Development of a Quantitative Sandwich Enzyme-Linked Immunosorbent Assay for Detecting the MPT64 Antigen of Mycobacterium tuberculosis

PubMed Central

Ji, Mijung; Cho, Byungki; Cho, Young Shik; Park, Song-Yong; Cho, Sang-Nae

2014-01-01

Purpose Tuberculosis (TB) is a major infectious disease and is responsible for two million deaths annually. For the identification and quantitation of Mycobacterium tuberculosis (M. tuberculosis), a causative agent of TB, a sandwich enzyme-linked immunosorbent assay (ELISA) against the MPT64 protein of M. tuberculosis, an antigen marker of the M. tuberculosis complex, was developed. Materials and Methods The MPT64 protein was expressed, and anti-MPT64 monoclonal antibodies were prepared. A sandwich ELISA was established using recombinant MPT64 protein and anti-MPT64 monoclonal antibodies. The sandwich MPT64 ELISA was evaluated using reference and clinical mycobacterial strains. Results The sandwich MPT64 ELISA detected MPT64 protein from 2.1 ng/mL to 250 ng/mL (equivalent to 1.7×104 CFU/mL and 2.0×106 CFU/mL). All 389 clinical M. tuberculosis isolates tested positive in the sandwich MPT64 ELISA (sensitivity, 100%), and the assay showed no cross reactivity to any tested nontuberculous mycobacterial strain (specificity, 100%). Conclusion The sandwich MPT64 ELISA is a highly sensitive and quantitative test for MPT64 protein, which can identify M. tuberculosis. PMID:24719143

Development of a quantitative sandwich enzyme-linked immunosorbent assay for detecting the MPT64 antigen of Mycobacterium tuberculosis.

PubMed

Ji, Mijung; Cho, Byungki; Cho, Young Shik; Park, Song-Yong; Cho, Sang-Nae; Jeon, Bo-Young; Yoon, Byoung-Su

2014-05-01

Tuberculosis (TB) is a major infectious disease and is responsible for two million deaths annually. For the identification and quantitation of Mycobacterium tuberculosis (M. tuberculosis), a causative agent of TB, a sandwich enzyme-linked immunosorbent assay (ELISA) against the MPT64 protein of M. tuberculosis, an antigen marker of the M. tuberculosis complex, was developed. The MPT64 protein was expressed, and anti-MPT64 monoclonal antibodies were prepared. A sandwich ELISA was established using recombinant MPT64 protein and anti-MPT64 monoclonal antibodies. The sandwich MPT64 ELISA was evaluated using reference and clinical mycobacterial strains. The sandwich MPT64 ELISA detected MPT64 protein from 2.1 ng/mL to 250 ng/mL (equivalent to 1.7×10⁴ CFU/mL and 2.0×10⁶ CFU/mL). All 389 clinical M. tuberculosis isolates tested positive in the sandwich MPT64 ELISA (sensitivity, 100%), and the assay showed no cross reactivity to any tested nontuberculous mycobacterial strain (specificity, 100%). The sandwich MPT64 ELISA is a highly sensitive and quantitative test for MPT64 protein, which can identify M. tuberculosis.

Regulation of the mitochondrial permeability transition in kidney proximal tubules and its alteration during hypoxia-reoxygenation

PubMed Central

Feldkamp, Thorsten; Park, Jeong Soon; Pasupulati, Ratna; Amora, Daniela; Roeser, Nancy F.; Venkatachalam, M. A.

2009-01-01

Development of the mitochondrial permeability transition (MPT) can importantly contribute to lethal cell injury from both necrosis and apoptosis, but its role varies considerably with both the type of cell and type of injury, and it can be strongly opposed by the normally abundant endogenous metabolites ADP and Mg2+. To better characterize the MPT in kidney proximal tubule cells and assess its contribution to injury to them, we have refined and validated approaches to follow the process in whole kidney proximal tubules and studied its regulation in normoxic tubules and after hypoxia-reoxygenation (H/R). Physiological levels of ADP and Mg2+ greatly decreased sensitivity to the MPT. Inhibition of cyclophilin D by cyclosporine A (CsA) effectively opposed the MPT only in the presence of ADP and/or Mg2+. Nonesterified fatty acids (NEFA) had a large role in the decreased resistance to the MPT seen after H/R irrespective of the available substrate or the presence of ADP, Mg2+, or CsA, but removal of NEFA was less effective at restoring normal resistance to the MPT in the presence of electron transport complex I-dependent substrates than with succinate. The data indicate that the NEFA accumulation that occurs during both hypoxia in vitro and ischemic acute kidney injury in vivo is a critical sensitizing factor for the MPT that overcomes the antagonistic effect of endogenous metabolites and cyclophilin D inhibition, particularly in the presence of complex I-dependent substrates, which predominate in vivo. PMID:19741014

Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells

PubMed Central

Carreira, Raquel S.; Lee, Youngil; Ghochani, Mariam; Gustafsson, Åsa B.; Gottlieb, Roberta A.

2013-01-01

Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles. The mitochondrial permeability transition (MPT) results in mitochondrial depolarization and increased reactive oxygen species production, which can trigger autophagy. Therefore, we hypothesized that the MPT may have a role in signaling autophagy in cardiac cells. Mitochondrial membrane potential was lower in HL-1 cells subjected to starvation compared to cells maintained in full medium. Mitochondrial membrane potential was preserved in starved cells treated with cyclosporin A (CsA), suggesting the MPT pore is associated with starvation-induced depolarization. Starvation-induced autophagy in HL-1 cells, neonatal rat cardiomyocytes and adult mouse cardiomyocytes was inhibited by CsA. Starvation failed to induce autophagy in CypD-deficient murine cardiomyocytes, whereas in myocytes from mice overexpressing CypD the levels of autophagy were enhanced even under fed conditions. Collectively, these results demonstrate a role for CypD and the MPT in the initiation of autophagy. We also analyzed the role of the MPT in the degradation of mitochondria by biochemical analysis and electron microscopy. HL-1 cells subjected to starvation in the presence of CsA had higher levels of mitochondrial proteins (by Western blot), more mitochondria and less autophagosomes (by electron microscopy) then cells starved in the absence of CsA. Our results suggest a physiologic function for CypD and the MPT in the regulation of starvation-induced autophagy. Starvation-induced autophagy regulated by CypD and the MPT may represent a homeostatic mechanism for cellular and mitochondrial quality control. PMID:20364102

Calcium-Induced Mitochondrial Permeability Transitions: Parameters of Ca2+ Ion Interactions with Mitochondria and Effects of Oxidative Agents.

PubMed

Golovach, Nina G; Cheshchevik, Vitali T; Lapshina, Elena A; Ilyich, Tatsiana V; Zavodnik, Ilya B

2017-04-01

We evaluated the parameters of Ca 2+ -induced mitochondrial permeability transition (MPT) pore formations, Ca 2+ binding constants, stoichiometry, energy of activation, and the effect of oxidative agents, tert-butyl hydroperoxide (tBHP), and hypochlorous acid (HOCl), on Ca 2+ -mediated process in rat liver mitochondria. From the Hill plot of the dependence of MPT rate on Ca 2+ concentration, we determined the order of interaction of Ca 2+ ions with the mitochondrial sites, n = 3, and the apparent K d = 60 ± 12 µM. We also found the apparent Michaelis-Menten constant, K m , for Ca 2+ interactions with mitochondria to be equal to 75 ± 20 µM, whereas that in the presence of 300 µM tBHP was 120 ± 20 µM. Using the Arrhenius plots of the temperature dependences of apparent mitochondrial swelling rate at various Ca 2+ concentrations, we calculated the activation energy of the MPT process. ΔE a was 130 ± 20 kJ/mol at temperatures below the break point of the Arrhenius plot (30-34 °C) and 50 ± 9 kJ/mol at higher temperatures. Ca 2+ ions induced rapid mitochondrial NADH depletion and membrane depolarization. Prevention of the pore formation by cyclosporin A inhibited Ca 2+ -dependent mitochondrial depolarization and Mg 2+ ions attenuated the potential dissipation. tBHP (10-150 µM) dose-dependently enhanced the rate of MPT opening, whereas the effect of HOCl on MPT depended on the ratio of HOCl/Ca 2+ . The apparent K m of tBHP interaction with mitochondria in the swelling reaction was found to be K m = 11 ± 3 µM. The present study provides evidence that three calcium ions interact with mitochondrial site with high affinity during MPT. Ca 2+ -induced MPT pore formations due to mitochondrial membrane protein denaturation resulted in membrane potential dissipation. Oxidants with different mechanisms, tBHP and HOCl, reduced mitochondrial membrane potential and oxidized mitochondrial NADH in EDTA-free medium and had an effect on Ca 2+ -induced MPT onset.

Characterization of the binding of metoprolol tartrate and guaifenesin drugs to human serum albumin and human hemoglobin proteins by fluorescence and circular dichroism spectroscopy.

PubMed

Duman, Osman; Tunç, Sibel; Kancı Bozoğlan, Bahar

2013-07-01

The interactions of metoprolol tartrate (MPT) and guaifenesin (GF) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins at pH 7.4 were studied by fluorescence and circular dichroism (CD) spectroscopy. Drugs quenched the fluorescence spectra of HSA and HMG proteins through a static quenching mechanism. For each protein-drug system, the values of Stern-Volmer quenching constant, bimolecular quenching constant, binding constant and number of binding site on the protein molecules were determined at 288.15, 298.15, 310.15 and 318.15 K. It was found that the binding constants of HSA-MPT and HSA-GF systems were smaller than those of HMG-MPT and HMG-GF systems. For both drugs, the affinity of HMG was much higher than that of HSA. An increase in temperature caused a negative effect on the binding reactions. The number of binding site on blood proteins for MPT and GF drugs was approximately one. Thermodynamic parameters showed that MPT interacted with HSA through electrostatic attraction forces. However, hydrogen bonds and van der Waals forces were the main interaction forces in the formation of HSA-GF, HMG-MPT and HMG-GF complexes. The binding processes between protein and drug molecules were exothermic and spontaneous owing to negative ∆H and ∆G values, respectively. The values of binding distance between protein and drug molecules were calculated from Förster resonance energy transfer theory. It was found from CD analysis that the bindings of MPT and GF drugs to HSA and HMG proteins altered the secondary structure of HSA and HMG proteins.

Expression, purification, and characterization of protective MPT64 antigen protein and identification of its multimers isolated from nontoxic Mycobacterium tuberculosis H37Ra.

PubMed

Chu, Teng-Ping J; Yuann, Jeu-Ming P

2011-05-01

MPT64, a secreted protein of Mycobacterium tuberculosis (MTB), stimulates the immune reactions within cells and is a protective antigen that is lost by the bacilli Calmette-Guérin (BCG) vaccine during propagation. To minimize the toxicity caused by MTB, we used the MPT64 gene encoded by nontoxic H37Ra MTB to carry out genetic expansion via polymerase chain reaction and gene clone MPT64. The plasmid DNA encoded MPT64 was expressed at 20°C for 22 H, and a large quantity of MPT64 was obtained. In the absence of urea, MPT64 multimers with subunits being covalently connected via disulfide bonds were detected by Western blot showing strong protein-protein interactions, as evidenced by the formation of MPT64 tetramers. Finally, with urea of decreasing concentrations, we refolded MPT64 purified in the presence of urea and determined its secondary structures using circular dichroism. MPT64 was found to contain 2.2% α-helix, 50.9% β-sheet, 19.5% turn, and 27.4% random coil. The molecular weight of MPT64 was determined by a matrix-assisted laser desorption ionization-time of flight mass spectrometer and found to be 23,497 Da, very close to the theoretical molecular weight of MPT64. The results presented here provide a sound basis for future biochemical and biophysical studies of MPT64 or any other proteins encoded by nontoxic H37Ra MTB. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Insect repellents and sunscreen: implications for personal protection strategies against mosquito-borne disease.

PubMed

Webb, Cameron E; Russell, Richard C

2009-10-01

To determine the protection times provided by insect repellent and sunscreen in combined formulations against biting mosquitoes. To determine if concurrent use of repellent and sunscreen influenced protection times. Insect repellent containing comparable concentrations of N, N-diethyl-3-methylbenzamide (DEET) with and without sunscreen were tested on human skin to determine the mean protection time (MPT) against Aedes aegypti (L.) in the laboratory. Further trials were undertaken to determine the effect on MPT of sunscreen reapplication over repellent every two hours. There was no significant difference in the MPT provided by 80% DEET with (MPT+/-SE=770+/-54.8 minutes) and without (MPT+/-SE=830+/-20.2 minutes) sunscreen or 7.14% DEET with (MPT+/-SE =240+/-15.5 minutes) and 6.98% DEET without (MPT+/-SE =230+/-18.4 minutes) sunscreen. Reapplication of sunscreen resulted in a significantly lower MPT of a 17.0% DEET formulation when sunscreen was reapplied concurrently (MPT+/-SE=330+/-25.2 minutes), compared with DEET alone (MPT+/-SE =400+/-12.7 minutes). When combined in a single formulation with sunscreen, the MPT provided by both high and low concentrations of DEET is not reduced. However, if sunscreen is reapplied over insect repellent, protection times can be reduced significantly. In areas of endemic mosquito-borne disease, the reapplication of a low concentration repellent and sunscreen formulation may provide the most effective protection from biting mosquitoes while minimising the risk of overexposure to DEET.

The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections

PubMed Central

Meiß, Thorsten; Eckelt, Elke; Basler, Tina; Meens, Jochen; Heinzmann, Julia; Suwandi, Abdulhadi; Oelemann, Walter M. R.; Trenkamp, Sandra; Holst, Otto; Weiss, Siegfried; Bunk, Boyke; Spröer, Cathrin; Gerlach, Gerald-F.; Goethe, Ralph

2014-01-01

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease, a chronic granulomatous enteritis in ruminants. Furthermore, infections of humans with MAP have been reported and a possible association with Crohn's disease and diabetes type I is currently discussed. MAP owns large sequence polymorphisms (LSPs) that were exclusively found in this mycobacteria species. The relevance of these LSPs in the pathobiology of MAP is still unclear. The mptD gene (MAP3733c) of MAP belongs to a small group of functionally uncharacterized genes, which are not present in any other sequenced mycobacteria species. mptD is part of a predicted operon (mptABCDEF), encoding a putative ATP binding cassette-transporter, located on the MAP-specific LSP14. In the present study, we generated an mptD knockout strain (MAPΔmptD) by specialized transduction. In order to investigate the potential role of mptD in the host, we performed infection experiments with macrophages. By this, we observed a significantly reduced cell number of MAPΔmptD early after infection, indicating that the mutant was hampered with respect to adaptation to the early macrophage environment. This important role of mptD was supported in mouse infection experiments where MAPΔmptD was significantly attenuated after peritoneal challenge. Metabolic profiling was performed to determine the cause for the reduced virulence and identified profound metabolic disorders especially in the lipid metabolism of MAPΔmptD. Overall our data revealed the mptD gene to be an important factor for the metabolic adaptation of MAP required for persistence in the host. PMID:25177550

The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections.

PubMed

Meißner, Thorsten; Eckelt, Elke; Basler, Tina; Meens, Jochen; Heinzmann, Julia; Suwandi, Abdulhadi; Oelemann, Walter M R; Trenkamp, Sandra; Holst, Otto; Weiss, Siegfried; Bunk, Boyke; Spröer, Cathrin; Gerlach, Gerald-F; Goethe, Ralph

2014-01-01

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease, a chronic granulomatous enteritis in ruminants. Furthermore, infections of humans with MAP have been reported and a possible association with Crohn's disease and diabetes type I is currently discussed. MAP owns large sequence polymorphisms (LSPs) that were exclusively found in this mycobacteria species. The relevance of these LSPs in the pathobiology of MAP is still unclear. The mptD gene (MAP3733c) of MAP belongs to a small group of functionally uncharacterized genes, which are not present in any other sequenced mycobacteria species. mptD is part of a predicted operon (mptABCDEF), encoding a putative ATP binding cassette-transporter, located on the MAP-specific LSP14. In the present study, we generated an mptD knockout strain (MAPΔmptD) by specialized transduction. In order to investigate the potential role of mptD in the host, we performed infection experiments with macrophages. By this, we observed a significantly reduced cell number of MAPΔmptD early after infection, indicating that the mutant was hampered with respect to adaptation to the early macrophage environment. This important role of mptD was supported in mouse infection experiments where MAPΔmptD was significantly attenuated after peritoneal challenge. Metabolic profiling was performed to determine the cause for the reduced virulence and identified profound metabolic disorders especially in the lipid metabolism of MAPΔmptD. Overall our data revealed the mptD gene to be an important factor for the metabolic adaptation of MAP required for persistence in the host.

Dopamine-dependent neurotoxicity of lipopolysaccharide in substantia nigra.

PubMed

De Pablos, Rocío M; Herrera, Antonio J; Villarán, Ruth F; Cano, Josefina; Machado, Alberto

2005-03-01

Intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation, induces degeneration of dopaminergic neurons, along with an inflammatory process that features activation of microglial cells and loss of astrocytes. To test the involvement of dopamine (DA) in this degeneration induced by LPS, we treated albino Wistar rats with different concentrations of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase (TH) activity. Results showed that alpha-MPT prevented LPS-induced loss of TH immunostaining and expression of mRNA for TH and DA transporter; it also prevented substantial activation of microglial cells. Loss of the astroglial population, a marker of damage in our model, was also prevented. This protective effect resulted from inhibition of TH and the consequent decrease in DA concentration, because treatment with L-DOPA/benserazide, which bypasses TH inhibition induced by alpha-MPT, reversed the protective effect produced by this drug. These results point out the important contribution of DA to the vulnerability and degeneration of dopaminergic neurons of the substantia nigra. Knowledge about the involvement of DA in this process may lead to the possibility of new protection strategies against this important degenerative process.

MPT-51/CpG DNA vaccine protects mice against Mycobacterium tuberculosis.

PubMed

Silva, Bruna Daniella de Souza; da Silva, Ediane Batista; do Nascimento, Ivan Pereira; Dos Reis, Michelle Cristina Guerreiro; Kipnis, André; Junqueira-Kipnis, Ana Paula

2009-07-16

Tuberculosis (TB) is a severe infectious disease that kills approximately two million people worldwide every year. Because BCG protection is variable and does not protects adults, there is a great need for a new vaccine against TB that does not represent a risk for immunocompromised patients and that is also capable of protecting adult individuals. MPT-51 is a protein found in the genome of mycobacteria and binds to the fibronectin of the extracellular matrix, which may have a role in host tissue attachment and virulence. In order to test the usefulness of MPT-51 as a subunit vaccine, BALB/c were vaccinated and challenged with Mycobacterium tuberculosis. The infection of BALB/c with M. tuberculosis increased the number of IFN-gamma(+) T lymphocytes specific to MPT-51 in the spleen and lungs. Inoculation with rMPT-51/FIA and with rMPT-51/CpG DNA in non-infected BALB/c increased the amounts of IFN-gamma(+) T lymphocytes. Inoculation with rMPT-51/FIA also induced a humoral response specific to MPT-51. CFU counts of lung tissues done 60 days after infection showed a reduction of about 2 log in the bacteria load in the group of animals inoculated with rMPT-51/CpG DNA. These results make MPT-51 a valuable component to be further evaluated in the development of other subunit vaccines.

The Study of Titanium and Zirconium Ions in Water by MPT-LTQ Mass Spectrometry in Negative Mode

PubMed Central

Yang, Junqing; Zheng, Mei; Liu, Qiuju; Zhu, Meiling; Yang, Chushan; Zhang, Yan; Zhu, Zhiqiang

2017-01-01

Microwave plasma torches (MPTs) can be used as simple and low power-consumption ambient ion sources. When MPT-mass spectrometry (MPT-MS) is applied in the detection of some metal elements, the metallic ions exhibit some novel features which are significantly different with those obtained by the traditional inductively coupled plasma (ICP)-mass spectrometry (ICP-MS) and may be helpful for metal element analysis. As the representative elements of group IVA, titanium and zirconium are both of importance and value in modern industry, and they have impacts on human health. Here, we first provide a study on the complex anions of titanium and zirconium in water by using the MPT as ion source and a linear ion trap mass spectrometer (LTQ-MS). These complex anions were produced in the plasma flame by an aqueous solution flowing through the central tube of the MPT, and were introduced into the inlet of the mass spectrometry working in negative ion mode to get the feature mass spectrometric signals. Moreover, the feature fragment patterns of these ions in multi-step collision- induced dissociation processes have been explained. Under the optimized conditions, the limit of detection (LOD) using the MS2 (the second tandem mass spectrometry) procedure was estimated to be at the level of 10 μg/L for titanium and 20 μg/L for zirconium with linear dynamics ranges that cover at least two orders of magnitude, i.e., between 0–500 μg/L and 20–200 μg/L, respectively. These experimental data demonstrated that the MPT-MS is a promising and useful tool in field analysis of titanium and zirconium ions in water, and can be applied in many fields, such as environmental control, hydrogeology, and water quality inspection. In addition, MPT-MS could also be used as a supplement of ICP-MS for the rapid and on-site analysis of metal ions. PMID:28954404

The Study of Titanium and Zirconium Ions in Water by MPT-LTQ Mass Spectrometry in Negative Mode.

PubMed

Yang, Junqing; Zheng, Mei; Liu, Qiuju; Yang, Meiling Zhu Chushan; Zhang, Yan; Zhu, Zhiqiang

2017-09-26

Microwave plasma torches (MPTs) can be used as simple and low power-consumption ambient ion sources. When MPT-mass spectrometry (MPT-MS) is applied in the detection of some metal elements, the metallic ions exhibit some novel features which are significantly different with those obtained by the traditional inductively coupled plasma (ICP)-mass spectrometry (ICP-MS) and may be helpful for metal element analysis. As the representative elements of group IVA, titanium and zirconium are both of importance and value in modern industry, and they have impacts on human health. Here, we first provide a study on the complex anions of titanium and zirconium in water by using the MPT as ion source and a linear ion trap mass spectrometer (LTQ-MS). These complex anions were produced in the plasma flame by an aqueous solution flowing through the central tube of the MPT, and were introduced into the inlet of the mass spectrometry working in negative ion mode to get the feature mass spectrometric signals. Moreover, the feature fragment patterns of these ions in multi-step collision- induced dissociation processes have been explained. Under the optimized conditions, the limit of detection (LOD) using the MS² (the second tandem mass spectrometry) procedure was estimated to be at the level of 10μg/L for titanium and 20 μg/L for zirconium with linear dynamics ranges that cover at least two orders of magnitude, i.e., between 0-500 μg/L and 20-200 μg/L, respectively. These experimental data demonstrated that the MPT-MS is a promising and useful tool in field analysis of titanium and zirconium ions in water, and can be applied in many fields, such as environmental control, hydrogeology, and water quality inspection. In addition, MPT-MS could also be used as a supplement of ICP-MS for the rapid and on-site analysis of metal ions.

Flexible Mixed-Potential-Type (MPT) NO₂ Sensor Based on An Ultra-Thin Ceramic Film.

PubMed

You, Rui; Jing, Gaoshan; Yu, Hongyan; Cui, Tianhong

2017-07-29

A novel flexible mixed-potential-type (MPT) sensor was designed and fabricated for NO₂ detection from 0 to 500 ppm at 200 °C. An ultra-thin Y₂O₃-doped ZrO₂ (YSZ) ceramic film 20 µm thick was sandwiched between a heating electrode and reference/sensing electrodes. The heating electrode was fabricated by a conventional lift-off process, while the porous reference and the sensing electrodes were fabricated by a two-step patterning method using shadow masks. The sensor's sensitivity is achieved as 58.4 mV/decade at the working temperature of 200 °C, as well as a detection limit of 26.7 ppm and small response time of less than 10 s at 200 ppm. Additionally, the flexible MPT sensor demonstrates superior mechanical stability after bending over 50 times due to the mechanical stability of the YSZ ceramic film. This simply structured, but highly reliable flexible MPT NO₂ sensor may lead to wide application in the automobile industry for vehicle emission systems to reduce NO₂ emissions and improve fuel efficiency.

Flexible Mixed-Potential-Type (MPT) NO2 Sensor Based on An Ultra-Thin Ceramic Film

PubMed Central

You, Rui; Jing, Gaoshan; Yu, Hongyan; Cui, Tianhong

2017-01-01

A novel flexible mixed-potential-type (MPT) sensor was designed and fabricated for NO2 detection from 0 to 500 ppm at 200 °C. An ultra-thin Y2O3-doped ZrO2 (YSZ) ceramic film 20 µm thick was sandwiched between a heating electrode and reference/sensing electrodes. The heating electrode was fabricated by a conventional lift-off process, while the porous reference and the sensing electrodes were fabricated by a two-step patterning method using shadow masks. The sensor’s sensitivity is achieved as 58.4 mV/decade at the working temperature of 200 °C, as well as a detection limit of 26.7 ppm and small response time of less than 10 s at 200 ppm. Additionally, the flexible MPT sensor demonstrates superior mechanical stability after bending over 50 times due to the mechanical stability of the YSZ ceramic film. This simply structured, but highly reliable flexible MPT NO2 sensor may lead to wide application in the automobile industry for vehicle emission systems to reduce NO2 emissions and improve fuel efficiency. PMID:28758933

Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

PubMed Central

Morota, Saori; Chen, Li; Matsuyama, Nagahisa; Suzuki, Yoshiaki; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; Ikeda, Yukio; Uchino, Hiroyuki; Elmér, Eskil

2011-01-01

Abstract The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration. PMID:21121808

Giant Tunnel Magnetoresistance with a Single Magnetic Phase-Transition Electrode

NASA Astrophysics Data System (ADS)

Zhang, Jia; Chen, X. Z.; Song, C.; Feng, J. F.; Wei, H. X.; Lü, Jing-Tao

2018-04-01

The magnetic phase-transition tunnel-magnetoresistance (MPT-TMR) effect with a single magnetic electrode is investigated by first-principles calculations. The calculations show that the MPT-TMR of an α'-FeRh /MgO /Cu tunnel junction can be as high as hundreds of percent when the magnetic structure of α'-FeRh changes from G -type antiferromagnetic (G -AFM ) to ferromagnetic order. This type of MPT-TMR may be superior to the tunnel anisotropic magnetoresistance because of its huge magnetoresistance effect and similar structural simplicity. The main mechanism for the giant MPT-TMR can be attributed to the formation of interface resonant states at the G -AFM FeRh /MgO interface. A direct FeRh /MgO interface is found to be necessary for achieving a high MPT-TMR experimentally. Moreover, we find the α'-FeRh /MgO interface with FeRh in the ferromagnetic phase has nearly full spin polarization due to the negligible majority transmission and significantly different Fermi surface of two spin channels. Thus, it may act as a highly efficient and tunable spin injector. In addition, the electric-field-driven MPT of FeRh-based heteromagnetic nanostructures can be utilized to design various energy-efficient tunnel-junction structures and the corresponding lower-power-consumption devices. We also discuss the consequence of various junction defects on MPT-TMR. The interface oxygen layer is found to be detrimental to MPT-TMR. The sign of MPT-TMR is reversed with Rh termination due to the lack of contribution from the interface resonance states. However, the MPT-TMR may be robust against the oxygen vacancy inside of MgO and the shift of the Fermi energy. Our results will stimulate further experimental investigations of MPT-TMR and other fascinating phenomenon of FeRh-based tunnel junctions that may be promising in antiferromagnetic spintronics.

Diagnostic accuracy of metronome-paced tachypnea to detect dynamic hyperinflation.

PubMed

Lahaije, Anke J M C; Willems, Laura M; van Hees, Hieronymus W H; Dekhuijzen, P N Richard; van Helvoort, Hanneke A C; Heijdra, Yvonne F

2013-01-01

This prospective study was carried out to investigate if metronome-paced tachypnea (MPT) can serve as an accurate diagnostic tool to identify patients with chronic obstructive pulmonary disease (COPD) who are susceptible to develop dynamic hyperinflation during exercise. Commonly, this is assessed by measuring change in inspiratory capacity (IC) during cardiopulmonary exercise testing (CPET), which, however, is complex and laborious. Fifty-three patients with COPD (FEV(1) 58 ± 22%pred) and 20 age-matched healthy subjects were characterized by lung function testing and performed CPET (reference standard) and MPT. The repeatability coefficient of IC (10·2%) was used as cut-off to classify subjects as hyperinflators during CPET. Subsequently, dynamic hyperinflation was measured after MPT. With receiver operating characteristic analysis, the optimal cut-off for MPT-induced dynamic hyperinflation was determined and sensitivity and specificity of MPT to identify hyperinflators were evaluated. With 10·2% decrease in IC as cut-off for CPET-induced dynamic hyperinflation, the optimal cut-off for MPT was 11·1% decrease in IC. Using these cut-offs, MPT had a sensitivity of 85% and specificity of 85% to identify the subjects who hyperinflated during CPET. The MPT test shows good overall accuracy to identify subjects who are susceptible to develop dynamic hyperinflation during CPET. Before considering the use of MPT as a screening tool for dynamic hyperinflation in COPD, sensitivity and specificity need further evaluation. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

A 38-Kilobase Pathogenicity Island Specific for Mycobacterium avium subsp. paratuberculosis Encodes Cell Surface Proteins Expressed in the Host

PubMed Central

Stratmann, Janin; Strommenger, Birgit; Goethe, Ralph; Dohmann, Karen; Gerlach, Gerald-F.; Stevenson, Karen; Li, Ling-ling; Zhang, Qing; Kapur, Vivek; Bull, Tim J.

2004-01-01

We have used representational difference analysis to identify a novel Mycobacterium avium subsp. paratuberculosis-specific ABC transporter operon (mpt), which comprises six open reading frames designated mptA to -F and is immediately preceded by two putative Fur boxes. Functional genomics revealed that the mpt operon is flanked on one end by a fep cluster encoding proteins involved in the uptake of Fe3+ and on the other end by a sid cluster encoding non-ribosome-dependent heterocyclic siderophore synthases. Together these genes form a 38-kb M. avium subsp. paratuberculosis-specific locus flanked by an insertion sequence similar to IS1110. Expression studies using Western blot analyses showed that MptC is present in the envelope fraction of M. avium subsp. paratuberculosis. The MptD protein was shown to be surface exposed, using a specific phage (fMptD) isolated from a phage-peptide library, by differential screening of Mycobacterium smegmatis transformants. The phage fMptD-derived peptide could be used in a peptide-mediated capture PCR with milk from infected dairy herds, thereby showing surface-exposed expression of the MptD protein in the host. Together, these data suggest that the 38-kb locus constitutes an M. avium subsp. paratuberculosis pathogenicity island. PMID:14977927

Fitzmaurice Voicework Pilot Study.

PubMed

Watson, Lynn; Nayak, Sadhana

2015-11-01

A repeated-measures pilot study was used to investigate acoustic changes in the voices of participants in a Fitzmaurice Voicework (FV) teacher certification program. Maximum phonation time (MPT) was also measured. Eleven participants with no reported voice problems were studied. Pretraining and posttraining recordings were made of each participant. Measures of MPT were made, and the recordings were analyzed for jitter, shimmer, and noise-to-harmonics ratio (NHR). The measure of effect size for MPT was moderate, and there was an overall increase in MPT from pretraining to posttraining, with 70% of participants showing an increase in MPT. The measure of effect sizes for jitter, shimmer, and NHR were small, with measurements showing no significant changes from pretraining to posttraining. There were indications that FV training may have positive outcomes for actors and professional voice users, particularly in increasing MPT. Further studies with larger subject groups are needed to investigate the significance of the increase in MPT noted in this study and to test whether FV training can help to lower rates of shimmer and jitter. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy.

PubMed

Manfredini, Marco; Arginelli, Federica; Dunsby, Christopher; French, Paul; Talbot, Clifford; König, Karsten; Pellacani, Giovanni; Ponti, Giovanni; Seidenari, Stefania

2013-02-01

The aim of this study was to compare morphological aspects of basal cell carcinoma (BCC) as assessed by two different imaging methods: in vivo reflectance confocal microscopy (RCM) and multiphoton tomography with fluorescence lifetime imaging implementation (MPT-FLIM). The study comprised 16 BCCs for which a complete set of RCM and MPT-FLIM images were available. The presence of seven MPT-FLIM descriptors was evaluated. The presence of seven RCM equivalent parameters was scored in accordance to their extension. Chi-squared test with Fisher's exact test and Spearman's rank correlation coefficient were determined between MPT-FLIM scores and adjusted-RCM scores. MPT-FLIM and RCM descriptors of BCC were coupled to match the descriptors that define the same pathological structures. The comparison included: Streaming and Aligned elongated cells, Streaming with multiple directions and Double alignment, Palisading (RCM) and Palisading (MPT-FLIM), Typical tumor islands, and Cell islands surrounded by fibers, Dark silhouettes and Phantom islands, Plump bright cells and Melanophages, Vessels (RCM), and Vessels (MPT-FLIM). The parameters that were significantly correlated were Melanophages/Plump Bright Cells, Aligned elongated cells/Streaming, Double alignment/Streaming with multiple directions, and Palisading (MPT-FLIM)/Palisading (RCM). According to our data, both methods are suitable to image BCC's features. The concordance between MPT-FLIM and RCM is high, with some limitations due to the technical differences between the two devices. The hardest difficulty when comparing the images generated by the two imaging modalities is represented by their different field of view. © 2012 John Wiley & Sons A/S.

Efficacy evaluations of Mimosa pudica tannin isolate (MPT) for its anti-ophidian properties.

PubMed

Ambikabothy, Jamunaa; Ibrahim, Halijah; Ambu, Stephen; Chakravarthi, Srikumar; Awang, Khalijah; Vejayan, Jaya

2011-09-01

Evaluations of the anti-snake venom efficacy of Mimosa pudica tannin isolate (MPT) obtained from root of the plant. MPT was investigated in vitro and in vivo for its efficacy against the venom of Naja kaouthia snake. In vitro: (1) mice injected i.p. with MPT pre-incubated with Naja kaouthia venom at concentrations as low as 0.625 mg/ml showed 100% survival after a 24-h observation period. (2) In the proteomics study, mice injected with MPT pre-incubated with the Naja kaouthia venom showed down-regulation of five serum proteins. (3) In the protein-dye-binding study, the percentage of Bradford dye-protein binding showed a reduction relative to the decrease in MPT concentration used to incubate with the venom. In vivo: the results from the animal studies showed that MPT had no in vivo protection against the Naja kaouthia venom (0.875 mg/kg) in four different rescue modes and in an oral pre-treatment experiment. The study indicated the promising ability of MPT to neutralize the Naja kaouthia venom in in vitro experiments but fell short in its in vivo potential. As such, the use of Mimosa pudica (Mimosaceae) as therapeutics for snake bites is questionable as all the possible in vivo rescue studies and pre-treatment of the active constituents showed no protection against the affected mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ice-Sheet Dynamics and Millennial-Scale Climate Variability in the North Atlantic across the Middle Pleistocene Transition (Invited)

NASA Astrophysics Data System (ADS)

Hodell, D. A.; Nicholl, J.

2013-12-01

During the Middle Pleistocene Transition (MPT), the climate system evolved from a more linear response to insolation forcing in the '41-kyr world' to one that was decidedly non-linear in the '100-kyr world'. Smaller ice sheets in the early Pleistocene gave way to larger ice sheets in the late Pleistocene with an accompanying change in ice sheet dynamics. We studied Sites U1308 (49° 52.7'N, 24° 14.3'W; 3871 m) and U1304 (53° 3.4'N, 33° 31.8'W; 3024 m) in the North Atlantic to determine how ice sheet dynamics and millennial-scale climate variability evolved as glacial boundary conditions changed across the MPT. The frequency of ice-rafted detritus (IRD) in the North Atlantic was greater during glacial stages prior to 650 ka (MIS 16), reflecting more frequent crossing of an ice volume threshold when the climate system spent more time in the 'intermediate ice volume' window, resulting in persistent millennial scale variability. The rarity of Heinrich Events containing detrital carbonate and more frequent occurrence of IRD events prior to 650 ka may indicate the presence of 'low-slung, slippery ice sheets' that flowed more readily than their post-MPT counterparts (Bailey et al., 2010). Ice volume surpassed a critical threshold across the MPT that permitted ice sheets to survive boreal summer insolation maxima, thereby increasing ice volume and thickness, lengthening glacial cycles, and activating the dynamical processes responsible for Laurentide Ice Sheet instability in the region of Hudson Strait (i.e., Heinrich events). The excess ice volume during post-MPT glacial maxima provided a large, unstable reservoir of freshwater to be released to the North Atlantic during glacial terminations with the potential to perturb Atlantic Meridional Overtunring Circulation. We speculate that orbital- and millennial-scale variability co-evolved across the MPT and the interaction of processes on orbital and suborbital time scales gave rise to the changing patterns of glacial-interglacial cycles through the Quaternary. Bailey, I., Bolton, C.T., DeConto, R.M., Pollard, D., Schiebel, R. and Wilson, P.A. (2010) A low threshold for North Atlantic ice rafting from "low-slung slippery" late Pliocene ice sheets. Paleoceanography, 25, PA1212-[14pp]. (doi:10.1029/2009PA001736).

Negative Illness Perceptions are Associated with a Pro-nociceptive Modulation Profile and Augmented Pelvic Pain.

PubMed

Grinberg, Keren; Granot, Michal; Lowenstein, Lior; Abramov, Liora; Weissman-Fogel, Irit

2018-05-25

A patient's personal interpretations of a health threat or "illness perceptions" (IPs) are associated with their clinical outcomes. This study explored whether IPs are associated with pain severity and ability to modulate pain in women with chronic pelvic pain syndrome (CPPS), as well as the predictive value of IPs on Myofascial Physical Therapy (MPT) success. Illness Perceptions Questionnaire - Revised (IPQ-R), mechanical and heat pain thresholds, mechanical temporal summation (mTS), and conditioned pain modulation (CPM) were evaluated in CPPS patients (n=39) before, and 3 months after MPT. CPPS severity was obtained by the Brief Pain Inventory (BPI). Stronger perceptions of illness chronicity were correlated with less efficient CPM (r=0.488, P=0.002) and increased mechanical pain intensity (r=0.405, P=0.02). Lower perceptions of control over illness were associated with enhanced mTS (r=0.399, P=0.01). Higher BPI scores were correlated with emotional representations ("negative emotional representations") and severe consequences due to CPPS. Regression analyses revealed that negative IPs predict less efficient MPT. Cognitive representations play a unique role in CPPS expression and MPT outcomes. The interplay between negative IPs and a pro-nociceptive modulation profile, mediated by enhanced facilitatory and reduced inhibitory processes, may be involved in the manifestation of CPPS.

Distribution of Tetrahydromethanopterin-Dependent Enzymes in Methylotrophic Bacteria and Phylogeny of Methenyl Tetrahydromethanopterin Cyclohydrolases

PubMed Central

Vorholt, Julia A.; Chistoserdova, Ludmila; Stolyar, Sergei M.; Thauer, Rudolf K.; Lidstrom, Mary E.

1999-01-01

The methylotrophic proteobacterium Methylobacterium extorquens AM1 possesses tetrahydromethanopterin (H4MPT)-dependent enzymes, which are otherwise specific to methanogenic and sulfate-reducing archaea and which have been suggested to be involved in formaldehyde oxidation to CO2 in M. extorquens AM1. The distribution of H4MPT-dependent enzyme activities in cell extracts of methylotrophic bacteria from 13 different genera are reported. H4MPT-dependent activities were detected in all of the methylotrophic and methanotrophic proteobacteria tested that assimilate formaldehyde by the serine or ribulose monophosphate pathway. H4MPT-dependent activities were also found in autotrophic Xanthobacter strains. However, no H4MPT-dependent enzyme activities could be detected in other autotrophic α-proteobacteria or in gram-positive methylotrophic bacteria. Genes encoding methenyl H4MPT cyclohydrolase (mch genes) were cloned and sequenced from several proteobacteria. Bacterial and archaeal Mch sequences have roughly 35% amino acid identity and form distinct groups in phylogenetic analysis. PMID:10482517

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

Amagai, Yosuke; Tanaka, Akane; Ohmori, Keitaro

Much is known regarding participations of mast cells with innate and acquired immunity by secreting various cytokines and chemical mediators. However, details of mast cell biology still remain unclear. In this study, we successfully established a novel growth factor-independent mast cell line (MPT-1) derived from canine mast cell tumor. MPT-1 cells manifested factor-independent proliferation as floating cells containing a large amount of histamine, as well as chymase-like dog mast cell protease 3, in cytosolic granules. Particularly, MPT-1 cells expressed high-affinity IgE receptors (Fc{epsilon}RI) and wild-type c-kit receptors. Degranulation of MPT-1 cells was induced not only by stimulation with calcium ionophoremore » but also by cross-linkage of the surface IgE. Given that MPT-1 is the first mast cell line with Fc{epsilon}RI which has no c-kit mutations, MPT-1 cells may provide great contribution for investigation of IgE-mediated activation mechanisms of mast cells, leading to development of effective treatment for allergic disorders.« less

Carvedilol: relation between antioxidant activity and inhibition of the mitochondrial permeability transition.

PubMed

Oliveira, Paulo J; Esteves, Telma; Rolo, Anabela P; Monteiro, Pedro; Gonçalves, Lino; Palmeira, Carlos M; Moreno, António J

2003-01-01

The mitochondrial permeability transition (MPT) is an event related to severe oxidative stress (for example, during myocardial ischemia and reperfusion) and excessive mitochondrial calcium accumulation, also being implicated in cell death. In this study, we compared the effect of carvedilol on the cardiac MPT induced by calcium and phosphate (Ca/Pi) and calcium/carboxyatractyloside (Ca/Catr). Oxidative stress plays a major role in MPT induction by Ca/Pi, leading to the oxidation of protein thiol groups, in contrast with Ca/Catr, where such oxidation is secondary to MPT induction and is not caused by oxidative stress. Mitochondria were isolated from rat hearts and parameters related to MPT induction were evaluated (n = 5 for each inducer): mitochondrial swelling and oxidation of protein thiol groups (both measured by spectrophotometry). Using Ca/Pi, carvedilol protected mitochondria from MPT induction, particularly in its high conductance form. Its effect was demonstrated by analyzing the decrease in mitochondrial swelling amplitude. Simultaneously, we observed inhibition of protein thiol group oxidation (p < 0.001). By contrast, carvedilol did not show any protective effect with Ca/Catr. Carvedilol was only effective against the MPT when the oxidation of protein thiol groups was the cause and not the consequence of the MPT phenomenon. The results clearly show that during myocardial aggressions (ischemia and reperfusion, for example), the protective effect of carvedilol is primarily due to an antioxidant mechanism, inhibiting the production and effects of reactive oxygen species.

Micro-heterogeneity of corn hulls cellulosic fiber biopolymer studied by multiple-particle tracking (MPT)

USDA-ARS?s Scientific Manuscript database

A novel technique named multiple-particle tracking (MPT) was used to investigate the micro-structural heterogeneities of Z-trim, a zero calorie cellulosic fiber biopolymer produced from corn hulls. The Multiple-Particle Tracking (MPT) method was used in this study, which was originally described by ...

The Dirichlet-Multinomial Model for Multivariate Randomized Response Data and Small Samples

ERIC Educational Resources Information Center

Avetisyan, Marianna; Fox, Jean-Paul

2012-01-01

In survey sampling the randomized response (RR) technique can be used to obtain truthful answers to sensitive questions. Although the individual answers are masked due to the RR technique, individual (sensitive) response rates can be estimated when observing multivariate response data. The beta-binomial model for binary RR data will be generalized…

Reconstruction of the North Atlantic end-member of the thermohaline circulation across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Kim, J.; Seguí, M. J.; Yehudai, M.; Goldstein, S. L.; Pena, L. D.; Raymo, M. E.; Ford, H. L.; Haynes, L.; Farmer, J. R.; Hoenisch, B.

2016-12-01

The dominant periodicity of glacial and interglacial cycles shifted from 41 ky to 100 ky at 1.2-0.8 Ma, marking the Mid-Pleistocene Transition (MPT). Pena and Goldstein (Science, 2014) investigated changes in the Earth's global thermohaline circulation (THC), focusing on South Atlantic cores, and concluded that the THC experienced major disruptions between 950-850 ka (MIS 25 to 21), which generated the climatic conditions that intensified cold periods, prolonged their duration, and stabilized 100 ky cycles. However, knowledge of the coeval North Atlantic is key for interpreting data from the Middle and South Atlantic. We report Nd isotope ratios on Fe-Mn oxide encrusted foraminifera and fish debris from DSDP Site 607 (41.001N; 32.957W, 3427m) between 1.2-0.4 Ma, as a representative of the deep North Atlantic. Pre-MPT results (MIS 35-25) show interglacial ɛNd-values of -13.5 to -14.0, similar to today, and glacial-interglacial variability of 1 ɛNd-unit. Post-MPT results after MIS 19 also show interglacial ɛNd-values of -13.5 to -14.0, but greater glacial-interglacial variability of 2 ɛNd-units. Interglacial-to-glacial transitions throughout the core shift to higher ɛNd-values indicative of weakening THC, except for MIS 26, which is uniquely more negative than the neighboring interglacials, with ɛNd reaching -14.5. During the critical MPT interval of MIS 25-21 recognized by Pena and Goldstein (2014), and continuing beyond it through MIS 19, DSDP 607 ɛNd shows higher values of -11.5 to -12.5, like post-MPT glacials. Thus for the North Atlantic, from the point of view of ɛNd in DSDP 607, post-MPT and pre-MPT interglacials are similar, and post-MPT glacials and MPT glacials are similar. Moreover, comparison to the Pena and Goldstein (2014) South Atlantic data indicates that disruptions to North Atlantic overturning may have begun as early as MIS 27, and the recovery to the pre-MPT interglacial conditions may have been delayed beyond MIS 19.

Micro-heterogeneity of corn hulls cellulosic fiber biopolymer studied by multiple-particle tracking (MPT)

USDA-ARS?s Scientific Manuscript database

A novel technique named multiple-particle tracking (MPT) was used to investigate the micro-structural heterogeneities of Z-trim, a zero calorie cellulosic fiber biopolymer produced from corn hulls. The principle of MPT technique is to monitor the thermally driven motion of inert micro-spheres, which...

Comparing dynamic hyperinflation and associated dyspnea induced by metronome-paced tachypnea versus incremental exercise.

PubMed

Calligaro, Gregory L; Raine, Richard I; Bateman, Mary E; Bateman, Eric D; Cooper, Christopher B

2014-02-01

Dynamic hyperinflation (DH) during exercise is associated with both dyspnea and exercise limitation in COPD. Metronome-paced tachypnoea (MPT) is a simple alternative for studying DH. We compared MPT with exercise testing (XT) as methods of provoking DH, and assessed their relationship with dyspnea. We studied 24 patients with moderate COPD (FEV1 59 ± 9% predicted) after inhalation of ipratropium/salbutamol combination or placebo in a double-blind, crossover design. Inspiratory capacity (IC) was measured at baseline and after 30 seconds of MPT with breathing frequencies (fR) of 20, 30 and 40 breaths/min and metronome-defined I:E ratios of 1:1 and 1:2, in random sequence, followed by incremental cycle ergometry with interval determinations of IC. DH was defined as a decline in IC from baseline (∆IC) for both methods. Dyspnea was assessed using a Borg CR-10 scale. ∆IC during MPT was greater with higher fR and I:E ratio of 1:1 versus 1:2, and less when patients were treated with bronchodilator rather than placebo (P = 0.032). DH occurred during 19 (40%) XTs, and during 35 (73%) tests using MPT. Eleven of 18 (61%) non-congruent XTs (where DH occurred on MPT but not XT) terminated before fR of 40 breaths/min was reached. Although greater during XT, the intensity of dyspnea bore no relationship to DH during either MPT and XT. MPT at 40 breaths/min and I:E of 1:1 elicits the greatest ∆IC, and is a more sensitive method for demonstrating DH. The relationship between DH and dyspnea is complex and not determined by DH alone.

Prolene hernia system compared with mesh plug technique: a prospective study of short- to mid-term outcomes in primary groin hernia repair.

PubMed

Huang, C S; Huang, C C; Lien, H H

2005-05-01

Two types of anterior tension-free hernioplasty, prolene hernia system (PHS) repair and mesh plug technique (MPT), were introduced to Taiwan in 2001. This study compared the short- to mid-term outcomes following primary groin hernia repair with PHS and MPT. From January 2001 to December 2003, 393 patients with 426 primary groin hernias were operated on by a single surgeon using MPT (n=192) and PHS (n=234). Baseline perioperative details and follow-up information were compared. Demographic characteristics of both groups were similar. The laterality, types of anesthesia, postoperative stay, postoperative wound pain scores, wound complications and days to return to activities of daily life were equally distributed between the two groups. However, the distribution of Gilbert types in the PHS group was shifted a little to the right compared with that of the MPT group. PHS repair had longer operative time (34+/-17 vs 25+/-9 minutes, p<0.01). No recurrence was noted in both groups during the follow-up from 5 to 41 months. Chronic non-disabling groin pains were noted in 2.8% (6/218) of patients in the PHS group and 8.9% (14/175) in the MPT group (p=0.01). Our results show that both PHS and MPT repairs can be performed with short operation time, minor wound pain and quick return to activities of daily life without short- to mid-term recurrences, but postoperatively the MPT group had higher incidence of chronic non-disabling groin pain. Although the MPT is less invasive, the additional protective patch in the preperitoneal space of the PHS may provide a further safeguard against recurrences, especially for those patients with attenuated inguinal floor. Long-term follow-up is needed.

Utility of MPT64 antigen test for differentiating mycobacteria: Can correlation with liquid culture smear morphology add further value?

PubMed

Nerurkar, Vidya; Kattungal, Sushma; Bhatia, Simi

2016-01-01

Clinical presentation of Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM) infections may or may not be the same, but the treatment is always different. Hence accurate differentiation between MTBC and NTM is of utmost importance. To assess in parallel, the utility of MPT64 antigen immunochromatography assay (MPT64 ICT) and bacillary morphology on liquid culture smear, for rapid differentiation between MTBC and NTM in clinical isolates. Private sector reference laboratory, prospective. Thousand and ninety-three mycobacterial isolates, recovered using Mycobacteria Growth Indicator Tube 960 liquid culture system (BD, USA), were subjected to MPT64 ICT (Standard Diagnostics Inc., Korea), para amino nitrobenzoicacid (PNB), niacin, and nitrate reduction tests. Smears prepared from culture vials were subjected to Ziehl-Neelsen staining and observed microscopically for typical patterns (chords, single cells, etc.,). PNB, nitrate and niacin tests served as the reference method for MTBC identification. Thousand and fourteen and 79 isolates were identified as MTBC and NTM, respectively. MPT64 ICT correctly identified 955/1014 MTBC and all NTM isolates, yielding sensitivity and specificity of 94.2% and 100%, respectively. 936/1014 (92.3%) MTBC isolates revealed characteristic serpentine chording on culture smear including 56/59 MPT64 ICT negative isolates. Sensitivity and specificity of liquid culture smear were 98.1% and 82.3%, respectively. Correlation of MPT64 ICT results with liquid culture smear was useful, especially in MPT64 ICT negative isolates, where the latter could help to determine need and/or type of additional confirmatory testing. Liquid culture smear, however, lacked specificity and cannot be used as a stand alone test.

Moco biosynthesis and the ATAC acetyltransferase engage translation initiation by inhibiting latent PKR activity.

PubMed

Suganuma, Tamaki; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Workman, Jerry L

2016-02-01

Molybdenum cofactor (Moco) biosynthesis is linked to c-Jun N-terminal kinase (JNK) signaling in Drosophila through MoaE, a molybdopterin (MPT) synthase subunit that is also a component of the Ada Two A containing (ATAC) acetyltransferase complex. Here, we show that human MPT synthase and ATAC inhibited PKR, a double-stranded RNA-dependent protein kinase, to facilitate translation initiation of iron-responsive mRNA. MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α). The suppression of eIF2α phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B, which recycles eIF2-GDP to eIF2-GTP, resulting in the promotion of translation initiation. Indeed, translation of the iron storage protein, ferritin, was reduced in the absence of MPT synthase or ATAC subunits. Thus, MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

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

Qi Xinming; Cai Yan; Gong Likun

Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca{sup 2+}, AAI caused mitochondrial swelling, leakage of Ca{sup 2+}, membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelialmore » cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid.« less

Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells

PubMed Central

Ogasawara, Takashi; Kohashi, Yuko; Ikari, Jun; Taniguchi, Toshibumi; Tsuruoka, Nobuhide; Watanabe-Takano, Haruko; Fujimura, Lisa; Sakamoto, Akemi; Hatano, Masahiko; Hirata, Hirokuni; Fukushima, Yasutsugu; Fukuda, Takeshi; Kurasawa, Kazuhiro; Tatsumi, Koichiro; Tokuhisa, Takeshi; Arima, Masafumi

2018-01-01

Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. PMID:29696026

[Microcontroller temperature regulator MPT110 for drying-sterilizing cabinets].

PubMed

Kostin, N N; Gavrishchuk, V I; Zelepukin, S A; Shkulepa, V M; Zharov, E N

2002-01-01

The paper describes a MPT-110 temperature microcontroller developed by the closed joint-stock company "OPLEKS" (Orel, Russia) and the results of comparative tests performed in the @IIICC-80 drying sterilizing cabinet. The use of the MPT-110 controller is shown to improve the quality of control and to shorten the times that is taken for the cabinet to reach the preset temperature point.

Indian Ocean circulation changes over the Middle Pleistocene Transition.

NASA Astrophysics Data System (ADS)

Petrick, B.; Auer, G.; De Vleeschouwer, D.; Christensen, B. A.; Stolfi, C.; Reuning, L.; Martinez-Garcia, A.; Haug, G. H.; Bogus, K.

2017-12-01

The Mid-Pleistocene Transition (MPT; 1.4 - 0.4 Ma) represents a climatic shift towards climate cycles at a quasi-100-kyr frequency. Although, several high-resolution records covering the MPT from globally distributed archives exist, there is only sparse evidence on changes in heat exchange between the Pacific and Indian Oceans, which represents a crucial part of the global thermohaline circulation (THC). Deciphering the influence of this heat exchange via the Indonesian Throughflow (ITF) is an important step in understanding the causes of the MPT. The Leeuwin Current off Western Australia is directly influenced by the ITF and can therefore be used to reconstruct ITF variability during the MPT. Today, the Leeuwin Current is the only southward flowing eastern boundary current in the southern hemisphere. The onset of the current is unknown but is proposed to have occurred 1 Ma and was likely related to significant changes in ITF dynamics during the MPT We present the first continuous reconstruction of changes in the Leeuwin Current during the MPT using data from IODP Expedition 356 Site U1460. The site is located at 29°S in the path of the current. High sedimentation rates ( 30 cm/ka) at Site U1460 provide the opportunity for high-resolution reconstruction of the MPT. We reconstruct paleoenvironmental variability by combining XRF, organic geochemistry, ICP-MS and XRD data with shipboard data, to reconstruct Leeuwin Current and ITF variability. Initial analyses show clear indications that upwelling off Western Australia intensified during the MPT, indicated by increased primary productivity related to increased nutrient levels, from 900-600 ka. Our results also suggest that the west Australian current (WAC) strengthened during this time supplying cool eutrophic waters from the high southern latitutes to the site. This intensification of the WAC may have had major implications for the Indian Ocean current system, but also the THC at large. This seems to be coupled with increased rainfall to western Australia after 600 ka. The data suggests a major reording of local currents during the MPT.

Formaldehyde activation factor, tetrahydromethanopterin, a coenzyme of methanogenesis

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

Escalante-Semerena, J.C.; Leigh, J.A.; Rinehart, K.L. Jr.

1984-04-01

An oxygen-labile formaldehyde activation factor (FAF) was isolated in highly purified form by use of anoxic fractionation procedures. The molecular weight of FAF was determined to be 776 and that of methanopterin (MPT) 772 by fast-atom-bombardment mass spectrometry (FABMS). High-resolution FABMS measurements on MPT and FAF indicated molecular formulas of C/sub 30/H/sub 41/N/sub 6/O/sub 16/P and C/sub 30/H/sub 45/N/sub 6/O/sub 16/P, respectively. The presence of phosphorus was confirmed by 100-MHz /sup 31/P NMR. The 360-MHz /sup 1/H NMR spectrum of FAF in deuterium oxide was similar to that of MPT. A functional relationship between MPT and FAF was documented; bothmore » compounds stimulated the reductive demethylation of 2-(methylthio)ethanesulfonic acid (CH/sub 3/-S-CoM) to CH/sub 4/ when formaldehyde oxidation provided a source of electrons, and FAF replaced MPT in the CH/sub 3/-S-CoM-stimulated conversion of CO/sub 2/ to CH/sub 4/ under H/sub 2/ (the RPG effect). MPT was enzymically converted to FAF during the reduction of CH/sub 3/-S-CoM, and HCHO to CH/sub 4/ under H/sub 2/. Evidence indicates that FAF is tetrahydromethanopterin. 14 references, 8 figures.« less

Biocompatibility of GaSb thin films grown by RF magnetron sputtering

NASA Astrophysics Data System (ADS)

Nishimoto, Naoki; Fujihara, Junko; Yoshino, Katsumi

2017-07-01

GaSb may be suitable for biological applications, such as cellular sensors and bio-medical instrumentation because of its low toxicity compared with As (III) compounds and its band gap energy. Therefore, the biocompatibility and the film properties under physiological conditions were investigated for GaSb thin films with or without a surface coating. GaSb thin films were grown on quartz substrates by RF magnetron sputtering, and then coated with (3-mercaptopropyl) trimethoxysilane (MPT). The electrical properties, surface morphology, and crystal structure of the GaSb thin film were unaffected by the MPT coating. The cell viability assay suggested that MPT-coated GaSb thin films are biocompatible. Bare GaSb was particularly unstable in pH9 buffer. Ga elution was prevented by the MPT coating, although the Ga concentration in the pH 9 buffer was higher than that in the other solutions. The surface morphology and crystal structure were not changed by exposure to the solutions, except for the pH 9 buffer, and the thin film properties of MPT-coated GaSb exposed to distilled water and H2O2 in saline were maintained. These results indicate that MPT-coated GaSb thin films are biocompatible and could be used for temporary biomedical devices.

The involvement of mitochondrial phosphate transporter in accelerating bud dormancy release during chilling treatment of tree peony (Paeonia suffruticosa).

