeslundii was perfused through the flow chamber at a shear rate of 30 s-1 for four hours, and the number of adhering bacteria n4h was enumerated by image analysis after buffer rinsing at the same shear rate. Then, a 25 wt%-dentifrice/water supernate was perfused through the flow chamber for four minutes, followed by eight minutes of buffer rinsing and another enumeration of the number of bacteria that had remained adhering nad. Finally, an air-bubble was passed through the flow chamber to mimic the occasionally high detachment forces occurring in the oral cavity, and the adhering bacteria nab were counted again. On average, S. sanguis was the easiest to detach (73% averaged over all dentifrice supernates), while A. naeslundii was the most difficult (22% on average). The combined detachment of bacteria by dentifrice supernates and air-bubble ranged from a low of 16% to a high of 80%. Dentifrices containing pyrophosphate and polymeric polyphosphate (hexametaphosphate) surface active ingredients appeared to produce the most consistent and strongest desorption effects on plaque bacteria. Factors apparently important to bacterial detachment from pellicle-covered tooth surfaces by dentifrice formulations include the nature of adhesion of bacterial strains and chemical composition of the dentifrice formulations, including pH, surfactant system and the effect of added ingredients (dispersants, metal ions, peroxides, baking soda). PMID:11507932

  13. Screening for anthracnose disease resistance in strawberry using a detached leaf assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inoculation of detached strawberry leaves with Colletotrichum species may provide a rapid, non-destructive method of identifying anthracnose resistant germplasm. The reliability and validity of assessing disease severity is critical to disease management decisions. We inoculated detached strawberr...

  14. Comparison of visual and electronic evaluations of detached strawberry leaves inoculated with colletotrichum species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inoculation of detached strawberry leaves with Colletotrichum species may provide an accurate, rapid, non-destructive method of identifying anthracnose resistant germplasm. Two measures of anthracnose disease severity were compared on detached strawberry leaves inoculated with Colletotrichum fragar...

  15. STAT1 Hyperphosphorylation and Defective IL12R/IL23R Signaling Underlie Defective Immunity in Autosomal Dominant Chronic Mucocutaneous Candidiasis

    PubMed Central

    Heinhuis, Bas; Hoischen, Alexander; Joosten, Leo A. B.; Arkwright, Peter D.; Gennery, Andrew; Kullberg, Bart Jan; Veltman, Joris A.; Lilic, Desa; van der Meer, Jos W. M.; Netea, Mihai G.

    2011-01-01

    We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning and transfection experiments demonstrate that mutated STAT1 inhibits IL12R/IL-23R signaling, with hyperphosphorylation of STAT1 as the likely underlying molecular mechanism. Inhibition of signaling through the receptors for IL-12 and IL-23 leads to strongly diminished Th1/Th17 responses and hence to increased susceptibility to fungal infections. The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency. PMID:22195034

  16. FLZ Alleviates the Memory Deficits in Transgenic Mouse Model of Alzheimer’s Disease via Decreasing Beta-Amyloid Production and Tau Hyperphosphorylation

    PubMed Central

    Wang, Tao; Kong, Xiang-Chen; Tai, Wen-Jiao; Sun, Hua; Zhang, Dan

    2013-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia worldwide and mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. FLZ is a novel synthetic derivative of natural squamosamide and has been proved to improve memory deficits in dementia animal models. In this study, we aimed to investigate the mechanisms of FLZ’s neuroprotective effect in APP/PS1 double transgenic mice and SH-SY5Y (APPwt/swe) cells. The results showed that treatment with FLZ significantly improved the memory deficits of APP/PS1 transgenic mice and decreased apoptosis of SH-SY5Y (APPwt/swe) cells. FLZ markedly attenuated Aβ accumulation and tau phosphorylation both in vivo and in vitro. Mechanistic study showed that FLZ interfered APP processing, i.e., FLZ decreased β-amyloid precursor protein (APP) phosphorylation, APP-carboxy-terminal fragment (APP-CTF) production and β-amyloid precursor protein cleaving enzyme 1 (BACE1) expression. These results indicated that FLZ reduced Aβ production through inhibiting amyloidogenic pathway. The mechanistic study about FLZ’s inhibitory effect on tau phosphorylation revealed t the involvement of Akt/glycogen synthase kinase 3β (GSK3β) pathway. FLZ treatment increased Akt activity and inhibited GSK3β activity both in vivo and in vitro. The inhibitory effect of FLZ on GSK3β activity and tau phosphorylation was suppressed by inhibiting Akt activity, indicating that Akt/GSK3β pathway might be the possible mechanism involved in the inhibitory effect of FLZ on tau hyperphosphorylation. These results suggested FLZ might be a potential anti-AD drug as it not only reduced Aβ production via inhibition amyloidogenic APP processing pathway, but also attenuated tau hyperphosphoylation mediated by Akt/GSK3β. PMID:24223757

  17. Strong positive cooperativity in binding to the A3T3 repeat by Hoechst 33258 derivatives attaching the quinoline units at the end of a branched linker.

    PubMed

    Koda, Hironori; Brazier, John Alan; Onishi, Ippei; Sasaki, Shigeki

    2015-08-01

    Hoechst 33258 derivatives with additional interacting moieties attached at the ends of branched linkers were synthesized, and their DNA binding properties were investigated with regard to the A3T3 repeat by measuring fluorescence spectra. The binding property of the ligand was investigated by fluorescence titration, and the titration data were analyzed using the McGhee-von Hippel method. Ligand 6Q with the quinolin-6-yloxyacetyl group and Ligand IQ with isoquinolin-6-yloxyacetyl group at the ends of the branched linkers exhibit highly positive cooperativity for the DNA having 5 A3T3 sites with 3 base-insertions between them with sequence selectivity. The strategy developed in this study may be generally applicable for designing ligands for repetitive DNA sequences. PMID:26154241

  18. Gene Transcription Profile of the Detached Retina (An AOS Thesis)

    PubMed Central

    Zacks, David N.