PubMed

Huang, Xin; Zhu, Wei; Dai, Silan; Gai, Shupeng; Zheng, Guosheng; Zheng, Chengchao

2008-09-01

A cDNA clone was isolated from tree peony (Paeonia suffruticosa) subtractive cDNA library of burst buds and characterized with regard to its sequence, expression in response to chilling treatment during the release of bud dormancy, and its function in transgenic Arabidopsis thaliana. The clone, designated as PsMPT, contains 1,615 nucleotides with an open reading frame of 1,119 nucleotides, and the deduced amino acid sequence shows high homology with mitochondrial phosphate transporters (MPTs) from various organisms. The mRNA accumulation of PsMPT in tree peony was strongly induced by chilling treatment during the release of bud dormancy. When the treated plants were transferred to normal growth conditions, the level of PsMPT transcripts induced by sufficient chilling could be maintained high, whereas that induced by insufficient chilling decreased sharply. The transgenic Arabidopsis plants that overexpress PsMPT showed rapid growth and earlier flowering than wild-type plants. ATP contents in the transgenic plants were much higher than that in wild-type plants through various developmental stages. Together, these results suggest that the product of PsMPT is a MPT and might play an important role during the release of bud dormancy in tree peony.

Age-Related Differences of Maximum Phonation Time in Patients after Cardiac Surgery

PubMed Central

Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-01-01

Background and aims: Maximum phonation time (MPT), which is related to respiratory function, is widely used to evaluate maximum vocal capabilities, because its use is non-invasive, quick, and inexpensive. We aimed to examine differences in MPT by age, following recovery phase II cardiac rehabilitation (CR). Methods: This longitudinal observational study assessed 50 consecutive cardiac patients who were divided into the middle-aged group (<65 years, n = 29) and older-aged group (≥65 years, n = 21). MPTs were measured at 1 and 3 months after cardiac surgery, and were compared. Results: The duration of MPT increased more significantly from month 1 to month 3 in the middle-aged group (19.2 ± 7.8 to 27.1 ± 11.6 s, p < 0.001) than in the older-aged group (12.6 ± 3.5 to 17.9 ± 6.0 s, p < 0.001). However, no statistically significant difference occurred in the % change of MPT from 1 month to 3 months after cardiac surgery between the middle-aged group and older-aged group, respectively (41.1% vs. 42.1%). In addition, there were no significant interactions of MPT in the two groups for 1 versus 3 months (F = 1.65, p = 0.20). Conclusion: Following phase II, CR improved MPT for all cardiac surgery patients. PMID:29267218

Age-Related Differences of Maximum Phonation Time in Patients after Cardiac Surgery.

PubMed

Izawa, Kazuhiro P; Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-12-21

Background and aims: Maximum phonation time (MPT), which is related to respiratory function, is widely used to evaluate maximum vocal capabilities, because its use is non-invasive, quick, and inexpensive. We aimed to examine differences in MPT by age, following recovery phase II cardiac rehabilitation (CR). Methods: This longitudinal observational study assessed 50 consecutive cardiac patients who were divided into the middle-aged group (<65 years, n = 29) and older-aged group (≥65 years, n = 21). MPTs were measured at 1 and 3 months after cardiac surgery, and were compared. Results: The duration of MPT increased more significantly from month 1 to month 3 in the middle-aged group (19.2 ± 7.8 to 27.1 ± 11.6 s, p < 0.001) than in the older-aged group (12.6 ± 3.5 to 17.9 ± 6.0 s, p < 0.001). However, no statistically significant difference occurred in the % change of MPT from 1 month to 3 months after cardiac surgery between the middle-aged group and older-aged group, respectively (41.1% vs. 42.1%). In addition, there were no significant interactions of MPT in the two groups for 1 versus 3 months (F = 1.65, p = 0.20). Conclusion: Following phase II, CR improved MPT for all cardiac surgery patients.

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion

PubMed Central

Asemu, Girma; O'Connell, Kelly A.; Cox, James W.; Dabkowski, Erinne R.; Xu, Wenhong; Ribeiro, Rogerio F.; Shekar, Kadambari C.; Hecker, Peter A.; Rastogi, Sharad; Sabbah, Hani N.; Hoppel, Charles L.

2013-01-01

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion. MPT was assessed in SSM and IFM by Ca2+ retention and swelling. Healthy young and old beagles had similar mitochondrial structure, respiratory function, and Ca2+-induced MPT within SSM and IFM subpopulations. On the other hand, oxidative capacity and resistance to Ca2+-induced MPT were significantly greater in IFM compared with SSM in all groups. Old beagles treated with aldosterone had greater LV wall thickness and worse diastolic filling but normal LV chamber volume and systolic function. Treatment with aldosterone did not alter mitochondrial respiratory function but accelerated Ca2+-induced MPT in SSM, but not IFM, compared with healthy old and young beagles. In conclusion, in a large animal model, oxidative capacity and resistance to MPT were greater in IFM than in SSM. Furthermore, aldosterone infusion increased susceptibility to MPT in SSM, but not IFM. Together this suggests that SSM are less resilient to acute stress than IFM in the healthy heart and are more susceptible to the development of pathology with chronic stress. PMID:23241318

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion.

PubMed

Asemu, Girma; O'Connell, Kelly A; Cox, James W; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hecker, Peter A; Rastogi, Sharad; Sabbah, Hani N; Hoppel, Charles L; Stanley, William C

2013-02-15

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion. MPT was assessed in SSM and IFM by Ca(2+) retention and swelling. Healthy young and old beagles had similar mitochondrial structure, respiratory function, and Ca(2+)-induced MPT within SSM and IFM subpopulations. On the other hand, oxidative capacity and resistance to Ca(2+)-induced MPT were significantly greater in IFM compared with SSM in all groups. Old beagles treated with aldosterone had greater LV wall thickness and worse diastolic filling but normal LV chamber volume and systolic function. Treatment with aldosterone did not alter mitochondrial respiratory function but accelerated Ca(2+)-induced MPT in SSM, but not IFM, compared with healthy old and young beagles. In conclusion, in a large animal model, oxidative capacity and resistance to MPT were greater in IFM than in SSM. Furthermore, aldosterone infusion increased susceptibility to MPT in SSM, but not IFM. Together this suggests that SSM are less resilient to acute stress than IFM in the healthy heart and are more susceptible to the development of pathology with chronic stress.

Impact of the Mycobaterium africanum West Africa 2 Lineage on TB Diagnostics in West Africa: Decreased Sensitivity of Rapid Identification Tests in The Gambia.

PubMed

Ofori-Anyinam, Boatema; Kanuteh, Fatoumatta; Agbla, Schadrac C; Adetifa, Ifedayo; Okoi, Catherine; Dolganov, Gregory; Schoolnik, Gary; Secka, Ousman; Antonio, Martin; de Jong, Bouke C; Gehre, Florian

2016-07-01

MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37°C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs.

Involvement of the mitochondrial permeability transition pore in chronic ethanol-mediated liver injury in mice

PubMed Central

King, Adrienne L.; Swain, Telisha M.; Mao, Zhengkuan; Udoh, Uduak S.; Oliva, Claudia R.; Betancourt, Angela M.; Griguer, Corrine E.; Crowe, David R.; Lesort, Mathieu

2013-01-01

Chronic ethanol consumption increases sensitivity of the mitochondrial permeability transition (MPT) pore induction in liver. Ca2+ promotes MPT pore opening, and genetic ablation of cyclophilin D (CypD) increases the Ca2+ threshold for the MPT. We used wild-type (WT) and CypD-null (CypD−/−) mice fed a control or an ethanol-containing diet to investigate the role of the MPT in ethanol-mediated liver injury. Ca2+-mediated induction of the MPT and mitochondrial respiration were measured in isolated liver mitochondria. Steatosis was present in WT and CypD−/− mice fed ethanol and accompanied by increased terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed CypD−/− mice, as reflected by an increase in the ratio of microtubule protein 1 light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62 were measured in CypD−/− than WT mice. Ethanol decreased mitochondrial respiratory control ratios and select complex activities in WT and CypD−/− mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from control- and ethanol-fed WT mice were more sensitive to Ca2+-mediated MPT pore induction than mitochondria from their CypD−/− counterparts. Mitochondria from ethanol-fed CypD−/− mice were also more sensitive to Ca2+-induced swelling than mitochondria from control-fed CypD−/− mice but were less sensitive than mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated with impaired autophagy and did not prevent ethanol-mediated steatosis. Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol-fed WT and CypD−/− mice. We conclude that chronic ethanol consumption likely lowers the threshold for CypD-regulated and -independent characteristics of the ethanol-mediated MPT pore in liver mitochondria. PMID:24356880

The 6-min push test is reliable and predicts low fitness in spinal cord injury.

PubMed

Cowan, Rachel E; Callahan, Morgan K; Nash, Mark S

2012-10-01

The objective of this study is to assess 6-min push test (6MPT) reliability, determine whether the 6MPT is sensitive to fitness differences, and assess if 6MPT distance predicts fitness level in persons with spinal cord injury (SCI) or disease. Forty individuals with SCI who could self-propel a manual wheelchair completed an incremental arm crank peak oxygen consumption assessment and two 6MPTs across 3 d (37% tetraplegia (TP), 63% paraplegia (PP), 85% men, 70% white, 63% Hispanic, mean age = 34 ± 10 yr, mean duration of injury = 13 ± 10 yr, and mean body mass index = 24 ± 5 kg.m). Intraclass correlation and Bland-Altman plots assessed 6MPT distance (m) reliability. Mann-Whitney U test compared 6MPT distance (m) of high and low fitness groups for TP and PP. The fitness status prediction was developed using N = 30 and validated in N = 10 (validation group (VG)). A nonstatistical prediction approach, below or above a threshold distance (TP = 445 m and PP = 604 m), was validated statistically by binomial logistic regression. Accuracy, sensitivity, and specificity were computed to evaluate the threshold approach. Intraclass correlation coefficients exceeded 0.90 for the whole sample and the TP/PP subsets. High fitness persons propelled farther than low fitness persons for both TP/PP (both P < 0.05). Binomial logistic regression (P < 0.008) predicted the same fitness levels in the VG as the threshold approach. In the VG, overall accuracy was 70%. Eighty-six percent of low fitness persons were correctly identified (sensitivity), and 33% of high fitness persons were correctly identified (specificity). The 6MPT may be a useful tool for SCI clinicians and researchers. 6MPT distance demonstrates excellent reliability and is sensitive to differences in fitness level. 6MPT distances less than a threshold distance may be an effective approach to identify low fitness in person with SCI.

Selection, characterization, and application of DNA aptamers for detection of Mycobacterium tuberculosis secreted protein MPT64.

PubMed

Sypabekova, Marzhan; Bekmurzayeva, Aliya; Wang, Ronghui; Li, Yanbin; Nogues, Claude; Kanayeva, Damira

2017-05-01

Rapid detection of Mycobacterium tuberculosis (Mtb), an etiological agent of tuberculosis (TB), is important for global control of this disease. Aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. The aim of the current study was to select and characterize single-stranded DNA aptamers against MPT64 protein, one of the predominant secreted proteins of Mtb pathogen. Aptamers specific to MPT64 protein were selected in vitro using systematic evolution of ligands through exponential enrichment (SELEX) method. The selection was started with a pool of ssDNA library with randomized 40-nucleotide region. A total of 10 cycles were performed and seventeen aptamers with unique sequences were identified by sequencing. Dot Blot analysis was performed to monitor the SELEX process and to conduct the preliminary tests on the affinity and specificity of aptamers. Enzyme linked oligonucleotide assay (ELONA) showed that most of the aptamers were specific to the MPT64 protein with a linear correlation of R 2  = 0.94 for the most selective. Using Surface Plasmon Resonance (SPR), dissociation equilibrium constant K D of 8.92 nM was obtained. Bioinformatics analysis of the most specific aptamers revealed the existence of a conserved as well as distinct sequences and possible binding site on MPT64. The specificity was determined by testing non-target ESAT-6 and CFP-10. Negligible cross-reactivity confirmed the high specificity of the selected aptamer. The selected aptamer was further tested on clinical sputum samples using ELONA and had sensitivity and specificity of 91.3% and 90%, respectively. Microscopy, culture positivity and nucleotide amplification methods were used as reference standards. The aptamers studied could be further used for the development of medical diagnostic tools and detection assays for Mtb. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Plasma Biomarker Analysis in Pediatric ARDS: Generating Future Framework from a Pilot Randomized Control Trial of Methylprednisolone: A Framework for Identifying Plasma Biomarkers Related to Clinical Outcomes in Pediatric ARDS.

PubMed

Kimura, Dai; Saravia, Jordy; Rovnaghi, Cynthia R; Meduri, Gianfranco Umberto; Schwingshackl, Andreas; Cormier, Stephania A; Anand, Kanwaljeet J

2016-01-01

Lung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial, and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS). Low-dose methylprednisolone therapy (MPT) improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial [Ang-2 and soluble intercellular adhesion molecule-1 (sICAM-1)] or epithelial [soluble receptor for activated glycation end products (sRAGE)] injury, neutrophil activation [matrix metalloproteinase-8 (MMP-8)], and coagulation (plasminogen activator inhibitor-1). Double-blind, placebo-controlled randomized trial. Tertiary-care pediatric intensive care unit (ICU). Mechanically ventilated children (0-18 years) with early ARDS. Blood samples were collected on days 0 (before MPT), 7, and 14 during low-dose MPT (n = 17) vs. placebo (n = 18) therapy. The MPT group received a 2-mg/kg loading dose followed by 1 mg/kg/day continuous infusions from days 1 to 7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for five biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier, including P/F ratio on days 8 and 9, plateau pressure on days 1 and 2, PaCO2 on days 2 and 3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge. No differences occurred in biomarker concentrations between the groups on day 0. On day 7, reduction in MMP-8 levels (p = 0.0016) occurred in the MPT group, whereas increases in sICAM-1 levels (p = 0.0005) occurred in the placebo group (no increases in sICAM-1 in the MPT group). sRAGE levels decreased in both MPT and placebo groups (p < 0.0001) from day 0 to day 7. On day 7, sRAGE levels were positively correlated with MPT group PaO2/FiO2 ratios on day 8 (r = 0.93, p = 0.024). O2 requirements at ICU transfer positively correlated with day 7 MMP-8 (r = 0.85, p = 0.016) and Ang-2 levels (r = 0.79, p = 0.036) in the placebo group and inversely correlated with day 7 sICAM-1 levels (r = -0.91, p = 0.005) in the MPT group. Biomarkers selected from endothelial, epithelial, or intravascular factors can be correlated with clinical endpoints in pediatric ARDS. For example, MPT could reduce neutrophil activation (⇓MMP-8), decrease endothelial injury (⇔sICAM-1), and allow epithelial recovery (⇓sRAGE). Large ARDS clinical trials should develop similar frameworks. https://clinicaltrials.gov, NCT01274260.

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.

PubMed

Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela; Catalano, John V; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-18

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma

PubMed Central

Dimopoulos, Meletios A.; Dispenzieri, Angela; Catalano, John V.; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J.; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D.; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C.; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-01

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months’ follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. PMID:29150421

Causes of ice age intensification across the Mid-Pleistocene Transition

PubMed Central

Foster, Gavin L.; Rohling, Eelco J.; Sexton, Philip F.; Cherry, Soraya G.; Hasenfratz, Adam P.; Haug, Gerald H.; Martínez-García, Alfredo; Pälike, Heiko; Pancost, Richard D.; Wilson, Paul A.

2017-01-01

During the Mid-Pleistocene Transition (MPT; 1,200–800 kya), Earth’s orbitally paced ice age cycles intensified, lengthened from ∼40,000 (∼40 ky) to ∼100 ky, and became distinctly asymmetrical. Testing hypotheses that implicate changing atmospheric CO2 levels as a driver of the MPT has proven difficult with available observations. Here, we use orbitally resolved, boron isotope CO2 data to show that the glacial to interglacial CO2 difference increased from ∼43 to ∼75 μatm across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle modeling, we attribute this decline primarily to the initiation of substantive dust-borne iron fertilization of the Southern Ocean during peak glacial stages. We also observe a twofold steepening of the relationship between sea level and CO2-related climate forcing that is suggestive of a change in the dynamics that govern ice sheet stability, such as that expected from the removal of subglacial regolith or interhemispheric ice sheet phase-locking. We argue that neither ice sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer that the MPT was initiated by a change in ice sheet dynamics and that longer and deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust fertilization of the Southern Ocean as a consequence of larger ice sheets. PMID:29180424

Causes of ice age intensification across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Chalk, Thomas B.; Hain, Mathis P.; Foster, Gavin L.; Rohling, Eelco J.; Sexton, Philip F.; Badger, Marcus P. S.; Cherry, Soraya G.; Hasenfratz, Adam P.; Haug, Gerald H.; Jaccard, Samuel L.; Martínez-García, Alfredo; Pälike, Heiko; Pancost, Richard D.; Wilson, Paul A.

2017-12-01

During the Mid-Pleistocene Transition (MPT; 1,200–800 kya), Earth's orbitally paced ice age cycles intensified, lengthened from ˜40,000 (˜40 ky) to ˜100 ky, and became distinctly asymmetrical. Testing hypotheses that implicate changing atmospheric CO2 levels as a driver of the MPT has proven difficult with available observations. Here, we use orbitally resolved, boron isotope CO2 data to show that the glacial to interglacial CO2 difference increased from ˜43 to ˜75 μatm across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle modeling, we attribute this decline primarily to the initiation of substantive dust-borne iron fertilization of the Southern Ocean during peak glacial stages. We also observe a twofold steepening of the relationship between sea level and CO2-related climate forcing that is suggestive of a change in the dynamics that govern ice sheet stability, such as that expected from the removal of subglacial regolith or interhemispheric ice sheet phase-locking. We argue that neither ice sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer that the MPT was initiated by a change in ice sheet dynamics and that longer and deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust fertilization of the Southern Ocean as a consequence of larger ice sheets.

A Streptomyces-specific member of the metallophosphatase superfamily contributes to spore dormancy and interaction with Aspergillus proliferans.

PubMed

Lamp, Jessica; Weber, Maren; Cingöz, Gökhan; Ortiz de Orué Lucana, Darío; Schrempf, Hildgund

2013-05-01

We have identified, cloned and characterized a formerly unknown protein from Streptomyces lividans spores. The deduced protein belongs to a novel member of the metallophosphatase superfamily and contains a phosphatase domain and predicted binding sites for divalent ions. Very close relatives are encoded in the genomic DNA of many different Streptomyces species. As the deduced related homologues diverge from other known phosphatase types, we named the protein MptS (metallophosphatase type from Streptomyces). Comparative physiological and biochemical investigations and analyses by fluorescence microscopy of the progenitor strain, designed mutants carrying either a disruption of the mptS gene or the reintroduced gene as fusion with histidine codons or the egfp gene led to the following results: (i) the mptS gene is transcribed in the course of aerial mycelia formation. (ii) The MptS protein is produced during the late stages of growth, (iii) accumulates within spores, (iv) functions as an active enzyme that releases inorganic phosphate from an artificial model substrate, (v) is required for spore dormancy and (vi) MptS supports the interaction amongst Streptomyces lividans spores with conidia of the fungus Aspergillus proliferans. We discuss the possible role(s) of MptS-dependent enzymatic activity and the implications for spore biology. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Effects of theory of mind performance training on reducing bullying involvement in children and adolescents with high-functioning autism spectrum disorder.

PubMed

Liu, Meng-Jung; Ma, Le-Yin; Chou, Wen-Jiun; Chen, Yu-Min; Liu, Tai-Ling; Hsiao, Ray C; Hu, Huei-Fan; Yen, Cheng-Fang

2018-01-01

Bullying involvement is prevalent among children and adolescents with autism spectrum disorder (ASD). This study examined the effects of theory of mind performance training (ToMPT) on reducing bullying involvement in children and adolescents with high-functioning ASD. Children and adolescents with high-functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23) programs. Participants in both groups and their mothers rated the pretraining and posttraining bullying involvement of participants on the Chinese version of the School Bullying Experience Questionnaire. The paired t test was used to evaluate changes in bullying victimization and perpetration between the pretraining and posttraining assessments. Furthermore, the linear mixed-effect model was used to examine the difference in the training effect between the ToMPT and SST groups. The paired t test indicated that in the ToMPT group, the severities of both self-reported (p = .039) and mother-reported (p = .003) bullying victimization significantly decreased from the pretraining to posttraining assessments, whereas in the SST group, only self-reported bullying victimization significantly decreased (p = .027). The linear mixed-effect model indicated that compared with the SST program, the ToMPT program significantly reduced the severity of mother-reported bullying victimization (p = .041). The present study supports the effects of ToMPT on reducing mother-reported bullying victimization in children and adolescents with high-functioning ASD.

Methenyl-Dephosphotetrahydromethanopterin Is a Regulatory Signal for Acclimation to Changes in Substrate Availability in Methylobacterium extorquens AM1.

PubMed

Martinez-Gomez, N Cecilia; Good, Nathan M; Lidstrom, Mary E

2015-06-15

During an environmental perturbation, the survival of a cell and its response to the perturbation depend on both the robustness and functionality of the metabolic network. The regulatory mechanisms that allow the facultative methylotrophic bacterium Methylobacterium extorquens AM1 to effect the metabolic transition from succinate to methanol growth are not well understood. Methenyl-dephosphotetrahydromethanopterin (methenyl-dH4MPT), an early intermediate during methanol metabolism, transiently accumulated 7- to 11-fold after addition of methanol to a succinate-limited culture. This accumulation partially inhibited the activity of the methylene-H4MPT dehydrogenase, MtdA, restricting carbon flux to the assimilation cycles. A strain overexpressing the gene (mch) encoding the enzyme that consumes methenyl-dH4MPT did not accumulate methenyl-dH4MPT and had a growth rate that was 2.7-fold lower than that of the wild type. This growth defect demonstrates the physiological relevance of this enzymatic regulatory mechanism during the acclimation period. Changes in metabolites and enzymatic activities were analyzed in the strain overexpressing mch. Under these conditions, the activity of the enzyme coupling formaldehyde with dH4MPT (Fae) remained constant, with concomitant formaldehyde accumulation. Release of methenyl-dH4MPT regulation did not affect the induction of the serine cycle enzyme activities immediately after methanol addition, but after 1 h, the activity of these enzymes decreased, likely due to the toxicity of formaldehyde accumulation. Our results support the hypothesis that in a changing environment, the transient accumulation of methenyl-dH4MPT and inhibition of MtdA activity are strategies that permit flexibility and acclimation of the metabolic network while preventing the accumulation of the toxic compound formaldehyde. The identification and characterization of regulatory mechanisms for methylotrophy are in the early stages. We report a nontranscriptional regulatory mechanism that was found to operate as an immediate response for acclimation during changes in substrate availability. Methenyl-dH4MPT, an early intermediate during methanol oxidation, reversibly inhibits the methylene-H4MPT dehydrogenase, MtdA, when Methylobacterium extorquens is challenged to switch from succinate to methanol growth. Bypassing this regulatory mechanism causes formaldehyde to accumulate. Fae, the enzyme catalyzing the conversion of formaldehyde to methylene-dH4MPT, was also identified as another potential regulatory target using this strategy. The results herein further our understanding of the complex regulatory network in methylotrophy and will allow us to improve metabolic engineering strategies of methylotrophs for the production of value-added products. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cloning, expression, and purification of recombinant protein MPT-64 from a virulent strain of Mycobacterium bovis in a prokaryotic system.

PubMed

Tashakkori, Maryam Mohammadi; Tebianian, Majid; Tabatabaei, Mohammad; Mosavari, Nader

2016-12-01

Tuberculosis (TB) is a zoonotic infectious disease common to humans and animals that is caused by the rod-shaped acid-fast bacterium Mycobacterium bovis. Rapid and sensitive detection of TB is promoted by specific antigens. Virulent strains of the TB complex from M. bovis contain 16 regions of difference (RD) in their genome that encode important proteins, including major protein of Mycobacterium Tuberculosis 64 (MBT-64, which is a primary immune-stimulating antigen encoded by RD-2. In this study, we cloned, expressed, and purified MPT-64 as a potent M. bovis antigen in a prokaryotic system for use in future diagnostic studies. The antigenic region of the Mpt64 gene was investigated by bioinformatics methods, cloned into the PQE-30 plasmid, and expressed in Escherichia coli M15 cells, followed by isopropyl β-d-1-thiogalactopyranoside induction. The expressed protein was analyzed sodium dodecyl sulfate polyacrylamide gel electrophoresis and purified using a nickel-affinity column. Biological activity was confirmed by western blot using specific antibodies. Our data verified the successful cloning of the Mpt64 gene (687-bp segment) via the expression vector and purification of recombinant MPT-64 as a 24-kDa protein. These results indicated successful expression and purification of recombinant MPT-64 protein in a prokaryotic system. This protein can be used for serological diagnosis, improved detection of pathogenicity and non-pathogenicity between infected cattle, and for verification of suspected cases of bovine TB. Copyright © 2016.

Effects of theory of mind performance training on reducing bullying involvement in children and adolescents with high-functioning autism spectrum disorder

PubMed Central

Chen, Yu-Min; Liu, Tai-Ling; Hsiao, Ray C.; Hu, Huei-Fan

2018-01-01

Bullying involvement is prevalent among children and adolescents with autism spectrum disorder (ASD). This study examined the effects of theory of mind performance training (ToMPT) on reducing bullying involvement in children and adolescents with high-functioning ASD. Children and adolescents with high-functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23) programs. Participants in both groups and their mothers rated the pretraining and posttraining bullying involvement of participants on the Chinese version of the School Bullying Experience Questionnaire. The paired t test was used to evaluate changes in bullying victimization and perpetration between the pretraining and posttraining assessments. Furthermore, the linear mixed-effect model was used to examine the difference in the training effect between the ToMPT and SST groups. The paired t test indicated that in the ToMPT group, the severities of both self-reported (p = .039) and mother-reported (p = .003) bullying victimization significantly decreased from the pretraining to posttraining assessments, whereas in the SST group, only self-reported bullying victimization significantly decreased (p = .027). The linear mixed-effect model indicated that compared with the SST program, the ToMPT program significantly reduced the severity of mother-reported bullying victimization (p = .041). The present study supports the effects of ToMPT on reducing mother-reported bullying victimization in children and adolescents with high-functioning ASD. PMID:29342210

Aluminum as an inducer of the mitochondrial permeability transition.

PubMed

Toninello, A; Clari, G; Mancon, M; Tognon, G; Zatta, P

2000-10-01

Treatment of rat liver mitochondria with aluminum in the presence of Ca2+ results in large amplitude swelling accompanied by loss of endogenous Mg2+ and K+ and oxidation of endogenous pyridine nucleotides. The presence of cyclosporin A, ADP, bongkrekic acid, N-ethylmaleimide and dithioerythritol prevent these effects, indicating that binding of aluminum to the inner mitochondrial membrane, most likely at the level of adenine nucleotide translocase, correlates with the induction of the membrane permeability transition (MPT). Indeed, aluminum binding promotes such a perturbation at the level of ubiquinol-cytochrome c reductase, which favors the production of reactive oxygen species. These metabolites generate an oxidative stress involving two previously defined sites in equilibrium with the glutathione and pyridine nucleotides pools, the levels of which correlate with the increase in MPT induction. Although the above-described phenomena are typical of MPT, they are not paralleled by other events normally observed in response to treatment with inducers of MPT (e.g., phosphate), such as the collapse of the electrochemical gradient and the release of accumulated Ca2+ and oxidized pyridine nucleotides. Biochemical and ultrastructural observations demonstrate that aluminum induces a pore opening having a conformation intermediate between fully open and closed in a subpopulation of mitochondria. While inorganic phosphate enhances the MPT induced by ruthenium red plus a deenergizing agent, aluminum instead inhibits this phenomenon. This finding suggests the presence of a distinct binding site for aluminum differing from that involved in MPT induction.

Hierarchical Multinomial Processing Tree Models: A Latent-Trait Approach

ERIC Educational Resources Information Center

Klauer, Karl Christoph

2010-01-01

Multinomial processing tree models are widely used in many areas of psychology. A hierarchical extension of the model class is proposed, using a multivariate normal distribution of person-level parameters with the mean and covariance matrix to be estimated from the data. The hierarchical model allows one to take variability between persons into…

A Multinomial Model of Event-Based Prospective Memory

ERIC Educational Resources Information Center

Smith, Rebekah E.; Bayen, Ute J.

2004-01-01

Prospective memory is remembering to perform an action in the future. The authors introduce the 1st formal model of event-based prospective memory, namely, a multinomial model that includes 2 separate parameters related to prospective memory processes. The 1st measures preparatory attentional processes, and the 2nd measures retrospective memory…

[In vitro metabolism of fenbendazole prodrug].

PubMed

Wen, Ai-Dan; Duan, Li-Ping; Liu, Cong-Shan; Tao, Yi; Xue, Jian; Wu, Ning-Bo; Jiang, Bin; Zhang, Hao-Bing

2013-02-01

Synthesized fenbendazole prodrug N-methoxycarbonyl-N'-(2-nitro-4-phenylthiophenyl) thiourea (MPT) was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MPT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.

Understanding Electrocatalytic Activity Enhancement of Bimetallic Particles to Ethanol Electro-oxidation: (1) Water Adsorption and Decomposition on PtnM (n=2,3 and 9; M=Pt, Ru, Sn)

PubMed Central

Wang, Yixuan; Mi, Yunjie; Redmon, Natalie; Holiday, Jessica

2009-01-01

The fundamental assumption of the bi-functional mechanism for PtSn alloy to catalyze ethanol electro-oxidation reaction (EER) is that Sn facilitates water dissociation and EER occurs over Pt site of the PtSn alloy. To clarify this assumption and achieve a good understanding about the EER, H2O adsorption and dissociation over bimetallic clusters PtM (M=Pt, Sn, Ru, Rh, Pd, Cu and Re) are systematically investigated in the present work. To discuss a variety of effects, PtnM (n=2, and 3; M=Pt, Sn and Ru), one-layer Pt6M (M=Pt, Sn and Ru), and two-layer (Pt6M)Pt3 (M=Pt, Sn, Ru, Rh, Pd, Cu and Re) clusters are used to model the PtM bimetallic catalysts. Water exhibits atop adsorption on Pt and Ru sites of the optimized clusters PtnM (n=2, and 3; M=Pt and Ru), yet bridge adsorption on Sn sites of Pt2Sn as well as distorted tetrahedral Pt3Sn. However, in the cases of one-layer Pt6M and two-layer Pt9M cluster models water preferentially binds to all of investigated central atom M of surface layer in atop configuration with the dipole moment of water almost parallel to the cluster surface. Water adsorption on the Sn site of PtnSn (n=2 and 3) is weaker than those on the Pt site of Ptn (n=3 and 4) and the Ru site of PtnRu (n=2 and 3), while water adsorptions on the central Sn atom of Pt6Sn and Pt9Sn are enhanced so significantly that they are even stronger than those on the central Pt and Ru atoms of PtnM (n=6 and 9; M=Pt and Ru). For all of the three cluster models, energy barrier (Ea) for the dissociation of adsorbed water over Sn is lower than over Ru and Pt atoms (e.g., Ea: 0.78 vs 0.96 and 1.07 eV for Pt9M), which also remains as external electric fields were added. It is interesting to note that the dissociation energy on Sn site is also the lowest (Ediss: 0.44 vs 0.61 and 0.67eV). The results show that from both kinetic and thermodynamic viewpoints Sn is more active to water decomposition than pure Pt and the PtRu alloy, which well supports the assumption of the bi-functional mechanism that Sn site accelerates the dissociation of H2O. The extended investigation for water behavior on the (Pt6M)Pt3 (M=Pt, Sn, Ru, Rh, Pd, Cu and Re) clusters indicate that the kinetic activity for water dissociation increases in the sequence of Cu < Pd < Rh < Pt < Ru < Sn < Re. PMID:20336187

46 CFR 64.11 - Design of MPTs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEMS Standards for an MPT § 64.11 Design of MPTs. An MPT must be designed— (a) In accordance with the... withstand dynamic loading conditions applied simultaneously. [CGD 84-043, 55 FR 37410, Sept. 11, 1990; 55 FR...

Thermohaline circulation crisis and impacts during the mid-Pleistocene transition.

PubMed

Pena, Leopoldo D; Goldstein, Steven L

2014-07-18

The mid-Pleistocene transition (MPT) marked a fundamental change in glacial-interglacial periodicity, when it increased from ~41-thousand-year to 100-thousand-year cycles and developed higher-amplitude climate variability without substantial changes in the Milankovitch forcing. Here, we document, by using Nd isotopes, a major disruption of the ocean thermohaline circulation (THC) system during the MPT between marine isotope stages (MISs) 25 and 21 at ~950 to 860 thousand years ago, which effectively marks the first 100-thousand-year cycle, including an exceptional weakening through a critical interglacial (MIS 23) at ~900 thousand years ago. Its recovery into the post-MPT 100-thousand-year world is characterized by continued weak glacial THC. The MPT ocean circulation crisis facilitated the coeval drawdown of atmospheric CO2 and high-latitude ice sheet growth, generating the conditions that stabilized 100-thousand-year cycles. Copyright © 2014, American Association for the Advancement of Science.

[Atomic/ionic fluorescence in microwave plasma torch discharge with excitation of high current and microsecond pulsed hollow cathode lamp: Ca atomic/ionic fluorescence spectrometry].

PubMed

Gong, Zhen-bin; Liang, Feng; Yang, Peng-yuan; Jin, Qin-han; Huang, Ben-li

2002-02-01

A system of atomic and ionic fluorescence spectrometry in microwave plasma torch (MPT) discharge excited by high current microsecond pulsed hollow cathode lamp (HCMP HCL) has been developed. The operation conditions for Ca atomic and ionic fluorescence spectrometry have been optimized. Compared with atomic fluorescence spectrometry (AFS) in argon microwave induced plasma (MIP) and MPT with the excitation of direct current and conventional pulsed HCL, the system with HCMP HCL excitation can improve AFS and ionic fluorescence spectrometry (IFS) detection limits in MPT atomizer and ionizer. Detection limits (3 sigma) with HCMP HCL-MPT-AFS/IFS are 10.1 ng.mL-1 for Ca I 422.7 nm, 14.6 ng.mL-1 for Ca II 393.4 nm, and 37.4 ng.mL-1 for Ca II 396.8 nm, respectively.

The middle Pleistocene transition: characteristics, mechanisms, and implications for long-term changes in atmospheric pCO 2

NASA Astrophysics Data System (ADS)

Clark, Peter U.; Archer, David; Pollard, David; Blum, Joel D.; Rial, Jose A.; Brovkin, Victor; Mix, Alan C.; Pisias, Nicklas G.; Roy, Martin

2006-12-01

The emergence of low-frequency, high-amplitude, quasi-periodic (˜100-kyr) glacial variability during the middle Pleistocene in the absence of any significant change in orbital forcing indicates a fundamental change internal to the climate system. This middle Pleistocene transition (MPT) began 1250 ka and was complete by 700 ka. Its onset was accompanied by decreases in sea surface temperatures (SSTs) in the North Atlantic and tropical-ocean upwelling regions and by an increase in African and Asian aridity and monsoonal intensity. During the MPT, long-term average ice volume gradually increased by ˜50 m sea-level equivalent, whereas low-frequency ice-volume variability experienced a 100-kyr lull centered on 1000 ka followed by its reappearance ˜900 ka, although as a broad band of power rather than a narrow, persistent 100-kyr cycle. Additional changes at 900 ka indicate this to be an important time during the MPT, beginning with an 80-kyr event of extreme SST cooling followed by the partial recovery and subsequent stabilization of long-term North Atlantic and tropical ocean SSTs, increasing Southern Ocean SST variability primarily associated with warmer interglacials, the loss of permanent subpolar sea-ice cover, and the emergence of low-frequency variability in Pacific SSTs and global deep-ocean circulation. Since 900 ka, ice sheets have been the only component of the climate system to exhibit consistent low-frequency variability. With the exception of a near-universal organization of low-frequency power associated with marine isotope stages 11 and 12, all other components show an inconsistent distribution of power in frequency-time space, suggesting a highly nonlinear system response to orbital and ice-sheet forcing. Most hypotheses for the origin of the MPT invoke a response to a long-term cooling, possibly induced by decreasing atmospheric pCO 2. None of these hypotheses, however, accounts for the geological constraint that the earliest Northern Hemisphere ice sheets covered a similar or larger area than those that followed the MPT. Given that the MPT was associated with an increase in ice volume, this constraint requires that post-MPT ice sheets were substantially thicker than pre-MPT ice sheets, indicating a change in subglacial conditions that influence ice dynamics. We review evidence in support of the hypothesis that such an increase in ice thickness occurred as crystalline Precambrian Shield bedrock became exposed by glacial erosion of a thick mantle of regolith. This exposure of a high-friction substrate caused thicker ice sheets, with an attendant change in their response to the orbital forcing. Marine carbon isotope data indicate a rapid transfer of organic carbon to inorganic carbon in the ocean system during the MPT. If this carbon came from terrigenous sources, an increase in atmospheric pCO 2 would be likely, which is inconsistent with evidence for widespread cooling, Apparently rapid carbon transfer from terrestrial sources is difficult to reconcile with gradual erosion of regolith. A more likely source of organic carbon and nutrients (which would mitigate pCO 2 rise) is from shelf and upper slope marine sediments, which were fully exposed for the first time in millions of years in response to thickening ice sheets and falling sealevels during the MPT. Modeling indicates that regolith erosion and resulting exposure of crystalline bedrock would cause an increase in long-term silicate weathering rates, in good agreement with marine Sr and Os isotopic records. We use a carbon cycle model to show that a post-MPT increase in silicate weathering rates would lower atmospheric pCO 2 by 7-12 ppm, suggesting that the attendant cooling may have been an important feedback in causing the MPT.

Modeling abundance using multinomial N-mixture models

USGS Publications Warehouse

Royle, Andy

2016-01-01

Multinomial N-mixture models are a generalization of the binomial N-mixture models described in Chapter 6 to allow for more complex and informative sampling protocols beyond simple counts. Many commonly used protocols such as multiple observer sampling, removal sampling, and capture-recapture produce a multivariate count frequency that has a multinomial distribution and for which multinomial N-mixture models can be developed. Such protocols typically result in more precise estimates than binomial mixture models because they provide direct information about parameters of the observation process. We demonstrate the analysis of these models in BUGS using several distinct formulations that afford great flexibility in the types of models that can be developed, and we demonstrate likelihood analysis using the unmarked package. Spatially stratified capture-recapture models are one class of models that fall into the multinomial N-mixture framework, and we discuss analysis of stratified versions of classical models such as model Mb, Mh and other classes of models that are only possible to describe within the multinomial N-mixture framework.

Effect of taurine on ischemia-reperfusion injury.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi

2014-01-01

Taurine is an abundant β-amino acid that regulates several events that dramatically influence the development of ischemia-reperfusion injury. One of these events is the extrusion of taurine and Na+ from the cell via the taurine/Na+ symport. The loss of Na+ during the ischemia-reperfusion insult limits the amount of available Na+ for Na+/Ca2+ exchange, an important process in the development of Ca2+ overload and the activation of the mitochondrial permeability transition, a key process in ischemia-reperfusion mediated cell death. Taurine also prevents excessive generation of reactive oxygen species by the respiratory chain, an event that also limits the activation of the MPT. Because taurine is an osmoregulator, changes in taurine concentration trigger "osmotic preconditioning," a process that activates an Akt-dependent cytoprotective signaling pathway that inhibits MPT pore formation. These effects of taurine have clinical implications, as experimental evidence reveals potential promise of taurine therapy in preventing cardiac damage during bypass surgery, heart transplantation and myocardial infarction. Moreover, severe loss of taurine from the heart during an ischemia-reperfusion insult may increase the risk of ventricular remodeling and development of heart failure.

Changes in melatonin secretion in tourists after rapid movement to another lighting zone without transition of time zone.

PubMed

Wieczorek, Joanna; Blazejczyk, Krzysztof; Morita, Takeshi

2016-01-01

Most of the research in the field of Chronobiology is focused on the problem of the circadian rhythms (CR) desynchronization. In travelers, it results mostly from the changes of surrounding: photoperiod, local climate conditions (radiation and thermal load) and behavior (e.g. type and place of tourism and activity level). Until now, it was not documented whether the changes in melatonin (MLT) secretion occur in effect of mid-distance transparallel travels (TpT), without complications arising due to time-zone transitions (e.g. jet-lag syndrome). To cope with this problem, a special field experiment was carried out. In the experiment, MLT characteristics were examined twice a year in real conditions through a group of young tourists (23-26 years old) at their place of habitual residence (Warsaw, Poland), and at their tourist destination (Tromso, Norway). Transition to circumpolar zone in summer has resulted in insignificant reduction in melatonin peak value (MPV) compared to preflight control (2 days before travel) and the melatonin peak time (MPT) was delayed. However, after traveling southward on the returning flight, MPV was lower compared to control and MPT was advanced. In winter, MPV was insignificantly higher in comparison to preflight control and MPT was almost unchanged. While changes in MPV do not depend on season, flight direction and day of stay after flight than MPT was differentiated seasonally and due to direction of flight. MPV and MPT were significantly modified by characteristics of individual light exposure during daytime and evening. The experiment showed also that in real conditions activity level is an important factor affected melatonin peak in tourists. In winter, greater daytime activity significantly influenced earlier MPT occurrence, both after northward and southward flights.

Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax.

PubMed

Baines, Christopher P; Molkentin, Jeffery D

2009-06-01

Overexpression of the adenine nucleotide translocase (ANT) has been shown to be cytotoxic in several cell types. Although ANT was originally proposed to be a critical component of the mitochondrial permeability transition (MPT) pore, recent data have suggested that this may not be the case. We therefore hypothesized that the cytotoxic actions of ANT are through an alternative mechanism, independent of the MPT pore. Infection of cultured neonatal cardiomyocytes with an ANT1-encoding adenovirus induced a gene dosage-dependent increase in cell death. However, ANT1 overexpression failed to induce MPT, and neither pharmacological nor genetic inhibition of the MPT pore was able to prevent ANT1-induced cell death. These data suggested that ANT1-induced death progressed through an MPT pore-independent pathway. Somewhat surprisingly, we observed that protein levels of Bax, a pro-apoptotic Bcl protein, were consistently elevated in ANT1-infected cardiomyocytes. Membranes isolated from ANT1-infected myocytes exhibited significantly increased amounts of membrane-inserted Bax, and immunocytochemistry revealed increased Bax activation in ANT1-infected myocytes. Co-expression with the Bax antagonist Bcl2 was able to greatly reduce the degree of ANT1-induced cell death. Furthermore, Bax/Bak-deficient fibroblasts were resistant to the cytotoxic effects of ANT1 overexpression. Interestingly, ANT1 overexpression was also associated with enhanced production of reactive oxygen species (ROS), and the antioxidant MnTBAP was able to significantly attenuate both the ANT1-induced upregulation of Bax and cell death. Taken together, these data indicate that ANT mediates cell death, not through the MPT pore, but rather via a ROS-dependent upregulation and activation of Bax.

Obsessional personality features in employed Japanese adults with a lifetime history of depression: assessment by the Munich Personality Test (MPT).

PubMed

Sakado, K; Sakado, M; Seki, T; Kuwabara, H; Kojima, M; Sato, T; Someya, T

2001-06-01

Although a number of studies have reported on the association between obsessional personality features as measured by the Munich Personality Test (MPT) "Rigidity" scale and depression, there has been no examination of these relationships in a non-clinical sample. The dimensional scores on the MPT were compared between subjects with and without lifetime depression, using a sample of employed Japanese adults. The odds ratio for suffering from lifetime depression was estimated by multiple logistic regression analysis. To diagnose a lifetime history of depression, the Inventory to Diagnose Depression, Lifetime version (IDDL) was used. The subjects with lifetime depression scored significantly higher on the "Rigidity" scale than the subjects without lifetime depression. In our logistic regression analysis, three risk factors were identified as each independently increasing a person's risk for suffering from lifetime depression: higher levels of "Rigidity", being of the female gender, and suffering from current depressive symptoms. The MPT "Rigidity" scale is a sensitive measure of personality features that occur with depression.

Change in Pulmonary Function after Incentive Spirometer Exercise in Children with Spastic Cerebral Palsy: A Randomized Controlled Study.

PubMed

Choi, Ja Young; Rha, Dong-wook; Park, Eun Sook

2016-05-01

The aim of this study was to investigate the effect of incentive spirometer exercise (ISE) on pulmonary function and maximal phonation time (MPT) in children with spastic cerebral palsy (CP). Fifty children with CP were randomly assigned to two groups: the experimental group and the control group. Both groups underwent comprehensive rehabilitation therapy. The experimental group underwent additional ISE. The forced vital capacity (FVC), forced expiratory volume at one second (FEV₁), FEV₁/FVC ratio, peak expiratory flow (PEF), and MPT were assessed as outcome measures before and after 4 weeks of training. There were significant improvements in FVC, FEV₁, PEF, and MPT in the experimental group, but not in the control group. In addition, the improvements in FVC, FEV₁, and MPT were significantly greater in the experimental group than in the control group. The results of this randomized controlled study support the use of ISE for enhancing pulmonary function and breath control for speech production in children with CP.

Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review.

PubMed

de Foucher, Tiphaine; Roussel, Hélène; Hivelin, Mikael; Rossi, Léa; Cornou, Caroline; Bats, Anne-Sophie; Deloménie, Myriam; Lécuru, Fabrice; Ngô, Charlotte

2017-01-01

Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

MPT Prediction of Aircraft-Engine Fan Noise

NASA Technical Reports Server (NTRS)

Connell, Stuart D.

2004-01-01

A collection of computer programs has been developed that implements a procedure for predicting multiple-pure-tone (MPT) noise generated by fan blades of an aircraft engine (e.g., a turbofan engine). MPT noise arises when the fan is operating with supersonic relative tip Mach No. Under this flow condition, there is a strong upstream running shock. The strength and position of this shock are very sensitive to blade geometry variations. For a fan where all the blades are identical, the primary tone observed upstream of the fan will be the blade passing frequency. If there are small variations in geometry between blades, then tones below the blade passing frequency arise MPTs. Stagger angle differences as small as 0.1 can give rise to significant MPT. It is also noted that MPT noise is more pronounced when the fan is operating in an unstarted mode. Computational results using a three-dimensional flow solver to compute the complete annulus flow with non-uniform fans indicate that MPT noise can be estimated in a relatively simple way. Hence, once the effect of a typical geometry variation of one blade in an otherwise uniform blade row is known, the effect of all the blades being different can be quickly computed via superposition. Two computer programs that were developed as part of this work are used in conjunction with a user s computational fluid dynamics (CFD) code to predict MPT spectra for a fan with a specified set of geometric variations: (1) The first program ROTBLD reads the users CFD solution files for a single blade passage via an API (Application Program Interface). There are options to replicate and perturb the geometry with typical variations stagger, camber, thickness, and pitch. The multi-passage CFD solution files are then written in the user s file format using the API. (2) The second program SUPERPOSE requires two input files: the first is the circumferential upstream pressure distribution extracted from the CFD solution on the multi-passage mesh, the second file defines the geometry variations of each blade in a complete fan. Superposition is used to predict the spectra resulting from the geometric variations.

Widen NomoGram for multinomial logistic regression: an application to staging liver fibrosis in chronic hepatitis C patients.

PubMed

Ardoino, Ilaria; Lanzoni, Monica; Marano, Giuseppe; Boracchi, Patrizia; Sagrini, Elisabetta; Gianstefani, Alice; Piscaglia, Fabio; Biganzoli, Elia M

2017-04-01

The interpretation of regression models results can often benefit from the generation of nomograms, 'user friendly' graphical devices especially useful for assisting the decision-making processes. However, in the case of multinomial regression models, whenever categorical responses with more than two classes are involved, nomograms cannot be drawn in the conventional way. Such a difficulty in managing and interpreting the outcome could often result in a limitation of the use of multinomial regression in decision-making support. In the present paper, we illustrate the derivation of a non-conventional nomogram for multinomial regression models, intended to overcome this issue. Although it may appear less straightforward at first sight, the proposed methodology allows an easy interpretation of the results of multinomial regression models and makes them more accessible for clinicians and general practitioners too. Development of prediction model based on multinomial logistic regression and of the pertinent graphical tool is illustrated by means of an example involving the prediction of the extent of liver fibrosis in hepatitis C patients by routinely available markers.

In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion.

PubMed

Saerens, Lien; Dierickx, Lien; Quinten, Thomas; Adriaensens, Peter; Carleer, Robert; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2012-05-01

The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion. Kollidon® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30% and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R(2)=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon® SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation. NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion. Copyright © 2012 Elsevier B.V. All rights reserved.

Ketone bodies are protective against oxidative stress in neocortical neurons.

PubMed

Kim, Do Young; Davis, Laurie M; Sullivan, Patrick G; Maalouf, Marwan; Simeone, Timothy A; van Brederode, Johannes; Rho, Jong M

2007-06-01

Ketone bodies (KB) have been shown to prevent neurodegeneration in models of Parkinson's and Alzheimer's diseases, but the mechanisms underlying these effects remain unclear. One possibility is that KB may exert antioxidant activity. In the current study, we explored the effects of KB on rat neocortical neurons exposed to hydrogen peroxide (H(2)O(2)) or diamide - a thiol oxidant and activator of mitochondrial permeability transition (mPT). We found that: (i) KB completely blocked large inward currents induced by either H(2)O(2) or diamide; (ii) KB significantly decreased the number of propidium iodide-labeled cells in neocortical slices after exposure to H(2)O(2) or diamide; (iii) KB significantly decreased reactive oxygen species (ROS) levels in dissociated neurons and in isolated neocortical mitochondria; (iv) the electrophysiological effects of KB in neurons exposed to H(2)O(2) or diamide were mimicked by bongkrekic acid and cyclosporin A, known inhibitors of mPT, as well as by catalase and DL - dithiothreitol, known antioxidants; (v) diamide alone did not significantly alter basal ROS levels in neurons, supporting previous studies indicating that diamide-induced neuronal injury may be mediated by mPT opening; and (vi) KB significantly increased the threshold for calcium-induced mPT in isolated mitochondria. Taken together, our data suggest that KB may prevent mPT and oxidative injury in neocortical neurons, most likely by decreasing mitochondrial ROS production.

Modeling Unconscious Gender Bias in Fame Judgments: Finding the Proper Branch of the Correct (Multinomial) Tree

PubMed

Draine; Greenwald; Banaji

1996-03-01

In the preceding article, Buchner and Wippich used a guessing-corrected, multinomial process-dissociation analysis to test whether a gender bias in fame judgments reported by Banaji and Greenwald (Journal of Personality and Social Psychology, 1995, 68, 181-198) was unconscious. In their two experiments, Buchner and Wippich found no evidence for unconscious mediation of this gender bias. Their conclusion can be questioned by noting that (a) the gender difference in familiarity of previously seen names that Buchner and Wippich modeled was different from the gender difference in criterion for fame judgments reported by Banaji and Greenwald, (b) the assumptions of Buchner and Wippich's multinomial model excluded processes that are plausibly involved in the fame judgment task, and (c) the constructs of Buchner and Wippich's model that corresponded most closely to Banaji and Greenwald's gender-bias interpretation were formulated so as to preclude the possibility of modeling that interpretation. Perhaps a more complex multinomial model can model the Banaji and Greenwald interpretation.

Modeling unconscious gender bias in fame judgments: finding the proper branch of the correct (multinomial) tree.

PubMed

Draine, S C; Greenwald, A G; Banaji, M R

1996-01-01

In the preceding article, Buchner and Wippich used a guessing-corrected, multinomial process-dissociation analysis to test whether a gender bias in fame judgements reported by Banaji and Greenwald (Journal of Personality and Social Psychology, 1995, 68, 181-198) was unconscious. In their two experiments, Buchner and Wippich found no evidence for unconscious mediation of this gender bias. Their conclusion can be questioned by noting that (a) the gender difference in familiarity of previously seen names that Buchner and Wippich modeled was different from the gender difference in criterion for fame judgements reported by Banaji and Greenwald, (b) the assumptions of Buchner and Wippich's multinomial model excluded processes that are plausibly involved in the fame judgement task, and (c) the constructs of Buchner and Wippich's model that corresponded most closely to Banaji and Greenwald's gender-bias interpretation were formulated so as to preclude the possibility of modeling that interpretation. Perhaps a more complex multinomial model can model the Banaji and Greenwald interpretation.

Order-disorder transition in conflicting dynamics leading to rank-frequency generalized beta distributions

NASA Astrophysics Data System (ADS)

Alvarez-Martinez, R.; Martinez-Mekler, G.; Cocho, G.

2011-01-01

The behavior of rank-ordered distributions of phenomena present in a variety of fields such as biology, sociology, linguistics, finance and geophysics has been a matter of intense research. Often power laws have been encountered; however, their validity tends to hold mainly for an intermediate range of rank values. In a recent publication (Martínez-Mekler et al., 2009 [7]), a generalization of the functional form of the beta distribution has been shown to give excellent fits for many systems of very diverse nature, valid for the whole range of rank values, regardless of whether or not a power law behavior has been previously suggested. Here we give some insight on the significance of the two free parameters which appear as exponents in the functional form, by looking into discrete probabilistic branching processes with conflicting dynamics. We analyze a variety of realizations of these so-called expansion-modification models first introduced by Wentian Li (1989) [10]. We focus our attention on an order-disorder transition we encounter as we vary the modification probability p. We characterize this transition by means of the fitting parameters. Our numerical studies show that one of the fitting exponents is related to the presence of long-range correlations exhibited by power spectrum scale invariance, while the other registers the effect of disordering elements leading to a breakdown of these properties. In the absence of long-range correlations, this parameter is sensitive to the occurrence of unlikely events. We also introduce an approximate calculation scheme that relates this dynamics to multinomial multiplicative processes. A better understanding through these models of the meaning of the generalized beta-fitting exponents may contribute to their potential for identifying and characterizing universality classes.

46 CFR 64.81 - 30-month inspection of an MPT.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false 30-month inspection of an MPT. 64.81 Section 64.81 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS... external examination for— (i) Corrosion; (ii) Cracking of base material; and (iii) Weld defects; and (2) A...

46 CFR 64.27 - Base.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Base. 64.27 Section 64.27 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.27 Base. The base of an MPT must be as wide and as long as the tank. ...

46 CFR 64.27 - Base.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Base. 64.27 Section 64.27 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.27 Base. The base of an MPT must be as wide and as long as the tank. ...

46 CFR 64.27 - Base.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Base. 64.27 Section 64.27 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.27 Base. The base of an MPT must be as wide and as long as the tank. ...

46 CFR 64.27 - Base.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Base. 64.27 Section 64.27 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.27 Base. The base of an MPT must be as wide and as long as the tank. ...

Determinants of dynamic hyperinflation during metronome-paced tachypnea in COPD and normal subjects.

PubMed

Cooper, C B; Calligaro, G L; Quinn, M M; Eshaghian, P; Coskun, F; Abrazado, M; Bateman, E D; Raine, R I

2014-01-01

In COPD, dynamic hyperinflation (DH) occurs during exercise and during metronome-paced tachypnea (MPT). We investigated the relationship of DH with breathing pattern and ventilation (V˙E) in COPD and normal subjects (NS). In 35 subjects with moderate COPD and 17 younger healthy volunteers we measured inspiratory capacity (IC), breathing frequency (fR), expiratory time (TE), ventilation (V˙E) and end-tidal carbon dioxide tension (PETCO2) at baseline and after 30s of MPT at 40breaths/min with metronome-defined I:E ratios of 1:1 and 1:2. A reduction in IC (ΔIC) was taken to indicate DH. In COPD subjects, DH correlated with TE but not with V˙E or PETCO2, and was best predicted by total lung capacity. NS also showed DH (although less than in COPD), which correlated with PETCO2 but not with fR, TE or V˙E. We conclude that MPT evokes DH in both NS and patients with COPD. TE is the most important determinant of DH during MPT in patients with COPD. Copyright © 2013 Elsevier B.V. All rights reserved.

Change in Pulmonary Function after Incentive Spirometer Exercise in Children with Spastic Cerebral Palsy: A Randomized Controlled Study

PubMed Central

Choi, Ja Young; Rha, Dong-wook

2016-01-01

Purpose The aim of this study was to investigate the effect of incentive spirometer exercise (ISE) on pulmonary function and maximal phonation time (MPT) in children with spastic cerebral palsy (CP). Materials and Methods Fifty children with CP were randomly assigned to two groups: the experimental group and the control group. Both groups underwent comprehensive rehabilitation therapy. The experimental group underwent additional ISE. The forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), and MPT were assessed as outcome measures before and after 4 weeks of training. Results There were significant improvements in FVC, FEV1, PEF, and MPT in the experimental group, but not in the control group. In addition, the improvements in FVC, FEV1, and MPT were significantly greater in the experimental group than in the control group. Conclusion The results of this randomized controlled study support the use of ISE for enhancing pulmonary function and breath control for speech production in children with CP. PMID:26996580

Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn.

PubMed

Freede, Margaret; Leasure, A Renee; Proskin, Howard M; Hatch, Daniel; Edwards, Karethy; Pascucci, MaryAnn; Smith, Patsy R

2016-01-01

This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.

Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

PubMed Central

FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

2010-01-01

Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

Markov switching multinomial logit model: An application to accident-injury severities.

PubMed

Malyshkina, Nataliya V; Mannering, Fred L

2009-07-01

In this study, two-state Markov switching multinomial logit models are proposed for statistical modeling of accident-injury severities. These models assume Markov switching over time between two unobserved states of roadway safety as a means of accounting for potential unobserved heterogeneity. The states are distinct in the sense that in different states accident-severity outcomes are generated by separate multinomial logit processes. To demonstrate the applicability of the approach, two-state Markov switching multinomial logit models are estimated for severity outcomes of accidents occurring on Indiana roads over a four-year time period. Bayesian inference methods and Markov Chain Monte Carlo (MCMC) simulations are used for model estimation. The estimated Markov switching models result in a superior statistical fit relative to the standard (single-state) multinomial logit models for a number of roadway classes and accident types. It is found that the more frequent state of roadway safety is correlated with better weather conditions and that the less frequent state is correlated with adverse weather conditions.

Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

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

Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu

Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivomore » I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential agent to improve liver function after liver surgery.« less

Evolution of surface and deep water conditions in the Antarctic Southern Ocean across the MPT

NASA Astrophysics Data System (ADS)

Hasenfratz, A. P.; Jaccard, S.; Martinez-Garcia, A.; Hodell, D. A.; Vance, D.; Bernasconi, S. M.; Kleiven, H. F.; Haug, G. H.

2016-12-01

The mid-Pleistocene transition (MPT; 1.25-0.7 Myr) marked a fundamental change in the periodicity of the climate cycles, shifting from a 41-kyr to a high-amplitude, asymmetric 100-kyr cycle without any noticeable change in orbital forcing. Hypotheses to explain the MPT involve non-linear responses to orbital forcing, changes in glacial dynamics and internal changes in the carbon cycle. Specifically, a decrease in pCO2 during peak ice age conditions and the associated global cooling has been proposed as one of the possible triggers for the MPT. Previous results have indicated that the Southern Ocean provides a coherent two-part mechanism for the timing and amplitude of the glacial/interglacial pCO2 variations. However, there is still much uncertainty and debate regarding the response of the Antarctic Southern Ocean biogeochemistry to changes invoked for the MPT, and its contribution to the proposed pCO2 variations. Here, we show 1.5 Myr-long records of export production, and planktonic (Neogloboquadrina pachyderma) and benthic (Melonis pompilioides) foraminiferal stable isotopes and trace metals from ODP Site 1094 retrieved from the Atlantic sector of the Antarctic Southern Ocean (53.2°S, 5.1°E, 2807m). While glacial planktonic δ18O increases across the MPT, glacial Mg/Ca-derived SST decrease later, around 700 ka, when glacial atmospheric pCO2 has already dropped. As glacial export production that is crucially related to micronutrients upwelled from the subsurface ocean remains unchanged across the past 1.5 Myr, it seems that cooling of the glacial surface ocean did not significantly alter the stability of the water column. Furthermore, paired measurements of benthic δ18O and Mg/Ca enables the determination of seawater δ18O of the deep ocean, which allows us to estimate changes in the density gradient and the salinity of the deep water.

A manual physical therapy approach versus subacromial corticosteroid injection for treatment of shoulder impingement syndrome: a protocol for a randomised clinical trial

PubMed Central

Boyles, Robert E; Cleland, Joshua A; Brown, David L

2011-01-01

Introduction Corticosteroid injections (CSI) are a recommended and often-used first-line intervention for shoulder impingement syndrome (SIS) in primary care and orthopaedic settings. Manual physical therapy (MPT) offers a non-invasive approach with negligible risk for managing SIS. There is limited evidence to suggest significant long-term improvements in pain, strength and disability with the use of MPT, and there are conflicting reports from systematic reviews that question the long-term efficacy of CSI. Specifically, the primary objective is to compare the effect of CSI and MPT on pain and disability in subjects with SIS at 12 months. Design This pragmatic randomised clinical trial will be a mixed-model 2×5 factorial design. The independent variables are treatment (MPT and CSI) and time with five levels from baseline to 1 year. The primary dependent variable is the Shoulder Pain and Disability Index, and the secondary outcome measures are the Global Rating of Change and the Numeric Pain Rating Scale. For each ANOVA, the hypothesis of interest will be the two-way group-by-time interaction. Methods and analysis The authors plan to recruit 104 participants meeting established impingement criteria. Following examination and enrolment, eligible participants will be randomly allocated to receive a pragmatic approach of either CSI or MPT. The MPT intervention will consist of six sessions, and the CSI intervention will consist of one to three sessions. All subjects will continue to receive usual care. Subjects will be followed for 12 months. Dissemination and ethics The protocol was approved by the Madigan Army Medical Center Institutional Review Board. The results may have an impact on clinical practice guidelines. This study was funded in part by the Orthopaedic Physical Therapy Products Grant through the American Academy of Orthopaedic Manual Physical Therapists. Trial Registration http://clinicaltrials.gov/ NCT01190891. PMID:22021870

Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

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

Lim, M.S.; Lim, Priscilla L.K.; Gupta, Rashi

2006-12-15

Diclofenac is a widely used nonsteroidal anti-inflammatory drug that has been associated with rare but serious hepatotoxicity. Experimental evidence indicates that diclofenac targets mitochondria and induces the permeability transition (mPT) which leads to apoptotic cell death in hepatocytes. While the downstream effector mechanisms have been well characterized, the more proximal pathways leading to the mPT are not known. The purpose of this study was to explore the role of free cytosolic calcium (Ca{sup 2+} {sub c}) in diclofenac-induced cell injury in immortalized human hepatocytes. We show that exposure to diclofenac caused time- and concentration-dependent cell injury, which was prevented bymore » the specific mPT inhibitor cyclosporin A (CsA, 5 {mu}M). At 8 h, diclofenac caused increases in [Ca{sup 2+}]{sub c} (Fluo-4 fluorescence), which was unaffected by CsA. Combined exposure to diclofenac/BAPTA (Ca{sup 2+} chelator) inhibited cell injury, indicating that Ca{sup 2+} plays a critical role in precipitating mPT. Diclofenac decreased the mitochondrial membrane potential, {delta}{psi}{sub m} (JC-1 fluorescence), even in the presence of CsA or BAPTA, indicating that mitochondrial depolarization was not a consequence of the mPT or elevated [Ca{sup 2+}]{sub c}. The CYP2C9 inhibitor sulphaphenazole (10 {mu}M) protected from diclofenac-induced cell injury and prevented increases in [Ca{sup 2+}]{sub c}, while it had no effect on the dissipation of the {delta}{psi}{sub m}. Finally, diclofenac exposure greatly increased the mitochondria-selective superoxide levels secondary to the increases in [Ca{sup 2+}]{sub c}. In conclusion, these data demonstrate that diclofenac has direct depolarizing effects on mitochondria which does not lead to cell injury, while CYP2C9-mediated bioactivation causes increases in [Ca{sup 2+}]{sub c}, triggering the mPT and precipitating cell death.« less

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

Hossain, Quazi Sohel; Department of Biochemistry, School of Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215; Ulziikhishig, Enkhbaatar

We recently reported that the glutathione transferase in rat liver mitochondrial membranes (mtMGST1) is activated by S-glutathionylation and the activated mtMGST1 contributes to the mitochondrial permeability transition (MPT) pore and cytochrome c release from mitochondria [Lee, K.K., Shimoji, M., Quazi, S.H., Sunakawa, H., Aniya, Y., 2008. Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria. Toxcol. Appl. Pharmacol. 232, 109-118]. In the present study we investigated the effect of reactive oxygen species (ROS), generator gallic acid (GA) and GST inhibitors on mtMGST1 and the MPT. When rat liver mitochondria were incubated withmore » GA, mtMGST1 activity was increased to about 3 fold and the increase was inhibited with antioxidant enzymes and singlet oxygen quenchers including 1,4-diazabicyclo [2,2,2] octane (DABCO). GA-mediated mtMGST1 activation was prevented by GST inhibitors such as tannic acid, hematin, and cibacron blue and also by cyclosporin A (CsA). In addition, GA induced the mitochondrial swelling which was also inhibited by GST inhibitors, but not by MPT inhibitors CsA, ADP, and bongkrekic acid. GA also released cytochrome c from the mitochondria which was inhibited completely by DABCO, moderately by GST inhibitors, and somewhat by CsA. Ca{sup 2+}-mediated mitochondrial swelling and cytochrome c release were inhibited by MPT inhibitors but not by GST inhibitors. When the outer mitochondrial membrane was isolated after treatment of mitochondria with GA, mtMGST1 activity was markedly increased and oligomer/aggregate of mtMGST1 was observed. These results indicate that mtMGST1 in the outer mitochondrial membrane is activated by GA through thiol oxidation leading to protein oligomerization/aggregation, which may contribute to the formation of ROS-mediated, CsA-insensitive MPT pore, suggesting a novel mechanism for regulation of the MPT by mtMGST1.« less

Trace element evidence for abrupt changes in deep South Atlantic Ocean nutrient and carbonate chemistry across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Farmer, J. R.; Hoenisch, B.; Haynes, L.; Kroon, D.; Bell, D. B.; Jung, S.; Seguí, M. J.; Raymo, M. E.; Goldstein, S. L.; Pena, L. D.

2016-12-01

Pleistocene glaciations underwent a profound transition from lower amplitude 40 kyr cycles to high amplitude 100 kyr cycles between 1.2 and 0.8 Ma, an interval termed the Mid-Pleistocene Transition (MPT). While the underlying causes of the MPT are uncertain, previous studies show quasi-contemporaneous reductions in North Atlantic Deep Water (NADW) export1 and glacial atmospheric pCO22 around 0.9 Ma. Although this suggests a possible role for enhanced deep-ocean carbon storage in amplifying climate change across the MPT, few direct records of deep ocean carbonate chemistry exist for this interval to test this hypothesis. Here we present South Atlantic benthic foraminiferal B/Ca and Cd/Ca records from International Ocean Discovery Program Sites 1088, 1264 and 1267 (2.1 to 4.3 km water depth) as part of a larger study of Atlantic-wide changes in deep ocean chemistry and circulation spanning the MPT. Results show an abrupt 15-20% decrease in benthic B/Ca and 40-50% increase in Cd/Ca at 4.3 km depth (Site 1267) between 1.0 and 0.9 Ma. Site 1088, which at 2.1 km depth is sensitive to input of southern-sourced Upper Circumpolar Deep Water, shows a prolonged 25% decrease in B/Ca and 50% increase in Cd/Ca from 1.0 to 0.6 Ma. In contrast, at Site 1264 ( 2.5 km depth within the core of modern NADW) B/Ca and Cd/Ca changes across the MPT are more modest (-5% and +10%, respectively). These observations reflect on the accumulation of regenerated carbon and nutrients in the deep South Atlantic, and varying contributions of northern- and southern-sourced watermasses to each core site. Implications for deep-ocean carbon storage and forcing of the MPT will be discussed. 1Pena, L. and Goldstein, S. (2014), Science 345, 318 2Hönisch, B. et al. (2009), Science 324, 1551

Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

PubMed Central

Thurman, Andrea Ries; Clark, Meredith R; Hurlburt, Jennifer A; Doncel, Gustavo F

2013-01-01

There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs). IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women’s health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV) genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT) products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not disrupt intercourse or have high rates of expulsion. Herein, we reviewed the microbicide and MPT IVRs currently in development, with a focus on the clinical aspects of IVR assessment and the challenges facing microbicide and MPT IVR product development, clinical testing, and implementation. The information in this review was drawn from PubMed searches and a recent microbicide/MPT product development workshop organized by CONRAD. PMID:24174884

Digital audio watermarking using moment-preserving thresholding

NASA Astrophysics Data System (ADS)

Choi, DooSeop; Jung, Hae Kyung; Choi, Hyuk; Kim, Taejeong

2007-09-01

The Moment-Preserving Thresholding technique for digital images has been used in digital image processing for decades, especially in image binarization and image compression. Its main strength lies in that the binary values that the MPT produces as a result, called representative values, are usually unaffected when the signal being thresholded goes through a signal processing operation. The two representative values in MPT together with the threshold value are obtained by solving the system of the preservation equations for the first, second, and third moment. Relying on this robustness of the representative values to various signal processing attacks considered in the watermarking context, this paper proposes a new watermarking scheme for audio signals. The watermark is embedded in the root-sum-square (RSS) of the two representative values of each signal block using the quantization technique. As a result, the RSS values are modified by scaling the signal according to the watermark bit sequence under the constraint of inaudibility relative to the human psycho-acoustic model. We also address and suggest solutions to the problem of synchronization and power scaling attacks. Experimental results show that the proposed scheme maintains high audio quality and robustness to various attacks including MP3 compression, re-sampling, jittering, and, DA/AD conversion.

[A study on vowel duration and word length of adductor spasmodic dysphonia].

PubMed

Chen, Zhipeng; Ge, Pingjiang

2016-03-01

To understand the vowel duration and statement reading of the adductor spasmodic dysphonia (ADSD) patients compared with their normal controls, and provide ideas for clinical diagnosis and treatment. Twenty-nine ADSD patients were included in the research, with 31 normal controls. All subjects filled in form voice handicap index (VHI) by themselves. Maximum phonetic time (MPT) and maximum loudness phonetic time(MLPT) were tested on /a/ sound for all patients. Also, all the patients were required to read aloud a standard mandarin assay named , duration were measured with Praat5. 0 software after sounds were collected. A one-way t-test was performed to compare spasmodic group with control group on VHI, MPT, MLPT and duration for reading standard sentences. Pearson/Spearman correlation was tested. Result: The VHI of the 29 ADSD patients is 89±12, and their normal controls 15±16, indicating that the VHI in ADSD group is significantly higher than in the control group(P<0. 01). The MPT of the ADSD group is(16. 9±9. 8 s), and the control group is (25. 3±10.0)s, indicating that MPT in the ADSD group is significantly shorter than the control group(P<0. 01). The MLPT of the ADSD group is (15.7±7. 6)s, and the control group is (26. 5±11. 4)s, indicating that MLPT in the ADSD group is significantly shorter than the control group (P<0. 01). The duration of standard sentence reading of the ADSD group is (55.0±14. 2)s, and the control group is (37. 8±4. 8)s, indicating that the duration of standard sentence reading in the ADSD group is significantly longer than the control group (P<0. 01). Correlation analysis showed that MPT and MLPT are related within the ADSD group(r=0. 697,P< 0.01), other indexes being tested have no significant correlations. The voice disorder condition of the ADSD patients is significantly worse than normal people. Their pronunciations on continuous vowels are not lasting compared with normal people. In the meantime, their ability to read sentences is worse than normal people, needing longer time to complete the reading task. There is a significant correlation between MLPT and MPT, which can be used as an alternative to MPT.

The cortisol and androgen pathways cross talk in high temperature-induced masculinization: the 11β-hydroxysteroid dehydrogenase as a key enzyme.

PubMed

Fernandino, Juan Ignacio; Hattori, Ricardo Shohei; Kishii, Ai; Strüssmann, Carlos Augusto; Somoza, Gustavo Manuel

2012-12-01

In many ectotherm species the gonadal fate is modulated by temperature early in life [temperature-dependent sex determination (TSD)] but the transducer mechanism between temperature and gonadal differentiation is still elusive. We have recently shown that cortisol, the glucocorticoid stress-related hormone in vertebrates, is involved in the TSD process of pejerrey, Odontesthes bonariensis. Particularly, all larvae exposed to a male-producing temperature (MPT, 29 C) after hatching showed increased whole-body cortisol and 11-ketotestosterone (11-KT; the main bioactive androgen in fish) levels and developed as males. Moreover, cortisol administration at an intermediate, mixed sex-producing temperature (MixPT, 24 C) caused increases in 11-KT and in the frequency of males, suggesting a relation between this glucocorticoid and androgens during the masculinization process. In order to clarify the link between stress and masculinization, the expression of hydroxysteroid dehydrogenase (hsd)11b2, glucocorticoid receptors gr1 and gr2, and androgen receptors ar1 and ar2 was analyzed by quantitative real time PCR and in situ hybridization in larvae reared at MPT, MixPT, and female-producing temperature (FPT, 17 C) during the sex determination period. We also analyzed the effects of cortisol treatment in larvae reared at MixPT and in adult testicular explants incubated in vitro. MPT and cortisol treatment produced significant increases in hsd11b2 mRNA expression. Also, gonadal explants incubated in the presence of cortisol showed increases of 11-KT levels in the medium. Taken together these results suggest that cortisol promotes 11-KT production during high temperature-induced masculinization by modulation of hsd11b2 expression and thus drives the morphogenesis of the testes.

Timber production assessment of a plantation forest: An integrated framework with field-based inventory, multi-source remote sensing data and forest management history

NASA Astrophysics Data System (ADS)

Gao, Tian; Zhu, Jiaojun; Deng, Songqiu; Zheng, Xiao; Zhang, Jinxin; Shang, Guiduo; Huang, Liyan

2016-10-01

Timber production is the purpose for managing plantation forests, and its spatial and quantitative information is critical for advising management strategies. Previous studies have focused on growing stock volume (GSV), which represents the current potential of timber production, yet few studies have investigated historical process-harvested timber. This resulted in a gap in a synthetical ecosystem service assessment of timber production. In this paper, we established a Management Process-based Timber production (MPT) framework to integrate the current GSV and the harvested timber derived from historical logging regimes, trying to synthetically assess timber production for a historical period. In the MPT framework, age-class and current GSV determine the times of historical thinning and the corresponding harvested timber, by using a ;space-for-time; substitution. The total timber production can be estimated by the historical harvested timber in each thinning and the current GSV. To test this MPT framework, an empirical study on a larch plantation (LP) with area of 43,946 ha was conducted in North China for a period from 1962 to 2010. Field-based inventory data was integrated with ALOS PALSAR (Advanced Land-Observing Satellite Phased Array L-band Synthetic Aperture Radar) and Landsat-8 OLI (Operational Land Imager) data for estimating the age-class and current GSV of LP. The random forest model with PALSAR backscatter intensity channels and OLI bands as input predictive variables yielded an accuracy of 67.9% with a Kappa coefficient of 0.59 for age-class classification. The regression model using PALSAR data produced a root mean square error (RMSE) of 36.5 m3 ha-1. The total timber production of LP was estimated to be 7.27 × 106 m3, with 4.87 × 106 m3 in current GSV and 2.40 × 106 m3 in harvested timber through historical thinning. The historical process-harvested timber accounts to 33.0% of the total timber production, which component has been neglected in the assessments for current status of plantation forests. Synthetically considering the RMSE for predictive GSV and misclassification of age-class, the error in timber production were supposed to range from -55.2 to 56.3 m3 ha-1. The MPT framework can be used to assess timber production of other tree species at a larger spatial scale, providing crucial information for a better understanding of forest ecosystem service.

46 CFR 64.77 - Inspection and test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... conducted by the owner or the owner's representative: (a) Pressure relief and vacuum relief devices must be... § 64.81. (c) An MPT must pass a hydrostatic test in accordance with § 64.83 during the 60 months before any month in which it is in service. (d) After each welded repair, an MPT must pass a hydrostatic test...

Acoustic performance of inlet multiple-pure-tone suppressors installed on NASA quiet engine C

NASA Technical Reports Server (NTRS)

Bloomer, H. E.; Schaefer, J. W.; Rice, E. J.; Feiler, C. E.

1977-01-01

The length of multiple-pure-tone (MPT) treatment required to reasonably suppress the MPT's produced by a supersonic tip speed fan was defined. Other suppression, broadband, and blade passing frequency, which might be accomplished were also determined. The experimental results are presented in terms of both far-field and duct acoustic data.

Item Specifications, Science Grade 8. Blue Prints for Testing Minimum Performance Test.

ERIC Educational Resources Information Center

Arkansas State Dept. of Education, Little Rock.

These item specifications were developed as a part of the Arkansas "Minimum Performance Testing Program" (MPT). There is one item specification for each instructional objective included in the MPT. The purpose of an item specification is to provide an overview of the general content and format of test items used to measure an…

Item Specifications, Science Grade 6. Blue Prints for Testing Minimum Performance Test.

ERIC Educational Resources Information Center

Arkansas State Dept. of Education, Little Rock.

These item specifications were developed as a part of the Arkansas "Minimum Performance Testing Program" (MPT). There is one item specification for each instructional objective included in the MPT. The purpose of an item specification is to provide an overview of the general content and format of test items used to measure an…

An INAR(1) Negative Multinomial Regression Model for Longitudinal Count Data.

ERIC Educational Resources Information Center

Bockenholt, Ulf

1999-01-01

Discusses a regression model for the analysis of longitudinal count data in a panel study by adapting an integer-valued first-order autoregressive (INAR(1)) Poisson process to represent time-dependent correlation between counts. Derives a new negative multinomial distribution by combining INAR(1) representation with a random effects approach.…

Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells

PubMed Central

Doczi, Judit; Torocsik, Beata; Echaniz-Laguna, Andoni; Mousson de Camaret, Bénédicte; Starkov, Anatoly; Starkova, Natalia; Gál, Aniko; Molnár, Mária J; Kawamata, Hibiki; Manfredi, Giovanni; Adam-Vizi, Vera; Chinopoulos, Christos

2016-01-01

The probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT’s voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the ‘thinness ratio’ and the ‘cobalt-calcein’ technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca2+ levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient. PMID:27221760

Latent factor structure of a behavioral economic marijuana demand curve.

PubMed

Aston, Elizabeth R; Farris, Samantha G; MacKillop, James; Metrik, Jane

2017-08-01

Drug demand, or relative value, can be assessed via analysis of behavioral economic purchase task performance. Five demand indices are typically obtained from drug purchase tasks. The goal of this research was to determine whether metrics of marijuana reinforcement from a marijuana purchase task (MPT) exhibit a latent factor structure that efficiently characterizes marijuana demand. Participants were regular marijuana users (n = 99; 37.4% female, 71.5% marijuana use days [5 days/week], 15.2% cannabis dependent) who completed study assessments, including the MPT, during a baseline session. Principal component analysis was used to examine the latent structure underlying MPT indices. Concurrent validity was assessed via examination of relationships between latent factors and marijuana use, past quit attempts, and marijuana expectancies. A two-factor solution was confirmed as the best fitting structure, accounting for 88.5% of the overall variance. Factor 1 (65.8% variance) reflected "Persistence," indicating sensitivity to escalating marijuana price, which comprised four MPT indices (elasticity, O max , P max , and breakpoint). Factor 2 (22.7% variance) reflected "Amplitude," indicating the amount consumed at unrestricted price (intensity). Persistence factor scores were associated with fewer past marijuana quit attempts and lower expectancies of negative use outcomes. Amplitude factor scores were associated with more frequent use, dependence symptoms, craving severity, and positive marijuana outcome expectancies. Consistent with research on alcohol and cigarette purchase tasks, the MPT can be characterized with a latent two-factor structure. Thus, demand for marijuana appears to encompass distinct dimensions of price sensitivity and volumetric consumption, with differential relations to other aspects of marijuana motivation.

Patterns of Functioning and Predictive Factors in Children Born Moderately Preterm or at Term

ERIC Educational Resources Information Center

Cserjesi, Renata; van Braeckel, Koenraad N. J. A.; Timmerman, Marieke; Butcher, Phillipa R.; Kerstjens, Jorien M.; Reijneveld, Sijmen A.; Bouma, Anke; Bos, Arend F.; Geuze, Reint H.

2012-01-01

Aim: The aim of this study was to identify subgroups of children born moderately preterm (MPT) and term with distinctive levels and patterns of functioning, and the perinatal and demographic factors that predict subgroup membership. Method: A total of 378 children aged 7 years, 248 MPT (138 males, 110 females; gestational age 32-36 wks) and a…

Low intensity ultrasound induces apoptosis via MPT channel on mitochondrial membrane: Target for regulating cancer therapy or not?

NASA Astrophysics Data System (ADS)

Feng, Yi; Wan, Mingxi

2017-03-01

To discuss how the mitochondrion is involved in low intensity ultrasound induced apoptosis, HepG2 cells were irradiated by low intensity focused ultrasound (ISPTA = 3W/cm2, 1 min) and then cultured from 3-12 h post irradiation in the study. The morphological alteration was examined by light and fluorescent microscopy respectively. Cell viability and apoptosis were examined by trypan blue staining and flow cytometry with double staining of FITC-labelled Annexin-V/PI. Key proteins responded to irradiation were screened out by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and shotgun proteomic methods with Agilent 1100 HPLC-Chip-MS technology. Representative apoptotic morphological characteristics and increased percentage of apoptotic cells were achieved. Six important proteins (4 up-regulated and 2 down-regulated) were selected and analyzed. It revealed low intensity focused ultrasound could induce apoptosis in HepG2 cells and the US-induced apoptosis was mitochondria-dependent and caspases-dependent. Moreover, mitochondrial membrane permeability transition (MPT) is related to ultrasound induced apoptosis, but VDAC may be not the main MPT channel. Understanding it could help to assist the cancer therapy by regulating the MPT as the target.

Evaluating the diagnostic specificity of the Munich Personality Test dimensions in major depression.

PubMed

Sakado, K; Sato, T; Uehara, T; Sato, S; Sakado, M; Kumagai, K

1997-05-01

This study explored the diagnostic specificity of the Munich Personality Test (MPT) in major depression, comparing its scores between patients with major depression, patients with panic disorder and control subjects. One of the 6 dimensions of the MPT, Rigidity, had been developed based on Tellenbach's description of depressive personality, and it was expected that especially this personality dimension would demonstrate a good facility for describing a specific personality feature of major depression. Comparisons were made in 2 ways: ignoring the effects of current depression and anxiety on the personality scorings; and partialling out these effects. Results of the 2 analyses differed radically. Scores on Rigidity and isolation Tendency were significantly different between groups, even after the effects of current depression and anxiety were partialled out. The multiple comparison procedure revealed that the depressive patients were differentiated from both the panic patients and the controls only in the dimension of Rigidity. The results of this study suggest that the Rigidity dimension of MPT may have a strong capability for describing the specific personality feature of depressive patients, and that the MPT may be quite useful for studies, particularly prospective ones, investigating premorbid personality of depression.

Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage

PubMed Central

Li, Pengyun; Meng, Xianzhong; Bian, Huining; Burns, Nana; Zhao, Ke-seng; Song, Rui

2015-01-01

Vascular hyporeactivity is one of the major causes responsible for refractory hypotension and associated mortality in severe hemorrhagic shock. Mitochondrial permeability transition (mPT) pore opening in arteriolar smooth muscle cells (ASMCs) is involved in the pathogenesis of vascular hyporeactivity. However, the molecular mechanism underlying mitochondrial injury in ASMCs during hemorrhagic shock is not well understood. Here we produced an in vivo model of severe hemorrhagic shock in adult Wistar rats. We found that sirtuin (SIRT)1/3 protein levels and deacetylase activities were decreased in ASMCs following severe shock. Immunofluorescence staining confirmed reduced levels of SIRT1 in the nucleus and SIRT3 in the mitochondria, respectively. Acetylation of cyclophilin D (CyPD), a component of mPT pore, was increased. SIRT1 activators suppressed mPT pore opening and ameliorated mitochondrial injury in ASMCs after severe shock. Furthermore, administration of SIRT1 activators improved vasoreactivity in rats under severe shock. Our data suggest that epigenetic mechanisms, namely histone post-translational modifications, are involved in regulation of mPT by SIRT1/SIRT3- mediated deacetylation of CyPD. SIRT1/3 is a promising therapeutic target for the treatment of severe hemorrhagic shock. PMID:26473372

Theoretical insights into the energetics and electronic properties of MPt12 (M = Fe, Co, Ni, Cu, and Pd) nanoparticles supported by N-doped defective graphene

NASA Astrophysics Data System (ADS)

Wang, Qing; Tian, Yu; Chen, Guangju; Zhao, Jingxiang

2017-03-01

Enhancing the catalytic activity and decreasing the usage of Pt catalysts has been a major target in widening their applications for developing proton-exchange membrane fuel cells. In this work, the adsorption energetics, structural features, and electronic properties of several MPt12 (M = Fe, Co, Ni, Cu, and Pd) nanoparticles (NPs) deposited on N-doped defective graphene were systemically explored by means of comprehensive density functional theory (DFT) computations. The computations revealed that the defective N-doped graphene substrate can provide anchoring site for these Pt-based alloying NPs due to their strong hybridization with the sp2 dangling bonds at the defect sites of substrate. Especially, these deposited MPt12 NPs exhibit reduced magnetic moment and their average d-band centers are shifted away from the Fermi level, as compared with the freestanding NPs, leading to the reduction of the adsorption energies of the O species. Thus, the defective N-doped graphene substrate not only enhances the stability of the deposited MPt12 NPs, but also endows them higher catalytic performance for the oxygen reduction reaction.

Intensive Study on the Catalytical Behavior of N-Methylphenothiazine as a Soluble Mediator to Oxidize the Li2O2 Cathode of the Li-O2 Battery.

PubMed

Feng, Ningning; Mu, Xiaowei; Zhang, Xueping; He, Ping; Zhou, Haoshen

2017-02-01

Aprotic Li-O 2 batteries have attracted worldwide interest owing to their ultrahigh theoretical energy density. However, the practical Li-O 2 batteries still suffer from high charge overpotential and low energy efficiency resulting from the sluggish kinetics in electrochemically oxidizing the insulating lithium peroxide (Li 2 O 2 ). Recently, dissolved redox mediators in the electrolyte have enabled the effective catalytic oxidation of Li 2 O 2 at the liquid-solid interface. Here, we report that the incorporation of N-methylphenothiazine (MPT), as a redox shuttle in Li-O 2 batteries, provides a dramatic reduction in charge overpotential to 0.67 V and an improved round-trip efficiency close to 76%. Moreover, the efficacy of MPT in Li-O 2 cells was further investigated by various characterizations. On charging, MPT + cations are first generated electrochemically at the cathode surface and subsequently oxidize the solid discharge products Li 2 O 2 through a chemical reaction. Furthermore, the presence of MPT has been demonstrated to improve the cycling stability of the cells and suppress side reactions arising from carbon and electrolytes at high potentials.

The Source of Adult Age Differences in Event-Based Prospective Memory: A Multinomial Modeling Approach

ERIC Educational Resources Information Center

Smith, Rebekah E.; Bayen, Ute J.

2006-01-01

Event-based prospective memory involves remembering to perform an action in response to a particular future event. Normal younger and older adults performed event-based prospective memory tasks in 2 experiments. The authors applied a formal multinomial processing tree model of prospective memory (Smith & Bayen, 2004) to disentangle age differences…

Judgments of Learning are Influenced by Multiple Cues In Addition to Memory for Past Test Accuracy.

PubMed

Hertzog, Christopher; Hines, Jarrod C; Touron, Dayna R

When people try to learn new information (e.g., in a school setting), they often have multiple opportunities to study the material. One of the most important things to know is whether people adjust their study behavior on the basis of past success so as to increase their overall level of learning (for example, by emphasizing information they have not yet learned). Monitoring their learning is a key part of being able to make those kinds of adjustments. We used a recognition memory task to replicate prior research showing that memory for past test outcomes influences later monitoring, as measured by judgments of learning (JOLs; confidence that the material has been learned), but also to show that subjective confidence in whether the test answer and the amount of time taken to restudy the items also have independent effects on JOLs. We also show that there are individual differences in the effects of test accuracy and test confidence on JOLs, showing that some but not all people use past test experiences to guide monitoring of their new learning. Monitoring learning is therefore a complex process of considering multiple cues, and some people attend to those cues more effectively than others. Improving the quality of monitoring performance and learning could lead to better study behaviors and better learning. An individual's memory of past test performance (MPT) is often cited as the primary cue for judgments of learning (JOLs) following test experience during multi-trial learning tasks (Finn & Metcalfe, 2007; 2008). We used an associative recognition task to evaluate MPT-related phenomena, because performance monitoring, as measured by recognition test confidence judgments (CJs), is fallible and varies in accuracy across persons. The current study used multilevel regression models to show the simultaneous and independent influences of multiple cues on Trial 2 JOLs, in addition to performance accuracy (the typical measure of MPT in cued-recall experiments). These cues include recognition CJs, perceived recognition fluency, and Trial 2 study time allocation (an index of reprocessing fluency). Our results expand the scope of MPT-related phenomena in recognition memory testing to show independent effects of recognition test accuracy and CJs on second-trial JOLs, while also demonstrating individual differences in the effects of these cues on JOLs (as manifested in significant random effects for those regression effects in the model). The effect of study time on second-trial JOLs controlling on other variables, including Trial 1 recognition memory accuracy, also demonstrates that second-trial encoding behavior influence JOLs in addition to MPT.

Thermohaline Circulation Crisis and Changes Through the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Goldstein, S. L.; Pena, L.

2013-12-01

The Mid-Pleistocene Transition (MPT) marked a fundamental change in glacial-interglacial periodicity, transitioning from ~41,000 to 100,000 year cycles, accompanied by higher amplitude climate variability. It occurred without a significant change in orbital forcing, and thus its causes are poorly understood. We report major changes in the pre- and post-MPT mode of the ocean thermohaline circulation (THC), and a THC crisis during the MPT, from Nd isotopes in ODP Sites 1088 (~42S, 2082m) and 1090 (~43S, 3702m). The core locations are at the transition between the South Atlantic and the Southern oceans, a major gateway for the exchange of northern- and southern-sourced water masses. The new data show that in the ';40-kyr world' prior to the MPT, NADW export was strong during both interglacials and glacials. At ~900 ka the THC system underwent a major crisis, with an unprecedented weakening in NADW export during Marine Isotope Stages (MIS) 22-24. The recovery of the THC system in the post-MPT ';100-kyr world' is characterized by strong THC during interglacials, similar to pre-MPT interglacials, but much weaker THC during glacials. The ';THC crisis' interval includes MIS 23, which is unique as an interglacial where the THC operated in the same weak mode as post-MPT glacials. The MIS 22-24 interval has been recognized as a time of abrupt atmospheric pCO2 drawdown (Hoenisch et al. 2009) and significant cooling of ocean deep water, and Antarctic ice sheet expansion (Elderfield et al. Science 2012). Our data indicate that THC changes played an important role as a primary driving force, and helped to generate a series of positive feedbacks. This drastic change in deep-ocean circulation had important implications for the coeval drawdown of atmospheric pCO2, and the absence of a strong THC system through a glacial-to-interglacial-to-glacial cycle had a major impact on high latitude ice sheet growth. We suggest that the weak NADW export during MIS 24-22 resulted in reduced vertical exchange between Antarctic surface and deep waters, which helped to induce the drop in atmospheric pCO2, and in turn generated significant cooling which facilitated ice sheet expansion. These impacts were amplified by anomalously low Southern Hemisphere summer insolation during MIS 23, which resulted in suppressed ice sheet melting. Increased sea-ice coverage around the Antarctic continent during this time period may have generated increased AABW formation, which would have further drawn down CO2 from the atmosphere.

Phthalocyanine Tetraamine Epoxy-Curing Agents

NASA Technical Reports Server (NTRS)

Fohlen, G. M.; Achar, B. N.; Parker, J. A.

1986-01-01

Tough fire- and chemical-resistant epoxies produced by using metalphthalocyanine tetraamines (MPT's) of copper, cobalt, or nickel as curing agents. Synthesis of MPT's commercially realizable and gives pure compounds with almost 90-percent yield. Synthesis applicable for metals with atomic radii of about 1.35 angstroms, including Cu, Co, Ni, Zn, Fe, Pt, Al, and V. Possible to use metal phthalocyanines to cure epoxy resins in homogeneous reaction.

Comparative Anatomy of Maintenance Tasks (CAMT): A Feasibility Study

DTIC Science & Technology

1992-03-01

systems. Methods for task primitive definition were developed, then taken into the field for testing . Task primitives were defined to cover three remove...engine maintenance) and to test whether task primitives developed for one weapon system could have applicability to other weapon systems (Phase 2...requirements, levying MPT constraints and predicting MPT requirements are only ritualistic exercises until the operational test and evaluation of a

Antitumor triptycene analogs directly interact with isolated mitochondria to rapidly trigger markers of permeability transition.

PubMed

Perchellet, Elisabeth M; Wang, Yang; Lou, Kaiyan; Zhao, Huiping; Battina, Srinivas K; Hua, Duy H; Perchellet, Jean-Pierre H

2007-01-01

Substituted triptycenes (TT code number), which block nucleoside transport, macromolecule syntheses and DNA topoisomerase activities, induce cytochrome c release and apoptotic DNA fragmentation, inhibit the proliferation of drug-sensitive and -resistant tumor cells in the nM range in vitro and rapidly trigger the collapse of mitochondrial transmembrane potential in cell and cell-free systems. Because mitochondrial permeability transition (MPT) requires more than depolarization, antitumor TTs were tested for their ability to directly trigger specific markers of MPT in isolated mitochondria. Large amplitude swelling and Ca2+ release were assayed in isolated mitochondria to demonstrate TT-induced MPT. Antitumor TTs interact with isolated mitochondria in a concentration- and time-dependent manner to rapidly cause large amplitude swelling and Ca2+ release in relation with their antiproliferative activities in L1210, HL-60 and LL/2 tumor cells in vitro. The ability of 4-10 uM TT15, TT16 and TT24 to maximally induce mitochondrial swelling and Ca2+ release within 20 min is similar to that of classic MPT inducers, such as 5 microg/ml alamethicin, 200 microM atractyloside, 5 microM phenylarsine oxide, 100 microM arsenic trioxide and a 100 microM Ca2+ overload. TT15 requires a priming concentration of 20 microM Ca2+ to trigger mitochondrial swelling and Ca2+ release and these 0.1 microM ruthenium red-sensitive MPT events are abolished by 1 microM cyclosporin A, 2 mM ADP and 20 microM bongkrekic acid, which block components of the permeability transition pore (PTP), and by 50-100 microM of various ubiquinones, which interact with the quinone binding site of the PTP and raise the Ca2+ load required for PTP opening. Antitumor TTs that trigger MPT in isolated mitochondria might interact with components of the PTP to boost its Ca2+-sensitive transition from the closed to the open state and might be valuable to develop mitochondriotoxic drugs that directly activate early components of apoptosis.

Lenticular mitoprotection. Part B: GSK-3β and regulation of mitochondrial permeability transition for lens epithelial cells in atmospheric oxygen

PubMed Central

Brooks, Morgan M.; Neelam, Sudha

2013-01-01

Purpose Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient that leads to mitochondrial membrane permeability transition (mMPT). This study emphasizes the role of glycogen synthase kinase 3beta (GSK-3β) in maintaining mitochondrial membrane potential, thus preventing mitochondrial depolarization (hereafter termed mitoprotection). Using 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), an inhibitor of GSK-3β, and drawing a distinction between it and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), an inhibitor of extracellular-signal-regulated kinase (ERK) phosphorylation, the means by which GSK-3β influences mitoprotection in cultured human lens epithelial (HLE-B3) cells and normal, secondary cultures of bovine lens epithelial cells, maintained in atmospheric oxygen, was investigated. Methods Virally transfected human lens epithelial cells (HLE-B3) and normal cultures of bovine lens epithelial cells were exposed to acute hypoxic conditions (about 1% O2) followed by exposure to atmospheric oxygen (about 21% O2). Specific antisera and western blot analysis was used to examine the state of phosphorylation of ERK and GSK-3β, as well as the phosphorylation of a downstream substrate of GSK-3β, glycogen synthase (GS, useful in monitoring GSK-3β activity). The potentiometric dye, 1H-benzimidazolium-5,6-dichloro-2-[3-(5,6-dichloro-1,3-diethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-1-propenyl]-1,3-diethyl-iodide (JC-1), was used to monitor mitochondrial depolarization upon exposure of inhibitor treatment relative to the control cells (mock inhibition) in atmospheric oxygen. Caspase-3 activation was scrutinized to determine whether mitochondrial depolarization inevitably leads to apoptosis. Results Treatment of HLE-B3 cells with SB216763 (12 µM) inactivated GSK-3β activity as verified by the enzyme’s inability to phosphorylate its substrate, GS. SB216763-treated cells were not depolarized relative to the control cells as demonstrated with JC-1 fluorescent dye analysis. The HLE-B3 cells treated with UO126, which similarly blocked phosphorylation of GS, were nevertheless prone to mMPT relative to the control cells. Western blot analysis determined that Bcl-2-associated X (BAX) levels were unchanged for SB216763-treated or UO126-treated HLE-B3 cells when compared to their respective control cells. However, unlike the SB216763-treated cells, the UO126-treated cells showed a marked absence of Bcl-2, as well as phosphorylated Bcl-2 relative to the controls. UO126 treatment of bovine lens epithelial cells showed similar results with pBcl-2 levels, while the Bcl-2 content appeared unchanged relative to the control cells. HLE-B3 and normal bovine lens cell cultures showed susceptibility to mMPT associated with the loss of pBcl-2 by UO126 treatment. Conclusions Mitochondrial depolarization may occur by one of two key occurrences: interruption of the electrochemical gradient across the inner mitochondrial membrane resulting in mMPT or by disruption of the integrity of the inner or outer mitochondrial membrane. The latter scenario is generally tightly regulated by members of the Bcl-2 family of proteins. Inhibition of GSK-3β activity by SB216763 blocks mMPT by preventing the opening of the mitochondrial permeability transition pore. UO126, likewise, inhibits GSK-3β activity, but unlike SB216763, inhibition of ERK phosphorylation induces the loss of intracellular pBcl-2 levels under conditions where intracellular BAX levels remain constant. These results suggest that the lenticular mitoprotection normally afforded by the inactivation of GSK-3β activity may, however, be bypassed by a loss of pBcl-2, an anti-apoptotic member of the Bcl-2 family. Bcl-2 prevents the translocation of BAX to the mitochondrial outer membrane inhibiting depolarization by disrupting the normal electrochemical gradient leading to mMPT. PMID:24319338

Lenticular mitoprotection. Part B: GSK-3β and regulation of mitochondrial permeability transition for lens epithelial cells in atmospheric oxygen.

PubMed

Brooks, Morgan M; Neelam, Sudha; Cammarata, Patrick R

2013-01-01

Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient that leads to mitochondrial membrane permeability transition (mMPT). This study emphasizes the role of glycogen synthase kinase 3beta (GSK-3β) in maintaining mitochondrial membrane potential, thus preventing mitochondrial depolarization (hereafter termed mitoprotection). Using 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), an inhibitor of GSK-3β, and drawing a distinction between it and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), an inhibitor of extracellular-signal-regulated kinase (ERK) phosphorylation, the means by which GSK-3β influences mitoprotection in cultured human lens epithelial (HLE-B3) cells and normal, secondary cultures of bovine lens epithelial cells, maintained in atmospheric oxygen, was investigated. Virally transfected human lens epithelial cells (HLE-B3) and normal cultures of bovine lens epithelial cells were exposed to acute hypoxic conditions (about 1% O2) followed by exposure to atmospheric oxygen (about 21% O2). Specific antisera and western blot analysis was used to examine the state of phosphorylation of ERK and GSK-3β, as well as the phosphorylation of a downstream substrate of GSK-3β, glycogen synthase (GS, useful in monitoring GSK-3β activity). The potentiometric dye, 1H-benzimidazolium-5,6-dichloro-2-[3-(5,6-dichloro-1,3-diethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-1-propenyl]-1,3-diethyl-iodide (JC-1), was used to monitor mitochondrial depolarization upon exposure of inhibitor treatment relative to the control cells (mock inhibition) in atmospheric oxygen. Caspase-3 activation was scrutinized to determine whether mitochondrial depolarization inevitably leads to apoptosis. Treatment of HLE-B3 cells with SB216763 (12 µM) inactivated GSK-3β activity as verified by the enzyme's inability to phosphorylate its substrate, GS. SB216763-treated cells were not depolarized relative to the control cells as demonstrated with JC-1 fluorescent dye analysis. The HLE-B3 cells treated with UO126, which similarly blocked phosphorylation of GS, were nevertheless prone to mMPT relative to the control cells. Western blot analysis determined that Bcl-2-associated X (BAX) levels were unchanged for SB216763-treated or UO126-treated HLE-B3 cells when compared to their respective control cells. However, unlike the SB216763-treated cells, the UO126-treated cells showed a marked absence of Bcl-2, as well as phosphorylated Bcl-2 relative to the controls. UO126 treatment of bovine lens epithelial cells showed similar results with pBcl-2 levels, while the Bcl-2 content appeared unchanged relative to the control cells. HLE-B3 and normal bovine lens cell cultures showed susceptibility to mMPT associated with the loss of pBcl-2 by UO126 treatment. MITOCHONDRIAL DEPOLARIZATION MAY OCCUR BY ONE OF TWO KEY OCCURRENCES: interruption of the electrochemical gradient across the inner mitochondrial membrane resulting in mMPT or by disruption of the integrity of the inner or outer mitochondrial membrane. The latter scenario is generally tightly regulated by members of the Bcl-2 family of proteins. Inhibition of GSK-3β activity by SB216763 blocks mMPT by preventing the opening of the mitochondrial permeability transition pore. UO126, likewise, inhibits GSK-3β activity, but unlike SB216763, inhibition of ERK phosphorylation induces the loss of intracellular pBcl-2 levels under conditions where intracellular BAX levels remain constant. These results suggest that the lenticular mitoprotection normally afforded by the inactivation of GSK-3β activity may, however, be bypassed by a loss of pBcl-2, an anti-apoptotic member of the Bcl-2 family. Bcl-2 prevents the translocation of BAX to the mitochondrial outer membrane inhibiting depolarization by disrupting the normal electrochemical gradient leading to mMPT.

Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.

PubMed

Harris-Hayes, Marcie; Czuppon, Sylvia; Van Dillen, Linda R; Steger-May, Karen; Sahrmann, Shirley; Schootman, Mario; Salsich, Gretchen B; Clohisy, John C; Mueller, Michael J

2016-06-01

Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.

Manganese ions enhance mitochondrial H2O2 emission from Krebs cycle oxidoreductases by inducing permeability transition.

PubMed

Bonke, Erik; Siebels, Ilka; Zwicker, Klaus; Dröse, Stefan

2016-10-01

Manganese-induced toxicity has been linked to mitochondrial dysfunction and an increased generation of reactive oxygen species (ROS). We could recently show in mechanistic studies that Mn 2+ ions induce hydrogen peroxide (H 2 O 2 ) production from the ubiquinone binding site of mitochondrial complex II (II Q ) and generally enhance H 2 O 2 formation by accelerating the rate of superoxide dismutation. The present study with intact mitochondria reveals that manganese additionally enhances H 2 O 2 emission by inducing mitochondrial permeability transition (mPT). In mitochondria fed by NADH-generating substrates, the combination of Mn 2+ and different respiratory chain inhibitors led to a dynamically increasing H 2 O 2 emission which was sensitive to the mPT inhibitor cyclosporine A (CsA) as well as Ru-360, an inhibitor of the mitochondrial calcium uniporter (MCU). Under these conditions, flavin-containing enzymes of the mitochondrial matrix, e.g. the mitochondrial 2-oxoglutaratedehydrogenase (OGDH), were major sources of ROS. With succinate as substrate, Mn 2+ stimulated ROS production mainly at complex II, whereby the applied succinate concentration had a marked effect on the tendency for mPT. Also Ca 2+ increased the rate of H 2 O 2 emission by mPT, while no direct effect on ROS-production of complex II was observed. The present study reveals a complex scenario through which manganese affects mitochondrial H 2 O 2 emission: stimulating its production from distinct sites (e.g. site II Q ), accelerating superoxide dismutation and enhancing the emission via mPT which also leads to the loss of soluble components of the mitochondrial antioxidant systems and favors the ROS production from flavin-containing oxidoreductases of the Krebs cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of Multiplane-Transmit Beamforming for Real-Time Volumetric Cardiac Imaging: A Simulation Study.

PubMed

Chen, Yinran; Tong, Ling; Ortega, Alejandra; Luo, Jianwen; D'hooge, Jan

2017-04-01

Today's 3-D cardiac ultrasound imaging systems suffer from relatively low spatial and temporal resolution, limiting their applicability in daily clinical practice. To address this problem, 3-D diverging wave imaging with spatial coherent compounding (DWC) as well as 3-D multiline-transmit (MLT) imaging have recently been proposed. Currently, the former improves the temporal resolution significantly at the expense of image quality and the risk of introducing motion artifacts, whereas the latter only provides a moderate gain in volume rate but mostly preserves quality. In this paper, a new technique for real-time volumetric cardiac imaging is proposed by combining the strengths of both approaches. Hereto, multiple planar (i.e., 2-D) diverging waves are simultaneously transmitted in order to scan the 3-D volume, i.e., multiplane transmit (MPT) beamforming. The performance of a 3MPT imaging system was contrasted to that of a 3-D DWC system and that of a 3-D MLT system by computer simulations during both static and moving conditions of the target structures while operating at similar volume rate. It was demonstrated that for stationary targets, the 3MPT imaging system was competitive with both the 3-D DWC and 3-D MLT systems in terms of spatial resolution and sidelobe levels (i.e., image quality). However, for moving targets, the image quality quickly deteriorated for the 3-D DWC systems while it remained stable for the 3MPT system while operating at twice the volume rate of the 3-D-MLT system. The proposed MPT beamforming approach was thus demonstrated to be feasible and competitive to state-of-the-art methodologies.

Repeated Famotidine Administration Results in a Diminished Effect on Intragastric pH in Dogs.

PubMed

Tolbert, M K; Graham, A; Odunayo, A; Price, J; Steiner, J M; Newkirk, K; Hecht, S

2017-01-01

Famotidine is an acid suppressant commonly administered to dogs. Prolonged famotidine use in people results in decreased efficacy, but the effect in dogs is unknown. To compare the effect of repeated oral administration of famotidine or placebo on intragastric pH and serum gastrin in dogs. We hypothesized that famotidine would have a diminished effect on intragastric pH on day 13 compared to day 1. Six healthy adult colony Beagles. Randomized, 2-factor repeated-measures crossover design. All dogs received oral placebo or 1.0 mg/kg famotidine q12h for 14 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH on treatment days 1-2 and 12-13. Mean pH as well as mean percentage time (MPT) that intragastric pH was ≥3 or ≥4 were compared between and within groups by analysis of variance. Serum gastrin was measured on days 0, 3, and 12 for each treatment. Continued administration of famotidine resulted in a significant decrease in mean pH, MPT ≥3, and MPT ≥4 (P < .0001) on day 12 and 13. This resulted in a mean decrease in pH by 1.63 on days 12 and 13 compared to days 1 and 2. Furthermore, a mean decrease of MPT ≥3 and MPT ≥4 by 33 and 45% was observed for the same time period, respectively. Continued administration of famotidine results in a diminished effect on intragastric pH in dogs. Caution is advised when recommending long-term, daily oral administration of famotidine to dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Microwave plasma torch mass spectrometry for the direct detection of copper and molybdenum ions in aqueous liquids.

PubMed

Xiong, Xiaohong; Jiang, Tao; Zhou, Runzhi; Wang, Shangxian; Zou, Wei; Zhu, Zhiqiang

2016-05-01

Microwave plasma torch (MPT) is a simple and low power-consumption ambient ion source. And the MPT Mass spectra of many metal elements usually exhibit some novel features different from their inductively coupled plasma (ICP) mass spectra, which may be helpful for metal element analysis. Here, we presented the results about the MPT mass spectra of copper and molybdenum elements by a linear ion trap mass spectrometer (LTQ). The generated copper or molybdenum contained ions in plasma were characterized further in collision-induced dissociated (CID) experiments. These researches built a novel, direct and sensitive method for the direct analysis of trace levels of copper and molybdenum in aqueous liquids. Quantitative results showed that the limit of detection (LOD) by using MS(2) procedure was estimated to be 0.265 µg/l (ppb) for copper and 0.497 µg/l for molybdenum. The linear dynamics ranges cover at least 2 orders of magnitude and the analysis of a single aqueous sample can be completed in 5-6 min with a reasonable semi-quantitative sense. Two practical aqueous samples, milk and urine, were also analyzed qualitatively with reasonable recovery rates and RSD. These experimental data demonstrated that the MPT MS is able to turn into a promising and hopeful tool in field analysis of copper and molybdenum ions in water and some aqueous media, and can be applied in many fields, such as environmental controlling, hydrogeology, and water quality inspection. Moreover, MPT MS could also be used as the supplement of ICP-MS for the rapid and in-situ analysis of metal ions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

First multiphoton tomography of brain in man

NASA Astrophysics Data System (ADS)

König, Karsten; Kantelhardt, Sven R.; Kalasauskas, Darius; Kim, Ella; Giese, Alf

2016-03-01

We report on the first two-photon in vivo brain tissue imaging study in man. High resolution in vivo histology by multiphoton tomography (MPT) including two-photon FLIM was performed in the operation theatre during neurosurgery to evaluate the feasibility to detect label-free tumor borders with subcellular resolution. This feasibility study demonstrates, that MPT has the potential to identify tumor borders on a cellular level in nearly real-time.

Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

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

Santra, Amal; Chowdhury, Abhijit; Ghatak, Subhadip

2007-04-15

Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology.more » Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects.« less

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

PubMed

O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

2012-09-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

PubMed Central

O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

2012-01-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius.

PubMed

Johnston, Christopher D; Bannantine, John P; Govender, Rodney; Endersen, Lorraine; Pletzer, Daniel; Weingart, Helge; Coffey, Aidan; O'Mahony, Jim; Sleator, Roy D

2014-01-01

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease.

Investigating the Incorporation of Personality Constructs into IMPRINT

DTIC Science & Technology

2009-02-01

early in the system acquisition process. The U.S. Navy took the lead by developing the HARDMAN Comparability Methodology (HCM) to analyze the trade...space between hardware and manpower. Subsequently, the U.S. Army then adapted HCM, renamed HARDMAN I to include a broader range of weapon systems. A...subsequent evolution by the U.S. Army automated the process and was called HARDMAN II. In the mid to late 1980s HARDMAN II evolved, linking MPT to

Sex Differences in Pitch Range and Speech Fundamental Frequency After Arytenoid Adduction and Thyroplasty.

PubMed

Konomi, Ujimoto; Watanabe, Yusuke; Komazawa, Daigo

2016-05-01

The purpose of this study was to clarify the sex differences in pitch range (PR) and speech fundamental frequency (SFF) after arytenoid adduction (AA) combined with type 1 thyroplasty (TP1) in patients with unilateral vocal fold paralysis (UVFP) and to assess the cause of these differences. This is a retrospective review of clinical records. The records of 50 patients with UVFP for whom PR, SFF, and maximum phonation time (MPT) had been evaluated before and 1 year after AA combined with TP1 were analyzed. Patients consisted of 36 men and 14 women. In particular, in the 37 patients (24 men and 13 women) who had ≥2 semitones (STs) in preoperative PR (pre-PR), the differences and correlations between the pre-PR and the postoperative PR (post-PR), SFF, and MPT were compared between the sexes. We also discussed cases of post-PR deterioration and abnormal SFF. The characteristics of PR in men are narrow pre-PR (14.7 ± 11.5 STs) and significant extension of post-PR (22.6 ± 6.3 STs). MPT extended from 4.6 ± 2.5 seconds to 14.8 ± 7.2 seconds. In contrast, women had a wide pre-PR (18.1 ± 7.2 STs) and showed no significant post-PR extension (21.7 ± 7.8 STs). MPT extended from 5.1 ± 1.9 seconds to 16.8 ± 7.2 seconds. Although there were no significant changes in average SFF, as well as the highest and lowest pitch after the operation, the variance of the pre-SFF tended to converge into the physiological range in the post-SFF (P = 0.08). Compared with the SFF data of normal adult controls, post-SFF in the normal range was 46.0% (23/50). In patients who showed a >20% improvement in PR, normal post-SFF appeared in 68.8% of the patients (11/16). Particularly in those women, 83.3% (5/6) showed a normal post-SFF. Men showed greater difficulty in recovery of normal PR, SFF, and MPT; however, there were fewer patients (4.2%; 1/24) with a PR deterioration of >20%. Regarding women, although some patients showed a parallel recovery in PR and SFF to the normal range, there was a high rate of patients showing PR deterioration (30.8%; 4/13). AA combined with TP1 resulted in the recovery of not only MPT but also PR and SFF. In addition, sex differences in operative effects were suggested. In men, although MPT is difficult to be fully recovered, PR deterioration was mild. In women, although MPT was more easily extended, PR deterioration occurred more readily because of operative effects such as hypermedialization of their smaller larynx. The post-PR variation appeared to be associated with SFF. Our results indicate the necessity to assess patients' PR and SFF even if their MPTs recover, particularly in patients with postoperative voice insufficiency. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Spectrophotometric Determination of Metoprolol Tartrate in Pharmaceutical Dosage Forms on Complex Formation with Cu(II)

PubMed Central

Cesme, Mustafa; Tarinc, Derya; Golcu, Aysegul

2011-01-01

A new, simple, sensitive and accurate spectrophotometric method has been developed for the assay of metoprolol tartrate (MPT), which is based on the complexation of drug with copper(II) [Cu(II)] at pH 6.0, using Britton-Robinson buffer solution, to produce a blue adduct. The latter has a maximum absorbance at 675 nm and obeys Beer's law within the concentration range 8.5-70 μg/mL. Regression analysis of the calibration data showed a good correlation coefficient (r = 0.998) with a limit of detection of 5.56 μg/mL. The proposed procedure has been successfully applied to the determination of this drug in its tablets. In addition, the spectral data and stability constant for the binuclear copper(II) complex of MPT (Cu2MPT2Cl2) have been reported.

Protection of ischaemic-reperfused rat heart by dimethylamiloride is associated with inhibition of mitochondrial permeability transition.

PubMed

Prendes, María G Marina; Torresín, Emilia; González, Marcela; Fernández, María A; Perazzo, Juan C; Savino, Enrique A; Varela, Alicia

2008-02-01

1. The aim of the present study was to assess whether protection afforded by the Na(+)/H(+) exchanger blocker dimethylamiloride (DMA) is associated with inhibition of mitochondrial permeability transition (MPT). The effects of DMA were compared with those of cyclosporine (Cs) A, an inhibitor of MPT. 2. Rat hearts were Langendorff perfused with Krebs'-bicarbonate medium containing 10 mmol/L glucose and were subjected to 25 min no-flow global ischaemia and 30 min reperfusion in the presence or absence of 10 micromol/L DMA or 0.2 micromol/L CsA. Cell viability was measured using tetrazolium stain. The MPT was determined by loading hearts with 2-deoxy-[(3)H]-glucose (2DG), which enters mitochondria only during MPT. Total heart 2DG content as an estimation of the extent of tissue damage was also measured. To assess whether DMA has any direct effect on glycolysis, a cell-free heart extract containing all the glycolytic enzymes was used. 3. Dimethylamiloride improved functional recovery (rate-pressure product) from 24 +/- 7 to 68 +/- 11% (P < 0.01) at reperfusion end, attenuated the increase in left ventricular end-diastolic pressure (from 29 +/- 7 to 6 +/- 3% 10 min after reperfusion onset; P < 0.01), improved cell viability (from 21.2 +/- 6.6 to 69.6 +/- 7.1% at reperfusion end; P < 0.05) and lessened lactate accumulation at the end of ischaemia (119 +/- 15 vs 163 +/- 14 micromol/g dry weight; P < 0.05). Dimethylamiloride limited MPT: 2DG mitochondrial entrapment, being 33.1 +/- 14.2 and 96.3 +/- 14.0 at reperfusion end in the treated and control hearts, respectively (P < 0.05), and concomitantly raised total 2DG content (51.3 +/- 4.4 vs 86.8 +/- 1.7 x 10(3) d.p.m./g wet weight in control and treated groups, respectively; P < 0.05). Cyclosporine A improved functional recovery and attenuated the amplitude of ventricular diastolic pressure in ischaemic-reperfused hearts. It also reduced mitochondrial entrapment (67.3 +/- 7.7%; P < 0.05 vs control) and increased total cell 2DG content (162.3 +/- 1.3 x 10(3) d.p.m./g wet weight; P < 0.01 vs control) at the end of reperfusion. Dimethylamiloride did not affect glucose consumption and lactate production in the cell-free heart extract. 4. In conclusion, DMA protects against the noxious effects of ischaemia-reperfusion and inhibits MPT, coinciding with present and previous findings concerning the effects of CsA. Dimethylamiloride also diminished lactate accumulation, although it did not exhibit any direct effect on glycolysis. These data suggest that blockade of Na(+)/H(+) exchange by DMA attenuates the extent of MPT in ischaemic-reperfused rat heart.