    2009-01-01

    Purpose: Separation of the neurosensory retina from the retinal pigment epithelium (RPE) yields many morphologic and functional consequences, including death of the photoreceptor cells, Müller cell hypertrophy, and inner retinal rewiring. Many of these changes are due to the separation-induced activation of specific genes. In this work, we define the gene transcription profile within the retina as a function of time after detachment. We also define the early activation of kinases that might be responsible for the detachment-induced changes in gene transcription. Methods: Separation of the retina from the RPE was induced in Brown-Norway rats by the injection of 1% hyaluronic acid into the subretinal space. Retinas were harvested at 1, 7, and 28 days after separation. Gene transcription profiles for each time point were determined using the Affymetrix Rat 230A gene microarray chip. Transcription levels in detached retinas were compared to those of nondetached retinas with the BRB-ArrayTools Version 3.6.0 using a random variance analysis of variance (ANOVA) model. Confirmation of the significant transcriptional changes for a subset of the genes was performed using microfluidic quantitative real-time polymerase chain reaction (qRT-PCR) assays. Kinase activation was explored using Western blot analysis to look for early phosphorylation of any of the 3 main families of mitogen-activated protein kinases (MAPK): the p38 family, the Janus kinase family, and the p42/p44 family. Results: Retinas separated from the RPE showed extensive alterations in their gene transcription profile. Many of these changes were initiated as early as 1 day after separation, with significant increases by 7 days. ANOVA analysis defined 144 genes that had significantly altered transcription levels as a function of time after separation when setting a false discovery rate at ≤0.1. Confirmatory RT-PCR was performed on 51 of these 144 genes. Differential transcription detected on the microarray

  19. Detached macroalgae: Its importance to inshore sandy beach fauna

    NASA Astrophysics Data System (ADS)

    Orr, Kyla K.; Wilding, Thomas A.; Horstmeyer, Lena; Weigl, Simon; Heymans, Johanna J.

    2014-10-01

    Kelp forests shed a large proportion of their biomass through storm-mediated defoliation, senescence of kelp blades, and constant erosion of particulate organic matter from the kelp fronds. Much of this detached macroalgae drifts in the water column and is deposited on intertidal zones of beaches. Detached macroalgae may provide inshore sandy beach fauna with refuge and food subsidies in an exposed and bare environment, with limited in situ primary production. We evaluated the relationship between detached macroalgae and the density of inshore fauna, where 'inshore' was the body of water extending from low water seawards for approximately 50 m. Inshore fauna were sampled using a push-net (1 mm mesh) on 11 beaches, and using a beam-trawl (4 mm mesh) on a subset of 8 beaches. On each beach, the density of detached macroalgae in the water column was quantified, together with a suite of physico-chemical beach characteristics. Push-net samples principally comprised omnivorous and detritivorous crustaceans such as gammarid amphipods, mysids and valviferan isopods, which have limited swimming abilities and reside inshore year-round. Beam-trawl fauna were mainly carnivorous decapods and fish, which undergo seasonal inshore-offshore migrations to utilize sandy beaches as nursery habitats. Linear models predicted increases of 11% (95% CI: 3.5-19%) and 2.4% (95% CI: 0.7-4.2%) in the density of push-net and beam-trawl fauna, respectively, with a 1 ℓ.100 m-3 increase in detached macroalgae. This suggests that detached macroalgae is more important in the provision of food and shelter to small, weak-swimming detritivores/omnivores than to larger and more mobile predators. The densities of large predators were mostly explained by physical beach characteristics, which overshadowed the role of macroalgae. Maximum abundances of decapods and fish were found on wide, flat beaches with low wave heights. Large accumulations of macroalgae may inhibit the foraging efficiencies of

  20. Effective bioassays for evaluating boxwood blight (Calonectria pseudonaviculata) susceptibility using detached stem inoculations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two simple and rapid in vitro bioassays using detached stems were developed for evaluating the susceptibility of boxwood genotypes to the blight disease caused by Calonectria pseudonaviculata. Individual leaves were inoculated on detached stems or entire detached stems were sprayed to assess suscept...

  1. A High Conductance Detachable Heat Switch for ADRs

    NASA Astrophysics Data System (ADS)

    Tai, C. Y.; Wong, Y.; Rodenbush, A. J.; Joshi, C. H.; Shirron, P. J.

    2004-06-01

    Adiabatic Demagnetization Refrigerators (ADRs) are being increasingly considered for instrumentation and detector cooling on space missions such as Constellation-X. A multistage ADR is presently under development to operate between 6 K and the detector temperature of 50 mK. Energen, Inc. has developed and demonstrated a high conductance detachable thermal link (the heat switch) for operation at sub-Kelvin temperatures using a high-force cryogenic magnetostrictive actuator. A more efficient detachable thermal link decreases the number of cooling stages, thereby reducing the weight, cost and complexity of the cooling system. This heat switch uses KelvinAll, a magnetostrictive material developed by Energen, as the active element. Unlike other magnetostrictive materials, KelvinAll operates over a broad temperature range. At cryogenic temperatures it delivers a long stroke allowing a large separation gap between the contacting surfaces when the switch is disengaged. This makes alignment and operation of the heat switch simple.