Comparison of in vivo and ex vivo laser scanning microscopy and multiphoton tomography application for human and porcine skin imaging

NASA Astrophysics Data System (ADS)

Darvin, M. E.; Richter, H.; Zhu, Y. J.; Meinke, M. C.; Knorr, F.; Gonchukov, S. A.; Koenig, K.; Lademann, J.

2014-07-01

Two state-of-the-art microscopic optical methods, namely, confocal laser scanning microscopy in the fluorescence and reflectance regimes and multiphoton tomography in the autofluorescence and second harmonic generation regimes, are compared for porcine skin ex vivo and healthy human skin in vivo. All skin layers such as stratum corneum (SC), stratum spinosum (SS), stratum basale (SB), papillary dermis (PD) and reticular dermis (RD) as well as transition zones between these skin layers are measured noninvasively at a high resolution, using the above mentioned microscopic methods. In the case of confocal laser scanning microscopy (CLSM), measurements in the fluorescence regime were performed by using a fluorescent dye whose topical application on the surface is well suited for the investigation of superficial SC and characterisation of the skin barrier function. For investigations of deeply located skin layers, such as SS, SB and PD, the fluorescent dye must be injected into the skin, which markedly limits fluorescence measurements using CLSM. In the case of reflection CLSM measurements, the obtained results can be compared to the results of multiphoton tomography (MPT) for all skin layers excluding RD. CLSM cannot distinguish between dermal collagen and elastin measuring their superposition in the RD. By using MPT, it is possible to analyse the collagen and elastin structures separately, which is important for the investigation of anti-aging processes. The resolution of MPT is superior to CLSM. The advantages and limitations of both methods are discussed and the differences and similarities between human and porcine skin are highlighted.

Expression of aromatase in the embryonic brain of the olive ridley sea turtle (Lepidochelys olivacea), and the effect of bisphenol-A in sexually differentiated embryos.

PubMed

Gómez-Picos, Patsy; Sifuentes-Romero, Itzel; Merchant-Larios, Horacio; Hernández-Cornejo, Rubí; Díaz-Hernández, Verónica; García-Gasca, Alejandra

2014-01-01

Brain aromatase participates in several biological processes, such as regulation of the reproductive-endocrine axis, memory, stress, sexual differentiation of the nervous system, male sexual behavior, and brain repair. Here we report the isolation and expression of brain aromatase in olive ridley sea turtle (Lepidochelys olivacea) embryos incubated at male- and female-promoting temperatures (MPT and FPT, respectively), at the thermosensitive period (TSP) and the sex-differentiated period. Also, aromatase expression was assessed in differentiated embryos exposed to bisphenol-A (BPA) during the TSP. BPA is a monomer of polycarbonate plastics and is considered an endocrine-disrupting compound. Normal aromatase expression was measured in both forebrain and hindbrain, showing higher expression levels in the forebrain of differentiated embryos at both incubation temperatures. Although no significant differences were detected in the hindbrain, expression was slightly higher at MPT. BPA did not affect aromatase expression neither in forebrains or hindbrains from embryos incubated at MPT, whereas at FPT an inverted U-shape curve was observed in forebrains with significant differences at lower concentrations, whereas in hindbrains a non-significant increment was observed at higher concentrations. Our data indicate that both incubation temperature and developmental stage are critical factors affecting aromatase expression in the forebrain. Because of the timing and location of aromatase expression in the brain, we suggest that brain aromatase may participate in the imprinting of sexual trends related to reproduction and sexual behavior at the onset of sex differentiation, and BPA exposure may impair aromatase function in the female forebrain.

Comparison of in vivo and ex vivo laser scanning microscopy and multiphoton tomography application for human and porcine skin imaging

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

Darvin, M E; Richter, H; Zhu, Y J

Two state-of-the-art microscopic optical methods, namely, confocal laser scanning microscopy in the fluorescence and reflectance regimes and multiphoton tomography in the autofluorescence and second harmonic generation regimes, are compared for porcine skin ex vivo and healthy human skin in vivo. All skin layers such as stratum corneum (SC), stratum spinosum (SS), stratum basale (SB), papillary dermis (PD) and reticular dermis (RD) as well as transition zones between these skin layers are measured noninvasively at a high resolution, using the above mentioned microscopic methods. In the case of confocal laser scanning microscopy (CLSM), measurements in the fluorescence regime were performed bymore » using a fluorescent dye whose topical application on the surface is well suited for the investigation of superficial SC and characterisation of the skin barrier function. For investigations of deeply located skin layers, such as SS, SB and PD, the fluorescent dye must be injected into the skin, which markedly limits fluorescence measurements using CLSM. In the case of reflection CLSM measurements, the obtained results can be compared to the results of multiphoton tomography (MPT) for all skin layers excluding RD. CLSM cannot distinguish between dermal collagen and elastin measuring their superposition in the RD. By using MPT, it is possible to analyse the collagen and elastin structures separately, which is important for the investigation of anti-aging processes. The resolution of MPT is superior to CLSM. The advantages and limitations of both methods are discussed and the differences and similarities between human and porcine skin are highlighted. (laser biophotonics)« less

Reconstructing Sea Surface Conditions in the Bay of Bengal during the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Lagos, A. D.; Dekens, P.; Reilly, B. T.; Selkin, P. A.; Meynadier, L.; Savian, J. F.

2017-12-01

During the Mid-Pleistocene Transition (MPT, 0.8-1.2Ma) Earth's glacial cycles transitioned from responding primarily to 41kyr obliquity cycles to responding to 100kyr eccentricity cycles. In the tropics, sea surface temperature (SST) in the eastern tropical Pacific cooled through the MPT, suggesting a strengthening of the equatorial Pacific zonal temperature gradient (Medina-Elizalde & Lea, 2005). The strong SST gradient would have intensified Walker Cell convection during the MPT and built up latent heat in the western Pacific, which could cause cold SST anomalies in the northern Indian Ocean (Liu et al., 2015). Due to a scarcity of records, it is unclear how climate and oceanic conditions evolved in the Indian Ocean during the MPT. A set of recent IODP expeditions, including 353 and 354, cored sediment from the Bay of Bengal. Several sites recovered by expedition 353 will be ideal for reconstructing monsoon intensity through time, while the expedition 354 cores from a longitudinal transect at 8°N are in a region not directly impacted by changes in freshwater input due to direct precipitation or run off. The sites are influenced by the northeastern migration of equatorial Indian Ocean water via the Southwest Monsoon Current, which supplies significant moisture to the monsoon. Expedition 354's southern Bay of Bengal sites are well situated for better understanding the link between the tropical Indian Ocean and the northern Bay of Bengal. We reconstructed sea surface conditions at IODP site 1452 (8°N, 87°E, 3670m water depth) in the distal Bengal Fan. A 3 meter long section of the core has been identified as the MPT using the Bruhnes/Matuyama, Jaramillo, and Cobb Mountain paleomagnetic reversals (France-Lanord et al., 2016). This section of site 1452 was sampled every 2cm ( 2kyr resolution). Approximately 30 G. sacculifer, a surface dwelling planktonic foraminifera, were picked from the 355-425μm size fraction. We measured Mg/Ca and δ18O on splits of the same material to reconstruct SST and δ18OSW. While this study will not reconstruct monsoon intensity, establishing the sea surface conditions for the southern Bay of Bengal will improve our understanding of the connection between the Indian Ocean and the monsoons through the MPT.

Novel substituted 1,4-anthracenediones with antitumor activity directly induce permeability transition in isolated mitochondria.

PubMed

Perchellet, Elisabeth M; Wang, Yang; Lou, Kaiyan; Zhao, Huiping; Battina, Srinivas K; Hua, Duy H; Perchellet, Jean-Pierre H

2007-11-01

Synthetic analogs of 1,4-anthraquinone (AQ code number), which block nucleoside transport, decrease DNA, RNA and protein syntheses, trigger cytochrome c release without caspase activation, induce apoptotic DNA fragmentation and inhibit the proliferation of wild-type and multidrug resistant tumor cells in the nM range in vitro, rapidly cause the collapse of mitochondrial transmembrane potential in cell and cell-free systems. Because mitochondrial permeability transition (MPT) requires more than depolarization to occur, antitumor AQs were tested for their ability to directly trigger specific markers of MPT in isolated mitochondria. In contrast to a spectrum of conventional anticancer drugs that are inactive, various AQs interact with isolated mitochondria in a concentration- and time-dependent manner to rapidly cause large amplitude swelling and Ca2+ release in relation with their effectiveness against L1210, HL-60 and LL/2 tumor cells in vitro. Indeed, the lead antitumor AQ8, AQ9 and AQ17 are also the most effective inducers of MPT in isolated mitochondria, whereas all AQ derivatives devoid of anti-proliferative activity also fail to trigger mitochondrial swelling and Ca2+ release. Moreover, the ability of 4 microM AQ17 to maximally induce mitochondrial swelling and Ca2+ release within 15 min is similar to that of classic MPT-inducing agents, such as 5 microg/ml alamethicin, 200 microM atractyloside, 5 microM phenylarsine oxide, 100 microM arsenic trioxide and a 100 microM Ca2+ overload. Interestingly, AQ17 requires a priming concentration of 20 microM Ca2+ to trigger mitochondrial swelling and Ca2+ release and these 0.1 microM ruthenium red-sensitive MPT events are abolished by 1 microM cyclosporin A, 2 mM ADP and 20 microM bongkrekic acid, which block components of the permeability transition pore (PTP), and also inhibited by 50-100 microM of various ubiquinones, which interact with the quinone binding site of the PTP and raise the Ca2+ load required for PTP opening. Hence, antitumor AQs that target isolated mitochondria and trigger MPT might directly interact with components of the PTP to induce conformational changes that increase its Ca2+ sensitivity and transition from the closed to the open state.

Research and Development Strategies for Human Centered and Group Support Technologies

DTIC Science & Technology

1992-05-01

al.,6 Rothwell, 7 Hidson,8 and Richards and Companion 9 provide detailed 3 R . Bruce Gould, AFHRI/MOD, MPT Technology Branch, Brooks AFB, TX, and...88 Transactions, Boston, 1988. Gould, R . Bruce , AFHRL/MOD, MPT Technology Branch, Brooks AFB, TX, and Thomas Nondorf, McDonnell Douglas Corp. MCAIR...future R &D activities. This paper reports the results of research performed by an Institute for Defense Analyses study team whose immediate goal was

Isokinetic and isometric strength in osteoarthrosis of the knee. A comparative study with healthy women.

PubMed

Tan, J; Balci, N; Sepici, V; Gener, F A

1995-01-01

Dynamic stability of the knee joint depends on the appropriate strength ratio of quadriceps and hamstring muscles. The purpose of this investigation was to determine the maximum peak torque (MPT) and MPT ratios of hamstrings to quadriceps (H/Q) muscles in patients with knee osteoarthritis (OA). Two groups of patients were included in the study. The first group consisted of 30 patients (Group A) with the clinical and radiologic findings of knee OA. The second group consisted of 30 patients (Group B) exhibiting knee joint pain without roentgenologic findings of knee OA. The findings of two patient groups were compared with each other and also with 30 healthy subjects (Group C). Isokinetic (at 60 degrees/s and at 180 degrees/s) and isometric (at 30 degrees and at 60 degrees of knee flexion) tests were performed by the rate-limiting isokinetic dynamometer system. Isokinetic and isometric MPT loss of knee flexors and extensors was found in both patient groups with respect to controls, but MPT ratios of H/Q muscles did not show a statistically significant difference compared with the control group. This may be related to the equal strength loss of knee flexors and knee extensors in patients with knee OA. It is concluded that strengthening exercises of hamstring muscles is as important as quadriceps strengthening in rehabilitation of knee OA.

Neonatal Morbidities among Moderately Preterm Infants with and without Exposure to Antenatal Corticosteroids.

PubMed

Chawla, Sanjay; Natarajan, Girija; Chowdhury, Dhuly; Das, Abhik; Walsh, Michele; Bell, Edward F; Laptook, Abbot R; Van Meurs, Krisa; D'Angio, Carl T; Stoll, Barbara J; DeMauro, Sara B; Shankaran, Seetha

2018-04-27

 We aimed to compare the rates of "surfactant treated respiratory disease" and other neonatal morbidities among moderately preterm (MPT) infants exposed to no, partial, or a complete course of antenatal corticosteroids (ANS).  This observational cohort study evaluated MPT infants (29 0/7 -33 6/7 weeks' gestational age), born between January 2012 and November 2013 and enrolled in the "MPT Registry" of the National Institute of Child Health and Human Development Neonatal Research Network.  Data were available for 5,886 infants, including 676 with no exposure, 1225 with partial, and 3,985 with a complete course of ANS. Among no, partial, and complete ANS groups, respectively, there were significant differences in rates of delivery room resuscitation (4.1, 1.4, and 1.2%), surfactant-treated respiratory disease (26.5, 26.3, and 20%), and severe intracranial hemorrhage (3, 2, and 0.8%). Complete ANS course was associated with lower surfactant-treated respiratory disease, compared with partial ANS (odds ratio [OR] 0.62; 95% confidence interval [CI] 0.52-0.74), and no ANS groups (OR 0.52; 95% CI 0.41-0.66) on adjusted analysis.  In MPT infants, ANS exposure is associated with lower delivery room resuscitation, surfactant-treated respiratory disease, and severe intracranial hemorrhage; with the lowest frequency of morbidities associated with a complete course. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging.

PubMed

Arginelli, Federica; Manfredini, Marco; Bassoli, Sara; Dunsby, Christopher; French, Paul; König, Karsten; Magnoni, Cristina; Ponti, Giovanni; Talbot, Clifford; Seidenari, Stefania

2013-05-01

Multiphoton Laser Tomography (MPT) has developed as a non-invasive tool that allows real-time observation of the skin with subcellular resolution. MPT is readily combined with time resolved detectors to achieve fluorescence lifetime imaging (FLIM). The aim of our study was to identify morphologic MPT/FLIM descriptors of melanocytic nevi, referring to cellular and architectural features. In the preliminary study, MPT/FLIM images referring to 16 ex vivo nevi were simultaneously evaluated by 3 observers for the identification of morphologic descriptors characteristic of melanocytic nevi. Proposed descriptors were discussed and the parameters referring to epidermal keratinocytes, epidermal melanocytes, dermo-epidermal junction, papillary dermis and overall architecture were selected. In the main study, the presence/absence of the specified criteria were blindly evaluated on a test set, comprising 102 ex vivo samples (51 melanocytic nevi, 51 miscellaneous skin lesions) by 2 observers. Twelve descriptors were identified: "short-lifetime cells in the stratum corneum", "melanin-containing keratinocytes", "dendritic cells", "small short-lifetime cells" in the upper and lower layers", "edged papillae", "non-edged papillae", "junctional nests of short-lifetime cells", "dermal cell clusters", "short-lifetime cells in the papilla", "monomorphic and regular histoarchitecture", "architectural disarray". Identified descriptors for benign melanocytic lesions proved sensitive and specific, enabling the differentiation between melanocytic nevi and non-melanocytic lesions. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Heat Capacity and Thermal Conductance Measurements of a Superconducting-Normal Mixed State by Detection of Single 3 eV Photons in a Magnetic Penetration Thermometer

NASA Technical Reports Server (NTRS)

Stevenson, T. R.; Balvin, M. A.; Bandler, S. R.; Denis, K. L.; Lee, S.-J.; Nagler, P. C.; Smith, S. J.

2015-01-01

We report on measurements of the detected signal pulses in a molybdenum-gold Magnetic Penetration Thermometer (MPT) in response to absorption of one or more 3 eV photons. We designed and used this MPT sensor for x-ray microcalorimetry. In this device, the diamagnetic response of a superconducting MoAu bilayer is used to sense temperature changes in response to absorbed photons, and responsivity is enhanced by a Meissner transition in which the magnetic flux penetrating the sensor changes rapidly to minimize free energy in a mixed superconducting normal state. We have previously reported on use of our MPT to study a thermal phonon energy loss to the substrate when absorbing x-rays. We now describe results of extracting heat capacity C and thermal conductance G values from pulse height and decay time of MPT pulses generated by 3 eV photons. The variation in C and G at temperatures near the Meissner transition temperature (set by an internal magnetic bias field) allow us to probe the behavior in superconducting normal mixed state of the condensation energy and the electron cooling power resulting from quasi-particle recombination and phonon emission. The information gained on electron cooling power is also relevant to the operation of other superconducting detectors, such as Microwave Kinetic Inductance Detectors.

Optimal portfolio design to reduce climate-related conservation uncertainty in the Prairie Pothole Region.

PubMed

Ando, Amy W; Mallory, Mindy L

2012-04-24

Climate change is likely to alter the spatial distributions of species and habitat types but the nature of such change is uncertain. Thus, climate change makes it difficult to implement standard conservation planning paradigms. Previous work has suggested some approaches to cope with such uncertainty but has not harnessed all of the benefits of risk diversification. We adapt Modern Portfolio Theory (MPT) to optimal spatial targeting of conservation activity, using wetland habitat conservation in the Prairie Pothole Region (PPR) as an example. This approach finds the allocations of conservation activity among subregions of the planning area that maximize the expected conservation returns for a given level of uncertainty or minimize uncertainty for a given expected level of returns. We find that using MPT instead of simple diversification in the PPR can achieve a value of the conservation objective per dollar spent that is 15% higher for the same level of risk. MPT-based portfolios can also have 21% less uncertainty over benefits or 6% greater expected benefits than the current portfolio of PPR conservation. Total benefits from conservation investment are higher if returns are defined in terms of benefit-cost ratios rather than benefits alone. MPT-guided diversification can work to reduce the climate-change-induced uncertainty of future ecosystem-service benefits from many land policy and investment initiatives, especially when outcomes are negatively correlated between subregions of a planning area.

Optimal portfolio design to reduce climate-related conservation uncertainty in the Prairie Pothole Region

PubMed Central

Ando, Amy W.; Mallory, Mindy L.

2012-01-01

Climate change is likely to alter the spatial distributions of species and habitat types but the nature of such change is uncertain. Thus, climate change makes it difficult to implement standard conservation planning paradigms. Previous work has suggested some approaches to cope with such uncertainty but has not harnessed all of the benefits of risk diversification. We adapt Modern Portfolio Theory (MPT) to optimal spatial targeting of conservation activity, using wetland habitat conservation in the Prairie Pothole Region (PPR) as an example. This approach finds the allocations of conservation activity among subregions of the planning area that maximize the expected conservation returns for a given level of uncertainty or minimize uncertainty for a given expected level of returns. We find that using MPT instead of simple diversification in the PPR can achieve a value of the conservation objective per dollar spent that is 15% higher for the same level of risk. MPT-based portfolios can also have 21% less uncertainty over benefits or 6% greater expected benefits than the current portfolio of PPR conservation. Total benefits from conservation investment are higher if returns are defined in terms of benefit–cost ratios rather than benefits alone. MPT-guided diversification can work to reduce the climate-change–induced uncertainty of future ecosystem-service benefits from many land policy and investment initiatives, especially when outcomes are negatively correlated between subregions of a planning area. PMID:22451914

Effect of geographical and ethnic variation on Dysphonia Severity Index: a study of Indian population.

PubMed

Jayakumar, T; Savithri, S R

2012-01-01

Dysphonia Severity Index (DSI) is a widely used multiparametric approach to objectively quantify the voice quality. Few research groups have investigated the test-retest, interobserver variability, and influence of age and gender. They have also verified the application of DSI in various voice rehabilitation conditions. However, all these studies have been conducted on European population. There is a possibility of variation in the basic parameters of DSI across geographical and ethnic groups. Hence, the present study evaluated DSI in Indian population. One hundred twenty voluntary participants (60 males, 60 females) who had G(0) on the Grade, Roughness, Breathiness, Aesthenia, Strain (GRBAS) scale participated in the study (age range of 18-25 years, M=21.8, standard deviation=2.7). Maximum phonation time (MPT), frequency intensity, and jitter measurements were made using CSL 4500 (Kay Elemetrics, Pine Brook, NJ). Results showed noticeable difference between Indian and European population on MPT, Highest frequency (F(0)-High), and DSI values. Significant gender difference was also observed on MPT and F(0)-High. Test-retest reliability showed >95% for all the parameters. The MPT decrement lead to a reduction in the overall DSI value in both the genders. These results of the study caution voice professionals to reinvestigate and establish their own norms for their geographical and ethnic groups. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

A simplified conjoint recognition paradigm for the measurement of gist and verbatim memory.

PubMed

Stahl, Christoph; Klauer, Karl Christoph

2008-05-01

The distinction between verbatim and gist memory traces has furthered the understanding of numerous phenomena in various fields, such as false memory research, research on reasoning and decision making, and cognitive development. To measure verbatim and gist memory empirically, an experimental paradigm and multinomial measurement model has been proposed but rarely applied. In the present article, a simplified conjoint recognition paradigm and multinomial model is introduced and validated as a measurement tool for the separate assessment of verbatim and gist memory processes. A Bayesian metacognitive framework is applied to validate guessing processes. Extensions of the model toward incorporating the processes of phantom recollection and erroneous recollection rejection are discussed.

Space-Time Processing for Tactical Mobile Ad Hoc Networks

DTIC Science & Technology

2008-08-01

vision for multiple concurrent communication settings, i.e., a many-to-many framework where multi-packet transmissions (MPTs) and multi-packet...modelling framework of capacity-delay tradeoffs We have introduced the first unified modeling framework for the computation of fundamental limits o We...dalities in wireless n twor i-packet modelling framework to account for the use of m lti-packet reception (MPR) f ad hoc networks with MPT under

Turn around to have a look? Spatial referencing in dorsal vs. frontal settings in cross-linguistic comparison

PubMed Central

Beller, Sieghard; Singmann, Henrik; Hüther, Lisa; Bender, Andrea

2015-01-01

When referring to an object in relation to another, speakers of many languages can adopt a relative frame of reference (FoR). Following Levinson (2003), this kind of FoR can be established by projecting an observer's perspective onto the ground object either by translation, reflection, or rotation. So far, research on spatial FoRs has largely ignored the extent of variation in which of these projections are preferred generally, and specifically what kind of FoR is established for spatial arrays in one's back. This may seem justified by assumptions on “natural” preferences: for reflection in frontal settings (Canonical Encounter Hypothesis), and for converting dorsal into frontal situations by a turn of the observer before a reference is made (Turn Hypothesis). We scrutinize these assumptions by comparing the FoRs adopted for small-scale, static spatial arrays by speakers of four languages (German, US-English, Mandarin Chinese, and Tongan). Addressing the problem of inherent ambiguities on the item level when assessing FoRs from spatial prepositions, we use a multinomial processing tree (MPT) model for estimating probabilities of referencing strategies across sets of items. Substantial differences in frontal settings, both between and within languages, disprove the Canonical Encounter Hypothesis—translation occurs as frequently as reflection across samples. In dorsal settings, in contrast, the same type of response dominates in all samples. We suggest that this response is produced by a backward projection of the observer's coordinate system in correspondence with the two main FoR preferences for frontal settings. However, none of these strategies involves a turn of the observer, thus also disproving the Turn Hypothesis. In conclusion, we discuss possible causes of the observed variability, explore links between the domains of space and time, and reflect the relation between language, communication, and culture. PMID:26388802

Evaluation of a new rapid kit, BD MGIT TBc identification test for confirmation of Mycobacterium tuberculosis complex.

PubMed

Kandhakumari, Gandhi; Stephen, Selvaraj

2017-01-01

At present, three rapid kits are available globally for the confirmation of Mycobacterium tuberculosis complex (MTBC) in cultures by MPT64 antigen (MPT64 Ag) detection. These include Capilia TB, SD Bioline, and BD MGIT TBc Identification (TBcID). The third kit is yet to be validated in India. We have tested this kit and compared with SD Bioline using conventional tests as gold standard. Seventy-one MTBC (70 M. tuberculosis and one Mycobacterium bovis) and four nontuberculous mycobacteria (NTM) were isolated from 649 clinical specimens in MGIT 960 and/or Lowenstein-Jensen slants (LJ). MPT64 Ag was detected by both TBcID and SD Bioline kits in all the 71 clinical isolates and the reference strain M. tuberculosis H37Rv. All NTM species tested were negative by the two different kits. Thus, TBcID kit showed 100% concordance in terms of sensitivity and specificity. Rapid kits confirm MTBC cultures within 15 min in contrast to several weeks' time required by conventional techniques.

Younger and Older Adults Weigh Multiple Cues in a Similar Manner to Generate Judgments of Learning

PubMed Central

Hines, Jarrod C.; Hertzog, Christopher; Touron, Dayna R.

2015-01-01

One's memory for past test performance (MPT) is a key piece of information individuals use when deciding how to restudy material. We used a multi-trial recognition memory task to examine adult age differences in the influence of MPT (measured by actual Trial 1 memory accuracy and subjective confidence judgments, CJs) along with Trial 1 judgments of learning (JOLs), objective and participant-estimated recognition fluencies, and Trial 2 study time on Trial 2 JOLs. We found evidence of simultaneous and independent influences of multiple objective and subjective (i.e., metacognitive) cues on Trial 2 JOLs, and these relationships were highly similar for younger and older adults. Individual differences in Trial 1 recognition accuracy and CJs on Trial 2 JOLs indicate that individuals may vary in the degree to which they rely on each MPT cue when assessing subsequent memory confidence. Aging appears to spare the ability to access multiple cues when making JOLs. PMID:25827630

Simulation of Glacial Cycles Before and After the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Ganopolski, A.; Willeit, M.; Calov, R.

2017-12-01

In spite of significant progress achieved in understanding of glacial cycles, the cause of Mid-Pleistocene transition (MPT) is still not fully understood. To study possible mechanisms of the MPT we used the Earth system model of intermediate complexity CLIMBER-2 which incorporates all major components of the Earth system - atmosphere, ocean, land surface, northern hemisphere ice sheets, terrestrial biota and soil carbon, aeolian dust and marine biogeochemistry. We run the model through the entire Quaternary. The only prescribed forcing in these simulations is variations in Earth orbital parameters. In addition we prescribed gradually evolving in time terrestrial sediment cover and global volcanic outgassing. We found that gradual removal of terrestrial sediment from the Northern Hemisphere continent by glacial processes is sufficient to explain transition from 40-ka to 100-ka worlds around 1 million years ago. By starting the model at different times and using the same initial conditions we found that modeling results converge to the same solution which depends only on the orbital forcing and lower boundary conditions. Our results thus strongly suggest that Quaternary glacial cycles are externally forced and nearly deterministic.

Discrete post-processing of total cloud cover ensemble forecasts

NASA Astrophysics Data System (ADS)

Hemri, Stephan; Haiden, Thomas; Pappenberger, Florian

2017-04-01

This contribution presents an approach to post-process ensemble forecasts for the discrete and bounded weather variable of total cloud cover. Two methods for discrete statistical post-processing of ensemble predictions are tested. The first approach is based on multinomial logistic regression, the second involves a proportional odds logistic regression model. Applying them to total cloud cover raw ensemble forecasts from the European Centre for Medium-Range Weather Forecasts improves forecast skill significantly. Based on station-wise post-processing of raw ensemble total cloud cover forecasts for a global set of 3330 stations over the period from 2007 to early 2014, the more parsimonious proportional odds logistic regression model proved to slightly outperform the multinomial logistic regression model. Reference Hemri, S., Haiden, T., & Pappenberger, F. (2016). Discrete post-processing of total cloud cover ensemble forecasts. Monthly Weather Review 144, 2565-2577.

MPT_DOE Final Report 12-15-16 rev1

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

Bunce, Michael

The goal of this project was to achieve breakthrough thermal efficiency on a light duty passenger car engine, with minimal impact to emissions. The enabling technology or technologies were to be relatively low cost and integrateable into existing production processes. Through the use of Turbulent Jet Ignition (TJI), an enabling technology for ultra-lean engine operation, the project team was able to meet or exceed all technical goals of this program.

Studies of Microdischarge Plasma Thrusters for Nanosatellite Propulsion

DTIC Science & Technology

2009-09-30

sections 0^ based on the Lennard - Jones interaction potentials14 are used to determine the neutral transport properties using vk = nk gkt^kb, where g... potential that exists between the MPT and the vacuum. The expulsion of hot gas and ions into the vacuum generates thrust. So far the MPT has been...cathode and e2 is at a potential between ej and e3. In fig. 3 b, ei is anode and e3 is cathode whereas e2 is floating. The power supply for ei is

Inlet noise on 0.5-meter-diameter NASA QF-1 fan as measured in an unmodified compressor aerodynamic test facility and in an anechoic chamber

NASA Technical Reports Server (NTRS)

Gelder, T. F.; Soltis, R. F.

1975-01-01

Narrowband analysis revealed grossly similar sound pressure level spectra in each facility. Blade passing frequency (BPF) noise and multiple pure tone (MPT) noise were superimposed on a broadband (BB) base noise. From one-third octave bandwidth sound power analyses the BPF noise (harmonics combined), and the MPT noise (harmonics combined, excepting BPF's) agreed between facilities within 1.5 db or less over the range of speeds and flows tested. Detailed noise and aerodynamic performance is also presented.

Ice Age Reboot: Thermohaline Circulation Crisis during the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Pena, L.; Goldstein, S. L.

2014-12-01

The mid-Pleistocene transition (MPT) marked a fundamental change in glacial-interglacial periodicity, when it increased from ~41- to 100-kyr cycles and developed higher amplitude climate variability. Because it took place without significant changes in the Milankovitch forcing, this fundamental change must reflect either non-linear responses of the climate system to these external forcings, or internal changes in the ocean-atmosphere-cryosphere system that led to longer periodicities and more intense glacial periods. We document using Nd isotopes a major disruption of the ocean thermohaline circulation (THC) system during the MPT between MIS 25-21 at ~950-860 ka, which effectively marks the first 100-kyr cycle, including an exceptional weakening through critical interglacial MIS 23 at ~900 ka. The data are from ODP Sites 1088 (41°8.163'S, 13°33.77'E, 2082m) and 1090 (42°54.82'S, 8°53.98E', 3702m) in the SE Atlantic Subantarctic Zone, near the upper and lower boundaries of NADW and Circumpolar Deep Water (CDW). Given evidence for nearly stable NADW and North Pacific Water (NPW) ɛNd-values over the last 2 Ma, we interpret the ɛNd variations to reflect changes in the NADW:NPW mixing fractions. During the studied pre-MPT 41-kyr world (MIS 31-25, 1,100-950 ka), at both sites the differences in glacial and interglacial ɛNd-values are small, indicating strong glacial as well as interglacial export of NADW. A major weakening of NADW export occurred during MIS 24-22, including MIS 23, which is unique as the only known interglacial in which the THC did not strengthen, and thus can be considered as a 'trans-glacial' period. The recovery into the post-MPT 100-kyr world is characterized by continued weak glacial THC. We conclude that the MPT ocean circulation crisis 'rebooted' the pacing and intensity of ice ages and facilitated the coeval drawdown of atmospheric CO2 and high latitude ice sheet growth, generating the conditions that stabilized 100-kyr cycles.

Effect of tropospheric models on derived precipitable water vapor over Southeast Asia

NASA Astrophysics Data System (ADS)

Rahimi, Zhoobin; Mohd Shafri, Helmi Zulhaidi; Othman, Faridah; Norman, Masayu

2017-05-01

An interesting subject in the field of GPS technology is estimating variation of precipitable water vapor (PWV). This estimation can be used as a data source to assess and monitor rapid changes in meteorological conditions. So far, numerous GPS stations are distributed across the world and the number of GPS networks is increasing. Despite these developments, a challenging aspect of estimating PWV through GPS networks is the need of tropospheric parameters such as temperature, pressure, and relative humidity (Liu et al., 2015). To estimate the tropospheric parameters, global pressure temperature (GPT) model developed by Boehm et al. (2007) is widely used in geodetic analysis for GPS observations. To improve the accuracy, Lagler et al. (2013) introduced GPT2 model by adding annual and semi-annual variation effects to GPT model. Furthermore, Boehm et al. (2015) proposed the GPT2 wet (GPT2w) model which uses water vapor pressure to improve the calculations. The global accuracy of GPT2 and GPT2w models has been evaluated by previous researches (Fund et al., 2011; Munekane and Boehm, 2010); however, investigations to assess the accuracy of global tropospheric models in tropical regions such as Southeast Asia is not sufficient. This study tests and examines the accuracy of GPT2w as one of the most recent versions of tropospheric models (Boehm et al., 2015). We developed a new regional model called Malaysian Pressure Temperature (MPT) model, and compared this model with GPT2w model. The compared results at one international GNSS service (IGS) station located in the south of Peninsula Malaysia shows that MPT model has a better performance than GPT2w model to produce PWV during monsoon season. According to the results, MPT has improved the accuracy of estimated pressure and temperature by 30% and 10%, respectively, in comparison with GPT2w model. These results indicate that MPT model can be a good alternative tool in the absence of meteorological sensors at GPS stations in Peninsula Malaysia. Therefore, for GPS-based studies, we recommend MPT model to be used as a complementary tool for the Malaysia Real-Time Kinematic Network to develop a real-time PWV monitoring system.

Oceanic heat pulses fueling moisture transport towards continental Europe across the mid-Pleistocene transition

NASA Astrophysics Data System (ADS)

Bahr, A.; Kaboth, S.; Hodell, D.; Zeeden, C.; Fiebig, J.; Friedrich, O.

2018-01-01

The mid-Pleistocene Transition (MPT; approx. 1.2-0.7 Ma), is characterized by growing Northern Hemisphere ice sheets and the shift from a 41 kyr to a 100 kyr glacial-interglacial cyclicity. Concomitant to the growth of large ice sheets, atmospheric and oceanic circulation pattern have changed. One key feature of the North Atlantic is the wind-driven Subtropical Gyre, a major provider of heat and moisture for continental Europe. Here, we investigate changes in the strength and spatial configuration of the Subtropical Gyre during the MPT and its impact on the continental moisture balance. To reconstruct Subtropical Gyre dynamics, we conducted paired δ18O and Mg/Ca analyses on the deep-dwelling foraminifera Globorotalia inflata from Iberian Margin Site U1385 yielding thermocline temperature (Ttherm) variability between 1400 and 500 ka at the eastern boundary of the Subtropical Gyre. Long-term trends of Ttherm at Site U1385 oppose the North Atlantic climatic evolution of progressively intensified glacials during the MPT. Particularly, glacials MIS 20 and 18 were marked by warm thermocline waters off Iberia. We infer that a southward shift of the (sub)polar front displaced the source region of thermocline waters within the Subtropical Gyre from high to mid-latitudes. In addition, a strong Mediterranean Outflow Water production during the MPT caused the advection of warm waters to Iberia. Humid conditions during MIS 20 and 18 in SE Europe indicate that atmospheric moisture derived from this warm water might have been advected deep into continental Europe and contributed to enhanced growth of Alpine glaciers.

Multipurpose prevention technologies for sexual and reproductive health: mapping global needs for introduction of new preventive products.

PubMed

Schelar, Erin; Polis, Chelsea B; Essam, Timothy; Looker, Katharine J; Bruni, Laia; Chrisman, Cara J; Manning, Judy

2016-01-01

Worldwide, women face sexual and reproductive health (SRH) risks including unintended pregnancy and sexually transmitted infections (STIs) including HIV. Multipurpose prevention technologies (MPTs) combine protection against two or more SRH risks into one product. Male and female condoms are the only currently available MPT products, but several other forms of MPTs are in development. We examined the global distribution of selected SRH issues to determine where various risks have the greatest geographical overlap. We examined four indicators relevant to MPTs in development: HIV prevalence, herpes simplex virus type 2 prevalence (HSV-2), human papillomavirus prevalence (HPV) and the proportion of women with unmet need for modern contraception. Using ArcGIS Desktop, we mapped these indicators individually and in combination on choropleth and graduated symbol maps. We conducted a principal components analysis to reduce data and enable visual mapping of all four indicators on one graphic to identify overlap. Our findings document the greatest overlapping risks in Sub-Saharan Africa, and we specify countries in greatest need by specific MPT indication. These results can inform strategic planning for MPT introduction, market segmentation and demand generation; data limitations also highlight the need for improved (non-HIV) STI surveillance globally. MPTs are products in development with the potential to empower women to prevent two or more SRH risks. Geographic analysis of overlapping SRH risks demonstrates particularly high need in Sub-Saharan Africa. This study can help to inform strategic planning for MPT introduction, market segmentation and demand generation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Changes After Voice Therapy in Acoustic Voice Analysis of Chinese Patients With Voice Disorders.

PubMed

Lu, Dan; Chen, Fei; Yang, Hui; Yu, Rong; Zhou, Qi; Zhang, Xinyuan; Ren, Jia; Zheng, Yitao; Zhang, Xiaoyan; Zou, Jian; Wang, Haiyang; Liu, Jun

2018-05-01

This study aimed to evaluate the effects of voice therapy on patients with voice disorders by comparing the acoustic parameter changes before and after treatment. This is a retrospective study. Forty-five female patients with early-stage vocal nodules or polyps, postoperative patients, and patients with chronic laryngitis were divided into three subgroups. Videostroboscopic, acoustic analysis (fundamental frequency, jitter, shimmer, mean harmonics-to-noise ratio), and maximum phonation time (MPT) were measured before and after treatment. Fifty healthy female volunteers were the control group. After treatment, 24.4% of nodules or polyps had decreased in size, 11.1% of patients with chronic laryngitis and postoperative patients had reduced edema, and the mucosal wave of vocal folds had different degrees of recovery in postoperative patients. All acoustic analysis values and MPT in the patient group were statistically worse than in the control group, except for fundamental frequency before treatment (P > 0.05). After treatment, the acoustic analysis and MPT values were improved. However, the jitter, mean harmonics-to-noise ratio, and MPT values in the patient group were still worse after voice therapy than in the control group (P < 0.05). Most of acoustic analysis values can be useful as a complementary tool in diagnosis and assessment of voice disorders; however, it is not recommended to use a single parameter to assess voice quality. Voice therapy can improve voice quality in patients with voice disorders, but a period longer than 8 weeks is recommended for these patients. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Identification and characterization of cannabinoids that induce cell death through mitochondrial permeability transition in Cannabis leaf cells.

PubMed

Morimoto, Satoshi; Tanaka, Yumi; Sasaki, Kaori; Tanaka, Hiroyuki; Fukamizu, Tomohide; Shoyama, Yoshinari; Shoyama, Yukihiro; Taura, Futoshi

2007-07-13

Cannabinoids are secondary metabolites stored in capitate-sessile glands on leaves of Cannabis sativa. We discovered that cell death is induced in the leaf tissues exposed to cannabinoid resin secreted from the glands, and identified cannabichromenic acid (CBCA) and Delta(1)-tetrahydrocannabinolic acid (THCA) as unique cell death mediators from the resin. These cannabinoids effectively induced cell death in the leaf cells or suspension-cultured cells of C. sativa, whereas pretreatment with the mitochondrial permeability transition (MPT) inhibitor cyclosporin A suppressed this cell death response. Examinations using isolated mitochondria demonstrated that CBCA and THCA mediate opening of MPT pores without requiring Ca(2+) and other cytosolic factors, resulting in high amplitude mitochondrial swelling, release of mitochondrial proteins (cytochrome c and nuclease), and irreversible loss of mitochondrial membrane potential. Therefore, CBCA and THCA are considered to cause serious damage to mitochondria through MPT. The mitochondrial damage was also confirmed by a marked decrease of ATP level in cannabinoid-treated suspension cells. These features are in good accord with those of necrotic cell death, whereas DNA degradation was also observed in cannabinoid-mediated cell death. However, the DNA degradation was catalyzed by nuclease(s) released from mitochondria during MPT, indicating that this reaction was not induced via a caspase-dependent apoptotic pathway. Furthermore, the inhibition of the DNA degradation only slightly blocked the cell death induced by cannabinoids. Based on these results, we conclude that CBCA and THCA have the ability to induce necrotic cell death via mitochondrial dysfunction in the leaf cells of C. sativa.

RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation.

PubMed

Jones, Robert A; Robinson, Tyler J; Liu, Jeff C; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E D; Pellecchia, Giovanna; Fell, Victoria L; Bae, SooIn; Muthuswamy, Lakshmi; Datti, Alessandro; Egan, Sean E; Jiang, Zhe; Leone, Gustavo; Bader, Gary D; Schimmer, Aaron; Zacksenhaus, Eldad

2016-10-03

Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low-like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration-approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC.

RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation

PubMed Central

Jones, Robert A.; Robinson, Tyler J.; Liu, Jeff C.; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E.D.; Pellecchia, Giovanna; Fell, Victoria L.; Bae, SooIn; Muthuswamy, Lakshmi; Egan, Sean E.; Jiang, Zhe; Leone, Gustavo; Bader, Gary D.; Schimmer, Aaron

2016-01-01

Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low–like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration–approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC. PMID:27571409

cGMP signalling in pre- and post-conditioning: the role of mitochondria.

PubMed

Costa, Alexandre D T; Pierre, Sandrine V; Cohen, Michael V; Downey, James M; Garlid, Keith D

2008-01-15

Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT. We believe that the cytosolic component of this trigger pathway terminates in activation of guanylyl cyclase resulting in increased production of cGMP and subsequent activation of protein kinase G (PKG). PKG phosphorylates a protein on the mitochondrial outer membrane (MOM), which then causes the mitochondrial K(ATP) channel (mitoK(ATP)) on the mitochondrial inner membrane to open, leading to increased production of reactive oxygen species (ROS) by the mitochondria. This implies that the protective signal is somehow transmitted from the MOM to its inner membrane. This is accomplished by a series of intermembrane signalling steps that includes protein kinase C (PKCepsilon) activation. The resulting ROS then activate a second PKC pool which, through another signal transduction pathway termed the mediator pathway, causes inhibition of MPT and reduction in cell death.

Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

PubMed

Costa, Rute A P; Fernandes, Mariana P; de Souza-Pinto, Nadja C; Vercesi, Aníbal E

2013-02-15

Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of conceptual models in a physical therapy curriculum: application of an integrated model of theory, research, and clinical practice.

PubMed

Darrah, Johanna; Loomis, Joan; Manns, Patricia; Norton, Barbara; May, Laura

2006-11-01

The Department of Physical Therapy, University of Alberta, Edmonton, Alberta, Canada, recently implemented a Master of Physical Therapy (MPT) entry-level degree program. As part of the curriculum design, two models were developed, a Model of Best Practice and the Clinical Decision-Making Model. Both models incorporate four key concepts of the new curriculum: 1) the concept that theory, research, and clinical practice are interdependent and inform each other; 2) the importance of client-centered practice; 3) the terminology and philosophical framework of the World Health Organization's International Classification of Functioning, Disability, and Health; and 4) the importance of evidence-based practice. In this article the general purposes of models for learning are described; the two models developed for the MPT program are described; and examples of their use with curriculum design and teaching are provided. Our experiences with both the development and use of models of practice have been positive. The models have provided both faculty and students with a simple, systematic structured framework to organize teaching and learning in the MPT program.

Effect of molecular weight on polymer processability

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

Karg, R.F.

1983-01-01

Differences in rheological behavior due to the polymer molecular weight and molecular weight distribution have been shown with the MPT. SBR polymers having high molecular weight fractions develop higher stress relaxation time values due to the higher degree of polymer entanglements. Tests conducted at increasing temperatures show the diminishing influence of the polymer entanglements upon stress relaxation time. EPDM polymers show stress relaxation time and head pressure behavior which correlates with mill processability. As anticipated, compounded stock of EPDM have broad molecular weight distribution has higher stress relaxation time values than EPDM compounds with narrow molecular weight distribution.

Immunocytochemical detection of Mycobacterium Tuberculosis complex specific antigen, MPT64, improves diagnosis of tuberculous lymphadenitis and tuberculous pleuritis.

PubMed

Tadele, Agerie; Beyene, Demissew; Hussein, Jemal; Gemechu, Tuffa; Birhanu, Asaye; Mustafa, Tehmina; Tsegaye, Aster; Aseffa, Abraham; Sviland, Lisbet

2014-11-25

A rapid, sensitive and accurate laboratory diagnosis is of prime importance in suspected extrapulmonary tuberculosis (EPTB) cases. However, traditional techniques for the detection of acid-fast bacilli have limitations. The aim of the study was to evaluate the diagnostic value of immunocytochemical staining for detection of Mycobacterium tuberculosis complex specific antigen, MPT64, in aspirates from pleural effusions and lymph nodes, the most common presentations of EPTB. A cross-sectional study was conducted by including patients at Tikur Anbessa Specialized Hospital and the United Vision Medical Services from December 2011 to June 2012. Lymph node aspirates and pleural fluid samples were collected and analyzed from a total of 51 cases (26 tuberculous (TB) pleuritis and 25 TB lymphadenitis) and 67 non-TB controls. Each specimen was subjected to Ziehl-Neelsen (ZN) staining, culture on Lowenstein- Jensen (LJ) medium, cytological examination, Polymerase Chain Reaction (PCR) using IS1081gene sequence as a primer and immunocytochemistry (ICC) with polyclonal anti-MPT64 antibody. All patients were screened for HIV. ICC was positive in 38 of 51 cases and in the 7 of 67 controls giving an overall sensitivity and specificity of 74.5% and 89.5%, respectively. Using IS1081-PCR as a reference method, the sensitivity and specificity, positive and negative predictive value of ICC was 88.1%, 89.5%, 82.2% and 93.2%, respectively. The case detection rate increased from 13.7% by ZN stain to 19.6% by LJ culture, to 66.7% by cytology and 74.5% by ICC. Immunocytochemistry with anti-MPT64 antigen improved detection of TB in pleural effusion and lymph node aspirates. Further studies using monoclonal antibodies on samples from other sites of EPTB is recommended to validate this relatively simple diagnostic method for EPTB.

Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice1

PubMed Central

Chaudhuri, Shubhra; McCullough, Sandra S.; Hennings, Leah; Brown, Aliza T.; Li, Shun-Hwa; Simpson, Pippa M.; Hinson, Jack A.; James, Laura P.

2012-01-01

Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A2, and cytosolic and secretory PLA2 activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E2 expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE2 expression and hepatocyte regeneration, likely through a mechanism involving PLA2. PMID:22902588

Meridional Transect of Atlantic Overturning Circulation across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Goldstein, S. L.; Pena, L. D.; Seguí, M. J.; Kim, J.; Yehudai, M.; Farmer, J. R.; Ford, H. L.; Haynes, L.; Hoenisch, B.; Raymo, M. E.; Ferretti, P.; Bickert, T.

2016-12-01

The Mid-Pleistocene Transition (MPT) marked a major transition in glacial-interglacial periodicity from dominantly 41 kyr to 100 kyr cycles between 1.3-0.7 Ma. From Nd isotope records in the South Atlantic, Pena and Goldstein (Science, 2014) concluded that the Atlantic overturning circulation circulation experienced major weakening between 950-850 ka (MIS 25-21), which generated the climatic conditions that intensified cold periods, prolonged their duration, and stabilized 100 kyr cycles. Such weakening would provide a mechanism for decreased atmospheric CO2 (Hönisch et al., Science, 2009) by allowing for additional atmospheric CO2 to be stored in the deep ocean. We present a summary of work in-progress to generate two dimensional representations of the Atlantic meridional overturning circulation, from the north Atlantic to the Southern Ocean, at different time slices over the past 2Ma, including the MPT, based on Nd isotope ratios measured on Fe-Mn-oxide encrusted foraminifera and fish debris. Thus far we are analyzing samples from DSDP/ODP Sites 607, 1063 from the North Atlantic, 926 from the Equatorial Atlantic, 1264, 1267, 1088, 1090 in the South Atlantic, and 1094 from the Southern Ocean. Our data generated thus far support important changes in the overturning circulation during the MPT, and greater glacial-interglacial variability in the 100 kyr world compared with the 40 kyr world. In addition, the data indicate a North Atlantic-sourced origin for the ocean circulation disruption during the MPT. Comparison with ɛNd records in different ocean basins and with benthic foraminiferal δ13C and B/Ca ratios will also allow us to understand the links between deep ocean circulation changes and the global carbon cycle.

PLGA particulate subunit tuberculosis vaccines promote humoral and Th17 responses but do not enhance control of Mycobacterium tuberculosis infection

PubMed Central

Parumasivam, Thaigarajan; Chan, John Gar Yan; Lin, Leon C. W.; Flórido, Manuela; West, Nicholas P.; Chan, Hak-Kim; Britton, Warwick J.

2018-01-01

Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL). Following delivery by the pulmonary or subcutaneous routes, the immunogenicity and protective efficacy of these vaccines were assessed in a murine model of M. tuberculosis infection. When delivered peripherally, these vaccines induced modest, antigen-specific Th1 and Th17 responses, but strong anti-MPT83 antibody responses. Mucosal delivery of the PLGA(MPT83) vaccine, with or without TDB, increased antigen-specific Th17 responses in the lungs, however, PLGA-encapsulated vaccines did not provide protection against M. tuberculosis challenge. By contrast, peripheral delivery of DDA liposomes containing MPT83 and TDB or MPL, stimulated both Th1 and Th17 responses and generated protection against M. tuberculosis challenge. Therefore, PLGA-formulated vaccines primarily stimulate strong humoral immunity, or Th17 responses if used mucosally, and may be a suitable carrier for vaccines against extracellular pathogens. This study emphasises the critical nature of the vaccine carrier, adjuvant and route of delivery for optimising vaccine efficacy against TB. PMID:29554138

Mitochondrial matrix metalloproteinase activation decreases myocyte contractility in hyperhomocysteinemia.

PubMed

Moshal, Karni S; Tipparaju, Srinivas M; Vacek, Thomas P; Kumar, Munish; Singh, Mahavir; Frank, Iluiana E; Patibandla, Phani K; Tyagi, Neetu; Rai, Jayesh; Metreveli, Naira; Rodriguez, Walter E; Tseng, Michael T; Tyagi, Suresh C

2008-08-01

Cardiomyocyte N-methyl-d-aspartate receptor-1 (NMDA-R1) activation induces mitochondrial dysfunction. Matrix metalloproteinase protease (MMP) induction is a negative regulator of mitochondrial function. Elevated levels of homocysteine [hyperhomocysteinemia (HHCY)] activate latent MMPs and causes myocardial contractile abnormalities. HHCY is associated with mitochondrial dysfunction. We tested the hypothesis that HHCY activates myocyte mitochondrial MMP (mtMMP), induces mitochondrial permeability transition (MPT), and causes contractile dysfunction by agonizing NMDA-R1. The C57BL/6J mice were administered homocystinemia (1.8 g/l) in drinking water to induce HHCY. NMDA-R1 expression was detected by Western blot and confocal microscopy. Localization of MMP-9 in the mitochondria was determined using confocal microscopy. Ultrastructural analysis of the isolated myocyte was determined by electron microscopy. Mitochondrial permeability was measured by a decrease in light absorbance at 540 nm using the spectrophotometer. The effect of MK-801 (NMDA-R1 inhibitor), GM-6001 (MMP inhibitor), and cyclosporine A (MPT inhibitor) on myocyte contractility and calcium transients was evaluated using the IonOptix video edge track detection system and fura 2-AM. Our results demonstrate that HHCY activated the mtMMP-9 and caused MPT by agonizing NMDA-R1. A significant decrease in percent cell shortening, maximal rate of contraction (-dL/dt), and maximal rate of relaxation (+dL/dt) was observed in HHCY. The decay of calcium transient amplitude was faster in the wild type compared with HHCY. Furthermore, the HHCY-induced decrease in percent cell shortening, -dL/dt, and +dL/dt was attenuated in the mice treated with MK-801, GM-6001, and cyclosporin A. We conclude that HHCY activates mtMMP-9 and induces MPT, leading to myocyte mechanical dysfunction by agonizing NMDA-R1.

IODP Site 1476: 7.5 Million Year Record of Southeast African Climate

NASA Astrophysics Data System (ADS)

Cantu, K.; Norris, R. D.

2017-12-01

The primary focus of IODP Expedition 361 was Southeast African Climate. Site 1476 in the northern Mozambique Channel yielded a sediment record going back roughly 7.6 million years, a time frame particularly interesting due to its relevance to hominid evolution. Previous paleoclimate studies from the region have included lake sediments and soil carbonate isotopes, which have been interpreted as showing a long-term trend toward increasing aridity. Lake Malawi records from the last 1.3 million years show a change during the Mid-Pleistocene Transition (MPT) from high frequency variability and generally lower lake levels to higher amplitude variability and higher lake levels punctuated by long, severe droughts resulting in extreme and long-lasting low-stands. Site 1476 cores were scanned using X-Ray Fluorescence (XRF), which gives semi-quantitative elemental abundances. Elemental abundance ratios are used as proxies for a variety of climate-related signals, such as changes in weathering rates, the nature of terrigenous material, and grain size. Looking at the site's Fe/Ca, K/Ca, and Rb/Zr ratios, the period of 4.5 to about 1.5 million years ago shows higher terrigenous flux, higher clay flux, and a smaller grain size respectively than most of the previous 3 million years, followed by a steep decline before the MPT, before transitioning to a pattern of high amplitude oscillations post-MPT. These higher amplitude oscillations seem to correspond to Lake Malawi low stands in the post-MPT period, suggesting that the higher flux of terrigenous material to site 1476 is due to higher aridity resulting in lower vegetative cover. This data also point to high climate variability in the last million years, likely contributing to the evolution and ecological adaptability of our species.

Shape of Thyroid Cartilage Influences Outcome of Montgomery Medialization Thyroplasty: A Gender Issue.

PubMed

Desuter, Gauthier; Henrard, Sylvie; Van Lith-Bijl, Julie T; Amory, Avigaëlle; Duprez, Thierry; van Benthem, Peter Paul; Sjögren, Elisabeth

2017-03-01

This study aimed to determine whether the shape of the thyroid cartilage and gender influence voice outcomes after a Montgomery thyroplasty implant system (MTIS). A retrospective cohort study was performed on 20 consecutive patients who underwent MTIS. Voice outcome variables were the relative decrease in Voice Handicap Index (%) and the absolute increase in maximum phonation time (MPT) (in seconds). Material variables were the angle between the thyroid cartilage laminae (α-angle), the size of the prosthesis, and a combination of both (the α-ratio). Continuous variables were analyzed using medians and were compared between groups using the Mann-Whitney U test. Factors associated with the outcome variables were assessed by multivariable linear regression. A Pearson coefficient was calculated between material variables. The absolute increase in MPT between the pre- and postoperative period was significantly different between men and women, with a median absolute increase of 11.0 seconds for men and of 1.3 seconds for women (P < 0.001). A strong inverse correlation between the α-ratio and the absolute increase in MPT is observed in all patients, with a Pearson correlation coefficient R = -0.769 (P < 0.001). No factors were significantly associated with the relative Voice Handicap Index decrease in univariable or multivariable analyses. A better Pearson coefficient between the α-angle and the prosthesis size was found for females (0.8 vs 0.71). The MTIS is a good thyroplasty modality for male patients, but inadequate design of MTIS female implants leads to poor MPT outcomes. This represents a gender issue that needs to be further studied and eventually tackled. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Cinnamon polyphenols attenuate cell swelling and mitochondrial dysfunction following oxygen-glucose deprivation in glial cells.

PubMed

Panickar, Kiran S; Polansky, Marilyn M; Anderson, Richard A

2009-04-01

Astrocyte swelling is an integral component of cytotoxic brain edema in ischemic injury. While mechanisms underlying astrocyte swelling are likely multifactorial, oxidative stress and mitochondrial dysfunction are hypothesized to contribute to such swelling. We investigated the protective effects of cinnamon polyphenol extract (CPE) that has anti-oxidant and insulin-potentiating effects on cell swelling and depolarization of the inner mitochondrial membrane potential (DeltaPsi(m)) in ischemic injury. C6 glial cells were subjected to oxygen-glucose deprivation (OGD) and cell volume determined using the 3-O-methyl-[3H]-glucose method at 90 min after the end of OGD. When compared with controls, OGD increased cell volume by 34%. This increase was blocked by CPE or insulin but not by blockers of oxidative/nitrosative stress including vitamin E, resveratrol, N-nitro-L-arginine methyl ester (L-NAME) or uric acid. Mitochondrial dysfunction, a key component of ischemic injury, contributes to cell swelling. Changes in DeltaPsi(m) were assessed at the end of OGD with tetramethylrhodamine ethyl ester (TMRE), a potentiometric dye. OGD induced a 39% decline in DeltaPsi(m) and this decline was blocked by CPE as well as insulin. To test the involvement of the mitochondrial permeability transition (mPT), we used Cyclosporin A (CsA), an immunosuppressant and a blocker of the mPT pore. CsA blocked cell swelling and the decline in DeltaPsi(m) but FK506, an immunosuppressant that does not block the mPT, did not. Our results show that CPE reduces OGD-induced cell swelling as well as the decline in DeltaPsi(m) in cultures and some of its protective effects may be through inhibiting the mPT.

Further Validation of a Marijuana Purchase Task

PubMed Central

Aston, Elizabeth R.; Metrik, Jane; MacKillop, James

2015-01-01

Background A valid measure of the relative economic value of marijuana is needed to characterize individual variation in the drug’s reinforcing value and inform evolving national marijuana policy. Relative drug value (demand) can be measured via purchase tasks, and demand for alcohol and cigarettes has been associated with craving, dependence, and treatment response. This study examined marijuana demand with a marijuana purchase task (MPT). Methods The 22-item self-report MPT was administered to 99 frequent marijuana users (37.4% female, 71.5% marijuana use days, 15.2% cannabis dependent). Results Pearson correlations indicated a negative relationship between intensity (free consumption) and age of initiation of regular use (r=−0.34, p<0.001), and positive associations with use days (r=0.26, p<0.05) and subjective craving (r=0.43, p<0.001). Omax (maximum expenditure) was positively associated with use days (r=0.29, p<0.01) and subjective craving (r=0.27, p<0.01). Income was not associated with demand. An exponential demand model provided an excellent fit to the data across users (R2=0.99). Group comparisons based on presence or absence of DSM-IV cannabis dependence symptoms revealed that users with any dependence symptoms showed significantly higher intensity of demand and more inelastic demand, reflecting greater insensitivity to price increases. Conclusions These results provide support for construct validity of the MPT, indicating its sensitivity to marijuana demand as a function of increasing cost, and its ability to differentiate between users with and without dependence symptoms. The MPT may denote abuse liability and is a valuable addition to the behavioral economic literature. Potential applications to marijuana pricing and tax policy are discussed. PMID:26002377

Disentangling stereotype activation and stereotype application in the stereotype misperception task.