  2. Modeling detachment physics in the NSTX snowflake divertor

    NASA Astrophysics Data System (ADS)

    Meier, E. T.; Soukhanovskii, V. A.; Bell, R. E.; Diallo, A.; Kaita, R.; LeBlanc, B. P.; McLean, A. G.; Podestà, M.; Rognlien, T. D.; Scotti, F.

    2015-08-01

    The snowflake divertor is a proposed technique for coping with the tokamak power exhaust problem in next-step experiments and eventually reactors, where extreme power fluxes to material surfaces represent a leading technological and physics challenge. In lithium-conditioned National Spherical Torus Experiment (NSTX) discharges, application of the snowflake divertor typically induced partial outer divertor detachment and severalfold heat flux reduction. UEDGE is used to analyze and compare conventional and snowflake divertor configurations in NSTX. Matching experimental upstream profiles and divertor measurements in the snowflake requires target recycling of 0.97 vs. 0.91 in the conventional case, implying partial saturation of the lithium-based pumping mechanism. Density scans are performed to analyze the mechanisms that facilitate detachment in the snowflake, revealing that increased divertor volume provides most of the parallel heat flux reduction. Also, neutral gas power loss is magnified by the increased wetted area in the snowflake, and plays a key role in generating volumetric recombination.

  3. Shape Evolution of Detached Bridgman Crystals Grown in Microgravity

    NASA Technical Reports Server (NTRS)

    Volz, M. P.; Mazuruk, K.

    2015-01-01

    Detached (or dewetted) Bridgman crystal growth defines that process in which a gap exists between a growing crystal and the crucible wall. In microgravity, the parameters that influence the existence of a stable gap are the growth angle of the solidifying crystal, the contact angle between the melt and the crucible wall, and the pressure difference across the meniscus. During actual crystal growth, the initial crystal radius will not have the precise value required for stable detached growth. Beginning with a crystal diameter that differs from stable conditions, numerical calculations are used to analyze the transient crystal growth process. Depending on the initial conditions and growth parameters, the crystal shape will either evolve towards attachment at the crucible wall, towards a stable gap width, or inwards towards eventual collapse of the meniscus. Dynamic growth stability is observed only when the sum of the growth and contact angles exceeds 180 degrees.

  4. The highly eccentric detached eclipsing binaries in ACVS and MACC

    NASA Astrophysics Data System (ADS)

    Shivvers, Isaac; Bloom, Joshua S.; Richards, Joseph W.

    2014-06-01

    Next-generation synoptic photometric surveys will yield unprecedented (for the astronomical community) volumes of data and the processes of discovery and rare-object identification are, by necessity, becoming more autonomous. Such autonomous searches can be used to find objects of interest applicable to a wide range of outstanding problems in astronomy, and in this paper we present the methods and results of a largely autonomous search for highly eccentric detached eclipsing binary systems in the Machine-learned All-Sky Automated Survey Classification Catalog. 106 detached eclipsing binaries with eccentricities of e ≳ 0.1 are presented, most of which are identified here for the first time. We also present new radial-velocity curves and absolute parameters for six of those systems with the long-term goal of increasing the number of highly eccentric systems with orbital solutions, thereby facilitating further studies of the tidal circularization process in binary stars.

  5. Intellectual property rights and detached human body parts.

    PubMed

    Pila, Justine

    2014-01-01

    This paper responds to an invitation by the editors to consider whether the intellectual property (IP) regime suggests an appropriate model for protecting interests in detached human body parts. It begins by outlining the extent of existing IP protection for body parts in Europe, and the relevant strengths and weaknesses of the patent system in that regard. It then considers two further species of IP right of less obvious relevance. The first are the statutory rights of ownership conferred by domestic UK law in respect of employee inventions, and the second are the economic and moral rights recognised by European and international law in respect of authorial works. In the argument made, both of these species of IP right may suggest more appropriate models of sui generis protection for detached human body parts than patent rights because of their capacity better to accommodate the relevant public and private interests in respect of the same. PMID:22844029

  6. Abrupt tectonics and rapid slab detachment with grain damage.

    PubMed

    Bercovici, David; Schubert, Gerald; Ricard, Yanick

    2015-02-01

    A simple model for necking and detachment of subducting slabs is developed to include the coupling between grain-sensitive rheology and grain-size evolution with damage. Necking is triggered by thickened buoyant crust entrained into a subduction zone, in which case grain damage accelerates necking and allows for relatively rapid slab detachment, i.e., within 1 My, depending on the size of the crustal plug. Thick continental crustal plugs can cause rapid necking while smaller plugs characteristic of ocean plateaux cause slower necking; oceanic lithosphere with normal or slightly thickened crust subducts without necking. The model potentially explains how large plateaux or continental crust drawn into subduction zones can cause slab loss and rapid changes in plate motion and/or induce abrupt continental rebound. PMID:25605890

  7. The Role of Pericyte Detachment in Vascular Rarefaction

    PubMed Central

    Schrimpf, Claudia; Teebken, Omke E.; Wilhelmi, Mathias; Duffield, Jeremy S.