PubMed

Krieglmeyer, Regina; Sherman, Jeffrey W

2012-08-01

When forming impressions about other people, stereotypes about the individual's social group often influence the resulting impression. At least 2 distinguishable processes underlie stereotypic impression formation: stereotype activation and stereotype application. Most previous research has used implicit measures to assess stereotype activation and explicit measures to assess stereotype application, which has several disadvantages. The authors propose a measure of stereotypic impression formation, the stereotype misperception task (SMT), together with a multinomial model that quantitatively disentangles the contributions of stereotype activation and application to responses in the SMT. The validity of the SMT and of the multinomial model was confirmed in 5 studies. The authors hope to advance research on stereotyping by providing a measurement tool that separates multiple processes underlying impression formation.

Compartmentalization of immune responses in human tuberculosis: few CD8+ effector T cells but elevated levels of FoxP3+ regulatory t cells in the granulomatous lesions.

PubMed

Rahman, Sayma; Gudetta, Berhanu; Fink, Joshua; Granath, Anna; Ashenafi, Senait; Aseffa, Abraham; Derbew, Milliard; Svensson, Mattias; Andersson, Jan; Brighenti, Susanna Grundström

2009-06-01

Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-beta and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-beta and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.

Proceedings of Interservice/Industry Training Systems and Education Conference (15th) Held November 29 - December 2, 1993

DTIC Science & Technology

1993-12-02

community) or not knowing MPT analysis evaluates human-in- loop costs and how to exploit data that were available to represent capabilities w;th intent...specification b. There is no closed loop ; the process may statements. An agency is preparing a System Specification with minimal security information...Item is one which musk alweys be provided by the CMI system to be AICC compliant. Core Items are those which a lesson may always depend upon being

Objective and Subjective Aspects of Voice in Pregnancy.

PubMed

Saltürk, Ziya; Kumral, Tolgar Lütfi; Bekiten, Güler; Atar, Yavuz; Ataç, Enes; Aydoğdu, İmran; Yıldırım, Güven; Kılıç, Aydın; Uyar, Yavuz

2016-01-01

This study aimed to evaluate vocal changes in pregnancy according to trimesters both objectively and subjectively. Fifty pregnant women and 15 nonpregnant women were included in the study. Eighteen of the 50 pregnant women were in the first trimester, 17 in the second trimester, and 15 in the third trimester of their pregnancies. The fundamental frequency (F0), jitter, shimmer, noise-to-harmonics ratio (NHR), and minimum and maximum pitch were determined during acoustic voice analysis. Laryngologic examination was evaluated via reflux finding score (RFS). Voice Handicap Index 10 (VHI-10) was used for subjective analysis. Maximum phonation time (MPT), VHI-10, and RFS were the parameters that differed significantly. MPT was significantly shorter in the third trimester. Acoustic analysis revealed that F0, jitter, shimmer, NHR, and minimum and maximum pitch values were not significantly different in any groups. RFS was higher in the first and third trimesters than the second trimester and control groups. VHI-10 scores were significantly higher in the third trimester. Our results showed that MPT is decreased during the third trimester, although acoustic parameters did not differ. VHI-10 results deteriorated in the third trimester significantly. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Use of multiphoton tomography and fluorescence lifetime imaging to investigate skin pigmentation in vivo

NASA Astrophysics Data System (ADS)

Dancik, Yuri; Favre, Amandine; Loy, Chong Jin; Zvyagin, Andrei V.; Roberts, Michael S.

2013-02-01

There is a growing body of literature showing the usefulness of multiphoton tomography (MPT) and fluorescence lifetime imaging for in situ characterization of skin constituents and the ensuing development of noninvasive diagnostic tools against skin diseases. Melanin and pigmentation-associated skin cancers constitute some of the major applications. We show that MPT and fluorescence lifetime imaging can be used to measure changes in cutaneous melanin concentration and that these can be related to the visible skin color. Melanin in the skin of African, Indian, Caucasian, and Asian volunteers is detected on the basis of its emission wavelength and fluorescence lifetimes in solution and in a melanocyte-keratinocyte cell culture. Fluorescence intensity is used to characterize the melanin content and distribution as a function of skin type and depth into the skin (stratum granulosum and stratum basale). The measured fluorescence intensities in given skin types agree with melanin amounts reported by others using biopsies. Our results suggest that spatial distribution of melanin in skin can be studied using MPT and fluorescence lifetime imaging, but further studies are needed to ascertain that the method can resolve melanin amount in smaller depth intervals.

In vivo detection of basal cell carcinoma: comparison of a reflectance confocal microscope and a multiphoton tomograph

NASA Astrophysics Data System (ADS)

Ulrich, Martina; Klemp, Marisa; Darvin, Maxim E.; König, Karsten; Lademann, Jürgen; Meinke, Martina C.

2013-06-01

The standard diagnostic procedure for basal cell carcinoma (BCC) is invasive tissue biopsy with time-consuming histological examination. To reduce the number of biopsies, noninvasive optical methods have been developed providing high-resolution skin examination. We present direct comparison of a reflectance confocal microscope (RLSM) and a multiphoton tomograph (MPT) for BCC diagnosis. Both systems are applied to nine patients prior to surgery, and the results are analyzed, including histological results. Both systems prove suitable for detecting typical characteristics of BCC in various stages. The RLSM allows large horizontal overview images to be obtained, enabling the investigator to find the regions of interest quickly, e.g., BCC nests. Elongated cells and palisading structures are easily recognized using both methods. Due to the higher resolution, changes in nucleus diameter or cytoplasm could be visualized with the MPT. Therefore, the nucleus diameter, nucleus/cytoplasm ratio, and cell density are estimated for normal and BCC cells using the MPT. The nucleus of elongated BCC cells is significantly longer than other measured normal skin cells, whereas the cell density and nucleus/cytoplasm ratio of BCC cannot be significantly distinguished from granular cells.

Use of multiphoton tomography and fluorescence lifetime imaging to investigate skin pigmentation in vivo.

PubMed

Dancik, Yuri; Favre, Amandine; Loy, Chong Jin; Zvyagin, Andrei V; Roberts, Michael S

2013-02-01

There is a growing body of literature showing the usefulness of multiphoton tomography (MPT) and fluorescence lifetime imaging for in situ characterization of skin constituents and the ensuing development of noninvasive diagnostic tools against skin diseases. Melanin and pigmentation-associated skin cancers constitute some of the major applications. We show that MPT and fluorescence lifetime imaging can be used to measure changes in cutaneous melanin concentration and that these can be related to the visible skin color. Melanin in the skin of African, Indian, Caucasian, and Asian volunteers is detected on the basis of its emission wavelength and fluorescence lifetimes in solution and in a melanocyte-keratinocyte cell culture. Fluorescence intensity is used to characterize the melanin content and distribution as a function of skin type and depth into the skin (stratum granulosum and stratum basale). The measured fluorescence intensities in given skin types agree with melanin amounts reported by others using biopsies. Our results suggest that spatial distribution of melanin in skin can be studied using MPT and fluorescence lifetime imaging, but further studies are needed to ascertain that the method can resolve melanin amount in smaller depth intervals.

Coupling Modern Portfolio Theory and Marxan enhances the efficiency of Lesser White-fronted Goose's (Anser erythropus) habitat conservation.

PubMed

Liang, Jie; Gao, Xiang; Zeng, Guangming; Hua, Shanshan; Zhong, Minzhou; Li, Xiaodong; Li, Xin

2018-01-09

Climate change and human activities cause uncertain changes to species biodiversity by altering their habitat. The uncertainty of climate change requires planners to balance the benefit and cost of making conservation plan. Here optimal protection approach for Lesser White-fronted Goose (LWfG) by coupling Modern Portfolio Theory (MPT) and Marxan selection were proposed. MPT was used to provide suggested weights of investment for protected area (PA) and reduce the influence of climatic uncertainty, while Marxan was utilized to choose a series of specific locations for PA. We argued that through combining these two commonly used techniques with the conservation plan, including assets allocation and PA chosing, the efficiency of rare bird's protection would be enhanced. In MPT analyses, the uncertainty of conservation-outcome can be reduced while conservation effort was allocated in Hunan, Jiangxi and Yangtze River delta. In Marxan model, the optimal location for habitat restorations based on existing nature reserve was identified. Clear priorities for the location and allocation of assets could be provided based on this research, and it could help decision makers to build conservation strategy for LWfG.

Evaluation of health plan member use of an online prescription drug price comparison tool.

PubMed

Carroll, Norman V; Mitchell, Matthew P; Cannon, H Eric; York, Bryan W York; Oscar, Robert S

2010-01-01

Health plans have implemented tiered copayment systems to incentivize members to use less expensive medications. However, members need drug price information to make comparisons among therapeutic alternatives. Many health plans and pharmacy benefit management companies have implemented online prescription drug price comparison tools to provide such information. There has been little published evaluation of these tools. To evaluate use of an online price comparison tool- MyPharmacyTools (MPT)- by the measures of (a) the extent to which the tool was used, (b) changes in use over the first year after implementation, and (c) the types of members who were most likely to use the tool. Data were provided by a 500,000-member integrated health plan with approximately 156,250 enrolled families. The sample included only families with continuous eligibility for all members from July 1, 2006, through June 30, 2008; use of 1 of 7 common copayment structures; and use of the pharmacy benefit in every quarter of the study period. Data collected on each member, using pharmacy claims for the time period July 1, 2007, through June 30, 2008, included annual drug costs (total, out-of-pocket, plan-paid, and mail order) and number of unique drugs and unique generic drugs taken during the third quarter of 2007. Data collected also included whether the member had each of several selected chronic diseases (as inferred from drug claims for the third quarter of 2007) and demographics. Age, gender, and family size were taken from eligibility files. Other demographic data were imputed to members from the demographics of the ZIP code in which they resided. MPT was made available to members on July 1, 2007. Use of MPT was measured as the number of times members logged into the site for each quarter during the subsequent year. Statistical analyses were conducted at the family rather than at the individual level, and families were defined as users if any family member used MPT at least once during the year. Between-group comparisons were evaluated with t-tests, Pearson chi-square tests, and analyses of variance. Data were analyzed for 8,909 families composed of 28,537 health plan members, of which 464 (5.2%) families used MPT at least once between July 2007 and June 2008. A total of 141 families used MPT in the first quarter it was available, 170 families used it in the second quarter, 185 families in the third quarter, and 182 families during the fourth quarter. Users had significantly higher mean [SD] total drug costs ($4,477 [$9,647] vs. $2,848 [$3,473], P < 0.001) and used significantly more unique drug products (7.7 [5.7] vs. 5.9 [4.5], P < 0.001) and unique generic drug products (5.0 [3.9] vs. 3.9 [3.2], P < 0.001) than did nonusers. Users were significantly more likely than nonusers to use drugs for behavioral diseases (47.0% vs. 39.7%, P = 0.002), hypercholesterolemia (35.8% vs. 27.0%, P < 0.001), gastric disorders (32.8% vs. 23.0%, P < 0.001), diabetes (18.3% vs. 12.8%, P < 0.001), epilepsy (21.1% vs. 10.6%, P < 0.001), cardiovascular problems (48.3% vs. 37.5%, P < 0.001), and asthma (14.0% vs. 10.7%, P = 0.025). Families that used MPT were less likely to have a female subscriber than were nonusers (39.7% vs. 49.0%, P < 0.001). Otherwise, here were no statistically significant demographic differences between users and nonusers. Families using MPT in more quarters of the year had higher out-of-pocket (P < 0.001) and mail order drug costs (P < 0.001), took a larger number of drugs (P = 0.003) and generic drugs (P = 0.019), were more likely to use drugs for diabetes (P = 0.049) and cardiovascular disease (P = 0.013), and used drugs for a greater number of chronic diseases (P = 0.049), compared with less frequent MPT users. About 5% of families in a sample from a large integrated health plan used an online prescription drug cost comparison tool during the first year it was available. Use increased over the year. Users were more likely to have several chronic diseases, took more prescription drugs, and had higher drug costs than nonusers. Further, users with more chronic diseases and more prescriptions were more likely to use the tool consistently throughout the year. These results indicate that the tool was successful in reaching health plan members who could most benefit from comparative prescription drug price information.

Predicting longitudinal trajectories of health probabilities with random-effects multinomial logit regression.

PubMed

Liu, Xian; Engel, Charles C

2012-12-20

Researchers often encounter longitudinal health data characterized with three or more ordinal or nominal categories. Random-effects multinomial logit models are generally applied to account for potential lack of independence inherent in such clustered data. When parameter estimates are used to describe longitudinal processes, however, random effects, both between and within individuals, need to be retransformed for correctly predicting outcome probabilities. This study attempts to go beyond existing work by developing a retransformation method that derives longitudinal growth trajectories of unbiased health probabilities. We estimated variances of the predicted probabilities by using the delta method. Additionally, we transformed the covariates' regression coefficients on the multinomial logit function, not substantively meaningful, to the conditional effects on the predicted probabilities. The empirical illustration uses the longitudinal data from the Asset and Health Dynamics among the Oldest Old. Our analysis compared three sets of the predicted probabilities of three health states at six time points, obtained from, respectively, the retransformation method, the best linear unbiased prediction, and the fixed-effects approach. The results demonstrate that neglect of retransforming random errors in the random-effects multinomial logit model results in severely biased longitudinal trajectories of health probabilities as well as overestimated effects of covariates on the probabilities. Copyright © 2012 John Wiley & Sons, Ltd.

Prospective memory after moderate-to-severe traumatic brain injury: a multinomial modeling approach.

PubMed

Pavawalla, Shital P; Schmitter-Edgecombe, Maureen; Smith, Rebekah E

2012-01-01

Prospective memory (PM), which can be understood as the processes involved in realizing a delayed intention, is consistently found to be impaired after a traumatic brain injury (TBI). Although PM can be empirically dissociated from retrospective memory, it inherently involves both a prospective component (i.e., remembering that an action needs to be carried out) and retrospective components (i.e., remembering what action needs to be executed and when). This study utilized a multinomial processing tree model to disentangle the prospective (that) and retrospective recognition (when) components underlying PM after moderate-to-severe TBI. Seventeen participants with moderate to severe TBI and 17 age- and education-matched control participants completed an event-based PM task that was embedded within an ongoing computer-based color-matching task. The multinomial processing tree modeling approach revealed a significant group difference in the prospective component, indicating that the control participants allocated greater preparatory attentional resources to the PM task compared to the TBI participants. Participants in the TBI group were also found to be significantly more impaired than controls in the when aspect of the retrospective component. These findings indicated that the TBI participants had greater difficulty allocating the necessary preparatory attentional resources to the PM task and greater difficulty discriminating between PM targets and nontargets during task execution, despite demonstrating intact posttest recall and/or recognition of the PM tasks and targets.

Care provider allocation on admissions to acute mental health wards: The development and validation of the Admission Team Score List.

PubMed

van den Berg, Sjobha R N; Stringer, Barbara; van de Sande, Roland; Draisma, Stasja

2018-05-18

Currently, support tools are lacking to prioritize steps in the care coordination process to enable safe practice and effective clinical pathways in the first phase of acute psychiatric admissions. This study describes the development, validity, and reliability of an acute care coordination support tool, the Admission Team Score List (ATSL). The ATSL assists in care provider allocation during admissions. Face validity and feasibility of the ATSL were tested in 77 acute admissions. Endscores of filled out ATSL's were translated to recommended team compositions. These ATSL team (ATSL-T) compositions were compared to the actually present team (AP-T) and the most preferred team (MP-T) composition in hindsight. Consistency between the ATSL-T and the MP-T was substantial; K w  = 0.70, P < 0.001, 95% CI [0.55-0.84]. The consistency between the ATSL-T and AP-T was moderate; K w  = 0.43, P < 0.001, 95% CI [0.23-0.62]. The ATSL has an adequate (inter-rater) reliability; ICC = 0.90, P < 0.001, 95% CI [0.65-0.91]. The ATSL study is an important step to promote safety and efficient care based on care provider allocation, for service users experiencing an acute admission. The ATSL may stimulate structured clinical decision-making during the hectic process around acute psychiatric admissions. © 2018 Australian College of Mental Health Nurses Inc.

Order-disorder effects on the elastic properties of CuMPt6 (M=Cr and Co) compounds

NASA Astrophysics Data System (ADS)

Huang, Shuo; Li, Rui-Zi; Qi, San-Tao; Chen, Bao; Shen, Jiang

2014-04-01

The elastic properties of CuMPt6 (M=Cr and Co) in disordered face-centered cubic (fcc) structure and ordered Cu3Au-type structure are studied with lattice inversion embedded-atom method. The calculated lattice constant and Debye temperature agree quite well with the comparable experimental data. The obtained formation enthalpy demonstrates that the Cu3Au-type structure is energetically more favorable. Numerical estimates of the elastic constants, bulk/shear modulus, Young's modulus, Poisson's ratio, elastic anisotropy, and Debye temperature for both compounds are performed, and the results suggest that the disordered fcc structure is much softer than the ordered Cu3Au-type structure.

Synthesis and hydrogenation application of Pt-Pd bimetallic nanocatalysts stabilized by macrocycle-modified dendrimer.

PubMed

Jin, Zhijun; Xiao, Haiyan; Zhou, Wei; Zhang, Dongqiao; Peng, Xiaohong

2017-12-01

Different generations of poly(propylene imine) (G n -PPI) terminated with N-containing 15-membered triolefinic macrocycle (G n M) ( n  = 2, 3, 4, 5) were prepared. The bimetallic nanoparticle catalysts G n M-(Pt x /Pd 10- x ) ( x  = 0, 3, 5, 7, 10) were prepared by the synchronous ligand-exchange reaction between G n M and the complexes of Pt(PPh 3 ) 4 and Pd(PPh 3 ) 4 . The structure and catalytic properties of G n M-(Pt x /Pd 10- x ) were characterized via Fourier transform infrared spectroscopy, 1 H nuclear magnetic resonance spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, energy-dispersive spectroscopy and inductively coupled plasma atomic emission spectroscopy. The novel bimetallic Pd-Pt nanoparticle catalysts stabilized by dendrimers (DSNs) present higher catalytic activities for the hydrogenation of dimeric acid (DA) than that of nitrile butadiene rubber (NBR). It can be concluded that bimetallic Pd-Pt DSNs possess alloying and synergistic electronic effects on account of the hydrogenation degree (HD) of DA and NBR. Furthermore, the HD of DA and NBR shows a remarkable decrease with the incremental generations ( n ) of G n M-(Pt 3 /Pd 7 ) ( n  = 2, 3, 4, 5).

Clinical optical coherence tomography combined with multiphoton tomography for evaluation of several skin disorders

NASA Astrophysics Data System (ADS)

König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J.; Elsner, Peter; Kaatz, Martin

2010-02-01

The first clinical trial of optical coherence tomography (OCT) combined with multiphoton tomography (MPT) and dermoscopy is reported. State-of-the-art (i) OCT systems for dermatology (e.g. multibeam swept source OCT), (ii) the femtosecond laser multiphoton tomograph DermaInspectTM, and (iii) digital dermoscopes were applied to 47 patients with a diversity of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases. Dermoscopy, also called 'epiluminescent microscopy', provides two-dimensional color images of the skin surface. OCT imaging is based on the detection of optical reflections within the tissue measured interferometrically whereas nonlinear excitation of endogenous fluorophores and the second harmonic generation are the bases of MPT images. OCT cross sectional "wide field" image provides a typical field of view of 5 x 2 mm2 and offers fast information on the depth and the volume of the investigated lesion. In comparison, multiphoton tomography presents 0.36 x 0.36 mm2 horizontal or diagonal sections of the region of interest within seconds with submicron resolution and down to a tissue depth of 200 μm. The combination of OCT and MPT provides a synergistic optical imaging modality for early detection of skin cancer and other skin diseases.

A New Protocol to Evaluate the Effect of Topical Anesthesia

PubMed Central

List, Thomas; Mojir, Katerina; Svensson, Peter; Pigg, Maria

2014-01-01

This double-blind, placebo-controlled, randomized cross-over clinical experimental study tested the reliability, validity, and sensitivity to change of punctuate pain thresholds and self-reported pain on needle penetration. Female subjects without orofacial pain were tested in 2 sessions at 1- to 2-week intervals. The test site was the mucobuccal fold adjacent to the first upper right premolar. Active lidocaine hydrochloride 2% (Dynexan) or placebo gel was applied for 5 minutes, and sensory testing was performed before and after application. The standardized quantitative sensory test protocol included mechanical pain threshold (MPT), pressure pain threshold (PPT), mechanical pain sensitivity (MPS), and needle penetration sensitivity (NPS) assessments. Twenty-nine subjects, mean (SD) age 29.0 (10.2) years, completed the study. Test-retest reliability intraclass correlation coefficient at 10-minute intervals between examinations was MPT 0.69, PPT 0.79, MPS 0.72, and NPS 0.86. A high correlation was found between NPS and MPS (r = 0.84; P < .001), whereas NPS and PPT were not significantly correlated. The study found good to excellent test-retest reliability for all measures. None of the sensory measures detected changes in sensitivity following lidocaine 2% or placebo gel. Electronic von Frey assessments of MPT/MPS on oral mucosa have good validity. PMID:25517548

Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases.

PubMed

König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J; Elsner, Peter; Kaatz, Martin

2009-07-01

We report on the first clinical study based on optical coherence tomography (OCT) in combination with multiphoton tomography (MPT) and dermoscopy. 47 patients with a variety of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art OCT systems for dermatology including multibeam swept source OCT, (ii) the femtosecond laser multiphoton tomograph, and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface. OCT images reflect modifications of the intratissue refractive index whereas MPT is based on nonlinear excitation of endogenous fluorophores and second harmonic generation. A stack of cross-sectional OCT "wide field" images with a typical field of view of 5 x 2 mm(2) gave fast information on the depth and the volume of the lesion. Multiphoton tomography provided 0.36 x 0.36 mm(2) horizontal/diagonal optical sections within seconds of a particular region of interest with superior submicron resolution down to a tissue depth of 200 mum. The combination of OCT and MPT provides a unique powerful optical imaging modality for early detection of skin cancer and other skin diseases as well as for the evaluation of the efficiency of treatments.

Predictors of assistive technology use: the importance of personal and psychosocial factors.

PubMed

Scherer, Marcia J; Sax, Caren; Vanbiervliet, Alan; Cushman, Laura A; Scherer, John V

2005-11-15

To validate an assistive technology (AT) baseline and outcomes measure and to quantify the measure's value in determining the best match of consumer and AT considering consumer ratings of their subjective quality of life, mood, support from others, motivation for AT use, program/therapist reliance, and self-determination/self-esteem. Prospective multi-cohort study. Vocational rehabilitation offices and community. Over 150 vocational rehabilitation counselors in 25 U.S. states with one consumer each receiving new AT. Counselor training in the Matching Person and Technology (MPT) Model and consumer completion of the MPT measure, Assistive Technology Device Predisposition Assessment (ATD PA). Total and subscale scores on the ATD PA as well as counselor-completed questionnaires. ATD PA items differentiated consumer predispositions to AT use as well as AT and user match. There were no significant differences due to gender, physical locality, or age within this sample of working-age adult consumers. Vocational rehabilitation counselors exposed to training in the MPT Model achieved enhanced AT service delivery outcomes. The ATD PA is a valid measure of predisposition to use an AT and the subsequent match of AT and user. Rehabilitation practitioners who use the ATD PA will achieve evidence-based practice and can expect to see enhanced AT service delivery outcomes.

Role of magnetic and atomic ordering in the martensitic transformation of Ni-Mn-In from a first-principles study

NASA Astrophysics Data System (ADS)

Li, Chun-Mei; Luo, Hu-Bin; Hu, Qing-Miao; Yang, Rui; Johansson, Börje; Vitos, Levente

2012-12-01

The composition-dependent lattice parameters, crystal structure, elastic properties, magnetic moment, and electronic structure of Ni2Mn1+xIn1-x (0≤x≤0.6) are studied by using first-principles calculations. It is shown that the martensitic phase transition (MPT) from cubic L21 to tetragonal L10 accompanies the MnMn-MnIn ferromagnetic (FM) to antiferromagnetic (AFM) transition, at around the critical composition x=0.32, in agreement with the experimental measurement. The Mn-In atomic disorder leads to decreasing stability of the martensite relative to the austenite, which depresses the MPT. The shear elastic constant C' of the parent phase first decreases slightly with increasing x and then remains almost unchanged above x=0.32, indicating C' alone cannot account for the increase of the MPT temperature with x. The total magnetic moments for the L21 phase are in good agreement with those determined by experiments, whereas for the L10 phase they are slightly larger than the experimental data due to the possible Mn-In atomic disorder in the sample. The calculated density of states demonstrate that the covalent bonding between the minority spin states of Ni and In plays an important role in both the magnetic and structural stability.

The effect of pressure and temperature on the magnetic and magnetocaloric properties of an MnNi0.9Ge1.1 alloy

NASA Astrophysics Data System (ADS)

Das, S. C.; Mandal, K.; Dutta, P.; Pramanick, S.; Chatterjee, S.

2018-02-01

The magnetic and magnetocaloric properties of a self-doped MnNiGe alloy of nominal composition MnNi0.9Ge1.1 have been investigated in ambient as well as in high pressure conditions. It orders ferromagnetically below around 225 K and undergoes first order martensitic phase transition (MPT) to an antiferromagnetic (AFM) martensite phase below 147 K. This self-doping results in a significant decrease in the lattice volume and hence the Mn-Mn intra-layer distance which induces ferromagnetism (FM) in otherwise AFM alloys. MPT affects this FM ordering and the alloy becomes predominantly AFM in nature below the structural transition temperature. The observed values of the magnetocaloric effects (MCE) are reasonably large at the magnetic (-5.5 J kg-1 K-1 for magnetic field changing from 0 to 50 kOe around 210 K) and structural (8.3 J kg-1 K-1 for magnetic field changing from 0 to 50 kOe around 136 K) transition temperatures in ambient condition. MCE is found to decrease with increasing external hydrostatic pressure (P) at MPT region, whilst this external P has vanishingly small effect on MCE around the magnetic transition temperature.

Study of commonly used organophosphate pesticides that induced oxidative stress and apoptosis in peripheral blood lymphocytes of rats.

PubMed

Ojha, A; Gupta, Y K

2017-11-01

In a previous study, we have found that organophosphate (OP) pesticides such as chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) significantly induced genotoxicity in peripheral blood lymphocytes of rats. To explore the mechanism of OP-induced genotoxicity, we measured the formation of DNA interstrand cross-links (DICs) and apoptosis in peripheral blood lymphocytes of rats. Peripheral blood lymphocytes of rats were treated with CPF, MPT, and MLT individually and in combination at concentrations of 0.1 and 0.25 LC 50 for 2, 4, 8, and 12 h at 37°C. Lipid peroxidation (LPO) was measured as a biomarker of oxidative stress. Apoptosis induced by CPF, MPT, and MLT individually and in combination was determined by measuring the intracellular level of active caspase-3 and caspase-9 by spectrofluorimetry. We found significant dose- and time-dependent increases in LPO, DICs formation and increase of intracellular active caspase-3 and caspase-9 in exposed peripheral blood lymphocytes of rats. These findings suggest that the studied pesticides have potential to induce oxidative stress, cause DNA adduct formation, and cause failure of adduct repair, which leads to apoptosis that is partially mediated by activation of intracellular caspase-3 and caspase-9.

Emotionally enhanced memory for negatively arousing words: storage or retrieval advantage?

PubMed

Nadarevic, Lena

2017-12-01

People typically remember emotionally negative words better than neutral words. Two experiments are reported that investigate whether emotionally enhanced memory (EEM) for negatively arousing words is based on a storage or retrieval advantage. Participants studied non-word-word pairs that either involved negatively arousing or neutral target words. Memory for these target words was tested by means of a recognition test and a cued-recall test. Data were analysed with a multinomial model that allows the disentanglement of storage and retrieval processes in the present recognition-then-cued-recall paradigm. In both experiments the multinomial analyses revealed no storage differences between negatively arousing and neutral words but a clear retrieval advantage for negatively arousing words in the cued-recall test. These findings suggest that EEM for negatively arousing words is driven by associative processes.

Respiratory uncoupling by increased H(+) or K(+) flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition.

PubMed

Morota, Saori; Piel, Sarah; Hansson, Magnus J

2013-09-22

Ischemic preconditioning has been proposed to involve changes in mitochondrial H(+) and K(+) fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K(+) channels (MitoKATP). The objectives of the present study were to explore how increased H(+) and K(+) fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H(+) and K(+) conductance, respectively. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. ROS generation was reduced by both K(+)- and H(+)-mediated respiratory uncoupling. The ability of heart mitochondria to detoxify H2O2 was substantially greater than the production rate. The H2O2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K(+) and H(+) conductance. It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H(+) or K(+) conductance is increased. The negative effects of respiratory uncoupling thus probably outweigh the reduction in ROS generation and a potential positive effect by increased matrix volume, resulting in a net sensitization of heart mitochondria to mPT activation.

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

Chaudhuri, Shubhra, E-mail: SCHAUDHURI@uams.edu; Arkansas Children's Hospital Research Institute, Little Rock, AR; McCullough, Sandra S., E-mail: mcculloughsandras@uams.edu

Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measuresmore » of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A{sub 2}, and cytosolic and secretory PLA{sub 2} activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E{sub 2} expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE{sub 2} expression and hepatocyte regeneration, likely through a mechanism involving PLA{sub 2}. -- Highlights: ► Trifluoperazine reduced acetaminophen toxicity and lowered HIF-1α induction. ► Trifluoperazine had no effect on the metabolism of acetaminophen. ► Trifluoperazine reduced hepatocyte regeneration. ► Trifluoperazine reduced phospholipase A{sub 2} activity and prostaglandin E{sub 2} levels.« less

Changes in Equatorial Atlantic Ocean Thermohaline Circulation Across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Yehudai, M.; Kim, J.; Seguí, M. J.; Goldstein, S. L.; Pena, L. D.; Haynes, L.; Hoenisch, B.; Farmer, J. R.; Ford, H. L.; Raymo, M. E.; Bickert, T.

2016-12-01

The Mid-Pleistocene Transition (MPT) marked a change in the duration of glacial-interglacial cycles from 41 to 100kyr between 1.3-0.7 Ma. A recent study (Pena and Goldstein, Science, 2014) from the Southern Atlantic Ocean found evidence for major disruptions in the global thermohaline circulation (THC) between MIS 25-21 ( 950-850ka), which may have triggered intensified glacial periods and the onset of the 100 kyr cycles. We report new Nd isotope data on Fe-Mn oxide encrusted foraminifera and fish debris from ODP Site 926 (3.719N, 42.908W, 3598m) between 1.2-0.4 Ma, in order to evaluate changes in the THC in the equatorial Atlantic, through comparison with North and South Atlantic sites. The ODP 926 ɛNd values fall in-between those in the North Atlantic (DSDP 607) and South Atlantic (ODP 1088 and 1090) throughout the studied interval, consistent with mixing between northern and southern end-members, and supporting the interpretation that the data represent the THC signal at this site. Pre-MPT data show smaller glacial-interglacial differences compared to the greater post-MPT glacial-interglacial variability. As Pena and Goldstein (2014) observed in the South Atlantic, during MIS 23 at 900 ka, ɛNd values do not shift significantly toward North Atlantic more negative values, consistent with a weak THC through this critical weak interglacial. Comparing ODP 926 and DSDP 607 data, ɛNd values converge during most interglacial peaks (excepting MIS 23) and diverge otherwise. This observation indicates that northern-sourced water masses dominate the site during peak interglacials, and confirms that the THC has been strongest during peak interglacials throughout the studied interval. Otherwise, diverging ɛNd values indicate a stronger southern-source signal and weaker northern-source signal at the ODP 926 site. This confirms that there was an active but variable THC system before, during, and after the MPT, with stronger deep water export from the North Atlantic during interglacials.

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

PubMed

Whitworth, James; Smith, Philip S; Martin, Jose-Ezequiel; West, Hannah; Luchetti, Andrea; Rodger, Faye; Clark, Graeme; Carss, Keren; Stephens, Jonathan; Stirrups, Kathleen; Penkett, Chris; Mapeta, Rutendo; Ashford, Sofie; Megy, Karyn; Shakeel, Hassan; Ahmed, Munaza; Adlard, Julian; Barwell, Julian; Brewer, Carole; Casey, Ruth T; Armstrong, Ruth; Cole, Trevor; Evans, Dafydd Gareth; Fostira, Florentia; Greenhalgh, Lynn; Hanson, Helen; Henderson, Alex; Hoffman, Jonathan; Izatt, Louise; Kumar, Ajith; Kwong, Ava; Lalloo, Fiona; Ong, Kai Ren; Paterson, Joan; Park, Soo-Mi; Chen-Shtoyerman, Rakefet; Searle, Claire; Side, Lucy; Skytte, Anne-Bine; Snape, Katie; Woodward, Emma R; Tischkowitz, Marc D; Maher, Eamonn R

2018-06-12

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ 2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Repeated Exposure of Epithelial Cells to Apoptotic Cells Induces the Specific Selection of an Adaptive Phenotype: Implications for Tumorigenesis.

PubMed

Feng, Lanfei; Vujicic, Snezana; Dietrich, Michael E; Litbarg, Natalia; Setty, Suman; Antoni, Angelika; Rauch, Joyce; Levine, Jerrold S

2018-05-16

The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU.MPT SEL ) resistant to apoptotic target-induced death. Resistance is exquisitely specific. Not only are BU.MPT SEL responders fully resistant to apoptotic target-induced death (~85% survival versus <10% survival of non-selected cells), but do so while retaining sensitivity to all other target-induced responses, including inhibition of proliferation and growth. Moreover, the resistance of BU.MPT SEL responders is specific to target-induced apoptosis, as apoptosis in response to other suicidal stimuli occurs normally. Comparison of the signaling events induced by apoptotic target exposure in selected versus non-selected responders indicated that the acquired resistance of BU.MPT SEL cells lies in a regulatory step affecting the generation of the pro-apoptotic protein, truncated BH3 interacting-domain death agonist (tBID), most likely at the level of BID cleavage by caspase-8. This specific adaptation has especial relevance for cancer, in which the prominence and persistence of cell death entail magnification of the post-mortem effects of apoptotic cells. Just as cancer cells acquire specific resistance to chemotherapeutic agents, we propose that cancer cells may also adapt to their ongoing exposure to apoptotic targets. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Wetland dynamics influence mid-continent duck recruitment

USGS Publications Warehouse

Anteau, Michael J.; Pearse, Aaron T.; Szymankski, Michael L.

2013-01-01

Recruitment is a key factor influencing duck population dynamics. Understanding what regulates recruitment of ducks is a prerequisite to informed habitat and harvest management. Quantity of May ponds (MP) has been linked to recruitment and population size (Kaminski and Gluesing 1987, Raveling and Heitmeyer 1989). However, wetland productivity (quality) is driven by inter-annual hydrological fluctuations. Periodic drying of wetlands due to wet-dry climate cycles releases nutrients and increases invertebrate populations when wet conditions return (Euliss et al. 1999). Wetlands may also become wet or dry within a breeding season. Accordingly, inter-annual and intra-seasonal hydrologic variation potentially influence duck recruitment. Here, we examined influences of wetland quantity, quality, and intra-seasonal dynamics on recruitment of ducks. We indexed duck recruitment by vulnerability-corrected age ratios (juveniles/adult females) for mid-continent Gadwall (Anas strepera). We chose Gadwall because the majority of the continental population breeds in the Prairie Pothole Region (PPR), where annual estimates of MP exist since 1974. We indexed wetland quality by calculating change in MP (?MP) over the past two years (?MP = 0.6[MPt – MPt-1] + 0.4[MPt – MPt-2]). We indexed intra-seasonal change in number of ponds by dividing the PPR mean standardized precipitation index for July by MP (hereafter summer index). MP and ?MP were positively correlated (r = 0.65); therefore, we calculated residual ?MP (?MPr) with a simple linear regression using MP, creating orthogonal variables. Finally, we conducted a multiple regression to examine how MP, ?MPr, and summer index explained variation in recruitment of Gadwall from 1976–2010. Our model explained 67% of the variation in mid-continent Gadwall recruitment and all three hydrologic indices were positively correlated with recruitment (Figure 1). Type II semi-partial R2 estimates indicated that MP accounted for 41%, ?MPr accounted for an additional 22%, and summer index accounted for the remaining 4% of the variation in recruitment. Our results are consistent with previous findings that quantity of MP was important for explaining variation in recruitment of ducks. However, our results also indicated that considering hydrologic dynamics was important for explaining recruitment. Additionally, the index for retention of MP within breeding year also was important, despite its coarse resolution as an average of precipitation events that can vary greatly spatially and in intensity within the PPR. Our results support the idea that wetland ecosystems in the PPR are ultimately regulated through bottom-up process driven by inter- and intra-annual hydrological dynamics. However from the ducks' perspective, hydrological dynamics could influence recruitment proximately through both bottom-up and top-down processes. Specifically, hydrological fluctuations may influence predator populations, prey switching by predators, or duckling vulnerability to predators (Cox et al. 1998). We will propose a conceptual model for understanding the potential role of bottom-up and top-down regulation of duck recruitment based on different hydrological contexts. Clearly, a better understanding of ultimate and proximate factors regulating duck recruitment would improve the effectiveness and efficiency of habitat conservation for ducks. Lastly, our findings could be used to improve models that predict fall flights for the purposes of informing harvest regulations.

Quick look test report: MPT static firing no. 2 test MPT-S2

NASA Technical Reports Server (NTRS)

1978-01-01

The three engine cluster was fired at 70 percent power level for a nominal 15 seconds to evaluate the integrated performance of the main propulsion system. Engine ignition occurred at approximately 1403 with the planned mainstage duration achieved for all three engines. Operation of all systems was as expected with the exception of the recirculation pumps. The pumps were started while the propellant loading was in fast fill, but they cavitated and lost head at the termination of fast fill. The pumps were subsequently restarted after pressurizing the tank and draining back propellant to get good quality. Post test inspection of the engines revealed some discoloration on the inside of the thrust chamber and distorted drain lines for engine #2.

An Empirical Bayes Estimate of Multinomial Probabilities.

DTIC Science & Technology

1982-02-01

multinomial probabilities has been considered from a decision theoretic point of view by Steinhaus (1957), Trybula (1958) and Rutkowska (1977). In a recent...variate Rypergeometric and Multinomial Distributions," Zastosowania Matematyki, 16, 9-21. Steinhaus , H. (1957), "The Problem of Estimation." Annals of

Modeling the dynamics of urban growth using multinomial logistic regression: a case study of Jiayu County, Hubei Province, China

NASA Astrophysics Data System (ADS)

Nong, Yu; Du, Qingyun; Wang, Kun; Miao, Lei; Zhang, Weiwei

2008-10-01

Urban growth modeling, one of the most important aspects of land use and land cover change study, has attracted substantial attention because it helps to comprehend the mechanisms of land use change thus helps relevant policies made. This study applied multinomial logistic regression to model urban growth in the Jiayu county of Hubei province, China to discover the relationship between urban growth and the driving forces of which biophysical and social-economic factors are selected as independent variables. This type of regression is similar to binary logistic regression, but it is more general because the dependent variable is not restricted to two categories, as those previous studies did. The multinomial one can simulate the process of multiple land use competition between urban land, bare land, cultivated land and orchard land. Taking the land use type of Urban as reference category, parameters could be estimated with odds ratio. A probability map is generated from the model to predict where urban growth will occur as a result of the computation.

Quality and provider choice: a multinomial logit-least-squares model with selectivity.

PubMed Central

Haas-Wilson, D; Savoca, E

1990-01-01

A Federal Trade Commission survey of contact lens wearers is used to estimate a multinomial logit-least-squares model of the joint determination of provider choice and quality of care in the contact lens industry. The effect of personal and industry characteristics on a consumer's choice among three types of providers--opticians, ophthalmologists, and optometrists--is estimated via multinomial logit. The regression model of the quality of care has two features that distinguish it from previous work in the area. First, it uses an outcome rather than a structural or process measure of quality. Quality is measured as an index of the presence of seven potentially pathological eye conditions caused by poorly fitted lenses. Second, the model controls for possible selection bias that may arise from the fact that the sample observations on quality are generated by consumers' nonrandom choices of providers. The multinomial logit estimates of provider choice indicate that professional regulations limiting the commercial practices of optometrists shift demand for contact lens services away from optometrists toward ophthalmologists. Further, consumers are more likely to have their lenses fitted by opticians in states that require the licensing of opticians. The regression analysis of variations in quality across provider types shows a strong positive selection bias in the estimate of the quality of care received by consumers of ophthalmologists' services. Failure to control for this selection bias results in an overestimate of the quality of care provided by ophthalmologists. PMID:2312308

Using Computational Text Classification for Qualitative Research and Evaluation in Extension

ERIC Educational Resources Information Center

Smith, Justin G.; Tissing, Reid

2018-01-01

This article introduces a process for computational text classification that can be used in a variety of qualitative research and evaluation settings. The process leverages supervised machine learning based on an implementation of a multinomial Bayesian classifier. Applied to a community of inquiry framework, the algorithm was used to identify…

Nonlinear Stress Relaxation of ``Quasi-monodisperse'' Miscible Blends of cis-Polyisoprene and Poly(ptert-butylstyrene)

NASA Astrophysics Data System (ADS)

Watanabe, Hiroshi; Matsumiya, Yumi

Viscoelastic relaxation was examined for entangled miscible blends of cis-polyisoprene (PI) and poly(ptert-butylstyrene) (PtBS). The terminal relaxation times of PI and PtBS therein, τPI and τPtBS, changed with the composition wPI and the molecular weights MPI and MPtBS. This ratio became unity when the wPI, MPI, and MPtBS values were chosen adequately. For example, in a blend with wPI = 0.75, MPI = 321k, and MPtBS = 91k at T = 40ûC, τPI/τPtBS = 1 and M/Me = 55 and 8.3 for PI and PtBS. Under small strains, this blend exhibited sharp, single-step terminal relaxation as similar to monodisperse homopolymers, thereby behaving as a ``quasi-monodisperse'' material. Under large step strains, the blend exhibited moderate nonlinear damping known as the type-A damping for entangled monodisperse homopolymers. Nevertheless, PI had M/Me = 55 in that blend, and homopolymers having such a large M/Me ratio exhibit very strong type-C damping. Thus, as compared to homopolymers, the nonlinearity was suppressed in the PI/PtBS blend having the large M/Me ratio. This suppression is discussed in relation to the slow Rouse retraction of the coexisting PtBS chains (having M/Me = 8.3 in the blend).

The Molybdenum Cofactor Biosynthetic Protein Cnx1 Complements Molybdate-Repairable Mutants, Transfers Molybdenum to the Metal Binding Pterin, and Is Associated with the Cytoskeleton

PubMed Central

Schwarz, Günter; Schulze, Jutta; Bittner, Florian; Eilers, Thomas; Kuper, Jochen; Bollmann, Gabriele; Nerlich, Andrea; Brinkmann, Henner; Mendel, Ralf R.

2000-01-01

Molybdenum (Mo) plays an essential role in the active site of all eukaryotic Mo-containing enzymes. In plants, Mo enzymes are important for nitrate assimilation, phytohormone synthesis, and purine catabolism. Mo is bound to a unique metal binding pterin (molybdopterin [MPT]), thereby forming the active Mo cofactor (Moco), which is highly conserved in eukaryotes, eubacteria, and archaebacteria. Here, we describe the function of the two-domain protein Cnx1 from Arabidopsis in the final step of Moco biosynthesis. Cnx1 is constitutively expressed in all organs and in plants grown on different nitrogen sources. Mo-repairable cnxA mutants from Nicotiana plumbaginifolia accumulate MPT and show altered Cnx1 expression. Transformation of cnxA mutants and the corresponding Arabidopsis chl-6 mutant with cnx1 cDNA resulted in functional reconstitution of their Moco deficiency. We also identified a point mutation in the Cnx1 E domain of Arabidopsis chl-6 that causes the molybdate-repairable phenotype. Recombinant Cnx1 protein is capable of synthesizing Moco. The G domain binds and activates MPT, whereas the E domain is essential for activating Mo. In addition, Cnx1 binds to the cytoskeleton in the same way that its mammalian homolog gephyrin does in neuronal cells, which suggests a hypothetical model for anchoring the Moco-synthetic machinery by Cnx1 in plant cells. PMID:11148290

Investigation of early molybdopterin biosynthetic intermediates

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

Wuebbens, M.M.; Rajagopalan, K.V.

1991-03-11

Little information is available regarding the early steps in the biosynthetic pathway of molybdopterin (MPT). In order to explore these early reactions, and in particular to investigate the origin of the ring and side chain carbons of MPT, a metabolic approach employing the incorporation of {sup 14}C label was chosen. This method was facilitated by the recent purification and characterization of desulfomolybdopterin 2{prime},4{prime}-cyclic phosphate, the precursor which is converted directly to active molybdopterin in Escherichia coli by the addition of vicinal sulfurs to the side chain. This labile precursor readily oxidizes to Compound Z, a stable 6-alkyl pterin which retainsmore » all of the carbon atoms present in molybdopterin. Compound Z, rather than molybdopterin itself was chosen as the end product for labeling due to its overproduction in some MPT-deficient strains, as well as its stability and ease of purification. The authors report here the isolation of {sup 14}C-labelled Compound Z from E.coli chlN cells cultured in minimal media supplemented with U-{sup 14}C guanosine. Successive cleavage of the side chain carbons by permanganate treatment and UV light produced a decrease in the specific radioactivity of the resulting pterins. These data indicate that the early portion of the molybdopterin biosynthetic pathway may be similar to that of the bioactive pterins folate and biopterin, both of which are derived from guanosine triphosphate.« less

Flurbiprofen, a Cyclooxygenase Inhibitor, Protects Mice from Hepatic Ischemia/Reperfusion Injury by Inhibiting GSK-3β Signaling and Mitochondrial Permeability Transition

PubMed Central

Fu, Hailong; Chen, Huan; Wang, Chengcai; Xu, Haitao; Liu, Fang; Guo, Meng; Wang, Quanxing; Shi, Xueyin

2012-01-01

Flurbiprofen acts as a nonselective inhibitor for cyclooxygenases (COX-1 and COX-2), but its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. Mice were randomized into sham, I/R and flurbiprofen (Flurb) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 90 min and unclamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with flurbiprofen prior to I/R insult significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and prevented hepatocytes from I/R-induced apoptosis/necrosis. Moreover, flurbiprofen dramatically inhibited mitochondrial permeability transition (MPT) pore opening, and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that flurbiprofen markedly inhibited glycogen synthase kinase (GSK)-3β activity and increased phosphorylation of GSK-3β at Ser9, which, consequently, could modulate the adenine nucleotide translocase (ANT)–cyclophilin D (CyP-D) complex and the susceptibility to MPT induction. Therefore, administration of flurbiprofen prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through inhibition of MPT and inactivation of GSK-3β, and provides experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings in addition to its conventional use for pain relief. PMID:22714712

A manual physical therapy intervention for symptoms of knee osteoarthritis and associated fall risk: A case series of four patients.

PubMed

Allen, Chris; Sheehan, Riley; Deyle, Gail; Wilken, Jason; Gill, Norman

2018-02-26

Patients with knee osteoarthritis (OA) are at an increased risk of falling. Further, the symptoms associated with knee OA are correlated with fall risk. A manual physical therapy (MPT) approach consisting of mobilizing techniques and reinforcing exercise improves the symptoms and functional limitations associated with knee OA. The purpose of this case series is to evaluate an MPT intervention of mobilization techniques and exercise for knee OA on improving symptoms and quantify the secondary benefit of improving stumble recovery. Four patients with symptomatic knee OA and four matched controls completed a fall risk assessment. Following 4 weeks of intervention, patients were reevaluated. Initial Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores indicated notable symptoms and functional limitations in all patients. In addition, all patients displayed elevated fall risk and/or impaired stumble responses. Following 4 weeks of intervention, all patients reported meaningful reductions in all three WOMAC subscales and demonstrated improvements in at least two of the three fall risk measures. We identified potential connections between symptom relief in patients with knee OA, stumble response, and ultimately fall risk. The results suggest that MPT intervention designed to improve the signs and symptoms of knee OA may lead to a secondary benefit of improved gait stability and stumble response.

Early developmental trajectories of preterm infants.

PubMed

Yaari, Maya; Mankuta, David; Harel-Gadassi, Ayelet; Friedlander, Edwa; Bar-Oz, Benjamin; Eventov-Friedman, Smadar; Maniv, Nimrod; Zucker, David; Yirmiya, Nurit

2017-11-04

Preterm infants are at risk for neuro-developmental impairments and atypical developmental trajectories. The aims of this study were to delineate early developmental trajectories of preterm and full-term infants. The cognitive, language, and motor development of 149 infants - 19 extremely preterm (EPT), 34 very preterm (VPT), 57 moderately preterm (MPT), and 39 full-term (FT) - was evaluated using Mullen Scales at 1, 4, 8, 12, and 18 months. Mixed models were applied to examine group differences. Gender, maternal education, and neurobehavior were included as predictors of developmental trajectories. The EPT and VPT infants achieved significantly lower scores than the FT infants in all domains, with a significantly increasing gap over time. The MPT infants' trajectories were more favorable than those of the EPT and VPT infants yet lower than the FT infants on the Visual Reception, Gross, and Fine Motor subscales. Male gender and lower maternal education were associated with lower scores that declined over time. Abnormal neonatal neurobehavior was associated lower Mullen scores and with less stability in scores over time. The EPT and VPT infants were found to have disadvantages across all domains. The MPT infants revealed more favorable developmental trajectories yet displayed vulnerability compared to the FT infants. Gender, maternal education, and neonatal neurobehavior are important in predicting the developmental outcomes of preterm infants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics.

PubMed

Fentoğlu, Özlem; Kirzioğlu, Fatma Yeşim; Tözüm Bulut, Memduha; Kurgan, Şivge; Koçak, Havva; Sütcü, Recep; Kale Köroğlu, Banu; Günhan, Meral

2015-01-01

To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis.

Multiple-Shrinkage Multinomial Probit Models with Applications to Simulating Geographies in Public Use Data.

PubMed

Burgette, Lane F; Reiter, Jerome P

2013-06-01

Multinomial outcomes with many levels can be challenging to model. Information typically accrues slowly with increasing sample size, yet the parameter space expands rapidly with additional covariates. Shrinking all regression parameters towards zero, as often done in models of continuous or binary response variables, is unsatisfactory, since setting parameters equal to zero in multinomial models does not necessarily imply "no effect." We propose an approach to modeling multinomial outcomes with many levels based on a Bayesian multinomial probit (MNP) model and a multiple shrinkage prior distribution for the regression parameters. The prior distribution encourages the MNP regression parameters to shrink toward a number of learned locations, thereby substantially reducing the dimension of the parameter space. Using simulated data, we compare the predictive performance of this model against two other recently-proposed methods for big multinomial models. The results suggest that the fully Bayesian, multiple shrinkage approach can outperform these other methods. We apply the multiple shrinkage MNP to simulating replacement values for areal identifiers, e.g., census tract indicators, in order to protect data confidentiality in public use datasets.

Multinomial N-mixture models improve the applicability of electrofishing for developing population estimates of stream-dwelling Smallmouth Bass

USGS Publications Warehouse

Mollenhauer, Robert; Brewer, Shannon K.

2017-01-01

Failure to account for variable detection across survey conditions constrains progressive stream ecology and can lead to erroneous stream fish management and conservation decisions. In addition to variable detection’s confounding long-term stream fish population trends, reliable abundance estimates across a wide range of survey conditions are fundamental to establishing species–environment relationships. Despite major advancements in accounting for variable detection when surveying animal populations, these approaches remain largely ignored by stream fish scientists, and CPUE remains the most common metric used by researchers and managers. One notable advancement for addressing the challenges of variable detection is the multinomial N-mixture model. Multinomial N-mixture models use a flexible hierarchical framework to model the detection process across sites as a function of covariates; they also accommodate common fisheries survey methods, such as removal and capture–recapture. Effective monitoring of stream-dwelling Smallmouth Bass Micropterus dolomieu populations has long been challenging; therefore, our objective was to examine the use of multinomial N-mixture models to improve the applicability of electrofishing for estimating absolute abundance. We sampled Smallmouth Bass populations by using tow-barge electrofishing across a range of environmental conditions in streams of the Ozark Highlands ecoregion. Using an information-theoretic approach, we identified effort, water clarity, wetted channel width, and water depth as covariates that were related to variable Smallmouth Bass electrofishing detection. Smallmouth Bass abundance estimates derived from our top model consistently agreed with baseline estimates obtained via snorkel surveys. Additionally, confidence intervals from the multinomial N-mixture models were consistently more precise than those of unbiased Petersen capture–recapture estimates due to the dependency among data sets in the hierarchical framework. We demonstrate the application of this contemporary population estimation method to address a longstanding stream fish management issue. We also detail the advantages and trade-offs of hierarchical population estimation methods relative to CPUE and estimation methods that model each site separately.

X-ray Diffraction Study of Order-Disorder Phase Transition in CuMPt6 (M=3d Elements) Alloys

NASA Astrophysics Data System (ADS)

Ahmed, Ejaz; Takahashi, Miwako; Iwasaki, Hiroshi; Ohshima, Ken-ichi

2009-01-01

We investigated the ordering behavior of ternary CuMPt6 alloys with M=Ti, V, Cr, Mn, Fe, Co, and Ni by high-temperature polycrystalline X-ray diffraction. The alloys undergo a phase transition from the fcc disordered state to the Cu3Au-type ordered state, except for the alloy with M=Ni, in which only short-range order forms. The transition temperature Tc is highest (1593 K) for M=Ti and decreases almost monotonically with increasing atomic number to 1153 K for M=Co. The observed dependence of ordering tendency on the atomic number of M is discussed in the light of the theory of ordering in transition-metal alloys and its significance for the study of ordering in ternary alloys.

Three faces of entropy for complex systems: Information, thermodynamics, and the maximum entropy principle

NASA Astrophysics Data System (ADS)

Thurner, Stefan; Corominas-Murtra, Bernat; Hanel, Rudolf

2017-09-01

There are at least three distinct ways to conceptualize entropy: entropy as an extensive thermodynamic quantity of physical systems (Clausius, Boltzmann, Gibbs), entropy as a measure for information production of ergodic sources (Shannon), and entropy as a means for statistical inference on multinomial processes (Jaynes maximum entropy principle). Even though these notions represent fundamentally different concepts, the functional form of the entropy for thermodynamic systems in equilibrium, for ergodic sources in information theory, and for independent sampling processes in statistical systems, is degenerate, H (p ) =-∑ipilogpi . For many complex systems, which are typically history-dependent, nonergodic, and nonmultinomial, this is no longer the case. Here we show that for such processes, the three entropy concepts lead to different functional forms of entropy, which we will refer to as SEXT for extensive entropy, SIT for the source information rate in information theory, and SMEP for the entropy functional that appears in the so-called maximum entropy principle, which characterizes the most likely observable distribution functions of a system. We explicitly compute these three entropy functionals for three concrete examples: for Pólya urn processes, which are simple self-reinforcing processes, for sample-space-reducing (SSR) processes, which are simple history dependent processes that are associated with power-law statistics, and finally for multinomial mixture processes.

Application of binomial and multinomial probability statistics to the sampling design process of a global grain tracing and recall system

USDA-ARS?s Scientific Manuscript database

Small, coded, pill-sized tracers embedded in grain are proposed as a method for grain traceability. A sampling process for a grain traceability system was designed and investigated by applying probability statistics using a science-based sampling approach to collect an adequate number of tracers fo...

Effect of Unmodulated 5-kHz Alternating Currents Versus Transcutaneous Electrical Nerve Stimulation on Mechanical and Thermal Pain, Tactile Threshold, and Peripheral Nerve Conduction: A Double-Blind, Placebo-Controlled Crossover Trial.

PubMed

Avendaño-Coy, Juan; Gómez-Soriano, Julio; Goicoechea-García, Carlos; Basco-López, Julian Angel; Taylor, Julian

2017-05-01

To investigate the effect of unmodulated 5-kHz alternating current on mechanical pain threshold (MPT), heat pain threshold (HPT), tactile threshold (TT), and peripheral nerve conduction (PNC) compared with transcutaneous electrical nerve stimulation (TENS) and sham stimulation. National referral center. Randomized, double-blind, placebo-controlled crossover trial. Healthy volunteers (N=38). No dropouts or adverse events were reported. TENS, unmodulated 5-kHz currents, and sham stimulation were applied on the radial nerve for 20 minutes with a 24-hour washout period between them and concealed intervention allocation. Four measures were taken: before, during, and 2 after the interventions. Algometry was used to assess MPT, a Peltier thermode for HPT using the method of limits, Von Frey filaments for TT, and radial nerve compound action potential. No differences were observed on MPT, HPT, and PNC when 5-kHz current and TENS were compared. However, TT increased 56.2mN (95% confidence interval [CI], 28.8-83.6) in the TENS group compared with the 5-kHz current group during intervention. Compared with sham stimulation during intervention, MPT increased 4.7N (95% CI, 0.3-9.2) using 5-kHz current and 10.4N (95% CI, 3.5-17.3) with TENS. TT increased 17.2mN (95% CI, 4.7-29.7) with 5-kHz current and 73.4mN (95% CI, 47.5-99.2) with TENS. However, HPT increased 1.0°C (95% CI, 0.2-2.0) only with TENS. For the PNC, no differences were found among the 3 groups. Unmodulated 5-kHz current produced an increase in somatosensory thresholds that was greater than placebo but not when compared with TENS; however, participants perceived 5-kHz currents to be more comfortable and showed more habituation to them. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Weathering fluxes to the Gulf of Mexico from the Pliocene to Holocene based on radiogenic isotopes

NASA Astrophysics Data System (ADS)

Portier, A. M.; Martin, E. E.; Hemming, S. R.; Thierens, M. M.; Raymo, M. E.

2014-12-01

Chemical weathering of the continents plays a key role in the global carbon cycle and delivers solutes to the ocean. Past studies, documented using radiogenic isotopes of detrital and seawater samples, show the intensity of weathering varies with climate over a range of time scales.. We analyzed Pb and Nd isotopic values of seawater extracted from dispersed Fe-Mn oxides, <2μm (clay) and <63μm (silt) detrital fractions of Pliocene to Holocene sediment from Gulf of Mexico ODP Site 625B to evaluate long term variations in weathering fluxes for three time slices: the Pliocene/early Pleistocene, Mid Pleistocene Transition (MPT), and late Pleistocene/Holocene. We also examine short term glacial/interglacial variations. Little variation is seen in Nd isotopes of detrital fractions with age, suggesting little change in the average age of material delivered to the Gulf. Seawater Nd values become less radiogenic over the Pleistocene, consistent with observed changes in Caribbean seawater. Pb isotopes of silt fractions are also relatively constant through time, but clay fractions are more radiogenic at the MPT and dispersed Fe-Mn oxides trend to more radiogenic values in the late Pleistocene. Consequently, the Pb isotopes of dispersed Fe-Mn oxides tend to be less radiogenic than the detrital fractions in samples older than 2000 ka and more radiogenic than the detrital fractions, particularly clays, at the MPT. This may reflect greater incongruent silicate weathering during the MPT, a change in weathering conditions that could be consistent with the Regolith Hypothesis. Over glacial/interglacial timescales, dispersed Fe-Mn oxides Pb isotopes become more radiogenic than detrital fractions, and clay fractions become more radiogenic than silt fractions, during glacial periods. However, all fractions have similar values during interglacials. This pattern is distinct from previous studies that found enhanced incongruent silicate weathering during warm intervals, but is consistent with recent work finding a correlation with carbonate content, whereby low carbonate during glacials at Site 625 corresponds to a greater offset between leachate and detrital Pb isotopes. Biases from "heavy mineral effects" and changes in circulation during periods of lower sea level also need to be considered.

The antiestrogen endoxifen protects rat liver mitochondria from permeability transition pore opening and oxidative stress at concentrations that do not affect the phosphorylation efficiency

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

Ribeiro, Mariana P.C.; Silva, Filomena S.G.; Santos, Armanda E.

2013-02-15

Endoxifen (EDX) is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptors that also inhibits aromatase activity. It is safe and well tolerated by healthy humans, but its use requires toxicological characterization. In this study, the effects of EDX on mitochondria, the primary targets for xenobiotic-induced toxicity, were monitored to clarify its potential side effects. EDX up to 30 nmol/mg protein did not affect the mitochondrial oxidative phosphorylation. At 50 nmol EDX/mg protein, EDX decreased the ADP phosphorylation rate and a partial collapse of mitochondrial membrane potential (Δψ), that parallels a state 4 stimulation,more » was observed. As the stimulation of state 4 was not inhibited by oligomycin and 50 nmol EDX/mg protein caused a slight decrease in the light scattering of mitochondria, these data suggest that EDX promotes membrane permeabilization to protons, whereas TAM at the same concentration induced mitochondrial membrane disruption. Moreover, EDX at 10 nmol/mg protein prevented and reversed the Ca{sup 2+}-induced depolarization of ΔΨ and the release of mitochondrial Ca{sup 2+}, similarly to cyclosporine A, indicating that EDX did not affect Ca{sup 2+} uptake, but directly interfered with the proteins of the mitochondrial permeability transition (MPT) megacomplex, inhibiting MPT induction. At this concentration, EDX exhibited antioxidant activity that may account for the protective effect against MPT pore opening. In conclusion, EDX within the range of concentrations reached in tissues did not significantly damage the bioenergetic functions of mitochondria, contrarily to the prodrug TAM, and prevented the MPT pore opening and the oxidative stress in mitochondria, supporting that EDX may be a less toxic drug for women with breast carcinoma. - Highlights: ► Mitochondria are important targets of Endoxifen. ► Endoxifen prevents mitochondrial permeability transition. ► Endoxifen prevents oxidative stress in mitochondria. ► Endoxifen slightly affects mitochondrial bioenergetics in comparison with tamoxifen. ► Endoxifen is a key active metabolite of tamoxifen relevant in cancer therapy.« less

Measure Projection Analysis: A Probabilistic Approach to EEG Source Comparison and Multi-Subject Inference

PubMed Central

Bigdely-Shamlo, Nima; Mullen, Tim; Kreutz-Delgado, Kenneth; Makeig, Scott

2013-01-01

A crucial question for the analysis of multi-subject and/or multi-session electroencephalographic (EEG) data is how to combine information across multiple recordings from different subjects and/or sessions, each associated with its own set of source processes and scalp projections. Here we introduce a novel statistical method for characterizing the spatial consistency of EEG dynamics across a set of data records. Measure Projection Analysis (MPA) first finds voxels in a common template brain space at which a given dynamic measure is consistent across nearby source locations, then computes local-mean EEG measure values for this voxel subspace using a statistical model of source localization error and between-subject anatomical variation. Finally, clustering the mean measure voxel values in this locally consistent brain subspace finds brain spatial domains exhibiting distinguishable measure features and provides 3-D maps plus statistical significance estimates for each EEG measure of interest. Applied to sufficient high-quality data, the scalp projections of many maximally independent component (IC) processes contributing to recorded high-density EEG data closely match the projection of a single equivalent dipole located in or near brain cortex. We demonstrate the application of MPA to a multi-subject EEG study decomposed using independent component analysis (ICA), compare the results to k-means IC clustering in EEGLAB (sccn.ucsd.edu/eeglab), and use surrogate data to test MPA robustness. A Measure Projection Toolbox (MPT) plug-in for EEGLAB is available for download (sccn.ucsd.edu/wiki/MPT). Together, MPA and ICA allow use of EEG as a 3-D cortical imaging modality with near-cm scale spatial resolution. PMID:23370059

Objective and subjective assessment of tracheoesophageal prosthesis voice outcome.

PubMed

D'Alatri, Lucia; Bussu, Francesco; Scarano, Emanuele; Paludetti, Gaetano; Marchese, Maria Raffaella

2012-09-01

To investigate the relationships between objective measures and the results of subjective assessment of voice quality and speech intelligibility in patients submitted to total laryngectomy and tracheoesophageal (TE) puncture. Retrospective. Twenty patients implanted with voice prosthesis were studied. After surgery, the entire sample performed speech rehabilitation. The assessment protocol included maximum phonation time (MPT), number of syllables per deep breath, acoustic analysis of the sustained vowel /a/ and of a bisyllabic word, perceptual evaluation (pleasantness and intelligibility%), and self-assessment. The correlation between pleasantness and intelligibility% was statistically significant. Both the latter were significantly correlated with the acoustic signal type, the number of formant peaks, and the F2-F1 difference. The intelligibility% and number of formant peaks were significantly correlated with the MPT and number of syllables per deep breath. Moreover, significant correlations were found between the number of formant peaks and both intelligibility% and pleasantness. The higher the number of syllables per deep breath and the longer the MPT, significantly higher was the number of formant peaks and the intelligibility%. The study failed to show significant correlation between patient's self-assessment of voice quality and both pleasantness and communication effectiveness. The multidimensional assessment seems to be a reliable tool to evaluate the TE functional outcome. Particularly, the results showed that both pleasantness and intelligibility of TE speech are correlated to the availability of expired air and the function of the vocal tract. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Impact of the surgical experience on cochleostomy location: a comparative temporal bone study between endaural and posterior tympanotomy approaches for cochlear implantation.

PubMed

Vandersteen, Clair; Demarcy, Thomas; Roger, Coralie; Fontas, Eric; Raffaelli, Charles; Ayache, Nicholas; Delingette, Hervé; Guevara, Nicolas

2016-09-01

The goal of this study was to evaluate, in the hands of an inexperienced surgeon, the cochleostomy location of an endaural approach (MINV) compared to the conventional posterior tympanotomy (MPT) approach. Since 2010, we use in the ENT department of Nice a new surgical endaural approach to perform cochlear implantation. In the hands of an inexperienced surgeon, the position of the cochleostomy has not yet been studied in detail for this technique. This is a prospective study of 24 human heads. Straight electrode arrays were implanted by an inexperienced surgeon: on one side using MPT and on the other side using MINV. The cochleostomies were all antero-inferior, but they were performed through an endaural approach with the MINV or a posterior tympanotomy approach with the MPT. The positioning of the cochleostomies into the scala tympani was evaluated by microdissection. Cochleostomies performed through the endaural approach were well placed into the scala tympani more frequently than those performed through the posterior tympanotomy approach (87.5 and 16.7 %, respectively, p ≤ 0.001). This study highlights the biggest challenge for an inexperienced surgeon to achieve a reliable cochleostomy through a posterior tympanotomy, which requires years of experience. In case of an uncomfortable view through a posterior tympanotomy, an inexperienced surgeon might be able to successfully perform a cochleostomy through an endaural (combined approach) or an extended round window approach in order to avoid opening the scala vestibuli.

Statistical Development and Application of Cultural Consensus Theory

DTIC Science & Technology

2012-03-31

Bulletin & Review , 17, 275-286. Schmittmann, V.D., Dolan, C.V., Raijmakers, M.E.J., and Batchelder, W.H. (2010). Parameter identification in...Wu, H., Myung, J.I., and Batchelder, W.H. (2010). Minimum description length model selection of multinomial processing tree models. Psychonomic

Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

PubMed

Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

2015-01-01

Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

An alternative didactic, functional and topographic systematization of the spinal muscles.

PubMed

de Araújo Baptista, Vivianne Izabelle; Mayer, William Paganini; Eustáquio da Silva, Ricardo; de Vasconcellos Fontes, Ricardo Bragança; da Silva Baptista, Josemberg

2017-09-01

Back muscles are commonly described in a topographically-oriented manner without necessarily following morphological criteria. In this manner, non-standard terms may be employed which convey incorrect morphological concepts and demanding more time from both faculty and students to transmit knowledge. We propose a classification system for spinal muscles incorporating morphological concepts with the goal of facilitating knowledge transfer and suggest the term "spinal muscles". Those muscles were systematically divided and classified in seven strata from anterior to posterior: vertebro-appendicular (VA), transversarium (Tr), deep post-transversarium (DPT), middle post-transversarium (MPT), superficial post-transversarium (SPT), deep spino-appendicular (DSA) and superficial spino-appendicular (SSA). Besides topography and function, this system incorporates innervation and embryological origins of each muscle. The extrinsic (VA, DSA, SSA) or intrinsic (Tr, DPT, MPT, SPT) nature of these muscles in relation to the spine and also the topographic relationship to the transverse process is represented in this system. Specific areas of functional, nervous and developmental transition exist on Tr and DPT strata due to being adjacent to extrinsic strata. We believe this system represents a more modern and concise teaching strategy for back muscles which may be employed partially or fully within any program. We envision its full version may be particularly useful in postgraduate medical training for specialties dealing with the spinal column such as neurosurgery, orthopedic surgery and physical medicine and rehabilitation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Comparative study on ambient ionization methods for direct analysis of navel orange tissues by mass spectrometry.

PubMed

Zhang, Hua; Bibi, Aisha; Lu, Haiyan; Han, Jing; Chen, Huanwen

2017-08-01

It is of sustainable interest to improve the sensitivity and selectivity of the ionization process, especially for direct analysis of complex samples without matrix separation. Herein, four ambient ionization methods including desorption atmospheric pressure chemical ionization (DAPCI), heat-assisted desorption atmospheric pressure chemical ionization (heat-assisted DAPCI), microwave plasma torch (MPT) and internal extractive electrospray ionization (iEESI) were employed for comparative analysis of the navel orange tissue samples by mass spectrometry. The volatile organic compounds (e.g. ethanol, vanillin, leaf alcohol and jasmine lactone) were successfully detected by non-heat-assisted DAPCI-MS, while semi-volatile organic compounds (e.g. 1-nonanol and ethyl nonanoate) together with low abundance of non-volatile organic compounds (e.g. sinensetin and nobiletin) were obtained by heat-assisted DAPCI-MS. Typical nonvolatile organic compounds [e.g. 5-(hydroxymethyl)furfural and glucosan] were sensitively detected with MPT-MS. Compounds of high polarity (e.g. amino acids, alkaloids and sugars) were easily profiled with iEESI-MS. Our data showed that more analytes could be detected when more energy was delivered for the desorption ionization purpose; however, heat-sensitive analytes would not be detected once the energy input exceeded the dissociation barriers of the analytes. For the later cases, soft ionization methods such as iEESI were recommended to sensitively profile the bioanalytes of high polarity. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The proposed factor structure of temperament and personality in Japan: combining traits from TEMPS-A and MPT.

PubMed

Akiyama, Tsuyoshi; Tsuda, Hitoshi; Matsumoto, Satoko; Miyake, Yuko; Kawamura, Yoshiya; Noda, Toshie; Akiskal, Kareen K; Akiskal, Hagop S

2005-03-01

In Japan, Kraepelin's descriptions on four "fundamental states" of manic depressive illness, the concepts of schizoid temperament by Kretschmer and obsessional and melancholic type temperament by Shimoda and Tellenbach have been widely accepted. This research investigates the construct validity of these temperaments through factor analysis. TEMPS-A measured depressive, cyclothymic, hyperthymic and irritable temperaments and MPT rigidity, esoteric and isolation subscales measured, respectively, melancholic type and schizoid temperaments. Factor analysis was implemented with TEMPS-A alone and TEMPS-A and MPT combined data. With TEMPS-A alone analysis, Factor 1 included 1 depressive, 11 cyclothymic and 12 irritable temperament items with a factor loading higher than 0.4; Factor 2 included 1 depressive and 10 hyperthymic temperament items; and Factor 3 included 2 depressive temperament items only. With TEMPS-A and MPT combined data, Factor 1 included 3 depressive, 11 cyclothymic and 5 irritable temperament items with a factor loading higher than 0.4 (interpreted as the central cyclothymic tendency for all affective temperaments along Kretschmerian lines and accounting for 11.7% of the variance); Factor 2 included 6 hyperthymic temperament items (6.22% of variance); Factor 3 included 1 cyclothymic, 7 irritable and 1 schizoid temperament items (interpreted as the irritable temperament and accounting for 3.24% of the variance); Factor 4 included 1 depressive temperament and 5 melancholic type items (interpreted as the latter, accounting for 2.66% of the variance); Factor 5 included 5 depressive temperament items, along interpersonal sensitivity and passivity lines, and accounting for 2.31% of the variance; and Factor 6 included 4 schizoid temperament items accounting for 2.07% of the variance. We did not use the Kasahara scale, which some believe to better capture the Japanese melancholic type. Sample was 70% male. These analyses confirm the factor validity of depressive, hyperthymic, cyclothymic and irritable temperaments (TEMPS-A), as well as the melancholic type and the schizoid temperament (MPT). Traits of the depressive and melancholic types emerge as rather distinct. Indeed, our results permit the delineation of an interpersonally sensitive type that "gives in to others" as the core features of the depressive temperament; this is to be contrasted with the higher functioning, perfectionistic, work-oriented melancholic type. Mood dysregulation is represented by the largest number of traits in this population. Contrary to a widely held belief that the melancholic type with its devotion to work and to others is the signature temperament in Japan, cyclothymic traits account for the largest variance in this nonclinical population. Hyperthymic temperament, melancholic type and schizoid temperaments appear largely independent of mood dysregulation. In this Japanese population, TEMPS-A may identify temperament constructs more comprehensively when implemented with melancholic type and schizoid temperament question items added to it. The proposed new Japanese Temperament and Personality (JTP) Scale has self-rated items divided into six subscales.

46 CFR 64.19 - External pressure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HANDLING SYSTEMS Standards for an MPT § 64.19 External pressure. (a) A tank without a vacuum breaker must be designed to withstand an external pressure of 71/2 psig or more. (b) A tank with a vacuum breaker...

46 CFR 64.19 - External pressure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HANDLING SYSTEMS Standards for an MPT § 64.19 External pressure. (a) A tank without a vacuum breaker must be designed to withstand an external pressure of 71/2 psig or more. (b) A tank with a vacuum breaker...

46 CFR 64.19 - External pressure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HANDLING SYSTEMS Standards for an MPT § 64.19 External pressure. (a) A tank without a vacuum breaker must be designed to withstand an external pressure of 71/2 psig or more. (b) A tank with a vacuum breaker...

46 CFR 64.19 - External pressure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HANDLING SYSTEMS Standards for an MPT § 64.19 External pressure. (a) A tank without a vacuum breaker must be designed to withstand an external pressure of 71/2 psig or more. (b) A tank with a vacuum breaker...

46 CFR 64.19 - External pressure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HANDLING SYSTEMS Standards for an MPT § 64.19 External pressure. (a) A tank without a vacuum breaker must be designed to withstand an external pressure of 71/2 psig or more. (b) A tank with a vacuum breaker...

Sea ice dynamics across the Mid-Pleistocene transition in the Bering Sea.

PubMed

Detlef, H; Belt, S T; Sosdian, S M; Smik, L; Lear, C H; Hall, I R; Cabedo-Sanz, P; Husum, K; Kender, S

2018-03-05

Sea ice and associated feedback mechanisms play an important role for both long- and short-term climate change. Our ability to predict future sea ice extent, however, hinges on a greater understanding of past sea ice dynamics. Here we investigate sea ice changes in the eastern Bering Sea prior to, across, and after the Mid-Pleistocene transition (MPT). The sea ice record, based on the Arctic sea ice biomarker IP 25 and related open water proxies from the International Ocean Discovery Program Site U1343, shows a substantial increase in sea ice extent across the MPT. The occurrence of late-glacial/deglacial sea ice maxima are consistent with sea ice/land ice hysteresis and land-glacier retreat via the temperature-precipitation feedback. We also identify interactions of sea ice with phytoplankton growth and ocean circulation patterns, which have important implications for glacial North Pacific Intermediate Water formation and potentially North Pacific abyssal carbon storage.

One-Electron Oxidation of [M(P(t) Bu3 )2 ] (M=Pd, Pt): Isolation of Monomeric [Pd(P(t) Bu3 )2 ](+) and Redox-Promoted C-H Bond Cyclometalation.

PubMed

Troadec, Thibault; Tan, Sze-Yin; Wedge, Christopher J; Rourke, Jonathan P; Unwin, Patrick R; Chaplin, Adrian B

2016-03-07

Oxidation of zero-valent phosphine complexes [M(P(t) Bu3 )2 ] (M=Pd, Pt) has been investigated in 1,2-difluorobenzene solution using cyclic voltammetry and subsequently using the ferrocenium cation as a chemical redox agent. In the case of palladium, a mononuclear paramagnetic Pd(I) derivative was readily isolated from solution and fully characterized (EPR, X-ray crystallography). While in situ electrochemical measurements are consistent with initial one-electron oxidation, the heavier congener undergoes C-H bond cyclometalation and ultimately affords the 14 valence-electron Pt(II) complex [Pt(κ(2) PC -P(t) Bu2 CMe2 CH2 )(P(t) Bu3 )](+) with concomitant formation of [Pt(P(t) Bu3 )2 H](+) . © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Acoustic results of supersonic tip speed fan blade modification

NASA Technical Reports Server (NTRS)

Jutras, R. R.; Kazin, S. B.

1974-01-01

A supersonic tip speed single stage fan was modified with the intent of reducing multiple pure tone (MPT) or buzz saw noise. There were three modifications to the blades from the original design. The modifications to the blade resulted in an increase in cascade throat area causing the shock to start at a lower corrected fan speed. The acoustic results without acoustically absorbing liners showed substantial reduction in multiple pure tone levels. However, an increase in the blade passing frequency noise at takeoff fan speed accompanied the MPT reduction. The net result however, was a reduction in the maximum 1000-foot (304.8 m) altitude level flyover PNL. For the case with acoustic treatment in the inlet outer wall, the takeoff noise increased relative to an acoustically treated baseline. This was largely due to the increased blade passing frequency noise which was not effectively reduced by the liner.

PubMed Central

SCHINDLER, A.; GINOCCHIO, D.; ATAC, M.; MARUZZI, P.; MADASCHI, S.; OTTAVIANI, F.; MOZZANICA, F.

2013-01-01

SUMMARY The objective of this study was to evaluate the reliability of the INFVo scale and its relationship with objective measures and VHI scores in 40 native Italian-speaking patients with substitution voice. The maximum phonation time (MPT), diadochokinesis (DDK) of the three syllabic sequence [pa/ta/ka], reading of a passage and a single word repetition test were recorded. Each patient completed the Italian version of the VHI. Three speech-language pathologists blindly rated the recordings using the auditory perceptual INFVo scale; one listened and assessed the voice recording twice. The INFVo intra- and inter-rater reliability reached good values. Strong to moderate correlations between the INFVo scale scores and MPT, DDK, distortions in the repetition test, speech rate during reading and the functional subscale of the VHI were found. In conclusion, the INFVo scale is a reliable tool and can be recommended for the perceptual assessment of substitution voices in Italian speaking patients. PMID:23853403

Evaluation of the HARDMAN comparability methodology for manpower, personnel and training

NASA Technical Reports Server (NTRS)

Zimmerman, W.; Butler, R.; Gray, V.; Rosenberg, L.

1984-01-01

The methodology evaluation and recommendation are part of an effort to improve Hardware versus Manpower (HARDMAN) methodology for projecting manpower, personnel, and training (MPT) to support new acquisition. Several different validity tests are employed to evaluate the methodology. The methodology conforms fairly well with both the MPT user needs and other accepted manpower modeling techniques. Audits of three completed HARDMAN applications reveal only a small number of potential problem areas compared to the total number of issues investigated. The reliability study results conform well with the problem areas uncovered through the audits. The results of the accuracy studies suggest that the manpower life-cycle cost component is only marginally sensitive to changes in other related cost variables. Even with some minor problems, the methodology seem sound and has good near term utility to the Army. Recommendations are provided to firm up the problem areas revealed through the evaluation.

Optical Probe of the Superconducting Normal Mixed State in a Magnetic Penetration Thermometer

NASA Technical Reports Server (NTRS)

Stevenson, T. R.; Balvin, M. A.; Bandler, S. R.; Denis, K. L.; Lee, S. -J.; Nagler, P. C.; Smith, S. J.

2016-01-01

Using ultraviolet photon pulses, we have probed the internal behavior of a molybdenum-gold Magnetic Penetration Thermometer (MPT) that we designed for x-ray microcalorimetry. In this low-temperature detector, the diamagnetic response of a superconducting MoAu bilayer is used to sense temperature changes in response to absorbed photons. We have previously described an approximate model that explains the high responsivity of the detector to temperature changes as a consequence of a Meissner transition of the molybdenum-gold film in the magnetic field applied by the superconducting circuit used to bias the detector. We compare measurements of MPT heat capacity and thermal conductance, derived from UV photon pulse data, to our model predictions for the thermodynamic properties of the sensor and for the electron cooling obtained by quasiparticle recombination. Our data on electron cooling power is also relevant to the operation of other superconducting detectors, such as Microwave Kinetic Inductance Detectors.

Risk and utility in portfolio optimization

NASA Astrophysics Data System (ADS)

Cohen, Morrel H.; Natoli, Vincent D.

2003-06-01

Modern portfolio theory (MPT) addresses the problem of determining the optimum allocation of investment resources among a set of candidate assets. In the original mean-variance approach of Markowitz, volatility is taken as a proxy for risk, conflating uncertainty with risk. There have been many subsequent attempts to alleviate that weakness which, typically, combine utility and risk. We present here a modification of MPT based on the inclusion of separate risk and utility criteria. We define risk as the probability of failure to meet a pre-established investment goal. We define utility as the expectation of a utility function with positive and decreasing marginal value as a function of yield. The emphasis throughout is on long investment horizons for which risk-free assets do not exist. Analytic results are presented for a Gaussian probability distribution. Risk-utility relations are explored via empirical stock-price data, and an illustrative portfolio is optimized using the empirical data.

An in-line micro-pyrolysis system to remove contaminating organic species for precise and accurate water isotope analysis by spectroscopic techniques

NASA Astrophysics Data System (ADS)

Panetta, R. J.; Hsiao, G.

2011-12-01

Trace levels of organic contaminants such as short alcohols and terpenoids have been shown to cause spectral interference in water isotope analysis by spectroscopic techniques. The result is degraded precision and accuracy in both δD and δ18O for samples such as beverages, plant extracts or slightly contaminated waters. An initial approach offered by manufacturers is post-processing software that analyzes spectral features to identify and flag contaminated samples. However, it is impossible for this software to accurately reconstruct the water isotope signature, thus it is primarily a metric for data quality. Here, we describe a novel in-line pyrolysis system (Micro-Pyrolysis Technology, MPT) placed just prior to the inlet of a cavity ring-down spectroscopy (CRDS) analyzer that effectively removes interfering organic molecules without altering the isotope values of the water. Following injection of the water sample, N2 carrier gas passes the sample through a micro-pyrolysis tube heated with multiple high temperature elements in an oxygen-free environment. The temperature is maintained above the thermal decomposition threshold of most organic compounds (≤ 900 oC), but well below that of water (~2000 oC). The main products of the pyrolysis reaction are non-interfering species such as elemental carbon and H2 gas. To test the efficacy and applicability of the system, waters of known isotopic composition were spiked with varying amounts of common interfering alcohols (methanol, ethanol, propanol, hexanol, trans-2-hexenol, cis-3-hexanol up to 5 % v/v) and common soluble plant terpenoids (carveol, linalool, geraniol, prenol). Spiked samples with no treatment to remove the organics show strong interfering absorption peaks that adversely affect the δD and δ18O values. However, with the MPT in place, all interfering absorption peaks are removed and the water absorption spectrum is fully restored. As a consequence, the δD and δ18O values also return to their original values, demonstrating effective removal of interfering species with no isotopic fractionation during the pyrolysis. Tests of water spiked quantitatively show the MPT is most effective at removing interferences up to 1 % v/v. This level is typical for plant extracts and interstitial waters, i.e. the majority of natural samples that suffer from spectral interference.

Risk Score Algorithm for Treatment of Persistent Apical Periodontitis

PubMed Central

Yu, V.S.; Khin, L.W.; Hsu, C.S.; Yee, R.; Messer, H.H.

2014-01-01

Persistent apical periodontitis related to a nonvital tooth that does not resolve following root canal treatment may be compatible with health and may not require further intervention. This research aimed to develop a Deterioration Risk Score (DRS) to differentiate lesions requiring further intervention from lesions likely to be compatible with health. In this cross-sectional study, patient records (2003-2008) were screened for root-filled teeth with periapical radiolucency visible on periapical radiographs taken at treatment and at recruitment at least 4 yr later. The final sample consisted of 228 lesions in 182 patients. Potential demographic and treatment risk factors were screened against 3 categorical outcomes (improved/unchanged/deteriorated), and a multivariate independent multinomial probit regression model was built. A 5-level DRS was constructed by summing values of adjusted regression coefficients in the model, based on predicted probabilities of deterioration. Most lesions (127, 55.7%) had improved over time, while 32 (14.0%) remained unchanged, and 69 (30.3%) had deteriorated. Significant predictors of deterioration were as follows: time since treatment (relative risk [RR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, p = .030, rounded beta value = 1, for every year increase after 4 yr), current pain (RR: 3.79, 95% CI: 1.48-9.70, p = .005, rounded beta value = 13), sinus tract present (RR: 4.13, 95% CI: 1.11-15.29, p = .034, rounded beta value = 14), and lesion size (RR: 7.20, 95% CI: 3.70-14.02, p < .001, rounded beta value = 20). Persistent apical periodontitis with DRS <15 represented very low risk; 15-20, low risk; 21-30, moderate risk; 31-40, high risk; and >40, very high risk. DRS could help the clinician identify persistent apical periodontitis at low risk for deterioration, and it would not require intervention. When validated, this tool could reduce the risk of overtreatment and contribute toward targeted care and better efficiency in the timely management of disease. PMID:25190267

Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

PubMed

Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

2016-05-06

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

Apixaban pharmacodynamic activity in umbilical cord, paediatric, and adult plasma.

PubMed

Yetman, Robert J; Barrett, Yu Chen; Wang, Zhaoqing; Adamczyk, Robert; Wang, Jessie; Ramacciotti, Eduardo; Frost, Charles

2017-07-26

The objective was to characterise apixaban pharmacodynamic (PD) activity in umbilical cord (UC), paediatric, and adult plasma. Plasma was obtained from blood samples from six UC donors, 70 paediatric (neonates [birth-≤1 month], infants [>1-≤6 months], toddlers [>6 months-≤2 years], young children [>2-≤6 years], children [>6-≤12 years], adolescents [>12-≤18 years]), and six adult (19-45 years) subjects. Plasma spiked with apixaban 0 (baseline), 30, or 110 ng/ml was analysed for anti-factor Xa activity, factor X levels, prothrombin time (PT), and modified PT (mPT). Apixaban had similar concentration-related effects on anti-factor Xa activity across groups (30 ng/ml: 0.223-0.295 IU/ml; 110 ng/ml: 1.212-1.474 IU/ml). Endogenous baseline factor X levels were 43 %-68 % lower in plasma from UC and subjects ≤6 months versus adults. Factor Xa inhibition (percentage change from baseline in apparent factor X levels) was similar for both apixaban concentrations across groups, except UC, neonate, and infant groups, which showed greater inhibition vs adults for apixaban 110 ng/ml. Baseline PT and mPT were similar across groups. Apixaban had no effect on PT at the concentrations tested. Apixaban 110 ng/ml prolonged mPT similarly across groups (44.4-53.2 s to 64.5-70.0 s); no prolongation was found with apixaban 30 ng/ml. Apixaban demonstrated consistent concentration-related effects on other PD endpoints in plasma samples from all age groups, except factor Xa inhibition.

Comparison of shear bond strength of orthodontic brackets using various zirconia primers.

PubMed

Lee, Ji-Yeon; Kim, Jin-Seok; Hwang, Chung-Ju

2015-07-01

The aim of this study was to compare the shear bond strength (SBS) of orthodontic brackets bonded to zirconia surfaces using three different zirconia primers and one silane primer, and subjected to thermocycling. We designed 10 experimental groups following the surface treatment and thermocycling. The surface was treated with one of the following method: no-primer (NP), Porcelain Conditioner (PC), Z-PRIME Plus (ZP), Monobond Plus (MP) and Zirconia Liner Premium (ZL) (n=20). Then each group was subdivided to non-thermocycled and thermocycled groups (NPT, PC, ZPT, MPT, ZLT) (n=10). Orthodontic brackets were bonded to the specimens using Transbond™ XT Paste and light cured for 15 s at 1,100 mW/cm(2). The SBS was measured at a 1 mm/min crosshead speed. The failure mode was assessed by examination with a stereomicroscope and the amount of bonding resin remaining on the zirconia surface was scored using the modified adhesive remnant index (ARI). The SBS of all experimental groups decreased after thermocycling. Before thermocycling, the SBS was ZL, ZP ≥ MP ≥ PC > NP but after thermocycling, the SBS was ZLT ≥ MPT ≥ ZPT > PCT = NPT (p > 0.05). For the ARI score, both of the groups lacking primer (NP and NPT) displayed adhesive failure modes, but the groups with zirconia primers (ZP, ZPT, MP, MPT, ZL, and ZLT) were associated with mixed failure modes. Surface treatment with a zirconia primer increases the SBS relative to no-primer or silane primer application between orthodontic brackets and zirconia prostheses.

Do body mass index and fat volume influence vocal quality, phonatory range, and aerodynamics in females?

PubMed

Barsties, Ben; Verfaillie, Rudi; Roy, Nelson; Maryn, Youri

2013-01-01

To analyze the impact of body weight and body fat volume on selected parameters of vocal quality, phonatory range, and aerodynamics in females. Based on measurements of body mass index in combination with body fat volume, 29 normophonic female subjects were classified as normal weight, underweight, and obese. Voice quality was investigated via auditory-perceptual ratings of breathiness, roughness, and overall dysphonia severity, via various acoustic measures and a multiparametric index. Phonatory range performance was examined using selected measures of the voice range profile and speech range profile. Measures of vocally relevant aerodynamics included vital capacity (i.e., VC), expected VC, phonation quotient, and maximum phonation time (i.e., MPT). Significant differences between the three weight groups were found across several measures of intensity, VC, MPT, and shimmer. As compared to the other groups, significantly higher values of maximum and minimum intensity levels, as well as sound pressure level during habitual running speech were observed for the obese group (all p-values<0.05); whereas, the underweight group had significantly lower values for VC and ratio of expected to measured VC (p-values<0.01). Furthermore, underweight subjects differed significantly as compared to normal weight subjects with lower MPT (p=0.025) and higher lowest-F0 (p=0.035). Finally the obese group showed significantly lower shimmer values than the normal weight subjects (p<0.05). Body weight and body fat volume appear to influence select objective measures of voice quality, vocal aerodynamics, and phonatory range performance.

Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

PubMed

Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

2008-09-30

Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

Calcineurin Regulates Myocardial Function during Acute Endotoxemia

PubMed Central

Joshi, Mandar S.; Julian, Mark W.; Huff, Jennifer E.; Bauer, John A.; Xia, Yong; Crouser, Elliott D.

2006-01-01

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia. PMID:16424445

Uncovering a latent multinomial: Analysis of mark-recapture data with misidentification

USGS Publications Warehouse

Link, W.A.; Yoshizaki, J.; Bailey, L.L.; Pollock, K.H.

2010-01-01

Natural tags based on DNA fingerprints or natural features of animals are now becoming very widely used in wildlife population biology. However, classic capture-recapture models do not allow for misidentification of animals which is a potentially very serious problem with natural tags. Statistical analysis of misidentification processes is extremely difficult using traditional likelihood methods but is easily handled using Bayesian methods. We present a general framework for Bayesian analysis of categorical data arising from a latent multinomial distribution. Although our work is motivated by a specific model for misidentification in closed population capture-recapture analyses, with crucial assumptions which may not always be appropriate, the methods we develop extend naturally to a variety of other models with similar structure. Suppose that observed frequencies f are a known linear transformation f = A???x of a latent multinomial variable x with cell probability vector ?? = ??(??). Given that full conditional distributions [?? | x] can be sampled, implementation of Gibbs sampling requires only that we can sample from the full conditional distribution [x | f, ??], which is made possible by knowledge of the null space of A???. We illustrate the approach using two data sets with individual misidentification, one simulated, the other summarizing recapture data for salamanders based on natural marks. ?? 2009, The International Biometric Society.

Uncovering a Latent Multinomial: Analysis of Mark-Recapture Data with Misidentification

USGS Publications Warehouse

Link, W.A.; Yoshizaki, J.; Bailey, L.L.; Pollock, K.H.

2009-01-01

Natural tags based on DNA fingerprints or natural features of animals are now becoming very widely used in wildlife population biology. However, classic capture-recapture models do not allow for misidentification of animals which is a potentially very serious problem with natural tags. Statistical analysis of misidentification processes is extremely difficult using traditional likelihood methods but is easily handled using Bayesian methods. We present a general framework for Bayesian analysis of categorical data arising from a latent multinomial distribution. Although our work is motivated by a specific model for misidentification in closed population capture-recapture analyses, with crucial assumptions which may not always be appropriate, the methods we develop extend naturally to a variety of other models with similar structure. Suppose that observed frequencies f are a known linear transformation f=A'x of a latent multinomial variable x with cell probability vector pi= pi(theta). Given that full conditional distributions [theta | x] can be sampled, implementation of Gibbs sampling requires only that we can sample from the full conditional distribution [x | f, theta], which is made possible by knowledge of the null space of A'. We illustrate the approach using two data sets with individual misidentification, one simulated, the other summarizing recapture data for salamanders based on natural marks.

Insights into the latent multinomial model through mark-resight data on female grizzly bears with cubs-of-the-year

USGS Publications Warehouse

Higgs, Megan D.; Link, William; White, Gary C.; Haroldson, Mark A.; Bjornlie, Daniel D.

2013-01-01

Mark-resight designs for estimation of population abundance are common and attractive to researchers. However, inference from such designs is very limited when faced with sparse data, either from a low number of marked animals, a low probability of detection, or both. In the Greater Yellowstone Ecosystem, yearly mark-resight data are collected for female grizzly bears with cubs-of-the-year (FCOY), and inference suffers from both limitations. To overcome difficulties due to sparseness, we assume homogeneity in sighting probabilities over 16 years of bi-annual aerial surveys. We model counts of marked and unmarked animals as multinomial random variables, using the capture frequencies of marked animals for inference about the latent multinomial frequencies for unmarked animals. We discuss undesirable behavior of the commonly used discrete uniform prior distribution on the population size parameter and provide OpenBUGS code for fitting such models. The application provides valuable insights into subtleties of implementing Bayesian inference for latent multinomial models. We tie the discussion to our application, though the insights are broadly useful for applications of the latent multinomial model.

Membrane processing technology in the food industry: food processing, wastewater treatment, and effects on physical, microbiological, organoleptic, and nutritional properties of foods.

PubMed

Kotsanopoulos, Konstantinos V; Arvanitoyannis, Ioannis S

2015-01-01

Membrane processing technology (MPT) is increasingly used nowadays in a wide range of applications (demineralization, desalination, stabilization, separation, deacidification, reduction of microbial load, purification, etc.) in food industries. The most frequently applied techniques are electrodialysis (ED), reverse osmosis (RO), nanofiltration (NF), ultrafiltration (UF), and microfiltration (MF). Several membrane characteristics, such as pore size, flow properties, and the applied hydraulic pressure mainly determine membranes' potential uses. In this review paper the basic membrane techniques, their potential applications in a large number of fields and products towards the food industry, the main advantages and disadvantages of these methods, fouling phenomena as well as their effects on the organoleptic, qualitative, and nutritional value of foods are synoptically described. Some representative examples of traditional and modern membrane applications both in tabular and figural form are also provided.

Biogeochemical Cycling and Sea Ice Dynamics in the Bering Sea across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Detlef, H.; Sosdian, S. M.; Belt, S. T.; Smik, L.; Lear, C. H.; Hall, I. R.; Kender, S.; Leng, M. J.; Husum, K.; Cabedo-Sanz, P.

2017-12-01

Today the Bering Sea is characterized by high primary productivity (PP) along the eastern shelf, maintained by CO2 and nutrient rich upwelled deep waters and nutrient release during spring sea ice melting. As such, low oxygen concentrations are pervasive in mid-depth waters. Changes in ventilation and export productivity in the past have been shown to impact this oxygen minimum zone. On glacial/interglacial (G/IG) timescales sea ice formation plays a pivotal role on intermediate water ventilation with evidence pointing to the formation of North Pacific Intermediate Water (NPIW) in the Bering Sea during Pleistocene glacial intervals. In addition, sea ice plays a significant role in both long- and short-term climate change via associated feedback mechanisms. Thus, records of sea ice dynamics and biogeochemical cycling in the Bering Sea are necessary to fully understand the interaction between PP, circulation patterns, and past G/IG climates with potential implications for the North Pacific carbon cycle. Here we use a multi-proxy approach to study sea ice dynamics and bottom water oxygenation, across three intervals prior to, across, and after the Mid-Pleistocene Transition (MPT, 1.2-0.7 Ma) from International Ocean Discovery Program Site U1343. The MPT, most likely driven by internal climate mechanisms, is ideal to study changes in sea ice dynamics and sedimentary redox conditions on orbital timescales and to investigate the implications for associated feedback mechanisms. The sea ice record, based on various biomarkers, including IP25, shows substantial increase in sea ice extent across the MPT and the occurrence of a late-glacial/deglacial sea ice spike, with consequences for glacial NPIW formation and land glacier retreat via the temperature-precipitation feedback. U/Mn of foraminiferal authigenic coatings, a novel proxy for bottom water oxygenation, also shows distinct variability on G/IG timescales across the MPT, most likely a result of PP and water mass changes in relation to sea ice dynamics. Additional records of benthic foraminiferal assemblages and biogenic opal accumulation rates further elucidate the influence of PP on U/Mn, which can help to investigate the strength of NPIW formation along the eastern Bering slope, important for CO2 outgassing and abyssal North Pacific carbon storage.

Redintegration and the benefits of long-term knowledge in verbal short-term memory: an evaluation of Schweickert's (1993) multinomial processing tree model.

PubMed

Thorn, Annabel S C; Gathercole, Susan E; Frankish, Clive R

2005-03-01

The impact of four long-term knowledge variables on serial recall accuracy was investigated. Serial recall was tested for high and low frequency words and high and low phonotactic frequency nonwords in 2 groups: monolingual English speakers and French-English bilinguals. For both groups the recall advantage for words over nonwords reflected more fully correct recalls with fewer recall attempts that consisted of fragments of the target memory items (one or two of the three target phonemes recalled correctly); completely incorrect recalls were equivalent for the 2 list types. However, word frequency (for both groups), nonword phonotactic frequency (for the monolingual group), and language familiarity all influenced the proportions of completely incorrect recalls that were made. These results are not consistent with the view that long-term knowledge influences on immediate recall accuracy can be exclusively attributed to a redintegration process of the type specified in multinomial processing tree model of immediate recall. The finding of a differential influence on completely incorrect recalls of these four long-term knowledge variables suggests instead that the beneficial effects of long-term knowledge on short-term recall accuracy are mediated by more than one mechanism.

Fuzzy multinomial logistic regression analysis: A multi-objective programming approach

NASA Astrophysics Data System (ADS)

Abdalla, Hesham A.; El-Sayed, Amany A.; Hamed, Ramadan

2017-05-01

Parameter estimation for multinomial logistic regression is usually based on maximizing the likelihood function. For large well-balanced datasets, Maximum Likelihood (ML) estimation is a satisfactory approach. Unfortunately, ML can fail completely or at least produce poor results in terms of estimated probabilities and confidence intervals of parameters, specially for small datasets. In this study, a new approach based on fuzzy concepts is proposed to estimate parameters of the multinomial logistic regression. The study assumes that the parameters of multinomial logistic regression are fuzzy. Based on the extension principle stated by Zadeh and Bárdossy's proposition, a multi-objective programming approach is suggested to estimate these fuzzy parameters. A simulation study is used to evaluate the performance of the new approach versus Maximum likelihood (ML) approach. Results show that the new proposed model outperforms ML in cases of small datasets.

Continuous 1.3-million-year record of East African hydroclimate, and implications for patterns of evolution and biodiversity

NASA Astrophysics Data System (ADS)

Lyons, Robert P.; Scholz, Christopher A.; Cohen, Andrew S.; King, John W.; Brown, Erik T.; Ivory, Sarah J.; Johnson, Thomas C.; Deino, Alan L.; Reinthal, Peter N.; McGlue, Michael M.; Blome, Margaret W.

2015-12-01

The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level variability derived from drill core data from Lake Malawi, East Africa (9-15° S). Over the Quaternary, we observe dramatic shifts in effective moisture, resulting in large-scale changes in one of the world's largest lakes and most diverse freshwater ecosystems. Results show evidence for 24 lake level drops of more than 200 m during the Late Quaternary, including 15 lowstands when water levels were more than 400 m lower than modern. A dramatic shift is observed at the Mid-Pleistocene Transition (MPT), consistent with far-field climate forcing, which separates vastly different hydroclimate regimes before and after ∼800,000 years ago. Before 800 ka, lake levels were lower, indicating a climate drier than today, and water levels changed frequently. Following the MPT high-amplitude lake level variations dominate the record. From 800 to 100 ka, a deep, often overfilled lake occupied the basin, indicating a wetter climate, but these highstands were interrupted by prolonged intervals of extreme drought. Periods of high lake level are observed during times of high eccentricity. The extreme hydroclimate variability exerted a profound influence on the Lake Malawi endemic cichlid fish species flock; the geographically extensive habitat reconfiguration provided novel ecological opportunities, enabling new populations to differentiate rapidly to distinct species.

Continuous 1.3-million-year record of East African hydroclimate, and implications for patterns of evolution and biodiversity

PubMed Central

Lyons, Robert P.; Scholz, Christopher A.; Cohen, Andrew S.; King, John W.; Brown, Erik T.; Ivory, Sarah J.; Johnson, Thomas C.; Deino, Alan L.; Reinthal, Peter N.; McGlue, Michael M.; Blome, Margaret W.

2015-01-01

The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level variability derived from drill core data from Lake Malawi, East Africa (9–15° S). Over the Quaternary, we observe dramatic shifts in effective moisture, resulting in large-scale changes in one of the world’s largest lakes and most diverse freshwater ecosystems. Results show evidence for 24 lake level drops of more than 200 m during the Late Quaternary, including 15 lowstands when water levels were more than 400 m lower than modern. A dramatic shift is observed at the Mid-Pleistocene Transition (MPT), consistent with far-field climate forcing, which separates vastly different hydroclimate regimes before and after ∼800,000 years ago. Before 800 ka, lake levels were lower, indicating a climate drier than today, and water levels changed frequently. Following the MPT high-amplitude lake level variations dominate the record. From 800 to 100 ka, a deep, often overfilled lake occupied the basin, indicating a wetter climate, but these highstands were interrupted by prolonged intervals of extreme drought. Periods of high lake level are observed during times of high eccentricity. The extreme hydroclimate variability exerted a profound influence on the Lake Malawi endemic cichlid fish species flock; the geographically extensive habitat reconfiguration provided novel ecological opportunities, enabling new populations to differentiate rapidly to distinct species. PMID:26644580

The comparison of muscle strength and short-term endurance in the different periods of type 2 diabetes

PubMed Central

2014-01-01

Background Patients with type 2 diabetes (T2DM) are subjected to reduction in the quality and oxidative capacity of muscles. The effect of duration of diabetes on the muscle endurance response is not clear and strength as well. Objective The aim of this study was the assessment of strength and endurance of knee extensor and flexor in the patients with T2DM < 10 and T2DM > 10 years in comparison with age, sex, BMI, ABI and PAI-matched health control subjects. Methods Isometric maximal peak torque (MPT) of knee extensor and flexor before and after 40 isokinetic repetitions with velocity of 150 degree/s were recorded in 18 patients with T2DM < 10 Y , 12 patients with T2DM > 10 Y and 20 matched health control (HC) groups. Results Both diabetic patient groups had significant lower isometric and isotonic knee extensor and flexor strength than HC. The endurance indices indicated that whereas the isometric MPT of flexor movement was reduced after isokinetic protocol in the both patient groups in comparison with HC, the less decline was seen in the isotonic torque and work during isokinetic protocol in the T2DM > 10 Y group in comparison with two other groups. The HbA1c and FPG were significantly correlated with strength not with endurance indices. Conclusions It seems the progression of diabetes accompanied with vascular, neural and muscular deficits activate, some adaptive and compensatory processes which can maintain muscle performance. PMID:24476108

Continuous 1.3-million-year record of East African hydroclimate, and implications for patterns of evolution and biodiversity.

PubMed

Lyons, Robert P; Scholz, Christopher A; Cohen, Andrew S; King, John W; Brown, Erik T; Ivory, Sarah J; Johnson, Thomas C; Deino, Alan L; Reinthal, Peter N; McGlue, Michael M; Blome, Margaret W

2015-12-22

The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level variability derived from drill core data from Lake Malawi, East Africa (9-15° S). Over the Quaternary, we observe dramatic shifts in effective moisture, resulting in large-scale changes in one of the world's largest lakes and most diverse freshwater ecosystems. Results show evidence for 24 lake level drops of more than 200 m during the Late Quaternary, including 15 lowstands when water levels were more than 400 m lower than modern. A dramatic shift is observed at the Mid-Pleistocene Transition (MPT), consistent with far-field climate forcing, which separates vastly different hydroclimate regimes before and after ∼800,000 years ago. Before 800 ka, lake levels were lower, indicating a climate drier than today, and water levels changed frequently. Following the MPT high-amplitude lake level variations dominate the record. From 800 to 100 ka, a deep, often overfilled lake occupied the basin, indicating a wetter climate, but these highstands were interrupted by prolonged intervals of extreme drought. Periods of high lake level are observed during times of high eccentricity. The extreme hydroclimate variability exerted a profound influence on the Lake Malawi endemic cichlid fish species flock; the geographically extensive habitat reconfiguration provided novel ecological opportunities, enabling new populations to differentiate rapidly to distinct species.

Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

PubMed

Balakirev, M Y; Zimmer, G

1998-08-01

Some compounds are known to induce solute-nonselective permeability of the inner mitochondrial membrane (IMM) in Ca2+-loaded mitochondria. Existing data suggest that this process, following the opening of a mitochondrial permeability transition pore, is preceded by different solute-selective permeable states of IMM. At pH 7, for instance, the K0.5 for Ca2+-induced pore opening is 16 microM, a value 80-fold above a therapeutically relevant shift of intracellular Ca2+ during ischemia in vivo. The present work shows that in the absence of Ca2+, phenylarsine oxide and tetraalkyl thiuram disulfides (TDs) are able to induce a complex sequence of IMM permeability changes. At first, these agents activated an electrogenic K+ influx into the mitochondria. This K+-specific pathway had K0.5 = 35 mM for K+ and was inhibited by bromsulfalein with Ki = 2.5 microM. The inhibitors of mitochondrial KATP channel, ATP and glibenclamide, did not inhibit K+ transport via this pathway. Moreover, 50 microM glibenclamide induced by itself K+ influx into the mitochondria. After the increase in K+ permeability of IMM, mitochondria become increasingly permeable to protons. Mechanisms of H+ leak and nonselective permeability increase could also be different depending on the type of mitochondrial permeability transition (MPT) inducer. Thus, permeabilization of mitochondria induced by phenylarsine oxide was fully prevented by ADP and/or cyclosporin A, whereas TD-induced membrane alterations were insensitive toward these inhibitors. It is suggested that MPT in vivo leading to irreversible apoptosis is irrelevant in reversible ischemia/reperfusion injury. Copyright 1998 Academic Press.

“Too Many betas do not Spoil the Broth”: The Role of Beta Brain Oscillations in Language Processing

PubMed Central

Weiss, Sabine; Mueller, Horst M.

2012-01-01

Over the past 20 years, brain oscillations have proven to be a gateway to the understanding of cognitive processes. It has been shown that different neurocognitive aspects of language processing are associated with brain oscillations at various frequencies. Frequencies in the beta range (13–30 Hz) turned out to be particularly important with respect to cognitive and linguistic manipulations during language processing. Beta activity has been involved in higher-order linguistic functions such as the discrimination of word categories and the retrieval of action semantics as well as semantic memory, and syntactic binding processes, which support meaning construction during sentence processing. From a neurophysiological point of view, the important role of the beta frequencies for such a complex cognitive task as language processing seems reasonable. Experimental evidence suggests that frequencies in the beta range are ideal for maintaining and preserving the activity of neuronal assemblies over time. In particular, recent computational and experimental evidence suggest that beta frequencies are important for linking past and present input and the detection of novelty of stimuli, which are essential processes for language perception as well as production. In addition, the beta frequency’s role in the formation of cell assemblies underlying short-term memory seems indispensable for language analysis. Probably the most important point is the well-known relation of beta oscillations with motor processes. It can be speculated that beta activities reflect the close relationship between language comprehension and motor functions, which is one of the core claims of current theories on embodied cognition. In this article, the importance of beta oscillations for language processing is reviewed based both on findings in psychophysiological and neurophysiological literature. PMID:22737138

A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini‐swine with compensated heart failure

PubMed Central

Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.

2014-01-01

Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034

The lipoprotein LpqW is essential for the mannosylation of periplasmic glycolipids in Corynebacteria.

PubMed

Rainczuk, Arek K; Yamaryo-Botte, Yoshiki; Brammananth, Rajini; Stinear, Timothy P; Seemann, Torsten; Coppel, Ross L; McConville, Malcolm J; Crellin, Paul K

2012-12-14

Phosphatidylinositol mannosides (PIM), lipomannan (LM), and lipoarabinomannan (LAM) are essential components of the cell wall and plasma membrane of mycobacteria, including the human pathogen Mycobacterium tuberculosis, as well as the related Corynebacterineae. We have previously shown that the lipoprotein, LpqW, regulates PIM and LM/LAM biosynthesis in mycobacteria. Here, we provide direct evidence that LpqW regulates the activity of key mannosyltransferases in the periplasmic leaflet of the cell membrane. Inactivation of the Corynebacterium glutamicum lpqW ortholog, NCgl1054, resulted in a slow growth phenotype and a global defect in lipoglycan biosynthesis. The NCgl1054 mutant lacked LAMs and was defective in the elongation of the major PIM species, AcPIM2, as well as a second glycolipid, termed Gl-X (mannose-α1-4-glucuronic acid-α1-diacylglycerol), which function as membrane anchors for LM-A and LM-B, respectively. Elongation of AcPIM2 and Gl-X was found to be dependent on expression of polyprenol phosphomannose (ppMan) synthase. However, the ΔNCgl1054 mutant synthesized normal levels of ppMan, indicating that LpqW is not required for synthesis of this donor. A spontaneous suppressor strain was isolated in which lipoglycan synthesis in the ΔNCgl1054 mutant was partially restored. Genome-wide sequencing indicated that a single amino acid substitution within the ppMan-dependent mannosyltransferase MptB could bypass the need for LpqW. Further evidence of an interaction is provided by the observation that MptB activity in cell-free extracts was significantly reduced in the absence of LpqW. Collectively, our results suggest that LpqW may directly activate MptB, highlighting the role of lipoproteins in regulating key cell wall biosynthetic pathways in these bacteria.

Zinc irreversibly damages major enzymes of energy production and antioxidant defense prior to mitochondrial permeability transition.

PubMed

Gazaryan, Irina G; Krasinskaya, Inna P; Kristal, Bruce S; Brown, Abraham M

2007-08-17

Recent observations point to the role played by Zn2+ as an inducer of neuronal death. Two Zn2+ targets have been identified that result in inhibition of mitochondrial respiration: the bc1 center and, more recently, alpha-ketoglutarate dehydrogenase. Zn2+ is also a mediator of oxidative stress, leading to mitochondrial failure, release of apoptotic peptides, and neuronal death. We now present evidence, by means of direct biochemical assays, that Zn2+ is imported through the Ca2+ uniporter and directly targets major enzymes of energy production (lipoamide dehydrogenase) and antioxidant defense (thioredoxin reductase and glutathione reductase). We demonstrate the following. (a) These matrix enzymes are rapidly inhibited by application of Zn2+ to intact mitochondria. (b) Delayed treatment with membrane-impermeable chelators has no effect, indicating rapid transport of biologically relevant quantities of Zn2+ into the matrix. (c) Membrane-permeable chelators stop but do not reverse enzyme inactivation. (d) Enzyme inhibition is rapid and irreversible and precedes the major changes associated with the mitochondrial permeability transition (MPT). (e) The extent and rate of enzyme inactivation linearly correlates with the MPT onset and propagation. (f) The Ca2+ uniporter blocker, Ruthenium Red, protects enzyme activities and delays pore opening up to 2 microm Zn2+. An additional, unidentified import route functions at higher Zn2+ concentrations. (g) No enzyme inactivation is observed for Ca2+-induced MPT. These observations strongly suggest that, unlike Ca2+, exogenous Zn2+ interferes with mitochondrial NADH production and directly alters redox protection in the matrix, contributing to mitochondrial dysfunction. Inactivation of these enzymes by Zn2+ is irreversible, and thus only their de novo synthesis can restore function, which may underlie persistent loss of oxidative carbohydrate metabolism following transient ischemia.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

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

Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 2+}] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified bymore » dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca{sup 2+} uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca{sup 2+}]{sub i} in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca{sup 2+}]{sub i} during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca{sup 2+}]{sub i} during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.« less

Fe Stabilization by Intermetallic L1 0-FePt and Pt Catalysis Enhancement in L1 0-FePt/Pt Nanoparticles for Efficient Oxygen Reduction Reaction in Fuel Cells

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

Li, Junrui; Xi, Zheng; Pan, Yung -Tin

We report in this article a detailed study on how to stabilize a first-row transition metal (M) in an intermetallic L1 0-MPt alloy nanoparticle (NP) structure and how to surround the L1 0-MPt with an atomic layer of Pt to enhance the electrocatalysis of Pt for oxygen reduction reaction (ORR) in fuel cell operation conditions. Using 8 nm FePt NPs as an example, we demonstrate that Fe can be stabilized more efficiently in a core/shell structured L1 0-FePt/Pt with a 5 Å Pt shell. The presence of Fe in the alloy core induces the desired compression of the thin Ptmore » shell, especially the 2 atomic layers of Pt shell, further improving the ORR catalysis. This leads to much enhanced Pt catalysis for ORR in 0.1 M HClO 4 solution (both at room temperature and 60°C) and in the membrane electrode assembly (MEA) at 80°C. The L1 0-FePt/Pt catalyst has a mass activity of 0.7 A/mg Pt from the half-cell ORR test and shows no obvious mass activity loss after 30,000 potential cycles between 0.6 V and 0.95 V at 80°C in the MEA, meeting the DOE 2020 target (<40% loss in mass activity). Here, we are extending the concept and preparing other L1 0-MPt/Pt NPs, such as L1 0-CoPt/Pt NPs, with reduced NP size as a highly efficient ORR catalyst for automotive fuel cell applications.« less

Comparison of MALDI-TOF MS, nucleic acid hybridization and the MPT64 immunochromatographic test for the identification of M. tuberculosis and non-tuberculosis Mycobacterium species.

PubMed

Şamlı, Asuman; İlki, Arzu

2016-10-01

Mycobacteria are an important cause of morbidity in humans. Rapid and accurate mycobacterial identification is important for improving patient outcomes. However, identification of Mycobacterium species is not easy, due to the slow and fastidious growth of mycobacteria. Recently, biochemical, sequencing, and probing methods have come to be used for identification. This study compared the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of M.tuberculosis and non-tuberculosis Mycobacteria (NTM) to those of nucleic acid hybridization (NAH) and the MPT64 immunochromatographic test. A total of 69 isolates from Marmara University Hospital, Microbiology Laboratory obtained between 2012 and 2013 were included in our study. All strains were grown on Lowenstein-Jensen and Middlebrook 7H9 medium. Among the 69 isolates, 56 (81%) were isolated as Mycobacterium tuberculosis complex (MTC), and 13 (19%) were isolated as NTM by the MPT64 ICT. NAH was able to identify all isolates to the species level. The isolated NTM included M. intracellulare (n:5), M. lentiflavum (n:3), M. xenopi (n:2), M. malmoense (n:1), M. abscessus (n:1), and M. avium (n:1). MALDI-TOF MS identified 88% of the mycobacterial isolates. All M. tuberculosis strains were identified correctly, but the ratio was 38.5% for NTM. Mycobacterial identification using MALDI-TOF MS takes 45 minutes and costs 3 Euro/test, whereas mycobacterial identification using NAH takes 6-7 hours and costs 30 Euro/test. In conclusion, MALDI-TOF MS has the potential to identify mycobacteria in the clinical laboratory setting by reducing identification turnaround time and laboratory costs for isolate referral.