    2015-01-01

    Background Pericytes surround endothelial cells at the perivascular interface. Signaling between endothelial cells and pericytes is crucial for capillary homeostasis, as pericytes stabilize vessels and regulate many microvascular functions. Recently it has been shown that pericytes are able to detach from the vascular wall and contribute to fibrosis by becoming scar-forming myofibroblasts in many organs including the kidney. At the same time, the loss of pericytes within the perivascular compartment results in vulnerable capillaries which are prone to instability, pathological angiogenesis, and, ultimately, rarefaction. Aims This review will give an overview of pericyte-endothelial cell interactions, summarize the signaling pathways that have been identified to be involved in pericyte detachment from the vascular wall, and present pathological endothelial responses in the context of disease of the kidney. PMID:25195856

  8. Aerosols optical propertites in Titan's Detached Haze Layer

    NASA Astrophysics Data System (ADS)

    Seignovert, Benoît; Rannou, Pascal; Lavvas, Panayotis; Cours, Thibaud; West, Robert A.

    2016-06-01

    Titan's Detached Haze Layer (DHL) first observed in 1983 by Rages and Pollack during the Voyager 2 [1] is a consistent spherical haze feature surrounding Titan's upper atmosphere and detached from the main haze. Since 2005, the Imaging Science Subsystem (ISS) instrument on board the Cassini mission performs a continuous survey of the Titan's atmosphere and confirmed its persistence at 500 km up to the equinox (2009) before its drop and disappearance in 2012 [2]. Previous analyses showed, that this layer corresponds to the transition area between small spherical aerosols and large fractal aggregates and play a key role in the aerosols formation in Titan's atmosphere [3-5]. In this study we perform UV photometric analyses on ISS observations taken from 2005 to 2007 based on radiative transfer inversion to retrieve aerosols particles properties in the DHL (bulk and monomer size, fractal dimension and local density).

  9. Abrupt tectonics and rapid slab detachment with grain damage

    PubMed Central

    Bercovici, David; Schubert, Gerald; Ricard, Yanick

    2015-01-01

    A simple model for necking and detachment of subducting slabs is developed to include the coupling between grain-sensitive rheology and grain-size evolution with damage. Necking is triggered by thickened buoyant crust entrained into a subduction zone, in which case grain damage accelerates necking and allows for relatively rapid slab detachment, i.e., within 1 My, depending on the size of the crustal plug. Thick continental crustal plugs can cause rapid necking while smaller plugs characteristic of ocean plateaux cause slower necking; oceanic lithosphere with normal or slightly thickened crust subducts without necking. The model potentially explains how large plateaux or continental crust drawn into subduction zones can cause slab loss and rapid changes in plate motion and/or induce abrupt continental rebound. PMID:25605890

  10. [Treatment of serous macular retinal detachment with antihistamines].

    PubMed

    Kirschfeld, K

    2015-01-01

    The etiology of retinal detachment in central serous retinopathy (CSR) is unknown; however, three facts are generally accepted: (1) the serous exudate which raises the layers of the receptors/pigment epithelium is formed due to hyperpermeability in the choriocapillaries, (2) patients frequently suffer from headaches and (3) stress promotes the incidence of CSR. A high blood plasma histamine concentration can cause the abovementioned symptoms which suggests that histamine might provoke CSR. Within 1 week after administration of the antihistamine loratadin a considerable reduction in the retinal exudate and restoration of vision were observed. This supports the hypothesis that histamine could be involved in the process of retinal detachment. Further investigations and large scale clinical trials should clarify if this hypothesis can be proved or disproved and whether antihistamines can be used for age-related macular degeneration (AMD). PMID:25278347

  11. Heat and detachment in core-complex extension

    NASA Technical Reports Server (NTRS)

    Lucchitta, I.

    1985-01-01

    It is proposed here that the Miocene to Recent structural and volcanic features of the Basin and Range Province can be explained by a single thermotectonic process acting through time. This process consists of a thermal pulse resulting in a high-temperature regime that includes a steep thermal front moving first up toward the topographic surface, then down owing to cooling induced by a combination of convection and conduction. Within the front is a condition defining a critical surface that separates brittle from ductile behavior, and is marked by a nearly horizonal detachment fault. The most prominent and structurally highest position of the detachment results from interaction between the critical surface and a hydrothermal system near the topographic surface. These various features can be superposed on older ones through thermal remobilization or structural reactivation.

  12. Evaluation of metal trace detachment from dosing pumps using PIXE

    NASA Astrophysics Data System (ADS)

    Lozano, Omar; Mejia, Jorge; Laloy, Julie; Alpan, Lütfiye; Toussaint, Olivier; Dogné, Jean-Michel; Lucas, Stéphane

    2014-07-01

    Metal trace detachment evaluation is essential for instruments destined for pharmaceutical applications, such as pumps. Particle-Induced X-ray Emission (PIXE) was used to determine and quantify metal traces originated from stainless steel and ceramic dosing pumps. Metal traces were quantified from either distilled water samples or cellulose filters in two tests: a short-term test of 16 h mimicking a daily cycle of a dosing pump for industrial applications, and a long-term test of 9 days evaluating the pump wearing. The main result is that ceramic dosing pumps present lower metal detachment than stainless steel counterparts. Traces of Si and Al were found originating from pieces around the pumps (pipes and joints).

  13. Attachment/detachment hysteresis of fiber-based magnetic grabbers.

    PubMed

    Gu, Yu; Kornev, Konstantin G

    2014-04-28

    We developed an experimental protocol to analyze the behaviour of a model fiber-based magnetic grabber. A fiber is vertically suspended and fixed to the substrate by its upper end. A magnetic droplet is attached to the free end of the fiber and when a permanent magnet approaches the droplet, the fiber is forced to bow and finally jumps to the magnet. It appears that one can flex the micro-fibers by very small micro or even nano-Newton forces. Using this setup, we discovered a hysteresis of fiber attachment/detachment: the pathway of the fiber jumping to and off the magnet depends on the distance between the magnet and the clamped end. This phenomenon was successfully explained by the Euler-Benoulli model of an elastic beam. The observed hysteresis of fiber attachment/detachment was attributed to the multiple equilibrium configurations of the fiber tip placed in a dipole-type magnetic field. PMID:24668160

  14. Detached cataclysmic variables are crossing the orbital period gap

    NASA Astrophysics Data System (ADS)

    Zorotovic, M.; Schreiber, M. R.; Parsons, S. G.; Gänsicke, B. T.; Hardy, A.; Agurto-Gangas, C.; Nebot Gómez-Morán, A.; Rebassa-Mansergas, A.; Schwope, A. D.

    2016-04-01

    A central hypothesis in the theory of cataclysmic variable (CV) evolution is the need to explain the observed lack of accreting systems in the ≃2-3 h orbital period range, known as the period gap. The standard model, disrupted magnetic braking (DMB), reproduces the gap by postulating that CVs transform into inconspicuous detached white dwarf (WD) plus main sequence systems, which no longer resemble CVs. However, observational evidence for this standard model is currently indirect and thus this scenario has attracted some criticism throughout the last decades. Here, we perform a simple but exceptionally strong test of the existence of detached CVs (dCVs). If the theory is correct, dCVs should produce a peak in the orbital period distribution of detached close binaries consisting of a WD and an M4-M6 secondary star. We measured six new periods which brings the sample of such binaries with known periods below 10 h to 52 systems. An increase of systems in the ≃2-3 h orbital period range is observed. Comparing this result with binary population models, we find that the observed peak cannot be reproduced by post-common envelope binaries (PCEBs) alone and that the existence of dCVs is needed to reproduce the observations. Also, the WD mass distribution in the gap shows evidence of two populations in this period range, i.e. PCEBs and more massive dCVs, which is not observed at longer periods. We therefore conclude that CVs are indeed crossing the gap as detached systems, which provides strong support for the DMB theory.

  15. A Promising Adjuvant to Detachable Coils for Cavernous Packing: Onyx

    PubMed Central

    Lv, X.; Jiang, C.; Li, Y.; Wu, Z.

    2009-01-01

    Summary Transvenous embolization of cavernous dural arteriovenous fistulae (CDAVFs) with Onyx has recently been reported. This study was undertaken to assess the value of Onyx in transvenous treatment of CDAVFs. We retrospectively reviewed 18 patients who underwent transvenous embolization for CDAVFs of Barrow Type D with detachable coils and Onyx at our institution over five years. Patients were divided into two groups: group A, patients who had been treated with detachable coils; group B, patients who had been treated with a combination of detachable coils and Onyx. The approach routes, angiographic results, complications and clinical outcome were assessed for both groups. Eighteen patients with CDAVFs of Barrow Type D were treated: nine women and nine men; mean age was 41.9 years. Eleven patients treated by 19 procedures of transvenous coiling belonged to group A. Seven patients treated by eight procedures of transvenous Onyx injection belonged to group B. The periprocedural complication rate associated with coiling for both groups was 18.2% vs 16.7% with Onyx. The duration of the procedure in both groups was 6.77±2.49 hours vs 3.75±1.63 hours with coiling vs Onyx, and the cost of Onyx was cheaper than coils. An excellent outcome was achieved in both groups: 90.9% vs 100% (group A vs group B). Our results associated with both modalities of CDAVFs treatment with clinical outcome show that transvenous embolization with Onyx is a safe alternative to detachable coils in the treatment of CDAVFs. However, more cases need to be evaluated. PMID:20465891

  16. Aetiology and management of the 'detached' rectus muscle.

    PubMed Central

    MacEwen, C J; Lee, J P; Fells, P

    1992-01-01

    The clinical features and management of 17 cases of detached extraocular muscles are described. They are classified into four groups: (1) the muscle which is cut and lost during squint surgery, (2) the muscle which breaks during squint surgery, (3) the muscle which slips following squint surgery, and (4) the muscle which is damaged during facial or orbital trauma. The prognosis for group 1 is poor whereas groups 2-4 have a good chance of successful muscle relocation. Images PMID:1540554

  17. Light scattering by coccoliths detached from Emiliania huxleyi.

    PubMed

    Gordon, Howard R; Smyth, Timothy J; Balch, William M; Boynton, G Chris; Tarran, Glen A

    2009-11-01

    We used in situ radiance/irradiance profiles to retrieve profiles of the spectral backscattering coefficient for all particles in an E. huxleyi coccolithophore bloom off the coast of Plymouth, UK. At high detached coccolith concentrations the spectra of backscattering all showed a minimum near approximately 550 to 600 nm. Using flow cytometry estimates of the detached coccolith concentration, and assuming all of the backscattering (over and above the backscattering by the water itself) was due to detached coccoliths, we determined the upper limit of the backscattering cross section (sigma(b)) of individual coccoliths to be 0.123+/-0.039 microm(2)/coccolith at 500 nm. Physical models of detached coccoliths were then developed and the discrete dipole approximation was used to compute their average backscattering cross section in random orientation. The result was 0.092 microm(2) at 500 nm, with the computed sigma(b) displaying a spectral shape similar to the measurements, but with less apparent increase in backscattering toward the red. When sigma(b) is computed on a per mole of calcite, rather than a per coccolith basis, it agreed reasonably well with that determined for acid-labile backscattering at 632 nm averaged over several species of cultured calcifying algae. Intact coccolithophore cells were taken into account by arguing that coccoliths attached to coccolithophore cells (forming a "coccosphere") backscatter in a manner similar to free coccoliths in random orientation. Estimating the number of coccoliths per coccosphere and using the observed number of coccolithophore cells resulted is an apparent backscattering cross section at 500 nm of 0.114+/-0.013 microm(2)/coccolith, in satisfactory agreement with the measured backscattering. PMID:19881674