Fe Stabilization by Intermetallic L1 0-FePt and Pt Catalysis Enhancement in L1 0-FePt/Pt Nanoparticles for Efficient Oxygen Reduction Reaction in Fuel Cells

DOE PAGES

Li, Junrui; Xi, Zheng; Pan, Yung -Tin; ...

2018-02-07

We report in this article a detailed study on how to stabilize a first-row transition metal (M) in an intermetallic L1 0-MPt alloy nanoparticle (NP) structure and how to surround the L1 0-MPt with an atomic layer of Pt to enhance the electrocatalysis of Pt for oxygen reduction reaction (ORR) in fuel cell operation conditions. Using 8 nm FePt NPs as an example, we demonstrate that Fe can be stabilized more efficiently in a core/shell structured L1 0-FePt/Pt with a 5 Å Pt shell. The presence of Fe in the alloy core induces the desired compression of the thin Ptmore » shell, especially the 2 atomic layers of Pt shell, further improving the ORR catalysis. This leads to much enhanced Pt catalysis for ORR in 0.1 M HClO 4 solution (both at room temperature and 60°C) and in the membrane electrode assembly (MEA) at 80°C. The L1 0-FePt/Pt catalyst has a mass activity of 0.7 A/mg Pt from the half-cell ORR test and shows no obvious mass activity loss after 30,000 potential cycles between 0.6 V and 0.95 V at 80°C in the MEA, meeting the DOE 2020 target (<40% loss in mass activity). Here, we are extending the concept and preparing other L1 0-MPt/Pt NPs, such as L1 0-CoPt/Pt NPs, with reduced NP size as a highly efficient ORR catalyst for automotive fuel cell applications.« less

Electroglottographic Comparison of Voice Outcomes in Patients With Advanced Laryngopharyngeal Cancer Treated by Chemoradiotherapy or Total Laryngectomy

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

Kazi, Rehan; Institute of Cancer Research, London; Venkitaraman, Ramachandran

2008-02-01

Purpose: To conduct prospective electroglottographic analyses of voice outcomes after radical chemoradiotherapy for locally advanced laryngopharyngeal cancers and to compare them with patients who have undergone total laryngectomy (TL). Patients and Methods: Twenty-one patients (19 male, 2 female, median age [range] 65 [50-85] years) with Stage III/IV laryngopharyngeal cancer received induction chemotherapy followed by radical chemoradiotherapy. Electroglottography, using the sustained vowel /i/ and connected speech, was performed before treatment and 1, 6, and 12 months after treatment. In addition, single voice recordings were taken from 21 patients (16 male, 5 female, aged 65 [50-84] years) who had undergone TL andmore » surgical voice restoration and from 21 normal controls (18 male, 3 female, aged 65 [33-80] years). Results: Before treatment the vocal measures for the chemoradiotherapy patients were significantly different from normal controls in jitter (p = 0.02), maximum phonation time (MPT) (p = 0.001), and words per minute (WPM) (p = 0.01). At 12 months after treatment MPT and WPM had normalized, but jitter and normalized noise energy were significantly worse than in normal controls. Comparison of voice outcomes at 12 months for chemoradiotherapy patients revealed superiority over the TL group in all parameters except MPT (18.2 s vs. 10.4 s, p = 0.06). Analysis of the recovery of voice up to 12 months after treatment revealed progressive improvement in most electroglottographic measures. Conclusions: This prospective study demonstrates significantly better outcome for patients treated with chemoradiotherapy as compared with TL. Progressive normalization of many voice parameters occurs over the 12 months following chemoradiotherapy.« less

Effect of duration of denervation on outcomes of ansa-recurrent laryngeal nerve reinnervation.

PubMed

Li, Meng; Chen, Shicai; Wang, Wei; Chen, Donghui; Zhu, Minhui; Liu, Fei; Zhang, Caiyun; Li, Yan; Zheng, Hongliang

2014-08-01

To investigate the efficacy of laryngeal reinnervation with ansa cervicalis among unilateral vocal fold paralysis (UVFP) patients with different denervation durations. We retrospectively reviewed 349 consecutive UVFP cases of delayed ansa cervicalis to the recurrent laryngeal nerve (RLN) anastomosis. Potential influencing factors were analyzed in multivariable logistic regression analysis. Stratification analysis performed was aimed at one of the identified significant variables: denervation duration. Videostroboscopy, perceptual evaluation, acoustic analysis, maximum phonation time (MPT), and laryngeal electromyography (EMG) were performed preoperatively and postoperatively. Gender, age, preoperative EMG status and denervation duration were analyzed in multivariable logistic regression analysis. Stratification analysis was performed on denervation duration, which was divided into three groups according to the interval between RLN injury and reinnervation: group A, 6 to 12 months; group B, 12 to 24 months; and group C, > 24 months. Age, preoperative EMG, and denervation duration were identified as significant variables in multivariable logistic regression analysis. Stratification analysis on denervation duration showed significant differences between group A and C and between group B and C (P < 0.05)-but showed no significant difference between group A and B (P > 0.05) with regard to parameters overall grade, jitter, shimmer, noise-to-harmonics ratio, MPT, and postoperative EMG. In addition, videostroboscopic and laryngeal EMG data, perceptual and acoustic parameters, and MPT values were significantly improved postoperatively in each denervation duration group (P < 0.01). Although delayed laryngeal reinnervation is proved valid for UVFP, surgical outcome is better if the procedure is performed within 2 years after nerve injury than that over 2 years. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

A large Ca2+-dependent channel formed by recombinant ADP/ATP carrier from Neurospora crassa resembles the mitochondrial permeability transition pore.

PubMed

Brustovetsky, Nickolay; Tropschug, Maximilian; Heimpel, Simone; Heidkämper, Doerthe; Klingenberg, Martin

2002-10-01

Strong support for the central role of the ADP/ATP carrier (AAC) in the mitochondrial permeability transition (mPT) is provided by the single-channel current measurements in patch-clamp experiments with the isolated reconstituted AAC. In previous work [Brustovetsky, N., and Klingenberg, M. (1996) Biochemistry 35, 8483-8488], this technique was applied to the AAC isolated from bovine heart mitochondria. Here we used recombinant AAC (rAAC) from Neurospora crassa expressed in E. coli, since AAC from mammalian sources cannot be expresssed in E. coli. The rAAC is free from residual mitochondrial components which might associate with the AAC in preparation from bovine heart. Ca(2+)-dependent channels with up to 600 pS are obtained, which are gated at >150 mV. The channel corresponds to a preferential matrix-outside orientation of rAAC in the patch membrane as shown with carboxyatractylate and a polar gating asymmetry. The channel is inhibited by ADP and bongkrekate, not by carboxyatractylate. Cyclophilin, isolated from Neurospora crassa, suppresses the gating, thus increasing conductivity at high positive voltage. Cyclosporin A abolishes the cyclophilin effect. ADP does not eliminate the cyclophilin effect but produces fast large-amplitude flickering of the channel without a stable decrease of the channel conductance. Also the pro-oxidant tert-butyl hydroperoxide reversibly suppresses voltage gating of the channel. The results show that the AAC can be a conducting component of the mPT pore, exhibiting similar characteristics as the mPT pore (response to Ca(2+), BKA, ADP), with a cyclophilin and pro-oxidant-sensitive gating at high voltage.

Climate changes in south western Iberia and Mediterranean Outflow variations during two contrasting cycles of the last 1 Myrs: MIS 31-MIS 30 and MIS 12-MIS 11

NASA Astrophysics Data System (ADS)

Sánchez Goñi, M. F.; Llave, E.; Oliveira, D.; Naughton, F.; Desprat, S.; Ducassou, E.; Hodell, D. A.; Hernández-Molina, F. J.

2016-01-01

Grain size analysis and physical properties of Sites U1388, U1389 and U1390 collected in the Contourite Depositional System of the Gulf of Cádiz during the Integrated Ocean Drilling Program (IODP) Expedition 339 "Mediterranean Outflow" reveal relative changes in bottom current strength, a tracer of the dynamics of the Mediterranean Outflow Water (MOW), before and after the Middle Pleistocene Transition (MPT). The comparison of MOW behavior with climate changes identified by the pollen analysis and δ18O benthic foraminifera measurements of Site U1385, the Shackleton Site, collected in the south western Iberian margin shows that the interval MIS 31-MIS 30, ~ 1.1-1.05 million years ago (Ma), before the MPT, was marked by wetter climate and weaker bottom current than the interval MIS 12-MIS 11 (0.47-0.39 Ma), after the MPT. Similarly, the increase in fine particles from these glacials to interglacials and in coarse fraction from interglacials to glacials was coeval with forest and semi-desert expansions, respectively, indicating the lowering/enhancement of MOW strength during periods of regional increase/decrease of moisture. While these findings may not necessarily apply to all glacial/interglacial cycles, they nonetheless serve as excellent supporting examples of the hypothesis that aridification can serve as a good tracer for MOW intensity. The strongest regional aridity during MIS 12 coincides with a remarkable increase of coarse grain size deposition and distribution that we interpret as a maximum in MOW strength. This MOW intensification may have pre-conditioned the North Atlantic by increasing salinity, thereby triggering the strong resumption of the Meridional Overturning Circulation that could contribute to the great warmth that characterizes the MIS 11c super-interglacial.

Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

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

Latchoumycandane, Calivarathan; Seah, Quee Ming; Tan, Rachel C.H.

2006-11-15

Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and themore » upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 {mu}M) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction.« less

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Liu, Jun Yao; Abebe, Worku; Sullivan, Jennifer C; El-Marakby, Ahmed

2011-03-01

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Mevalonolactone disrupts mitochondrial functions and induces permeability transition pore opening in rat brain mitochondria: Implications for the pathogenesis of mevalonic aciduria.

PubMed

Cecatto, Cristiane; Amaral, Alexandre Umpierrez; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Gonçalves, Aline de Mello; Vargas, Carmen Regla; Wajner, Moacir

2017-09-01

Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca 2+ in the brain, besides inducing mitochondrial swelling. These biochemical alterations were totally prevented by the classical inhibitors of mitochondrial permeability transition (MPT) cyclosporine A and ADP, as well as by ruthenium red in Ca 2+ -loaded mitochondria, indicating the involvement of MPT and an important role for mitochondrial Ca 2+ in these effects. ML also induced lipid peroxidation and markedly inhibited aconitase activity, an enzyme that is highly susceptible to free radical attack, in brain mitochondrial fractions, indicating that lipid and protein oxidative damage may underlie some of ML-induced deleterious effects including MTP induction. In contrast, ML and MA did not compromise oxidative phosphorylation in the brain and all mitochondrial functions evaluated in the liver, evidencing a selective toxicity of ML towards the central nervous system. Our present study provides for the first time evidence that ML impairs essential brain mitochondrial functions with the involvement of MPT pore opening. It is therefore presumed that disturbance of brain mitochondrial homeostasis possibly contributes to the neurologic symptoms in MVA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of an omni-directional shear horizontal mode magnetostrictive patch transducer

NASA Astrophysics Data System (ADS)

Liu, Zenghua; Hu, Yanan; Xie, Muwen; Fan, Junwei; He, Cunfu; Wu, Bin

2018-04-01

The fundamental shear horizontal wave, SH0 mode, has great potential in defect detection and on-line monitoring with large scale and high efficiency in plate-like structures because of its non-dispersive characteristics. Aiming at consistently exciting single SH0 mode in plate-like structures, an omni-directional shear horizontal mode magnetostrictive patch transducer (OSHM-MPT) is developed on the basis of magnetostrictive effect. It consists of four fan-shaped array elements and corresponding plane solenoid array (PSA) coils, four fan-shaped permanent magnets and a circular nickel patch. The experimental results verify that the developed transducer can effectively produce the single SH0 mode in an aluminum plate. The frequency response characteristics of this developed transducer are tested. The results demonstrate that the proposed OSHM-MPT has a center frequency of 300kHz related to the distance between adjacent arc-shaped steps of the PSA coils. Furthermore, omni-directivity of this developed transducer is tested. The results demonstrate that the developed transducer has a high omnidirectional consistency.

How Framing Statistical Statements Affects Subjective Veracity: Validation and Application of a Multinomial Model for Judgments of Truth

ERIC Educational Resources Information Center

Hilbig, Benjamin E.

2012-01-01

Extending the well-established negativity bias in human cognition to truth judgments, it was recently shown that negatively framed statistical statements are more likely to be considered true than formally equivalent statements framed positively. However, the underlying processes responsible for this effect are insufficiently understood.…

Generalized Processing Tree Models: Jointly Modeling Discrete and Continuous Variables.

PubMed

Heck, Daniel W; Erdfelder, Edgar; Kieslich, Pascal J

2018-05-24

Multinomial processing tree models assume that discrete cognitive states determine observed response frequencies. Generalized processing tree (GPT) models extend this conceptual framework to continuous variables such as response times, process-tracing measures, or neurophysiological variables. GPT models assume finite-mixture distributions, with weights determined by a processing tree structure, and continuous components modeled by parameterized distributions such as Gaussians with separate or shared parameters across states. We discuss identifiability, parameter estimation, model testing, a modeling syntax, and the improved precision of GPT estimates. Finally, a GPT version of the feature comparison model of semantic categorization is applied to computer-mouse trajectories.

46 CFR 64.35 - Bottom filling or discharge connection.

Code of Federal Regulations, 2010 CFR

2010-10-01

....35 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.35 Bottom filling or discharge... the product, and a manually operated valve that is located— (a) Inside the tank and operated outside...

46 CFR 64.3 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS General § 64.3 Applicability. (a) This part applies to each MPT for which the Commanding Officer.... (b) Subpart F of this part also applies to portable tanks and to cargo-handling systems for portable...

46 CFR 64.3 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS General § 64.3 Applicability. (a) This part applies to each MPT for which the Commanding Officer.... (b) Subpart F of this part also applies to portable tanks and to cargo-handling systems for portable...

46 CFR 64.3 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS General § 64.3 Applicability. (a) This part applies to each MPT for which the Commanding Officer.... (b) Subpart F of this part also applies to portable tanks and to cargo-handling systems for portable...

46 CFR 64.3 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS General § 64.3 Applicability. (a) This part applies to each MPT for which the Commanding Officer.... (b) Subpart F of this part also applies to portable tanks and to cargo-handling systems for portable...

46 CFR 98.30-4 - Vessels carrying MPTs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Portable Tanks and Intermediate Bulk Containers § 98.30-4 Vessels carrying MPTs. Each MPT on a vessel to which this part applies...

Proteolytic processing of endogenous and recombinant beta 4 integrin subunit

PubMed Central

1992-01-01

The alpha 6 beta 4 integrin is a receptor involved in the interaction of epithelial cells with basement membranes. This integrin is unique among the known integrins in that its beta 4 subunit has a large cytoplasmic domain. The function of this cytoplasmic domain is not known. In this paper we show that the beta 4 subunit undergoes proteolytic processing in cultured cells and provide evidence that this also happens in tissues. Immunoprecipitation experiments indicated that the cytoplasmic domain of beta 4 is susceptible to a calcium-dependent protease present in cellular extracts. In vitro assays with purified calpain showed that this enzyme can cleave beta 4 at two distinct sites in the cytoplasmic domain, generating truncated molecules of 165 and 130 kD. Immunoblotting experiments performed on cultured epithelial cells using an antibody to a peptide modeled after the COOH-terminus of the beta 4 subunit showed 70-kD fragments and several fragments of molecular masses between 185 and 115 kD. Similar fragments were detected in CHO cells transfected with the full-length beta 4 cDNA, but not in control transfected cells or in cells transfected with a mutant cDNA lacking the epitope of the cytoplasmic peptide antibody. The sizes of the fragments indicated that both the intracellular and extracellular domains of beta 4 are proteolytically processed. To examine the processing of the beta 4 subunit in epithelial tissues in vivo, human skin frozen sections were stained with antibodies to the ectodomain or the cytoplasmic domain of beta 4. The distinct staining patterns obtained with the two types of antibodies provided evidence that beta 4 is proteolytically processed in vivo in skin. Analogous experiments performed on sections of the cornea suggested that beta 4 is not proteolytically processed at a detectable level in this tissue. Thus, cleavage of the beta 4 subunit occurs in a tissue-specific fashion. These results suggest a potential mechanism of modulating the activities of the alpha 6 beta 4 integrin. PMID:1500432

Influence of season, age and management on scrotal thermal profile in Murrah bulls using scrotal infrared digital thermography

NASA Astrophysics Data System (ADS)

Ahirwar, Maneesh Kumar; Kataktalware, Mukund Amritrao; Ramesha, Kerekoppa Puttaiah; Pushpadass, Heartwin Amaladhas; Jeyakumar, Sakthivel; Revanasiddu, Deginal; Kour, Reen Jagish; Nath, Sapna; Nagaleekar, Anand Kumar; Nazar, Sayyad

2017-12-01

The aim of the present study was to examine the effects of non-genetic factors on scrotal thermographic profile viz., proximal pole temperature (PPT °C), mid pole temperature (MPT °C), distal pole temperature (DPT °C) and ocular temperature (OcT) of Murrah ( Bubalus bubalis) breeding bulls. A total of 109 buffalo bulls, maintained at three semen stations (SS), were monitored for scrotal surface and ocular temperatures using infrared thermography twice daily during rainy, winter and summer seasons using an FLIR i5 infrared camera and temperatures were measured. Thermograms were analysed by FLIR QuickReport v.1.2 SP2 software. Statistical analysis revealed that semen station, season, temperature humidity index (THI), housing system and timing of observations had significant ( P < 0.05) effect on scrotal surface temperature (SST) and OcT. In SS-I, the PPT and MPT were significantly ( P < 0.05) higher as compared to SS-II and SS-III. THI had significant ( P < 0.05) effect on SST and OcT, whereas PPT (°C), MPT (°C), DPT (°C) and OcT (°C) values during high THI (>80.88; <0.05) period were higher as compared to medium THI period (70.06-80.88) and during low THI period (<70.06). Temperature gradient (TG) of the testes was significantly ( P < 0.05) higher during low THI period (4.50 ± 0.06 °C) as compared to medium THI (2.38 ± 0.03 °C) and high THI (1.61 ± 0.05 °C). Season of the year had a significant effect ( P < 0.05) on the SST and OcT. During the rainy season, PPT (34.50 ± 0.09 °C), MPT (33.44 ± 0.12 °C) and DPT (32.11 ± 0.15 °C) were significantly ( P < 0.05) higher as compared to winter and summer seasons. Age of the bulls had non-significant effect on SST and OcT but had a marked influence on thermal profile of scrotum. It could be concluded semen station, season, temperature humidity index, housing system and timing of observations had a significant influence on scrotal surface temperature. The monitoring of scrotal surface temperature by infrared thermography was found to be useful in evaluating the effects of thermal stress on physiology and health of buffalo bulls.

Influence of season, age and management on scrotal thermal profile in Murrah bulls using scrotal infrared digital thermography.

PubMed

Ahirwar, Maneesh Kumar; Kataktalware, Mukund Amritrao; Ramesha, Kerekoppa Puttaiah; Pushpadass, Heartwin Amaladhas; Jeyakumar, Sakthivel; Revanasiddu, Deginal; Kour, Reen Jagish; Nath, Sapna; Nagaleekar, Anand Kumar; Nazar, Sayyad

2017-12-01

The aim of the present study was to examine the effects of non-genetic factors on scrotal thermographic profile viz., proximal pole temperature (PPT °C), mid pole temperature (MPT °C), distal pole temperature (DPT °C) and ocular temperature (OcT) of Murrah (Bubalus bubalis) breeding bulls. A total of 109 buffalo bulls, maintained at three semen stations (SS), were monitored for scrotal surface and ocular temperatures using infrared thermography twice daily during rainy, winter and summer seasons using an FLIR i5 infrared camera and temperatures were measured. Thermograms were analysed by FLIR QuickReport v.1.2 SP2 software. Statistical analysis revealed that semen station, season, temperature humidity index (THI), housing system and timing of observations had significant (P < 0.05) effect on scrotal surface temperature (SST) and OcT. In SS-I, the PPT and MPT were significantly (P < 0.05) higher as compared to SS-II and SS-III. THI had significant (P < 0.05) effect on SST and OcT, whereas PPT (°C), MPT (°C), DPT (°C) and OcT (°C) values during high THI (>80.88; <0.05) period were higher as compared to medium THI period (70.06-80.88) and during low THI period (<70.06). Temperature gradient (TG) of the testes was significantly (P < 0.05) higher during low THI period (4.50 ± 0.06 °C) as compared to medium THI (2.38 ± 0.03 °C) and high THI (1.61 ± 0.05 °C). Season of the year had a significant effect (P < 0.05) on the SST and OcT. During the rainy season, PPT (34.50 ± 0.09 °C), MPT (33.44 ± 0.12 °C) and DPT (32.11 ± 0.15 °C) were significantly (P < 0.05) higher as compared to winter and summer seasons. Age of the bulls had non-significant effect on SST and OcT but had a marked influence on thermal profile of scrotum. It could be concluded semen station, season, temperature humidity index, housing system and timing of observations had a significant influence on scrotal surface temperature. The monitoring of scrotal surface temperature by infrared thermography was found to be useful in evaluating the effects of thermal stress on physiology and health of buffalo bulls.

Measuring Response Styles Across the Big Five: A Multiscale Extension of an Approach Using Multinomial Processing Trees.

PubMed

Khorramdel, Lale; von Davier, Matthias

2014-01-01

This study shows how to address the problem of trait-unrelated response styles (RS) in rating scales using multidimensional item response theory. The aim is to test and correct data for RS in order to provide fair assessments of personality. Expanding on an approach presented by Böckenholt (2012), observed rating data are decomposed into multiple response processes based on a multinomial processing tree. The data come from a questionnaire consisting of 50 items of the International Personality Item Pool measuring the Big Five dimensions administered to 2,026 U.S. students with a 5-point rating scale. It is shown that this approach can be used to test if RS exist in the data and that RS can be differentiated from trait-related responses. Although the extreme RS appear to be unidimensional after exclusion of only 1 item, a unidimensional measure for the midpoint RS is obtained only after exclusion of 10 items. Both RS measurements show high cross-scale correlations and item response theory-based (marginal) reliabilities. Cultural differences could be found in giving extreme responses. Moreover, it is shown how to score rating data to correct for RS after being proved to exist in the data.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

PubMed

Galluzzi, Lorenzo; Vitale, Ilio; Aaronson, Stuart A; Abrams, John M; Adam, Dieter; Agostinis, Patrizia; Alnemri, Emad S; Altucci, Lucia; Amelio, Ivano; Andrews, David W; Annicchiarico-Petruzzelli, Margherita; Antonov, Alexey V; Arama, Eli; Baehrecke, Eric H; Barlev, Nickolai A; Bazan, Nicolas G; Bernassola, Francesca; Bertrand, Mathieu J M; Bianchi, Katiuscia; Blagosklonny, Mikhail V; Blomgren, Klas; Borner, Christoph; Boya, Patricia; Brenner, Catherine; Campanella, Michelangelo; Candi, Eleonora; Carmona-Gutierrez, Didac; Cecconi, Francesco; Chan, Francis K-M; Chandel, Navdeep S; Cheng, Emily H; Chipuk, Jerry E; Cidlowski, John A; Ciechanover, Aaron; Cohen, Gerald M; Conrad, Marcus; Cubillos-Ruiz, Juan R; Czabotar, Peter E; D'Angiolella, Vincenzo; Dawson, Ted M; Dawson, Valina L; De Laurenzi, Vincenzo; De Maria, Ruggero; Debatin, Klaus-Michael; DeBerardinis, Ralph J; Deshmukh, Mohanish; Di Daniele, Nicola; Di Virgilio, Francesco; Dixit, Vishva M; Dixon, Scott J; Duckett, Colin S; Dynlacht, Brian D; El-Deiry, Wafik S; Elrod, John W; Fimia, Gian Maria; Fulda, Simone; García-Sáez, Ana J; Garg, Abhishek D; Garrido, Carmen; Gavathiotis, Evripidis; Golstein, Pierre; Gottlieb, Eyal; Green, Douglas R; Greene, Lloyd A; Gronemeyer, Hinrich; Gross, Atan; Hajnoczky, Gyorgy; Hardwick, J Marie; Harris, Isaac S; Hengartner, Michael O; Hetz, Claudio; Ichijo, Hidenori; Jäättelä, Marja; Joseph, Bertrand; Jost, Philipp J; Juin, Philippe P; Kaiser, William J; Karin, Michael; Kaufmann, Thomas; Kepp, Oliver; Kimchi, Adi; Kitsis, Richard N; Klionsky, Daniel J; Knight, Richard A; Kumar, Sharad; Lee, Sam W; Lemasters, John J; Levine, Beth; Linkermann, Andreas; Lipton, Stuart A; Lockshin, Richard A; López-Otín, Carlos; Lowe, Scott W; Luedde, Tom; Lugli, Enrico; MacFarlane, Marion; Madeo, Frank; Malewicz, Michal; Malorni, Walter; Manic, Gwenola; Marine, Jean-Christophe; Martin, Seamus J; Martinou, Jean-Claude; Medema, Jan Paul; Mehlen, Patrick; Meier, Pascal; Melino, Sonia; Miao, Edward A; Molkentin, Jeffery D; Moll, Ute M; Muñoz-Pinedo, Cristina; Nagata, Shigekazu; Nuñez, Gabriel; Oberst, Andrew; Oren, Moshe; Overholtzer, Michael; Pagano, Michele; Panaretakis, Theocharis; Pasparakis, Manolis; Penninger, Josef M; Pereira, David M; Pervaiz, Shazib; Peter, Marcus E; Piacentini, Mauro; Pinton, Paolo; Prehn, Jochen H M; Puthalakath, Hamsa; Rabinovich, Gabriel A; Rehm, Markus; Rizzuto, Rosario; Rodrigues, Cecilia M P; Rubinsztein, David C; Rudel, Thomas; Ryan, Kevin M; Sayan, Emre; Scorrano, Luca; Shao, Feng; Shi, Yufang; Silke, John; Simon, Hans-Uwe; Sistigu, Antonella; Stockwell, Brent R; Strasser, Andreas; Szabadkai, Gyorgy; Tait, Stephen W G; Tang, Daolin; Tavernarakis, Nektarios; Thorburn, Andrew; Tsujimoto, Yoshihide; Turk, Boris; Vanden Berghe, Tom; Vandenabeele, Peter; Vander Heiden, Matthew G; Villunger, Andreas; Virgin, Herbert W; Vousden, Karen H; Vucic, Domagoj; Wagner, Erwin F; Walczak, Henning; Wallach, David; Wang, Ying; Wells, James A; Wood, Will; Yuan, Junying; Zakeri, Zahra; Zhivotovsky, Boris; Zitvogel, Laurence; Melino, Gerry; Kroemer, Guido

2018-03-01

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

A Dirichlet-Multinomial Bayes Classifier for Disease Diagnosis with Microbial Compositions.

PubMed

Gao, Xiang; Lin, Huaiying; Dong, Qunfeng

2017-01-01

Dysbiosis of microbial communities is associated with various human diseases, raising the possibility of using microbial compositions as biomarkers for disease diagnosis. We have developed a Bayes classifier by modeling microbial compositions with Dirichlet-multinomial distributions, which are widely used to model multicategorical count data with extra variation. The parameters of the Dirichlet-multinomial distributions are estimated from training microbiome data sets based on maximum likelihood. The posterior probability of a microbiome sample belonging to a disease or healthy category is calculated based on Bayes' theorem, using the likelihood values computed from the estimated Dirichlet-multinomial distribution, as well as a prior probability estimated from the training microbiome data set or previously published information on disease prevalence. When tested on real-world microbiome data sets, our method, called DMBC (for Dirichlet-multinomial Bayes classifier), shows better classification accuracy than the only existing Bayesian microbiome classifier based on a Dirichlet-multinomial mixture model and the popular random forest method. The advantage of DMBC is its built-in automatic feature selection, capable of identifying a subset of microbial taxa with the best classification accuracy between different classes of samples based on cross-validation. This unique ability enables DMBC to maintain and even improve its accuracy at modeling species-level taxa. The R package for DMBC is freely available at https://github.com/qunfengdong/DMBC. IMPORTANCE By incorporating prior information on disease prevalence, Bayes classifiers have the potential to estimate disease probability better than other common machine-learning methods. Thus, it is important to develop Bayes classifiers specifically tailored for microbiome data. Our method shows higher classification accuracy than the only existing Bayesian classifier and the popular random forest method, and thus provides an alternative option for using microbial compositions for disease diagnosis.

A human factors methodology for real-time support applications

NASA Technical Reports Server (NTRS)

Murphy, E. D.; Vanbalen, P. M.; Mitchell, C. M.

1983-01-01

A general approach to the human factors (HF) analysis of new or existing projects at NASA/Goddard is delineated. Because the methodology evolved from HF evaluations of the Mission Planning Terminal (MPT) and the Earth Radiation Budget Satellite Mission Operations Room (ERBS MOR), it is directed specifically to the HF analysis of real-time support applications. Major topics included for discussion are the process of establishing a working relationship between the Human Factors Group (HFG) and the project, orientation of HF analysts to the project, human factors analysis and review, and coordination with major cycles of system development. Sub-topics include specific areas for analysis and appropriate HF tools. Management support functions are outlined. References provide a guide to sources of further information.

Nuclear medicine technology progress report for quarter ending June 30, 1978. ABELLED COMPOUNDS; PATIENTS; POSITRON SOURCES; CARBON 11; ISOMERIC NUCLEI; LABELLED COMPOUNDS; BIOLOGICAL LOCALIZATION; CHEMICAL PREPARATION; ISOMERIC NUCLEI; LABELLED COMPOUNDS; RATS; CHEMICAL PREPARATION; LABELLED COMPOUNDS; RATS; TISSUE DISTRIBUTION

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

Knapp, Jr., F. F.

Progress is reported for the applications of /sup 11/C, /sup 195m/Pt, /sup 75/Se, and /sup 123m/Te. Additional human clinical trials with /sup 11/C-DL-tryptophan and /sup 11/C-l-aminocyclobutane carboxylic acid have been completed. The modified Buecherer-Strecker amino acid synthesis has been used to prepare /sup 11/C-DL-phenylglycine and /sup 11/C-DL-phenylalanine. These two new /sup 11/C-labeled amino acids will be studied as potential tumor localizing agents. Preliminary studies concerning the comparative organ and subcellular distribution of /sup 195m/Pt-labeled cis- and trans- dichlorodiamineplatinum(II) have been completed. The results of in vivo studies have shown the cis isomer to bind to nuclear DNA to a significantlymore » greater extent than the trans isomer. A series of /sup 123m/Te-labeled long-chain fatty acid analogs have been prepared as isosteres of unsaturated fatty acids. Several of these compounds show pronounced heart uptake in rats and may represent a new class of potential myocardial imaging agents. Studies on the preparation and tissue distribution of /sup 75/Se-..beta..-aminoethyl selenosulfate continue.« less

46 CFR 64.29 - Tank saddles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Tank saddles. 64.29 Section 64.29 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.29 Tank saddles. If a tank is not completely supported by a framework...

46 CFR 64.29 - Tank saddles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Tank saddles. 64.29 Section 64.29 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.29 Tank saddles. If a tank is not completely supported by a framework...

46 CFR 64.29 - Tank saddles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Tank saddles. 64.29 Section 64.29 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.29 Tank saddles. If a tank is not completely supported by a framework...

46 CFR 64.29 - Tank saddles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Tank saddles. 64.29 Section 64.29 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.29 Tank saddles. If a tank is not completely supported by a framework...

46 CFR 64.29 - Tank saddles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Tank saddles. 64.29 Section 64.29 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.29 Tank saddles. If a tank is not completely supported by a framework...

46 CFR 64.21 - Material.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Material. 64.21 Section 64.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.21 Material. The material for a tank must meet the requirements in...

46 CFR 64.21 - Material.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Material. 64.21 Section 64.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.21 Material. The material for a tank must meet the requirements in...

46 CFR 64.21 - Material.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Material. 64.21 Section 64.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.21 Material. The material for a tank must meet the requirements in...

46 CFR 64.21 - Material.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Material. 64.21 Section 64.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.21 Material. The material for a tank must meet the requirements in...

46 CFR 64.21 - Material.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Material. 64.21 Section 64.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.21 Material. The material for a tank must meet the requirements in...

46 CFR 64.33 - Pipe connection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.33 Pipe connection. Each pipe connection that is not a pressure relief device must be fitted with a manually operated stop valve or closure located as close to the tank...

Analysis of multinomial models with unknown index using data augmentation

USGS Publications Warehouse

Royle, J. Andrew; Dorazio, R.M.; Link, W.A.

2007-01-01

Multinomial models with unknown index ('sample size') arise in many practical settings. In practice, Bayesian analysis of such models has proved difficult because the dimension of the parameter space is not fixed, being in some cases a function of the unknown index. We describe a data augmentation approach to the analysis of this class of models that provides for a generic and efficient Bayesian implementation. Under this approach, the data are augmented with all-zero detection histories. The resulting augmented dataset is modeled as a zero-inflated version of the complete-data model where an estimable zero-inflation parameter takes the place of the unknown multinomial index. Interestingly, data augmentation can be justified as being equivalent to imposing a discrete uniform prior on the multinomial index. We provide three examples involving estimating the size of an animal population, estimating the number of diabetes cases in a population using the Rasch model, and the motivating example of estimating the number of species in an animal community with latent probabilities of species occurrence and detection.

Emotional Stroop interference for threatening words is related to reduced EEG δ-β coupling and low attentional control.

PubMed

Putman, Peter; Arias-Garcia, Elsa; Pantazi, Ioanna; van Schie, Charlotte

2012-05-01

Previously, electroencephalographic (EEG) delta-beta coupling (positive correlation between power in the fast beta and slow delta frequency bands) has been related to affective processing. For instance, differences in delta-beta coupling have been observed between people in a psychological stress condition and controls. We previously reported relationships between attentional threat processing and delta-beta coupling and individual differences in attentional control. The present study extended and replicated these findings in a large mixed gender sample (N=80). Results demonstrated that emotional Stroop task interference for threatening words was related to self-reported attentional inhibition capacity and frontal delta-beta coupling. There was no clear gender difference for delta-beta coupling (only a non-significant trend) and the relationship between delta-beta coupling and attentional threat-processing was not affected by gender. These results replicate and extend an earlier finding concerning delta-beta coupling and cognitive affect regulation and further clarify relationships between delta-beta coupling, attentional control, and threat-processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Estimation from incomplete multinomial data. Ph.D. Thesis - Harvard Univ.

NASA Technical Reports Server (NTRS)

Credeur, K. R.

1978-01-01

The vector of multinomial cell probabilities was estimated from incomplete data, incomplete in that it contains partially classified observations. Each such partially classified observation was observed to fall in one of two or more selected categories but was not classified further into a single category. The data were assumed to be incomplete at random. The estimation criterion was minimization of risk for quadratic loss. The estimators were the classical maximum likelihood estimate, the Bayesian posterior mode, and the posterior mean. An approximation was developed for the posterior mean. The Dirichlet, the conjugate prior for the multinomial distribution, was assumed for the prior distribution.

The analysis of the pilot's cognitive and decision processes

NASA Technical Reports Server (NTRS)

Curry, R. E.

1975-01-01

Articles are presented on pilot performance in zero-visibility precision approach, failure detection by pilots during automatic landing, experiments in pilot decision-making during simulated low visibility approaches, a multinomial maximum likelihood program, and a random search algorithm for laboratory computers. Other topics discussed include detection of system failures in multi-axis tasks and changes in pilot workload during an instrument landing.

A Process View on Implementing an Antibullying Curriculum: How Teachers Differ and What Explains the Variation

ERIC Educational Resources Information Center

Haataja, Anne; Ahtola, Annarilla; Poskiparta, Elisa; Salmivalli, Christina

2015-01-01

The present study provides a person-centered view on teachers' adherence to the KiVa antibullying curriculum over a school year. Factor mixture modeling was used to examine how teachers (N = 282) differed in their implementation profiles and multinomial logistic regression was used to identify factors related to these profiles. On the basis of…

Latent profile analysis of regression-based norms demonstrates relationship of compounding MS symptom burden and negative work events.

PubMed

Frndak, Seth E; Smerbeck, Audrey M; Irwin, Lauren N; Drake, Allison S; Kordovski, Victoria M; Kunker, Katrina A; Khan, Anjum L; Benedict, Ralph H B

2016-10-01

We endeavored to clarify how distinct co-occurring symptoms relate to the presence of negative work events in employed multiple sclerosis (MS) patients. Latent profile analysis (LPA) was utilized to elucidate common disability patterns by isolating patient subpopulations. Samples of 272 employed MS patients and 209 healthy controls (HC) were administered neuroperformance tests of ambulation, hand dexterity, processing speed, and memory. Regression-based norms were created from the HC sample. LPA identified latent profiles using the regression-based z-scores. Finally, multinomial logistic regression tested for negative work event differences among the latent profiles. Four profiles were identified via LPA: a common profile (55%) characterized by slightly below average performance in all domains, a broadly low-performing profile (18%), a poor motor abilities profile with average cognition (17%), and a generally high-functioning profile (9%). Multinomial regression analysis revealed that the uniformly low-performing profile demonstrated a higher likelihood of reported negative work events. Employed MS patients with co-occurring motor, memory and processing speed impairments were most likely to report a negative work event, classifying them as uniquely at risk for job loss.

Extracellular heat shock protein HSP90{beta} secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-{beta}1

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

Suzuki, Shigeki; Kulkarni, Ashok B., E-mail: ak40m@nih.gov

2010-07-30

Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-{beta} signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understandingmore » of the latent TGF-{beta} activation process. In this study, we have identified heat shock protein 90 {beta} (HSP90{beta}) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90{beta} into extracellular space which inhibits the activation of latent TGF-{beta}1, and that there is a subsequent decrease in cell proliferation. TGF-{beta}1-mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90{beta}. Thus, extracellular HSP90{beta} is a negative regulator for the activation of latent TGF-{beta}1 modulating TGF-{beta} signaling in the extracellular domain. -- Research highlights: {yields} Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex. {yields} This complex consists of latency-associated peptide (LAP) and the mature ligand. {yields} The release of the mature ligand from LAP is the first step in TGF-{beta} activation. {yields} We identified for the first time a novel mechanism for this activation process. {yields} Heat shock protein 90 {beta} is discovered as a negative regulator for this process.« less

Multinomial Logistic Regression Predicted Probability Map To Visualize The Influence Of Socio-Economic Factors On Breast Cancer Occurrence in Southern Karnataka

NASA Astrophysics Data System (ADS)

Madhu, B.; Ashok, N. C.; Balasubramanian, S.

2014-11-01

Multinomial logistic regression analysis was used to develop statistical model that can predict the probability of breast cancer in Southern Karnataka using the breast cancer occurrence data during 2007-2011. Independent socio-economic variables describing the breast cancer occurrence like age, education, occupation, parity, type of family, health insurance coverage, residential locality and socioeconomic status of each case was obtained. The models were developed as follows: i) Spatial visualization of the Urban- rural distribution of breast cancer cases that were obtained from the Bharat Hospital and Institute of Oncology. ii) Socio-economic risk factors describing the breast cancer occurrences were complied for each case. These data were then analysed using multinomial logistic regression analysis in a SPSS statistical software and relations between the occurrence of breast cancer across the socio-economic status and the influence of other socio-economic variables were evaluated and multinomial logistic regression models were constructed. iii) the model that best predicted the occurrence of breast cancer were identified. This multivariate logistic regression model has been entered into a geographic information system and maps showing the predicted probability of breast cancer occurrence in Southern Karnataka was created. This study demonstrates that Multinomial logistic regression is a valuable tool for developing models that predict the probability of breast cancer Occurrence in Southern Karnataka.

Expression mapping using a retroviral vector for CD8+ T cell epitopes: definition of a Mycobacterium tuberculosis peptide presented by H2-Dd.

PubMed

Aoshi, Taiki; Suzuki, Mina; Uchijima, Masato; Nagata, Toshi; Koide, Yukio

2005-03-01

Identification of CD8+ T cell epitopes is important because detection of specific CD8+ T cells after infection or immunization requires prior knowledge of epitope specificity. Furthermore, identification of CD8+ T cell epitopes permits the development of specific preventive and therapeutic approaches to both infections and tumors. Thus far, CD8+ T cell epitopes have been identified either using an overlapping peptide library covering an entire protein, or using algorithms designed to identify likely peptides that bind to major histocompatibility complex (MHC) class I molecules. The synthesis of overlapping peptides can be prohibitively expensive, and the algorithm programs used to predict CD8+ T cell epitopes are not always accurate. Here we describe a retroviral expression system that specifically allows longer polypeptides and shorter peptides to be expressed in the cytoplasm, and thereby to be processed onto class I MHC molecules. T cells from mice that were immunized with a DNA vaccine encoding MPT-51 were probed against MHC-compatible cell lines retrovirally transduced with overlapping gene fragments encoding 120-140 amino acids of the MPT-51 molecule. After further testing of shorter peptide sequences, we identified a CD8+ T cell epitope using cell lines expressing a relatively small number of algorithm-predicted candidate epitopes. We found that one of the requirements for cell surface display of the 20-mer peptide was the need for cotranslational ubiquitination. The restriction molecule was identified as Dd following transduction with MHC class I genes followed by transduction with the oligonucleotide encoding the epitope. The retroviral expression system described here is cost-effective, particularly if the target molecule is large, and could be adapted to identifying T cell epitopes recognized in infectious disease and against tumor cell antigens.

Design and intestinal mucus penetration mechanism of core-shell nanocomplex.

PubMed

Zhang, Xin; Cheng, Hongbo; Dong, Wei; Zhang, Meixia; Liu, Qiaoyu; Wang, Xiuhua; Guan, Jian; Wu, Haiyang; Mao, Shirui

2018-02-28

The objective of this study was to design intestinal mucus-penetrating core-shell nanocomplex by functionally mimicking the surface of virus, which can be used as the carrier for peroral delivery of macromolecules, and further understand the influence of nanocomplex surface properties on the mucosal permeation capacity. Taking insulin as a model drug, the core was formed by the self-assembly among positively charged chitosan, insulin and negatively charged sodium tripolyphosphate, different types of alginates were used as the shell forming material. The nanocomplex was characterized by dynamic light scattering (DLS), atomic force microscopy (AFM) and FTIR. Nanocomplex movement in mucus was recorded using multiple particle tracking (MPT) method. Permeation and uptake of different nanocomplex were studied in rat intestine. It was demonstrated that alginate coating layer was successfully formed on the core and the core-shell nanocomplex showed a good physical stability and improved enzymatic degradation protection. The mucus penetration and MPT study showed that the mucus penetration capacity of the nanocomplex was surface charge and coating polymer structure dependent, nanocomplex with negative alginate coating had 1.6-2.5 times higher mucus penetration ability than that of positively charged chitosan-insulin nanocomplex. Moreover, the mucus penetration ability of the core-shell nanocomplex was alginate structure dependent, whereas alginate with lower G content and lower molecular weight showed the best permeation enhancing ability. The improvement of intestine permeation and intestinal villi uptake of the core-shell nanocomplex were further confirmed in rat intestine and multiple uptake mechanisms were involved in the transport process. In conclusion, core-shell nanocomplex composed of oppositely charged materials could provide a strategy to overcome the mucus barrier and enhance the mucosal permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

Beta-decay spectroscopy relevant to the r-process nucleosynthesis

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

Nishimura, Shunji; Collaboration: RIBF Decay Collaboration

2012-11-12

A scientific program of beta-decay spectroscopy relevant to r-process nucleosynthesis has been started using high intensity U-beam at the RIBF. The first results of {beta}-decay half-lives of very neutron-rich Kr to Tc nuclides, all of which lie close to the r-process path, suggest a systematic enhancement of the the {beta}-decay rates of the Zr and Nb isotopes around A110 with respect to the predictions of the deformed quasiparticle-random-phase-approximation model (FRDM + QRPA). An impact of the results on the astrophysical r-process is discussed together with the future perspective of the {beta}-decay spectroscopy with the EURICA.

An investigation on fatality of drivers in vehicle-fixed object accidents on expressways in China: Using multinomial logistic regression model.

PubMed

Peng, Yong; Peng, Shuangling; Wang, Xinghua; Tan, Shiyang

2018-06-01

This study aims to identify the effects of characteristics of vehicle, roadway, driver, and environment on fatality of drivers in vehicle-fixed object accidents on expressways in Changsha-Zhuzhou-Xiangtan district of Hunan province in China by developing multinomial logistic regression models. For this purpose, 121 vehicle-fixed object accidents from 2011-2017 are included in the modeling process. First, descriptive statistical analysis is made to understand the main characteristics of the vehicle-fixed object crashes. Then, 19 explanatory variables are selected, and correlation analysis of each two variables is conducted to choose the variables to be concluded. Finally, five multinomial logistic regression models including different independent variables are compared, and the model with best fitting and prediction capability is chosen as the final model. The results showed that the turning direction in avoiding fixed objects raised the possibility that drivers would die. About 64% of drivers died in the accident were found being ejected out of the car, of which 50% did not use a seatbelt before the fatal accidents. Drivers are likely to die when they encounter bad weather on the expressway. Drivers with less than 10 years of driving experience are more likely to die in these accidents. Fatigue or distracted driving is also a significant factor in fatality of drivers. Findings from this research provide an insight into reducing fatality of drivers in vehicle-fixed object accidents.

Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects

EPA Science Inventory

Past epidemiologic studies suggest maternal ambient air pollution exposure during critical periods of the pregnancy is associated with fetal development. We introduce a multinomial probit model that allows for the joint identification of susceptible daily periods during the pregn...

Pig Data and Bayesian Inference on Multinomial Probabilities

ERIC Educational Resources Information Center

Kern, John C.

2006-01-01

Bayesian inference on multinomial probabilities is conducted based on data collected from the game Pass the Pigs[R]. Prior information on these probabilities is readily available from the instruction manual, and is easily incorporated in a Dirichlet prior. Posterior analysis of the scoring probabilities quantifies the discrepancy between empirical…

Beta-decay half-lives for short neutron rich nuclei involved into the r-process

NASA Astrophysics Data System (ADS)

Panov, I.; Lutostansky, Yu; Thielemann, F.-K.

2018-01-01

The beta-strength function model based on Finite Fermi-Systems Theory is applied for calculations of the beta-decay half-lives for short neutron rich nuclei involved into the r- process. It is shown that the accuracy of beta-decay half-lives of short-lived neutron-rich nuclei is improving with increasing neutron excess and can be used for modeling of nucleosynthesis of heavy nuclei in the r-process.

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.15 - Allowable stress; framework.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Allowable stress; framework. 64.15 Section 64.15... AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.15 Allowable stress; framework. The calculated stress for the framework must be 80 percent or less of the minimum yield stress of the framework material...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.15 - Allowable stress; framework.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Allowable stress; framework. 64.15 Section 64.15... AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.15 Allowable stress; framework. The calculated stress for the framework must be 80 percent or less of the minimum yield stress of the framework material...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.15 - Allowable stress; framework.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Allowable stress; framework. 64.15 Section 64.15... AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.15 Allowable stress; framework. The calculated stress for the framework must be 80 percent or less of the minimum yield stress of the framework material...

46 CFR 64.15 - Allowable stress; framework.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Allowable stress; framework. 64.15 Section 64.15... AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.15 Allowable stress; framework. The calculated stress for the framework must be 80 percent or less of the minimum yield stress of the framework material...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.5 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEMS General § 64.5 Definitions. As used in this part: (a) Marine portable tank or MPT means a liquid... consisting of the absolute vapor pressure of the product at 122 °F added to the dynamic pressure, based on... maximum allowable working pressure. (f) Dynamic loading conditions means the following: (1) A loading in...

46 CFR 64.41 - Stop valve closure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Stop valve closure. 64.41 Section 64.41 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.41 Stop valve closure. A stop valve that operates by a screwed...

46 CFR 64.15 - Allowable stress; framework.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Allowable stress; framework. 64.15 Section 64.15... AND CARGO HANDLING SYSTEMS Standards for an MPT § 64.15 Allowable stress; framework. The calculated stress for the framework must be 80 percent or less of the minimum yield stress of the framework material...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

A Markov Model for Forecasting Inventory Levels for U.S Navy Medical Service Corps Healthcare Administrators

DTIC Science & Technology

2014-03-01

Administration, Medical Allied Sciences, Optometry , and Pharmacy. Today, the MSC comprises 31 subspecialties, organized under three major categories...Exper Psych 30 4% Clinical Dietetics 26 3% Financial Mgt 78 8% Research Psych 17 3% Optometry 109 11% MPT&E 31 3% Entomology 39 6% Pharmacy, General 136

Transmission and scattering of acoustic energy in turbulent flows

NASA Astrophysics Data System (ADS)

Gaitonde, Datta; Unnikrishnan, S.

2017-11-01

Sound scattering and transmission in turbulent jets are explored through a control volume analysis of a Large-Eddy Simulation. The fluctuating momentum flux across any control surface is first split into its rotational turbulent ((ρu)'H) and the irrotational-isentropic acoustic ((ρu)'A) components using momentum potential theory (MPT). The former has low spatio-temporal coherence, while the latter exhibits a persistent wavepacket form. The energy variable, specifically, total fluctuating enthalpy, is also split into its turbulent and acoustic modes, HH' and HA' respectively. Scattering of acoustic energy is then (ρu)'HHA' , and transmission is (ρu)'AHA' . This facilitates a quantitative comparison of scattering versus transmission in the presence of acoustic energy sources, also obtained from MPT, in any turbulent scenario. The wavepacket converts stochastic sound sources into coherent sound radiation. Turbulent eddies are not only sources of sound, but also play a strong role in scattering, particularly near the lipline. The net acoustic flux from the jet is the transport of HA' by the wavepacket, whose axisymmetric and higher azimuthal modes contribute to downstream and sideline radiation respectively.

Ultrasensitive electrochemical immunosensors for multiplexed determination using mesoporous platinum nanoparticles as nonenzymatic labels.

PubMed

Cui, Zhentao; Wu, Dan; Zhang, Yong; Ma, Hongmin; Li, He; Du, Bin; Wei, Qin; Ju, Huangxian

2014-01-07

An ultrasensitive multiplexed immunoassay method was developed at a disposable immunosensor array using mesoporous platinum nanoparticles (M-Pt NPs) as nonenzymatic labels. M-Pt NPs were prepared by ultrasonic method and employed to label the secondary antibody (Ab2) for signal amplification. The immunosensor array was constructed by covalently immobilizing capture antibody (Ab1) on graphene modified screen printed carbon electrodes (SPECs). After the sandwich-type immunoreactions, the M-Pt-Ab2 was bound to immunosensor surface to catalyze the electro-reduction of H2O2 reaction, which produced detectable signals for readout of analytes. Using breast cancer related panel of tumor markers (CA125, CA153 and CEA) as model analytes, this method showed wide linear ranges of over 4 orders of magnitude with the detection limits of 0.002 U mL(-1), 0.001 U mL(-1) and 7.0 pg mL(-1) for CA125, CA153 and CEA, respectively. The disposable immunosensor array possessed excellent clinical value in cancer screening as well as convenient point of care diagnostics. Copyright © 2013 Elsevier B.V. All rights reserved.

Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames.

PubMed Central

Stallmeyer, B; Drugeon, G; Reiss, J; Haenni, A L; Mendel, R R

1999-01-01

A universal molybdenum-containing cofactor (MoCo) is essential for the activity of all human molybdoenzymes, including sulphite oxidase. The free cofactor is highly unstable, and all organisms share a similar biosynthetic pathway. The involved enzymes exhibit homologies, even between bacteria and humans. We have exploited these homologies to isolate a cDNA for the heterodimeric molybdopterin (MPT)-synthase. This enzyme is necessary for the conversion of an unstable precursor into molybdopterin, the organic moiety of MoCo. The corresponding transcript shows a bicistronic structure, encoding the small and large subunits of the MPT-synthase in two different open reading frames (ORFs) that overlap by 77 nucleotides. In various human tissues, only one size of mRNA coinciding with the bicistronic transcript was detected. In vitro translation and mutagenesis experiments demonstrated that each ORF is translated independently, leading to the synthesis of a 10-kDa protein and a 21-kDa protein for the small and large subunits, respectively, and indicated that the 3'-proximal ORF of the bicistronic transcript is translated by leaky scanning. PMID:10053003

On the development of a semi-nonparametric generalized multinomial logit model for travel-related choices

PubMed Central

Ye, Xin; Pendyala, Ram M.; Zou, Yajie

2017-01-01

A semi-nonparametric generalized multinomial logit model, formulated using orthonormal Legendre polynomials to extend the standard Gumbel distribution, is presented in this paper. The resulting semi-nonparametric function can represent a probability density function for a large family of multimodal distributions. The model has a closed-form log-likelihood function that facilitates model estimation. The proposed method is applied to model commute mode choice among four alternatives (auto, transit, bicycle and walk) using travel behavior data from Argau, Switzerland. Comparisons between the multinomial logit model and the proposed semi-nonparametric model show that violations of the standard Gumbel distribution assumption lead to considerable inconsistency in parameter estimates and model inferences. PMID:29073152

On the development of a semi-nonparametric generalized multinomial logit model for travel-related choices.

PubMed

Wang, Ke; Ye, Xin; Pendyala, Ram M; Zou, Yajie

2017-01-01

A semi-nonparametric generalized multinomial logit model, formulated using orthonormal Legendre polynomials to extend the standard Gumbel distribution, is presented in this paper. The resulting semi-nonparametric function can represent a probability density function for a large family of multimodal distributions. The model has a closed-form log-likelihood function that facilitates model estimation. The proposed method is applied to model commute mode choice among four alternatives (auto, transit, bicycle and walk) using travel behavior data from Argau, Switzerland. Comparisons between the multinomial logit model and the proposed semi-nonparametric model show that violations of the standard Gumbel distribution assumption lead to considerable inconsistency in parameter estimates and model inferences.

Influence of food acidulants and antioxidant spices on the bioaccessibility of beta-carotene from selected vegetables.

PubMed

Veda, Supriya; Platel, Kalpana; Srinivasan, Krishnapura

2008-09-24

Four common food acidulants--amchur, lime, tamarind, and kokum--and two antioxidant spices--turmeric and onion--were examined for their influence on the bioaccessibility of beta-carotene from two fleshy and two leafy vegetables. Amchur and lime generally enhanced the bioaccessibility of beta-carotene from these test vegetables in many instances. Such an improved bioaccessibility was evident in both raw and heat-processed vegetables. The effect of lime juice was generally more pronounced than that of amchur. Turmeric significantly enhanced the bioaccessibility of beta-carotene from all of the vegetables tested, especially when heat-processed. Onion enhanced the bioaccessibility of beta-carotene from pressure-cooked carrot and amaranth leaf and from open-pan-boiled pumpkin and fenugreek leaf. Lime juice and the antioxidant spices turmeric and onion minimized the loss of beta-carotene during heat processing of the vegetables. In the case of antioxidant spices, improved bioaccessibility of beta-carotene from heat-processed vegetables is attributable to their role in minimizing the loss of this provitamin. Lime juice, which enhanced the bioaccessibility of this provitamin from both raw and heat-processed vegetables, probably exerted this effect by some other mechanism in addition to minimizing the loss of beta-carotene. Thus, the presence of food acidulants (lime juice/amchur) and antioxidant spices (turmeric/onion) proved to be advantageous in the context of deriving maximum beta-carotene from the vegetable sources.

A General Family of Limited Information Goodness-of-Fit Statistics for Multinomial Data

ERIC Educational Resources Information Center

Joe, Harry; Maydeu-Olivares, Alberto

2010-01-01

Maydeu-Olivares and Joe (J. Am. Stat. Assoc. 100:1009-1020, "2005"; Psychometrika 71:713-732, "2006") introduced classes of chi-square tests for (sparse) multidimensional multinomial data based on low-order marginal proportions. Our extension provides general conditions under which quadratic forms in linear functions of cell residuals are…

Institutional Climate and Student Departure: A Multinomial Multilevel Modeling Approach

ERIC Educational Resources Information Center

Yi, Pyong-sik

2008-01-01

This study applied a multinomial HOLM technique to examine the extent to which the institutional climate for diversity influences the different types of college student withdrawal, such as stop out, drop out, and transfer. Based on a reformulation of Tinto's model along with the conceptualization of institutional climate for diversity by Hurtado…

Modeling Polytomous Item Responses Using Simultaneously Estimated Multinomial Logistic Regression Models

ERIC Educational Resources Information Center

Anderson, Carolyn J.; Verkuilen, Jay; Peyton, Buddy L.

2010-01-01

Survey items with multiple response categories and multiple-choice test questions are ubiquitous in psychological and educational research. We illustrate the use of log-multiplicative association (LMA) models that are extensions of the well-known multinomial logistic regression model for multiple dependent outcome variables to reanalyze a set of…

Redintegration and the Benefits of Long-Term Knowledge in Verbal Short-Term Memory: An Evaluation of Schweickert's (1993) Multinomial Processing Tree Model

ERIC Educational Resources Information Center

Thorn, Annabel S. C.; Gathercole, Susan E.; Frankish, Clive R.

2005-01-01

The impact of four long-term knowledge variables on serial recall accuracy was investigated. Serial recall was tested for high and low frequency words and high and low phonotactic frequency nonwords in 2 groups: monolingual English speakers and French-English bilinguals. For both groups the recall advantage for words over nonwords reflected more…

Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis

PubMed Central

Qi, Guo-Yan; Liu, Peng

2013-01-01

Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721

STEPS at CSUN: Increasing Retention of Engineering and Physical Science Majors

NASA Astrophysics Data System (ADS)

Pedone, V. A.; Cadavid, A. C.; Horn, W.