  18. Antimicrobials Influence Bond Stiffness and Detachment of Oral Bacteria.

    PubMed

    Song, L; Hou, J; van der Mei, H C; Veeregowda, D H; Busscher, H J; Sjollema, J

    2016-07-01

    Oral biofilm can never be fully removed by oral hygiene measures. Biofilm left behind after brushing is often left behind on the same sites and exposed multiple times to antimicrobials from toothpastes and mouthrinses, after which removal becomes increasingly difficult. On the basis of this observation, we hypothesize that oral bacteria adhering to salivary conditioning films become more difficult to remove after adsorption of antimicrobials due to stiffening of their adhesive bond. To verify this hypothesis, bacteria adhering to bare and saliva-coated glass were exposed to 3 different mouthrinses, containing chlorhexidine-digluconate, cetylpyridinium-chloride, or amine-fluoride, after which bacterial vibration spectroscopy was carried out or a liquid-air interface was passed over the adhering bacteria to stimulate their detachment. Brownian motion-induced nanoscopic vibration amplitudes of 4 oral streptococcal strains, reflecting their bond stiffness, decreased after exposure to mouthrinses. Concurrently, the percentage detachment of adhering bacteria upon the passage of a liquid-air interface decreased after exposure to mouthrinses. A buffer control left both vibration amplitudes and detachment percentages unaffected. Exposure to either of the selected mouthrinses yielded more positively charged bacteria by particulate microelectrophoresis, suggesting antimicrobial adsorption to bacterial cell surface components. To rule out that exposure of adhering bacteria to the mouthrinses stimulated polysaccharide production with an impact on their detachment, Fourier transform infrared spectroscopy was carried out on bacteria adhering to an internal reflection element, prior to and after exposure to the mouthrinses. Infrared absorption band areas indicated no significant change in amount of polysaccharides after exposure of adhering bacteria to mouthrinses, but wave number shifts demonstrated stiffening of polysaccharides in the bond, as a result of antimicrobial

  19. A rare case of traumatic posterior phacocele with retinal detachment

    PubMed Central

    Sindal, Manavi D; Mourya, Deepesh

    2016-01-01

    Dislocation of crystalline lens into the anterior subconjunctival or subtenon's space is a rare but known complication of blunt trauma. Dislocation into the posterior subtenon's space is even rarer and can be associated with a complication such as occult scleral tear and retinal detachment. We report a case of traumatic posterior subtenon's dislocation of crystalline lens after blunt trauma and its successful surgical management. PMID:26953031

  20. Multiples Among Detached Eclipsing Binaries from the ASAS Catalog

    NASA Astrophysics Data System (ADS)

    Hełminiak, K. G.; Konacki, M.; Ratajczak, M.; Jordán, A.; Espinoza, N.; Brahm, R.; Kambe, E.; Ukita, N.

    2015-07-01

    We have been conducting a spectroscopic survey of detached eclipsing binaries (DEBs) from the All-Sky Automated Survey (ASAS) database for more than three years. Thousands of high-resolution spectra of >300 systems have been secured, and used for radial velocity measurements and spectral analysis. We have found a zoo of multiple systems in our sample, such as spectroscopic triples and quadruples, visual binaries with eclipsing components, and circumbinary low-mass companions, including sub-stellar-mass candidates.

  1. Detachable connection for a nuclear reactor fuel assembly

    DOEpatents

    Christiansen, David W.; Karnesky, Richard A.

    1986-01-01

    A locking connection for releasably attaching a handling socket to the duct tube of a fuel assembly for a nuclear reactor. The connection comprises a load pad housing mechanically attached to the duct tube and a handling socket threadably secured within the housing. A retaining ring is interposed between the housing and the handling socket and is formed with a projection and depression engageable within a cavity and groove of the housing and handling socket, respectively, to form a detachable interlocked connection assembly.

  2. Detachable connection for a nuclear reactor fuel assembly

    DOEpatents

    Christiansen, D.W.; Karnesky, R.A.

    1983-08-29

    A locking connection for releasably attaching a handling socket to the duct tube of a fuel assembly for a nuclear reactor. The connection comprises a load pad housing mechanically attached to the duct tube and a handling socket threadably secured within the housing. A retaining ring is interposed between the housing and the handling socket and is formed with a projection and depression engagable within a cavity and groove of the housing and handling socket, respectively, to form a detachable interlocked connection assembly.

  3. Retinal Detachment in Down Syndrome: Characteristics and Surgical Outcomes

    PubMed Central

    AlAhmadi, Badr O.; Alsulaiman, Sulaiman M.; Arevalo, J. Fernando

    2016-01-01

    Purpose. To determine the functional and anatomic outcomes of rhegmatogenous retinal detachment (RRD) surgery in patients with Down syndrome. Methods. A retrospective chart review was performed of patients with Down syndrome who had undergone surgery for RRD at King Khalid Eye Specialist Hospital between 1995 and 2014. Results. A total of 245 patients with Down syndrome were evaluated during the study period. Eighteen eyes of 15 patients (6.1%) with RRD were identified. Three out of 15 patients (20%) presented with bilateral retinal detachment. All eyes presented with macula off retinal detachment. The retina was successfully reattached in 16/18 (88.8%) eyes after a mean follow-up of 48 months. The final postoperative visual acuity ranged from light perception to 20/125 (median: hand motion) (11/18 eyes). Conclusions. The anatomic success rate of retinal reattachment surgery in patients with Down syndrome is comparable to the general population. Patients with Down syndrome should undergo regular ophthalmic examinations for early diagnosis. Despite late diagnosis and the presence of proliferative vitreoretinopathy (PVR) in some patients, favorable anatomical outcomes can be achieved. PMID:27123341

  4. Characteristics of rhegmatogenous retinal detachment in pseudophakic and phakic eyes

    PubMed Central

    Mahroo, O AR; Dybowski, R; Wong, R; Williamson, T H

    2012-01-01

    Aims To investigate whether pseudophakic and phakic rhegmatogenous retinal detachment (RRD) patterns differ. Methods Retrospective review of electronic database of patients, aged 50 years or over, presenting to our vitreoretinal service. Data included baseline characteristics, digital drawings, and outcomes. Retinal drawings were analysed in a masked fashion for site, size, and number of retinal breaks. Comparisons were made between the following groups and subgroups: pseudophakic eyes, phakic eyes, phakic eyes with cataract, and phakic eyes without cataract. Results Of 500 eyes included, 146 were pseudophakic; 177 of the phakic eyes had cataract. The following were significant by univariate analysis: pseudophakic patients were older than phakic patients in general, but the same age as patients with cataract; in the pseudophakic group, there were lower proportions of females and of patients presenting with vitreous haemorrhage or with large or superotemporal breaks; higher proportions of pseudophakic eyes had small breaks and inferonasal breaks. Some differences remained significant when comparing pseudophakia eyes with cataract. Multivariate analysis comparing pseudophakia with phakia confirmed a lower chance in pseudophakia of large breaks, vitreous haemorrhage and superotemporal breaks, but higher chance of detached inferior breaks. Some variables were age dependent. Conclusion Differences were found between pseudophakic and phakic RRD patterns. These suggest special pathogenetic mechanisms in pseudophakic retinal detachment, which could help explain increased incidences of RRD after cataract surgery. PMID:22678050

  5. Physics of Coanda jet detachment at high-pressure ratio

    NASA Astrophysics Data System (ADS)

    Cornelius, Kenneth C.; Lucius, Gerald A.

    1994-05-01

    Experimental measurements of surface pressure for an underexpanded two-dimensional supersonic Coanda flow with static conditions exterior to the jet flow was obtained for a fixed slot height to a radius ratio of 0.04. The data demonstrate that an oblique shock forms near the jet exit plane which vectors the jet flow from the curved surface at a pressure ratio of 7.6. The jet detachment occurs at a pressure ratio which is a function of the ratio of slot height to cylinder radius. An increase in the pressure ratio to 11.5 before jet detachment has been demonstrated by the translation of the upper wall providing for a converging-diverging geometry. The physics of the Coanda expansion and the jet detachment are qualitatively described using an optical schlieren system. A compressible inviscid model was derived analytically to demonstrate the variation in Mach number and surface pressure as a function of the geometric parameters with increasing pressure ratio.

  6. Retinal Detachment in Down Syndrome: Characteristics and Surgical Outcomes.

    PubMed

    AlAhmadi, Badr O; Alsulaiman, Sulaiman M; Arevalo, J Fernando

    2016-01-01

    Purpose. To determine the functional and anatomic outcomes of rhegmatogenous retinal detachment (RRD) surgery in patients with Down syndrome. Methods. A retrospective chart review was performed of patients with Down syndrome who had undergone surgery for RRD at King Khalid Eye Specialist Hospital between 1995 and 2014. Results. A total of 245 patients with Down syndrome were evaluated during the study period. Eighteen eyes of 15 patients (6.1%) with RRD were identified. Three out of 15 patients (20%) presented with bilateral retinal detachment. All eyes presented with macula off retinal detachment. The retina was successfully reattached in 16/18 (88.8%) eyes after a mean follow-up of 48 months. The final postoperative visual acuity ranged from light perception to 20/125 (median: hand motion) (11/18 eyes). Conclusions. The anatomic success rate of retinal reattachment surgery in patients with Down syndrome is comparable to the general population. Patients with Down syndrome should undergo regular ophthalmic examinations for early diagnosis. Despite late diagnosis and the presence of proliferative vitreoretinopathy (PVR) in some patients, favorable anatomical outcomes can be achieved. PMID:27123341

  7. Farnesol induces cell detachment from established S. epidermidis biofilms.

    PubMed

    Cerca, Nuno; Gomes, Fernanda; Bento, Joana C; França, Angela; Rolo, Joana; Miragaia, Maria; Teixeira, Pilar; Oliveira, Rosário

    2013-05-01

    Antibiotic resistance is a serious problem in Staphylococcus epidermidis infections as many clinical isolates of this organism are resistant to up to eight different antibiotics. The increased resistance to conventional antibiotic therapy has lead to the search for new antimicrobial therapeutic agents. Farnesol, an essential oil found in many plants, has been shown to be active against S. epidermidis. Using a type control strain we recently described that although farnesol was not efficient at killing biofilm bacteria, a strong reduction on biofilm biomass was detected, and we hypothesize that farnesol could, somehow, induce biofilm detachment. In this report, to test our hypothesis we used 36 representative clinical strains of S. epidermidis from different geographic locations and characterized them in terms of genetic variability by multilocus sequence typing and staphylococcal chromosome cassette mec. Strains were tested for biofilm formation, and the presence of ica, bhp and aap genes was determined. Stronger biofilms had always the presence of ica operon but often co-harbored bhp and aap genes. Farnesol was then used in biofilm-forming strains, and biofilm detachment was detected in half of the strains tested. Furthermore, we also showed that farnesol inability to kill biofilm bacteria was not the result of the biofilm structure but was related to high cell density. Our results demonstrate, for the first time, that the biomass reduction previously found by us, and many other groups, is the result not of cell killing but instead is the result of biofilm detachment. PMID:23549353

  8. Retinal Detachment in Southwest Ethiopia: A Hospital Based Prospective Study

    PubMed Central

    Asaminew, Tsedeke; Gelaw, Yeshigeta; Bekele, Sisay; Solomon, Berhan

    2013-01-01

    Purpose The incidence of retinal detachment in Blacks is generally considered to be low though there are few supporting studies in Africa. This study, thus, aimed at describing the clinical profile of patients with retinal detachment in Southwest Ethiopia. Methods A hospital-based study was done on all consecutive retinal detachment patients who presented to Jimma University Hospital over six months period. A semi-structured questionnaire was used to collect patients’ sociodemographic characteristics and clinical history. Comprehensive anterior and posterior segment eye examinations were done and risk factors were sought for. Statistical tests were considered significant if P < 0.05. Results A total of 94 eyes of 80 patients (1.5%) had retinal detachment (RD) and about 69% of patients were symptomatic for over a month before presentation. The mean age was 41.4 years (SD ±16.5). Fourteen patients (17.5%) had bilateral RD. At presentation, 61 eyes (64.9%) were blind from RD and 11 (13.8%) patients were bilaterally blind from RD. Rhegmatogenous RD was seen in 55 eyes (58.5%) and tractional RD in 22 eyes (23.4%). The most common risk factors were ocular trauma (32 eyes, 34.0%), myopia (23 eyes, 24.5%), posterior uveitis (13 eyes, 13.8%) and diabetic retinopathy (9 eyes, 9.6%). Most retinal breaks (25 eyes, 43.1%) were superotemporal and horse-shoe tear was the most common (19 eyes, 20.2%). Macula was off in 77 eyes (81.9%) and 38 eyes (69.1% of RRD eyes) had grade C proliferative vitreoretinopathy (PVR). Macular status was significantly associated with PVR (P=0.011), and duration of symptoms (RR=1.25, 95%CI: 1.059-1.475, P=0.040). Conclusions A significant numbers of patients with ocular problem had retinal detachment, and nearly two third of the patients presented late. Trauma and myopia were the most important risk factors. People should be educated to improve their health seeking behavior and use eye safety precautions to prevent ocular trauma. PMID:24086614

  9. Fibronectin Binding to the Salmonella enterica Serotype Typhimurium ShdA Autotransporter Protein Is Inhibited by a Monoclonal Antibody Recognizing the A3 Repeat

    PubMed Central

    Kingsley, Robert A.; Abi Ghanem, Daad; Puebla-Osorio, Nahum; Keestra, A. Marijke; Berghman, Luc; Bäumler, Andreas J.

    2004-01-01

    ShdA is a large outer membrane protein of the autotransporter family whose passenger domain binds the extracellular matrix proteins fibronectin and collagen I, possibly by mimicking the host ligand heparin. The ShdA passenger domain consists of ∼1,500 amino acid residues that can be divided into two regions based on features of the primary amino acid sequence: an N-terminal nonrepeat region followed by a repeat region composed of two types of imperfect direct amino acid repeats, called type A and type B. The repeat region bound bovine fibronectin with an affinity similar to that for the complete ShdA passenger domain, while the nonrepeat region exhibited comparatively low fibronectin-binding activity. A number of fusion proteins containing truncated fragments of the repeat region did not bind bovine fibronectin. However, binding of the passenger domain to fibronectin was inhibited in the presence of immune serum raised to one truncated fragment of the repeat region that contained repeats A2, B8, A3, and B9. Furthermore, a monoclonal antibody that specifically recognized an epitope in a recombinant protein containing the A3 repeat inhibited binding of ShdA to fibronectin. PMID:15262930

  10. Fibronectin binding to the Salmonella enterica serotype Typhimurium ShdA autotransporter protein is inhibited by a monoclonal antibody recognizing the A3 repeat.

    PubMed

    Kingsley, Robert A; Abi Ghanem, Daad; Puebla-Osorio, Nahum; Keestra, A Marijke; Berghman, Luc; Bäumler, Andreas J

    2004-08-01

    ShdA is a large outer membrane protein of the autotransporter family whose passenger domain binds the extracellular matrix proteins fibronectin and collagen I, possibly by mimicking the host ligand heparin. The ShdA passenger domain consists of approximately 1,500 amino acid residues that can be divided into two regions based on features of the primary amino acid sequence: an N-terminal nonrepeat region followed by a repeat region composed of two types of imperfect direct amino acid repeats, called type A and type B. The repeat region bound bovine fibronectin with an affinity similar to that for the complete ShdA passenger domain, while the nonrepeat region exhibited comparatively low fibronectin-binding activity. A number of fusion proteins containing truncated fragments of the repeat region did not bind bovine fibronectin. However, binding of the passenger domain to fibronectin was inhibited in the presence of immune serum raised to one truncated fragment of the repeat region that contained repeats A2, B8, A3, and B9. Furthermore, a monoclonal antibody that specifically recognized an epitope in a recombinant protein containing the A3 repeat inhibited binding of ShdA to fibronectin. PMID:15262930