2012-12-01

STEPS at CSUN seeks to increase the retention rate of first-time freshman in engineering, math, and physical science (STEM) majors from ~55% to 65%. About 40% of STEM first-time freshmen start in College Algebra because they do not take or do not pass the Mathematics Placement Test (MPT). This lengthens time to graduation, which contributes to dissatisfaction with major. STEPS at CSUN has made substantial changes to the administration of the MPT. Initial data show increases in the number of students who take the test and who place out of College Algebra, as well as increases in overall scores. STEPS at CSUN also funded the development of supplemental labs for Trigonometry and Calculus I and II, in partnership with similar labs created by the Math Department for College Algebra and Precalculus. These labs are open to all students, but are mandatory for at-risk students who have low scores on the MPT, low grades in the prerequisite course, or who failed the class the first time. Initial results are promising. Comparison of the grades of 46 Fall 2010 "at-risk" students without lab to those of 36 Fall 2011 students who enrolled in the supplementary lab show D-F grades decreased by 10% and A-B grades increased by 27%. A final retention strategy is aimed at students in the early stages of their majors. At CSUN the greatest loss of STEM majors occurs between sophomore-level and junior-level coursework because course difficulty increases and aspirations to potential careers weaken. The Summer Interdisciplinary Team Experience (SITE) is an intensive 3-week-long summer program that engages small teams of students from diverse STEM majors in faculty-mentored, team-based problem solving. This experience simulates professional work and creates strong bonds between students and between students and faculty mentors. The first two cohorts of students who have participated in SITE indicate that this experience has positively impacted their motivation to complete their STEM degree.

Lenticular mitoprotection. Part A: Monitoring mitochondrial depolarization with JC-1 and artifactual fluorescence by the glycogen synthase kinase-3β inhibitor, SB216763.

PubMed

Brooks, Morgan M; Neelam, Sudha; Fudala, Rafal; Gryczynski, Ignacy; Cammarata, Patrick R

2013-01-01

Dissipation of the electrochemical gradient across the inner mitochondrial membrane results in mitochondrial membrane permeability transition (mMPT), a potential early marker for the onset of apoptosis. In this study, we demonstrate a role for glycogen synthase kinase-3β (GSK-3β) in regulating mMPT. Using direct inhibition of GSK-3β with the GSK-3β inhibitor SB216763, mitochondria may be prevented from depolarizing (hereafter referred to as mitoprotection). Cells treated with SB216763 showed an artifact of fluorescence similar to the green emission spectrum of the JC-1 dye. We demonstrate the novel use of spectral deconvolution to negate the interfering contributing fluorescence by SB216763, thus allowing an unfettered analysis of the JC-1 dye to determine the mitochondrial membrane potential. Secondary cultures of virally transfected human lens epithelial cells (HLE-B3) were exposed to acute hypoxic conditions (approximately 1% O₂) followed by exposure to atmospheric oxygen (approximately 21% O₂). The fluorescent dye JC-1 was used to monitor the extent of mitochondrial depolarization upon exposure of inhibitor treatment relative to the control cells (mock inhibition) in atmospheric oxygen. Annexin V-fluorescein isothiocyanate/propidium iodide staining was implemented to determine cell viability. Treatment of HLE-B3 cells with SB216763 (12 µM), when challenged by oxidative stress, suppressed mitochondrial depolarization relative to control cells as demonstrated with JC-1 fluorescent dye analysis. Neither the control nor the SB216763-treated HLE-B3 cells tested positive with annexin V-fluorescein isothiocyanate/propidium iodide staining under the conditions of the experiment. Inhibition of GSK-3β activity by SB216763 blocked mMPT relative to the slow but consistent depolarization observed with the control cells. We conclude that inhibition of GSK-3β activity by the GSK-3β inhibitor SB216763 provides positive protection against mitochondrial depolarization.

The Atlantic Meridional Overturning Circulation over time: a Nd isotope perspective

NASA Astrophysics Data System (ADS)

Goldstein, S. L.; Pena, L. D.; Yehudai, M.; Seguí, M. J.; Kim, J.; Knudson, K. P.; Basak, C.

2017-12-01

The Atlantic Meridional Overturning Circulation (AMOC) is a major means for distributing heat between the tropics and the high latitudes, and thus its temporal variability has major impacts on ice age cycles. We present a summary of work in-progress to generate north-south profiles of the AMOC from the North Atlantic to the Southern Ocean, at various time slices over the past 2 Ma, based on Nd isotopes in Fe-Mn oxide encrusted foraminifera and fish debris. Our sites show a consistent north-south gradient in the North Atlantic source water (NSW) signal strength throughout, providing strong evidence that the data represent the fluctuations of the AMOC. The North Atlantic data show strong evidence that the eNd of the NSW end-member remained similar to today through this time interval (Kim et al. this meeting). We have identified 5 modes of the AMOC circulation. The most common ones are the (1) "interglacial norm" where the NSW signal remains strong into the South Atlantic similar to the present-day, and the (2) "glacial norm" where moderate southern source water (SSW) signals extend into the deep North Atlantic. Less common are the (3) "weak AMOC" mode, typical of Heinrich events, the Mid-Pleistocene Transition (MPT), and MIS 10,16, where even the deep North Atlantic shows a strong SSW signal, and its counterpart the (4) "ultra-strong AMOC", in MIS 9, 11, 19, 21 and 25, when the NSW signal is unusually strong south of the equator. Finally, during the (5) "pre-MPT" mode, in MIS 26 and 27, uniquely low Nd isotope ratios in the North Atlantic signals major input of Nd from the Canadian Shield directly preceding the MPT AMOC crisis (Pena and Goldstein, Science 2014), reflecting events there that likely triggered it. Overall we expect that the AMOC profiles will be useful as a means to directly relate climate to concurrent ocean circulation through time.

Assessing Deep Ocean Carbon Storage Across the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Haynes, L.; Hoenisch, B.; Farmer, J. R.; Ford, H. L.; Raymo, M. E.; Yehudai, M.; Goldstein, S. L.; Pena, L. D.; Bickert, T.

2017-12-01

The Mid-Pleistocene Transition (MPT) was a profound reorganization of the climate system between 0.8 to 1.2 million years ago (Ma) that led to the establishment of 100 thousand year (kyr)-paced glacial cycles. At the midpoint of the transition at around 900 ka (the "900 ka event"), observations of a globally synchronous decrease in benthic δ13C suggest a large-scale perturbation to the oceanic carbon cycle. While the cause of the MPT remains elusive, recent geochemical evidence suggests that this δ13C minimum was concurrent with an increased presence of Southern Sourced Waters (SSW) in the South Atlantic, a decrease in Δ[CO32-] in the deep North Atlantic, and a decrease in glacial atmospheric CO2, pointing to increased carbon storage in the deep ocean as a possible amplifier for glacial intensification. Here we utilize the B/Ca proxy for carbonate saturation ( Δ[CO32-]) in the benthic foraminifer C. wuellerstorfi to investigate the storage of carbon in the deep western equatorial Atlantic at ODP sites 925 and 926 (3040 and 3590 m water depths, respectively). Reconstructed Δ[CO32-] covaries with benthic δ13C and follows the slope anticipated from the Redfield relationship predicted from organic matter degradation, suggesting control of respired CO2 content on the deep ocean's saturation state. Data spanning the 900-ka event suggest a decrease in minimum Δ[CO32-] of deep waters during glacial periods, concurrent with the documented expansion of SSW as captured by records of ɛNd. The coherence between shifts in δ13C, ɛNd, and Δ[CO32-] point to ocean circulation as a partial driver for increased oceanic CO2 storage. Comparison of Atlantic data to new records from the deep Pacific will explore the consequences of weakening Atlantic overturning across the MPT for CO2 storage in this expansive deep ocean reservoir.

The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease.

PubMed

King, Adrienne L; Mantena, Sudheer K; Andringa, Kelly K; Millender-Swain, Telisha; Dunham-Snary, Kimberly J; Oliva, Claudia R; Griguer, Corinne E; Bailey, Shannon M

2016-10-01

Mitochondrial dysfunction and bioenergetic stress play an important role in the etiology of alcoholic liver disease. Previous studies from our laboratory show that the primary methyl donor S-Adenosylmethionine (SAM) minimizes alcohol-induced disruptions in several mitochondrial functions in the liver. Herein, we expand on these earlier observations to determine whether the beneficial actions of SAM against alcohol toxicity extend to changes in the responsiveness of mitochondrial respiration to inhibition by nitric oxide (NO), induction of the mitochondrial permeability transition (MPT) pore, and the hypoxic state of the liver. For this, male Sprague-Dawley rats were pair-fed control and alcohol-containing liquid diets with and without SAM for 5 weeks and liver hypoxia, mitochondrial respiration, MPT pore induction, and NO-dependent control of respiration were examined. Chronic alcohol feeding significantly enhanced liver hypoxia, whereas SAM supplementation attenuated hypoxia in livers of alcohol-fed rats. SAM supplementation prevented alcohol-mediated decreases in mitochondrial state 3 respiration and cytochrome c oxidase activity. Mitochondria isolated from livers of alcohol-fed rats were more sensitive to calcium-mediated MPT pore induction (i.e., mitochondrial swelling) than mitochondria from pair-fed controls, whereas SAM treatment normalized sensitivity for calcium-induced swelling in mitochondria from alcohol-fed rats. Liver mitochondria from alcohol-fed rats showed increased sensitivity to NO-dependent inhibition of respiration compared with pair-fed controls. In contrast, mitochondria isolated from the livers of SAM treated alcohol-fed rats showed no change in the sensitivity to NO-mediated inhibition of respiration. Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the attenuation of hypoxic stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Identification of a lineage specific zinc responsive genomic island in Mycobacterium avium ssp. paratuberculosis.

PubMed

Eckelt, Elke; Jarek, Michael; Frömke, Cornelia; Meens, Jochen; Goethe, Ralph

2014-12-06

Maintenance of metal homeostasis is crucial in bacterial pathogenicity as metal starvation is the most important mechanism in the nutritional immunity strategy of host cells. Thus, pathogenic bacteria have evolved sensitive metal scavenging systems to overcome this particular host defence mechanism. The ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) displays a unique gut tropism and causes a chronic progressive intestinal inflammation. MAP possesses eight conserved lineage specific large sequence polymorphisms (LSP), which distinguish MAP from its ancestral M. avium ssp. hominissuis or other M. avium subspecies. LSP14 and LSP15 harbour many genes proposed to be involved in metal homeostasis and have been suggested to substitute for a MAP specific, impaired mycobactin synthesis. In the present study, we found that a LSP14 located putative IrtAB-like iron transporter encoded by mptABC was induced by zinc but not by iron starvation. Heterologous reporter gene assays with the lacZ gene under control of the mptABC promoter in M. smegmatis (MSMEG) and in a MSMEG∆furB deletion mutant revealed a zinc dependent, metalloregulator FurB mediated expression of mptABC via a conserved mycobacterial FurB recognition site. Deep sequencing of RNA from MAP cultures treated with the zinc chelator TPEN revealed that 70 genes responded to zinc limitation. Remarkably, 45 of these genes were located on a large genomic island of approximately 90 kb which harboured LSP14 and LSP15. Thirty-five of these genes were predicted to be controlled by FurB, due to the presence of putative binding sites. This clustering of zinc responsive genes was exclusively found in MAP and not in other mycobacteria. Our data revealed a particular genomic signature for MAP given by a unique zinc specific locus, thereby suggesting an exceptional relevance of zinc for the metabolism of MAP. MAP seems to be well adapted to maintain zinc homeostasis which might contribute to the peculiarity of MAP pathogenicity.

Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

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

Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun

Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake wasmore » measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective tetracyclines protect by inhibiting the MCU.« less

Comparison of multinomial logistic regression and logistic regression: which is more efficient in allocating land use?

NASA Astrophysics Data System (ADS)

Lin, Yingzhi; Deng, Xiangzheng; Li, Xing; Ma, Enjun

2014-12-01

Spatially explicit simulation of land use change is the basis for estimating the effects of land use and cover change on energy fluxes, ecology and the environment. At the pixel level, logistic regression is one of the most common approaches used in spatially explicit land use allocation models to determine the relationship between land use and its causal factors in driving land use change, and thereby to evaluate land use suitability. However, these models have a drawback in that they do not determine/allocate land use based on the direct relationship between land use change and its driving factors. Consequently, a multinomial logistic regression method was introduced to address this flaw, and thereby, judge the suitability of a type of land use in any given pixel in a case study area of the Jiangxi Province, China. A comparison of the two regression methods indicated that the proportion of correctly allocated pixels using multinomial logistic regression was 92.98%, which was 8.47% higher than that obtained using logistic regression. Paired t-test results also showed that pixels were more clearly distinguished by multinomial logistic regression than by logistic regression. In conclusion, multinomial logistic regression is a more efficient and accurate method for the spatial allocation of land use changes. The application of this method in future land use change studies may improve the accuracy of predicting the effects of land use and cover change on energy fluxes, ecology, and environment.

Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis.

PubMed

Habers, G Esther A; Huber, Adam M; Mamyrova, Gulnara; Targoff, Ira N; O'Hanlon, Terrance P; Adams, Sharon; Pandey, Janardan P; Boonacker, Chantal; van Brussel, Marco; Miller, Frederick W; van Royen-Kerkhof, Annet; Rider, Lisa G

2016-03-01

To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs). Univariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms. Multivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis-specific autoantibodies (multinomial odds ratio [OR] 4.2 and 2.8, respectively), myositis-associated autoantibodies (multinomial OR 4.8 and 3.5), and a documented infection within 6 months of illness onset (multinomial OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to a polycyclic course. Furthermore, severe illness onset was associated with a chronic course compared to monocyclic or polycyclic courses (multinomial OR 2.1 and 2.6, respectively), while anti-p155/140 autoantibodies were associated with chronic or polycyclic courses compared to a monocyclic course (multinomial OR 3.9 and 2.3, respectively). Additional univariable associations of a chronic course compared to a monocyclic course included photosensitivity, V-sign or shawl sign rashes, and cuticular overgrowth (OR 2.2-3.2). The mean ultraviolet index and highest ultraviolet index in the month before diagnosis were associated with a chronic course compared to a polycyclic course in boys (OR 1.5 and 1.3), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2). Our findings indicate that myositis autoantibodies, in particular anti-p155/140, and a number of early clinical features and environmental exposures are associated with a chronic course in patients with juvenile IIM. These findings suggest that early factors, which are associated with poorer outcomes in juvenile IIM, can be identified. © 2016, American College of Rheumatology.

FBIS report. Science and technology: Japan, December 10, 1996

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

NONE

1996-12-10

Contents (partial): Japan: Fabrication of Diamond Single Crystal Thin Film by Ion Beam Deposition; Japan: Hitachi Metal Develops New Semi Solid Metal Processing Technology; Japan: NTT Develops Fuel Cell System That Uses Both City Gas, LPG; Japan: Daihatsu Motor Completes Prototype EV; Japan: NIRIM Announces Success With Synthetic Bone Development; Japan: Sandoz Pharmaceuticals Plans Clinical Trials of Gene Therapy to Cerebral Tumor in Japan; Japan: MITI To Provide Aid for Residential Solar Power Generation Systems; Japan: MELCO To Provide Satellite Solar Cell Panel for SSL, USA; Japan: Japan Atomic Energy Research Institute Leads Nuclear Research; Japan: Kobe Steel`s Superconducting Magnetmore » Ready to Go Fast; Japan: MPT To Begin Validation Test for Electric Money Implementation; and Japan: Defense Agency to Send ASDF`s Pilots to Russia for Training.« less

Location specific solidification microstructure control in electron beam melting of Ti-6Al-4V

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

Narra, Sneha P.; Cunningham, Ross; Beuth, Jack

Relationships between prior beta grain size in solidified Ti-6Al-4V and melting process parameters in the Electron Beam Melting (EBM) process are investigated. Samples are built by varying a machine-dependent proprietary speed function to cover the process space. Optical microscopy is used to measure prior beta grain widths and assess the number of prior beta grains present in a melt pool in the raster region of the build. Despite the complicated evolution of beta grain sizes, the beta grain width scales with melt pool width. The resulting understanding of the relationship between primary machine variables and prior beta grain widths ismore » a key step toward enabling the location specific control of as-built microstructure in the EBM process. Control of grain width in separate specimens and within a single specimen is demonstrated.« less

Composite Linear Models | Division of Cancer Prevention

Cancer.gov

By Stuart G. Baker The composite linear models software is a matrix approach to compute maximum likelihood estimates and asymptotic standard errors for models for incomplete multinomial data. It implements the method described in Baker SG. Composite linear models for incomplete multinomial data. Statistics in Medicine 1994;13:609-622. The software includes a library of thirty

Wide distribution of genes for tetrahydromethanopterin/methanofuran-linked C1 transfer reactions argues for their presence in the common ancestor of bacteria and archaea

DOE PAGES

Chistoserdova, Ludmila

2016-09-13

In this opinion study, I wish to highlight the fact that reactions linked to tetrahydromethanopterin (H 4MPT) and methanofuran (MF), the ones involved in methanogenesis as well as in methylotrophy, are much more widespread among both Bacteria and Archaea than originally thought.

Review of Literature on Probability of Detection for Magnetic Particle Nondestructive Testing

DTIC Science & Technology

2013-01-01

4 3.2 Offshore welded structures..................................................................................... 8 3.3 Aerospace...presented in Section 6. 2. Overview of Magnetic Particle Testing MPT is used in heavy engineering to inspect welds for surface-breaking... welded structures, and concluding with a summary of reliability information embedded in aerospace standards. 3.1 Aerospace It appears that the

An Analysis of Human Resource Officers in Support of MPT&E Enterprise Management: A Succession Management Plan for Human Capital Managers

DTIC Science & Technology

2007-09-01

creating incentives to motivate and cultivate an atmosphere of constant progress. This is often referred to as “ kaizen ,” the Japanese concept of...improvement, mainly to jumpstart the moribund Japanese industrial system. Eventually, this gave rise to the kaizen revolution and the concept was quickly

Associations between the home environment and children's sweet beverage consumption at 2-year follow-up: the 'Be active, eat right' study.

PubMed

van Grieken, A; Renders, C M; van de Gaar, V M; Hirasing, R A; Raat, H

2015-04-01

This study evaluates the association between home environmental characteristics and sweet beverage consumption (i.e. beverages that contain sugar) of 7-year-old children. The population for analysis consisted of n = 2047 parents and their children from the population-based 'Be active, eat right' study. Data on sociodemographic characteristics, parental beliefs, parenting practices and child's sweet beverage consumption were obtained by parental report with questionnaires. We performed linear and multinomial regression analyses evaluating associations between characteristics at age 5 years and (i) consumption at 7 years and (ii) consumption patterns between age 5 and 7 years with reference category 'low consumption'. Based on the report from their parents, 5-year-old children drank on average 3.0 (SD:1.4) sweet beverage per day. Children consumed less sweet beverages at age 7 years (beta -0.16, 95% confidence interval [CI] -0.24 to -0.09) when there were less sweet beverages available at home. The multinomial regression model showed that children with parents who discouraged sweet beverage consumption were more likely to decrease their sweet beverage consumption over the study period (odds ratio: 1.24, 95% CI 1.07 to 1.43). Moreover, when there were less sweet beverages available at home, children were less likely to increase their consumption or have a high consumption over the study period (odds ratio: 0.70, 95% CI 0.59 to 0.83 and 0.61, 95% CI 0.54 to 0.70, respectively). The results showed that characteristics of the home environment are associated with the consumption of sweet beverages among children. Specifically, the availability of sweet beverages at home is associated with the child's sweet beverage consumption. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

The empathy impulse: A multinomial model of intentional and unintentional empathy for pain.

PubMed

Cameron, C Daryl; Spring, Victoria L; Todd, Andrew R

2017-04-01

Empathy for pain is often described as automatic. Here, we used implicit measurement and multinomial modeling to formally quantify unintentional empathy for pain: empathy that occurs despite intentions to the contrary. We developed the pain identification task (PIT), a sequential priming task wherein participants judge the painfulness of target experiences while trying to avoid the influence of prime experiences. Using multinomial modeling, we distinguished 3 component processes underlying PIT performance: empathy toward target stimuli (Intentional Empathy), empathy toward prime stimuli (Unintentional Empathy), and bias to judge target stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow) response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing imagine-self (vs. imagine-other) perspective-taking uniquely increased Unintentional Empathy. In Experiment 3, Intentional and Unintentional Empathy were stronger toward targets with typical (vs. atypical) pain outcomes, suggesting that outcome information matters and that effects on the PIT are not reducible to affective priming. Typicality of pain outcomes more weakly affected task performance when target stimuli were merely categorized rather than judged for painfulness, suggesting that effects on the latter are not reducible to semantic priming. In Experiment 4, Unintentional Empathy was stronger for participants who engaged in costly donation to cancer charities, but this parameter was also high for those who donated to an objectively worse but socially more popular charity, suggesting that overly high empathy may facilitate maladaptive altruism. Theoretical and practical applications of our modeling approach for understanding variation in empathy are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

On Subset Selection Procedures for Poisson Processes and Some Applications to the Binomial and Multinomial Problems

DTIC Science & Technology

1976-07-01

PURDUE UNIVERSITY DEPARTMENT OF STATISTICS DIVISION OF MATHEMATICAL SCIENCES ON SUBSET SELECTION PROCEDURES FOR POISSON PROCESSES AND SOME...Mathematical Sciences Mimeograph Series #457, July 1976 This research was supported by the Office of Naval Research under Contract NOOO14-75-C-0455 at Purdue...11 CON PC-111 riFIC-F ,A.F ANO ADDPFS Office of INaval ResearchJu#07 Washington, DC07 36AE 14~~~ rjCr; NF A ’ , A FAA D F 6 - I S it 9 i 1, - ,1 I

Investigation on the Size Effect in Large-Scale Beta-Processed Ti-17 Disks Based on Quantitative Metallography

NASA Astrophysics Data System (ADS)

Zhang, Saifei; Zeng, Weidong; Gao, Xiongxiong; Zhao, Xingdong; Li, Siqing

2017-10-01

The present study investigates the mechanical properties of large-scale beta-processed Ti-17 forgings because of the increasing interest in beta thermal-mechanical processing method for fabricating compressor disks or blisks in aero-engines due to its advantage in damage tolerance performance. Three Ti-17 disks with different weights of 57, 250 and 400 kg were prepared by beta processing techniques firstly for comparative study. The results reveal a significant `size effect' in beta-processed Ti-17 disks, i.e., dependences of high cycle fatigue, tensile properties and fracture toughness of beta-processed Ti-17 disks on disk size (or weight). With increasing disk weight from 57 to 400 kg, the fatigue limit (fatigue strength at 107 cycles, R = -1) was reduced from 583 to 495 MPa, tensile yield strength dropped from 1073 to 1030 MPa, while fracture toughness ( K IC) rose from 70.9 to 95.5 MPaṡm1/2. Quantitative metallography analysis shows that the `size effect' of mechanical properties can be attributed to evident differences between microstructures of the three disk forgings. With increasing disk size, nearly all microstructural components in the basket-weave microstructure, including prior β grain, α layers at β grain boundaries (GB- α) and α lamellas at the interior of the grains, get coarsened to different degrees. Further, the microstructural difference between the beta-processed disks is proved to be the consequence of longer pre-forging soaking time and lower post-forging cooling rate for large disks than small ones. Finally, suggestions are made from the perspective of microstructural control on how to improve mechanical properties of large-scale beta-processed Ti-17 forgings.

Classification of vegetation types in military region

NASA Astrophysics Data System (ADS)

Gonçalves, Miguel; Silva, Jose Silvestre; Bioucas-Dias, Jose

2015-10-01

In decision-making process regarding planning and execution of military operations, the terrain is a determining factor. Aerial photographs are a source of vital information for the success of an operation in hostile region, namely when the cartographic information behind enemy lines is scarce or non-existent. The objective of present work is the development of a tool capable of processing aerial photos. The methodology implemented starts with feature extraction, followed by the application of an automatic selector of features. The next step, using the k-fold cross validation technique, estimates the input parameters for the following classifiers: Sparse Multinomial Logist Regression (SMLR), K Nearest Neighbor (KNN), Linear Classifier using Principal Component Expansion on the Joint Data (PCLDC) and Multi-Class Support Vector Machine (MSVM). These classifiers were used in two different studies with distinct objectives: discrimination of vegetation's density and identification of vegetation's main components. It was found that the best classifier on the first approach is the Sparse Logistic Multinomial Regression (SMLR). On the second approach, the implemented methodology applied to high resolution images showed that the better performance was achieved by KNN classifier and PCLDC. Comparing the two approaches there is a multiscale issue, in which for different resolutions, the best solution to the problem requires different classifiers and the extraction of different features.

Who Is Overeducated and Why? Probit and Dynamic Mixed Multinomial Logit Analyses of Vertical Mismatch in East and West Germany

ERIC Educational Resources Information Center

Boll, Christina; Leppin, Julian Sebastian; Schömann, Klaus

2016-01-01

Overeducation potentially signals a productivity loss. With Socio-Economic Panel data from 1984 to 2011 we identify drivers of educational mismatch for East and West medium and highly educated Germans. Addressing measurement error, state dependence and unobserved heterogeneity, we run dynamic mixed multinomial logit models for three different…

Method for preparing Pb-. beta. ''-alumina ceramic

DOEpatents

Hellstrom, E.E.

1984-08-30

A process is disclosed for preparing impermeable, polycrystalline samples of Pb-..beta..''-alumina ceramic from Na-..beta..''-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-..beta..''-alumina ceramic that is substantially crack-free.

Method for preparing Pb-.beta."-alumina ceramic

DOEpatents

Hellstrom, Eric E.

1986-01-01

A process is disclosed for preparing impermeable, polycrystalline samples of Pb-.beta."-alumina ceramic from Na-.beta."-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-.beta."-alumina ceramic that is substantially crack-free.

Top-Down Beta Enhances Bottom-Up Gamma

PubMed Central

Thompson, William H.

2017-01-01

Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection. SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. PMID:28592697

Aerodynamic Performance Measurements for a Forward Swept Low Noise Fan

NASA Technical Reports Server (NTRS)

Fite, E. Brian

2006-01-01

One source of noise in high tip speed turbofan engines, caused by shocks, is called multiple pure tone noise (MPT's). A new fan, called the Quiet High Speed Fan (QHSF), showed reduced noise over the part speed operating range, which includes MPT's. The QHSF showed improved performance in most respects relative to a baseline fan; however, a partspeed instability discovered during testing reduced the operating range below acceptable limits. The measured QHSF adiabatic efficiency on the fixed nozzle acoustic operating line was 85.1 percent and the baseline fan 82.9 percent, a 2.2 percent improvement. The operating line pressure rise at design point rotational speed and mass flow was 1.764 and 1.755 for the QHSF and baseline fan, respectively. Weight flow at design point speed was 98.28 lbm/sec for the QHSF and 97.97 lbm/sec for the baseline fan. The operability margin for the QHSF approached 0 percent at the 75 percent speed operating condition. The baseline fan maintained sufficient margin throughout the operating range as expected. Based on the stage aerodynamic measurements, this concept shows promise for improved performance over current technology if the operability limitations can be solved.

Contour-Based Corner Detection and Classification by Using Mean Projection Transform

PubMed Central

Kahaki, Seyed Mostafa Mousavi; Nordin, Md Jan; Ashtari, Amir Hossein

2014-01-01

Image corner detection is a fundamental task in computer vision. Many applications require reliable detectors to accurately detect corner points, commonly achieved by using image contour information. The curvature definition is sensitive to local variation and edge aliasing, and available smoothing methods are not sufficient to address these problems properly. Hence, we propose Mean Projection Transform (MPT) as a corner classifier and parabolic fit approximation to form a robust detector. The first step is to extract corner candidates using MPT based on the integral properties of the local contours in both the horizontal and vertical directions. Then, an approximation of the parabolic fit is calculated to localize the candidate corner points. The proposed method presents fewer false-positive (FP) and false-negative (FN) points compared with recent standard corner detection techniques, especially in comparison with curvature scale space (CSS) methods. Moreover, a new evaluation metric, called accuracy of repeatability (AR), is introduced. AR combines repeatability and the localization error (Le) for finding the probability of correct detection in the target image. The output results exhibit better repeatability, localization, and AR for the detected points compared with the criteria in original and transformed images. PMID:24590354

Contour-based corner detection and classification by using mean projection transform.

PubMed

Kahaki, Seyed Mostafa Mousavi; Nordin, Md Jan; Ashtari, Amir Hossein

2014-02-28

Image corner detection is a fundamental task in computer vision. Many applications require reliable detectors to accurately detect corner points, commonly achieved by using image contour information. The curvature definition is sensitive to local variation and edge aliasing, and available smoothing methods are not sufficient to address these problems properly. Hence, we propose Mean Projection Transform (MPT) as a corner classifier and parabolic fit approximation to form a robust detector. The first step is to extract corner candidates using MPT based on the integral properties of the local contours in both the horizontal and vertical directions. Then, an approximation of the parabolic fit is calculated to localize the candidate corner points. The proposed method presents fewer false-positive (FP) and false-negative (FN) points compared with recent standard corner detection techniques, especially in comparison with curvature scale space (CSS) methods. Moreover, a new evaluation metric, called accuracy of repeatability (AR), is introduced. AR combines repeatability and the localization error (Le) for finding the probability of correct detection in the target image. The output results exhibit better repeatability, localization, and AR for the detected points compared with the criteria in original and transformed images.

[MusicPlayTherapy--a parent-child psychotherapy for children 0-4 years old].

PubMed

Stumptner, Katrin; Thomsen, Cornelia

2005-10-01

The early stage of building up the parent-child relationship is especially important. It is the basis for the child's development of the ability to relate to others and his or her further emotional, social and cognitive development. In this important early phase various risk factors may alienate parents from their intuitive parental competence towards their children. Such interaction problems indicate an intervention in the form of parent-children psychotherapy. This constitutes an entry point for the concept of MusicPlayTherapy (MPT): The early relationship is characterized mainly by complex communication sequences that address the senses at all levels. Therefore, the MPT concept integrates music as medium to communicate and opens up a playing space for play that allows emotions and experiences to be expressed. The components of music such as rhythm, sound, and melody stimulate babies and toddlers to express, play, and communicate preverbally. We work with the child and a parent in the MusicPlayTherapy sessions. Parents learn again to play and thereby learn to reach their children emotionally and to communicate with them. We complement the therapy sessions by counselling sessions with both parents.

Mangifera indica L. extract (Vimang) and its main polyphenol mangiferin prevent mitochondrial oxidative stress in atherosclerosis-prone hypercholesterolemic mouse.

PubMed

Pardo-Andreu, Gilberto L; Paim, Bruno A; Castilho, Roger F; Velho, Jesus A; Delgado, René; Vercesi, Anibal E; Oliveira, Helena C F

2008-05-01

Atherosclerosis is linked to a number of oxidative events ranging from low-density lipoprotein (LDL) oxidation to the increased production of intracellular reactive oxygen species (ROS). We have recently demonstrated that liver mitochondria isolated from the atherosclerosis-prone hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice have lower content of NADP(H)-linked substrates than the controls and, as consequence, higher sensitivity to oxidative stress and mitochondrial membrane permeability transition (MPT). In the present work, we show that oral supplementation with the antioxidants Mangifera indica L. extract (Vimang) or its main polyphenol mangiferin shifted the sensitivity of LDLr(-/-) liver mitochondria to MPT to control levels. These in vivo treatments with Vimang and mangiferin also significantly reduced ROS generation by both isolated LDLr(-/-) liver mitochondria and spleen lymphocytes. In addition, these antioxidant treatments prevented mitochondrial NAD(P)H-linked substrates depletion and NADPH spontaneous oxidation. In summary, Vimang and mangiferin spared the endogenous reducing equivalents (NADPH) in LDLr(-/-) mice mitochondria correcting their lower antioxidant capacity and restoring the organelle redox homeostasis. The effective bioavailability of these compounds makes them suitable antioxidants with potential use in atherosclerosis susceptible conditions.

Mitochondrial flashes: From indicator characterization to in vivo imaging.

PubMed

Wang, Wang; Zhang, Huiliang; Cheng, Heping

2016-10-15

Mitochondrion is an organelle critically responsible for energy production and intracellular signaling in eukaryotic cells and its dysfunction often accompanies and contributes to human disease. Superoxide is the primary reactive oxygen species (ROS) produced in mitochondria. In vivo detection of superoxide has been a challenge in biomedical research. Here we describe the methods used to characterize a circularly permuted yellow fluorescent protein (cpYFP) as a biosensor for mitochondrial superoxide and pH dynamics. In vitro characterization reveals the high selectivity of cpYFP to superoxide over other ROS species and its dual sensitivity to pH. Confocal and two-photon imaging in conjunction with transgenic expression of the biosensor cpYFP targeted to the mitochondrial matrix detects mitochondrial flash events in living cells, perfused intact hearts, and live animals. The mitochondrial flashes are discrete and stochastic single mitochondrial events triggered by transient mitochondrial permeability transition (tMPT) and composed of a bursting superoxide signal and a transient alkalization signal. The real-time monitoring of single mitochondrial flashes provides a unique tool to study the integrated dynamism of mitochondrial respiration, ROS production, pH regulation and tMPT kinetics under diverse physiological and pathophysiological conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Library Book Circulation and the Beta-Binomial Distribution.

ERIC Educational Resources Information Center

Gelman, E.; Sichel, H. S.

1987-01-01

Argues that library book circulation is a binomial rather than a Poisson process, and that individual book popularities are continuous beta distributions. Three examples demonstrate the superiority of beta over negative binomial distribution, and it is suggested that a bivariate-binomial process would be helpful in predicting future book…

Catalytic asymmetric epoxidation of alpha,beta-unsaturated amides: efficient synthesis of beta-aryl alpha-hydroxy amides using a one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process.

PubMed

Nemoto, Tetsuhiro; Kakei, Hiroyuki; Gnanadesikan, Vijay; Tosaki, Shin-Ya; Ohshima, Takashi; Shibasaki, Masakatsu

2002-12-11

The catalytic asymmetric epoxidation of alpha,beta-unsaturated amides using Sm-BINOL-Ph3As=O complex was succeeded. Using 5-10 mol % of the asymmetric catalyst, a variety of amides were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy amides in up to 99% yield and in more than 99% ee. Moreover, the novel one-pot tandem process, one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process, was developed. This method was successfully utilized for the efficient synthesis of beta-aryl alpha-hydroxy amides, including beta-aryllactyl-leucine methyl esters. Interestingly, it was found that beneficial modifications on the Pd catalyst were achieved by the constituents of the first epoxidation, producing a more suitable catalyst for the Pd-catalyzed epoxide opening reaction in terms of chemoselectivity.

Functional correlates of brain aging: beta and gamma frequency band responses to age-related cortical changes.

PubMed

Christov, Mario; Dushanova, Juliana

2016-01-01

The brain as a system with gradually declined resources by age maximizes its performance by neural network reorganization for greater efficiency of neuronal oscillations in a given frequency band. Whether event-related high-frequency band responses are related to plasticity in neural recruitment contributed to the stability of sensory/cognitive mechanisms accompanying aging or are underlined pathological changes seen in aging brain remains unknown. Aged effect on brain electrical activity was studied in auditory discrimination task (low-frequency and high-frequency tone) at particular cortical locations in beta (β1: 12.5-20; β2: 20.5-30 Hz) and gamma frequency bands (γ1: 30.5-49; γ2: 52-69 Hz) during sensory (post-stimulus interval 0-250 ms) and cognitive processing (250-600 ms). Beta1 activity less affected by age during sensory processing. Reduced beta1 activity was more widespread during cognitive processing. This difference increased in fronto-parietal direction more expressed after high-frequency tone stimulation. Beta2 and gamma activity were more pronounced with progressive age during sensory processing. Reducing regional-process specificity with progressing age characterized age-related and tone-dependent beta2 changes during sensory, but not during cognitive processing. Beta2 and gamma activity diminished with age on cognitive processes, except the higher frontal tone-dependent gamma activity during cognitive processing. With increasing age, larger gamma2 activity was more expressed over the frontal brain areas to high tone discrimination and hand reaction choice. These gamma2 differences were shifted from posterior to anterior brain regions with advancing age. The aged influence was higher on cognitive processes than on perceptual ones.

The effect of stereochemistry on the thermodynamic characteristics of the binding of fenoterol stereoisomers to the beta(2)-adrenoceptor.

PubMed

Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Woo, Anthony Yiu-Ho; Xiao, Rui-Ping; Wainer, Irving W

2010-06-01

The binding thermodynamics of the stereoisomers of fenoterol, (R,R')-, (S,S')-, (R,S')-, and (S,R')-fenoterol, to the beta(2)-adrenergic receptor (beta(2)-AR) have been determined. The experiments utilized membranes obtained from HEK cells stably transfected with cDNA encoding human beta(2)-AR. Competitive displacement studies using [(3)H]CGP-12177 as the marker ligand were conducted at 4, 15, 25, 30 and 37 degrees C, the binding affinities calculated and the standard enthalpic (DeltaH degrees ) and standard entropic (DeltaS degrees ) contribution to the standard free energy change (DeltaG degrees ) associated with the binding process determined through the construction of van't Hoff plots. The results indicate that the binding of (S,S')- and (S,R')-fenoterol were predominately enthalpy-driven processes while the binding of (R,R')- and (R,S')-fenoterol were entropy-driven. All of the fenoterol stereoisomers are full agonists of the beta(2)-AR, and, therefore, the results of this study are inconsistent with the previously described "thermodynamic agonist-antagonist discrimination", in which the binding of an agonist to the beta-AR is entropy-driven and the binding of an antagonist is enthalpy-driven. In addition, the data demonstrate that the chirality of the carbon atom containing the beta-hydroxyl group of the fenoterol molecule (the beta-OH carbon) is a key factor in the determination of whether the binding process will be enthalpy-driven or entropy-driven. When the configuration at the beta-OH carbon is S the binding process is enthalpy-driven while the R configuration produces an entropy-driven process. Published by Elsevier Inc.

Microstructural stability and thermomechanical processing of boron modified beta titanium alloys

NASA Astrophysics Data System (ADS)

Cherukuri, Balakrishna

One of the main objectives during primary processing of titanium alloys is to reduce the prior beta grain size. Producing an ingot with smaller prior beta grain size could potentially eliminate some primary processing steps and thus reduce processing cost. Trace additions of boron have been shown to decrease the as-cast grain size in alpha + beta titanium alloys. The primary focus of this dissertation is to investigate the effect of boron on microstructural stability and thermomechanical processing in beta titanium alloys. Two metastable beta titanium alloys: Ti-15Mo-2.6Nb-3Al-0.2Si (Beta21S) and Ti-5Al-5V-5Mo-3Cr (Ti5553) with 0.1 wt% B and without boron additions were used in this investigation. Significant grain refinement of the as-cast microstructure and precipitation of TiB whiskers along the grain boundaries was observed with boron additions. Beta21S and Beta21S-0.1B alloys were annealed above the beta transus temperature for different times to investigate the effect of boron on grain size stability. The TiB precipitates were very effective in restricting the beta grain boundary mobility by Zener pinning. A model has been developed to predict the maximum grain size as a function of TiB size, orientation, and volume fraction. Good agreement was obtained between model predictions and experimental results. Beta21S alloys were solution treated and aged for different times at several temperatures below the beta transus to study the kinetics of alpha precipitation. Though the TiB phase did not provide any additional nucleation sites for alpha precipitation, the grain refinement obtained by boron additions resulted in accelerated aging. An investigation of the thermomechanical processing behavior showed different deformation mechanisms above the beta transus temperature. The non-boron containing alloys showed a non-uniform and fine recrystallized necklace structure at grain boundaries whereas uniform intragranular recrystallization was observed in boron containing alloys. Micro-voids were observed at the ends of the TiB needles at high temperature, slow strain rates as a result of decohesion at the TiB/matrix interfaces. At low temperatures and faster strain rates micro voids were also formed due to fracture of TiB needles. Finite element analysis on void formation in TiB containing alloys were in agreement with experimental observations. Microhardness and tensile testing of as-cast + forged and aged Beta21S and Ti5553 alloys with and without boron did not show any significant differences in mechanical properties. The primary benefits of boron modified alloys are in as-cast condition.

The H,K-ATPase beta-subunit can act as a surrogate for the beta-subunit of Na,K-pumps.

PubMed

Horisberger, J D; Jaunin, P; Reuben, M A; Lasater, L S; Chow, D C; Forte, J G; Sachs, G; Rossier, B C; Geering, K

1991-10-15

Na,K-ATPase and H,K-ATPase are the only members of the P-type ATPases in which a glycosylated beta-subunit is part of the purified active enzyme. In this study, we have followed the synthesis and the posttranslational processing of the beta-subunit of H,K-ATPase (beta HK) in Xenopus oocytes injected with beta HK cRNA and have tested whether it can act as a surrogate for the beta-subunit of Na,K-ATPase (beta NaK) to support the functional expression of Na,K-pumps. In Xenopus oocytes, beta HK is processed from an Endo H-sensitive 51-kDa coreglycosylated form to an Endo H-resistant 71-kDa fully glycosylated form. Similar to beta NaK, beta HK can stabilize and increase the trypsin resistance of alpha-subunits of Na,K-ATPase (alpha NaK). Finally, expression of beta HK together with alpha NaK leads to an increased number of ouabain binding sites at the plasma membrane accompanied by an increased Rb+ uptake and Na,K-pump current. Our data suggest that beta HK, similar to beta NaK, can assemble to alpha NaK, support the structural maturation and the intracellular transport of catalytic alpha NaK, and ultimately form active alpha NaK-beta HK complexes with Na,K-pump transport properties.

A Bayesian Multinomial Probit MODEL FOR THE ANALYSIS OF PANEL CHOICE DATA.

PubMed

Fong, Duncan K H; Kim, Sunghoon; Chen, Zhe; DeSarbo, Wayne S

2016-03-01

A new Bayesian multinomial probit model is proposed for the analysis of panel choice data. Using a parameter expansion technique, we are able to devise a Markov Chain Monte Carlo algorithm to compute our Bayesian estimates efficiently. We also show that the proposed procedure enables the estimation of individual level coefficients for the single-period multinomial probit model even when the available prior information is vague. We apply our new procedure to consumer purchase data and reanalyze a well-known scanner panel dataset that reveals new substantive insights. In addition, we delineate a number of advantageous features of our proposed procedure over several benchmark models. Finally, through a simulation analysis employing a fractional factorial design, we demonstrate that the results from our proposed model are quite robust with respect to differing factors across various conditions.

beta-Hexachlorocyclohexane (beta-HCH)

Integrated Risk Information System (IRIS)

beta - Hexachlorocyclohexane ( beta - HCH ) ; CASRN 319 - 85 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced by nigericin is a result of activation of p45 IL-1beta-converting enzyme processing.

PubMed

Cheneval, D; Ramage, P; Kastelic, T; Szelestenyi, T; Niggli, H; Hemmig, R; Bachmann, M; MacKenzie, A

1998-07-10

Perregaux and Gabel (Perregaux, D., and Gabel, C. A. (1994) J. Biol. Chem. 269, 15195-15203) reported that potassium depletion of lipopolysaccharide-stimulated mouse macrophages induced by the potassium ionophore, nigericin, leads to the rapid release of mature interleukin-1beta (IL-1beta). We have now shown a similar phenomenon in lipopolysaccharide-stimulated human monocytic leukemia THP-1 cells. Rapid secretion of mature, 17-kDa IL-1beta occurred, in the presence of nigericin (4-16 microM). No effects on the release of tumor necrosis factor-alpha, IL-6, or proIL-1beta were seen. Addition of the irreversible interleukin-1beta-converting enzyme (ICE) inhibitor, Z-Val-Ala-Asp-dichlorobenzoate, or a radicicol analog, inhibited nigericin-induced mature IL-1beta release and activation of p45 ICE precursor. The radicicol analog itself did not inhibit ICE, but markedly, and very rapidly depleted intracellular levels of 31-kDa proIL-1beta. By contrast, dexamethasone, cycloheximide, and the Na+/H+ antiporter inhibitor, 5-(N-ethyl-N-isopropyl)amiloride, had no effect on nigericin-induced release of IL-1beta. We have therefore shown conclusively, for the first time, that nigericin-induced release of IL-1beta is dependent upon activation of p45 ICE processing. So far, the mechanism by which reduced intracellular potassium ion concentration triggers p45 ICE processing is not known, but further investigation in this area could lead to the discovery of novel molecular targets whereby control of IL-1beta production might be effected.

Paleoceanography of the Bering Sea during the past five million years: results from IODP Expedition 323

NASA Astrophysics Data System (ADS)

Takahashi, K.; Onodera, J.; Asahi, H.; Okazaki, Y.; Kanematsu, Y.; Iwasaki, S.; Ikenoue, T.; Ikehara, M.; Seki, O.; Sakamoto, T.; Horikawa, K.; Khim, B.; Kim, S.; Teraishi, A.; Suto, I.; Ravelo, A. C.

2012-12-01

Based on high quality cores collected by IODP Expedition 323, we reconstructed the paleoceanography of the Bering Sea for the past 5 My. Among 7 sites, two hemipelagic sites drilled to 600 mbsf on Bowers Ridge provided records back to 4.3 Ma at U1341 and 5.0 at U1340, respectively. Two Beringian Slope sites provided the bottom ages of 2.4 Ma at U1343 (745 mbsf) and 0.5 Ma at U1345 (150 mbsf). Analyses of the core samples include microfossils such as diatoms, silicoflagellates, and radiolarians, biogenic opal, δ18O of benthic foraminifers, biomarkers, and neodymium isotopes. During the early Pliocene, siliceous microfossil assemblage analyses and alkenone paleothermometry indicate that relatively warm waters were present in the Bering Sea. Around 3 Ma a decrease in %Stephanopyxis spp., warm water diatoms, is seen, indicating water mass advection from the subarctic Pacific. Fragilariopsis cylindrus, a sea-ice diatom, was present since 2.90 Ma. Initial dominance of silicoflagellate Distephanus medianoctisol is observed at 2.66 Ma. The changes in microfossils assemblages coincide with those observed in alkenone-SST data. The significant intensification of the Northern Hemisphere Glaciation (NHG) at 2.75 Ma appears to be linked to our new data from the Bering Sea. During 2.65-2.0 Ma, prevailing summer stratification due to sea-ice melting is interpreted from an increase of %Actinocyclus spp. Furthermore, the dominance of silicoflagellate Distephanus speculum during 2.4-2.0 Ma suggests a nearly ice-free condition. Changes in %biogenic opal are consistent with what are implied by the siliceous microfossil data. In particular during 2.4-2.0 Ma, the conditions became warmer and more productive than before the NHG. High %Thalassiosira antarctica resting spore after 2 Ma suggests sea-ice formation. Several peaks of %T. antarctica reflects the temporal influence of sea-ice transportation from the Beringian Slope region to Site U1341 after 2 Ma. Dominance of D. medianoctisol during 1.6-2.0 Ma reflects colder environments. The Mid Pleistocene Transition (MPT, ca. 1 Ma) is the time period of interest because of the global change in increased amplitude of warm-cold climatic intervals and shift from 41 k obliquity to 100 k eccentricity cyclicity of glacial-interglacials. During the MPT %Cycladophora davisiana, an intermediate water dwelling radiolarian taxon, increased, indicating increased extent of sea-ice cover. After the MPT since 0.8 Ma, colder conditions are inferred from decreased %N. seminae, abundant %Thalassiosira trifulta group, %T. antarctica, and high% of sea-ice related silicoflagellates. After the MPT, abundant sea-ice related diatoms and silicoflagellates significantly reflect the drifting sea-ice from the Bering Sea shelf. Sea-ice formation at Site U1341 was limited with 1% Fragilaripsis cylindrus while typical seasonal sea-ice area was with greater than 10%.

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

PubMed Central

Ghosal, Abhisek; Sekar, Thillai V.

2014-01-01

Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na+-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na+-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS. PMID:24904078

Dielectric characterization of neutralized and nonneutralized chitosan upon drying.

PubMed

Viciosa, M T; Dionísio, M; Mano, J F

2006-02-15

Isothermal dielectric loss spectra of neutralized and nonneutralized chitosan were acquired in successive runs from -130 degrees C up to increasing final temperatures, in a frequency range between 20 Hz and 1 MHz. Essentially, three relaxation processes were detected in the temperature range covered: (i) a beta-wet process, detected when the sample has a higher water content that vanishes after heating to 150 degrees C; (ii) a beta process, which is located at temperatures below 0 degrees C, becoming better defined and maintaining its location after annealing at 150 degrees C independently of the protonation state of the amino side group; and (iii) a sigma process that deviates to higher temperatures with drying, being more mobile in the nonneutralized form. Moreover, in dried neutralized chitosan, a fourth process was detected in the low frequency side of the secondary beta process that diminishes after annealing. Whether this process is a distinct relaxation of the dried polymer or a deviated beta-wet process due to the loss of water residues achieved by annealing is not straightforward. Only beta and sigma processes persist after annealing at 150 degrees C. The changes in molecular mobility upon drying of these two relaxation processes were evaluated. Copyright (c) 2005 Wiley Periodicals, Inc.

The complex roles of space and environment in structuring functional, taxonomic and phylogenetic beta diversity of frogs in the Atlantic Forest

PubMed Central

Luiz, Amom Mendes; Sawaya, Ricardo J.

2018-01-01

Ecological communities are complex entities that can be maintained and structured by niche-based processes such as environmental conditions, and spatial processes such as dispersal. Thus, diversity patterns may be shaped simultaneously at different spatial scales by very distinct processes. Herein we assess whether and how functional, taxonomic, and phylogenetic beta diversities of frog tadpoles are explained by environmental and/or spatial predictors. We implemented a distance–based redundancy analysis to explore variation in components of beta diversity explained by pure environmental and pure spatial predictors, as well as their interactions, at both fine and broad spatial scales. Our results indicated important but complex roles of spatial and environmental predictors in structuring phylogenetic, taxonomic and functional beta diversities. The pure fine-scales spatial fraction was more important in structuring all beta diversity components, especially to functional and taxonomical spatial turnover. Environmental variables such as canopy cover and vegetation structure were important predictors of all components, but especially to functional and taxonomic beta diversity. We emphasize that distinct factors related to environment and space are affecting distinct components of beta diversity in different ways. Although weaker, phylogenetic beta diversity, which is structured more on biogeographical scales, and thus can be represented by spatially structured processes, was more related to broad spatial processes than other components. However, selected fine-scale spatial predictors denoted negative autocorrelation, which may be revealing the existence of differences in unmeasured habitat variables among samples. Although overall important, local environmental-based processes explained better functional and taxonomic beta diversity, as these diversity components carry an important ecological value. We highlight the importance of assessing different components of diversity patterns at different scales by spatially explicit models in order to improve our understanding of community structure and help to unravel the complex nature of biodiversity. PMID:29672575

"The empathy impulse: A multinomial model of intentional and unintentional empathy for pain": Correction.

PubMed

2018-04-01

Reports an error in "The empathy impulse: A multinomial model of intentional and unintentional empathy for pain" by C. Daryl Cameron, Victoria L. Spring and Andrew R. Todd ( Emotion , 2017[Apr], Vol 17[3], 395-411). In this article, there was an error in the calculation of some of the effect sizes. The w effect size was manually computed incorrectly. The incorrect number of total observations was used, which affected the final effect size estimates. This computing error does not change any of the results or interpretations about model fit based on the G² statistic, or about significant differences across conditions in process parameters. Therefore, it does not change any of the hypothesis tests or conclusions. The w statistics for overall model fit should be .02 instead of .04 in Study 1, .01 instead of .02 in Study 2, .01 instead of .03 for the OIT in Study 3 (model fit for the PIT remains the same: .00), and .02 instead of .03 in Study 4. The corrected tables can be seen here: http://osf.io/qebku at the Open Science Framework site for the article. (The following abstract of the original article appeared in record 2017-01641-001.) Empathy for pain is often described as automatic. Here, we used implicit measurement and multinomial modeling to formally quantify unintentional empathy for pain: empathy that occurs despite intentions to the contrary. We developed the pain identification task (PIT), a sequential priming task wherein participants judge the painfulness of target experiences while trying to avoid the influence of prime experiences. Using multinomial modeling, we distinguished 3 component processes underlying PIT performance: empathy toward target stimuli (Intentional Empathy), empathy toward prime stimuli (Unintentional Empathy), and bias to judge target stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow) response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing imagine-self (vs. imagine-other) perspective-taking uniquely increased Unintentional Empathy. In Experiment 3, Intentional and Unintentional Empathy were stronger toward targets with typical (vs. atypical) pain outcomes, suggesting that outcome information matters and that effects on the PIT are not reducible to affective priming. Typicality of pain outcomes more weakly affected task performance when target stimuli were merely categorized rather than judged for painfulness, suggesting that effects on the latter are not reducible to semantic priming. In Experiment 4, Unintentional Empathy was stronger for participants who engaged in costly donation to cancer charities, but this parameter was also high for those who donated to an objectively worse but socially more popular charity, suggesting that overly high empathy may facilitate maladaptive altruism. Theoretical and practical applications of our modeling approach for understanding variation in empathy are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Development of Systems Engineering Maturity Models and Management Tools

DTIC Science & Technology

2011-01-21

Ph.D., Senior Personnel, Stevens Institute of Technology Abhi Deshmukh, Ph.D., Senior Personnel, Texas A&M University Matin Sarfaraz, Research ...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Stevens Institute of Technology,Systems Engineering Research Center (SERC),1...tools (MPT) for effectively and efficiently addressing these challenges are likewise being challenged. The goal of this research was to develop a

A conceptual model for glacial cycles and the middle Pleistocene transition

NASA Astrophysics Data System (ADS)

Daruka, István; Ditlevsen, Peter D.

2016-01-01

Milankovitch's astronomical theory of glacial cycles, attributing ice age climate oscillations to orbital changes in Northern-Hemisphere insolation, is challenged by the paleoclimatic record. The climatic response to the variations in insolation is far from trivial. In general the glacial cycles are highly asymmetric in time, with slow cooling from the interglacials to the glacials (inceptions) and very rapid warming from the glacials to the interglacials (terminations). We shall refer to this fast-slow dynamics as the "saw-tooth" shape of the paleoclimatic record. This is non-linearly related to the time-symmetric variations in the orbital forcing. However, the most pronounced challenge to the Milankovitch theory is the middle Pleistocene transition (MPT) occurring about one million years ago. During that event, the prevailing 41 kyr glacial cycles, corresponding to the almost harmonic obliquity cycle were replaced by longer saw-tooth shaped cycles with a time-scale around 100 kyr. The MPT must have been driven by internal changes in climate response, since it does not correspond to any apparent changes in the orbital forcing. In order to identify possible mechanisms causing the observed changes in glacial dynamics, it is relevant to study simplified models with the capability of generating temporal behavior similar to the observed records. We present a simple oscillator type model approach, with two variables, a temperature anomaly and a climatic memory term. The generalization of the ice albedo feedback is included in terms of an effective multiplicative coupling between this latter climatic memory term (representing the internal degrees of freedom) and the external drive. The simple model reproduces the temporal asymmetry of the late Pleistocene glacial cycles and suggests that the MPT can be explained as a regime shift, aided by climatic noise, from a period 1 frequency locking to the obliquity cycle to a period 2-3 frequency locking to the same obliquity cycle. The change in dynamics has been suggested to be a result of a slow gradual decrease in atmospheric greenhouse gas concentration. The critical dependence on initial conditions in the (non-autonomous) glacial dynamics raises fundamental questions about climate predictability.

Changing climatic response: a conceptual model for glacial cycles and the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Daruka, I.; Ditlevsen, P. D.

2014-03-01

Milankovitch's astronomical theory of glacial cycles, attributing ice age climate oscillations to orbital changes in Northern Northern-Hemisphere insolation, is challenged by the paleoclimatic record. The climatic response to the variations in insolation is far from trivial. In general the glacial cycles are highly asymmetric in time, with slow cooling from the interglacials to the glacials (inceptions) and very rapid warming from the glacials to the interglacials (terminations). We shall refer to this fast-slow dynamics as the "saw-tooth" shape of the paleoclimatic record. This is non-linearly related to the time-symmetric variations in the orbital forcing. However, the most pronounced challenge to the Milankovitch theory is the Mid-Pleistocene Transition (MPT) occurring about one million years ago. During that event, the prevailing 41 kyr glacial cycles, corresponding to the almost harmonic obliquity cycle were replaced by longer saw-tooth shaped cycles with a time scale around 100 kyr. The MPT must have been driven by internal changes in climate response, since it does not correspond to any apparent changes in the orbital forcing. In order to identify possible mechanisms causing the observed changes in glacial dynamics, it is relevant to study simplified models with the capability of generating temporal behavior similar to the observed records. We present a simple oscillator type model approach, with two variables, a temperature anomaly and an ice volume analogous, climatic memory term. The generalization of the ice albedo feedback is included in terms of an effective multiplicative coupling between this latter climatic memory term (representing the internal degrees of freedom) and the external drive. The simple model reproduces the temporal asymmetry of the late Pleistocene glacial cycles and suggests that the MPT can be explained as a regime shift, aided by climatic noise, from a period 1 frequency locking to the obliquity cycle to a period 2-3 frequency locking to the same obliquity cycle. The change in dynamics has been suggested to be a result of a slow gradual decrease in atmospheric greenhouse gas concentration. The presence of chaos in the (non-autonomous) glacial dynamics and a critical dependence on initial conditions raises fundamental questions about climate predictability.

Mangiferin, a natural occurring glucosyl xanthone, increases susceptibility of rat liver mitochondria to calcium-induced permeability transition.

PubMed

Andreu, Gilberto Lázaro Pardo; Delgado, René; Velho, Jesus Antonio; Curti, Carlos; Vercesi, Anibal E

2005-07-15

Mitochondrial permeability transition (MPT) is a Ca(2+)-dependent, cyclosporine A-sensitive, non-selective inner membrane permeabilization induced by a wide range of agents or conditions, which has often been associated with necrotic or apoptotic cell death. When mitochondria isolated from livers of rats treated with the natural occurring glucosyl xanthone mangiferin (40 mg/kg body weight) were exposed in vitro to Ca(2+), they underwent CsA, NEM, and ADP-sensitive high amplitude swelling and associated membrane potential dissipation, release of pre-accumulated Ca(2+), oxidation of thiol groups, and depletion of GSH, without changes in the NAD(P)H redox state. The same treatment reduced the phosphorylation rate of mitochondria and the resting respiration by around 4 and 11%, respectively, as well as generation of reactive oxygen species (ROS) by organelle. The in vitro exposure of untreated mitochondria to mangiferin plus Ca(2+) also resulted in oxidation of thiol groups, in the same way that the compound inhibited the Ca(2+)-induced peroxidation of mitochondrial membrane lipids. The spectrum of mangiferin during its oxidation by the H(2)O(2)/HRP system showed a characteristic absorption peak at 380 nm, which decreased immediately after reaction was started; two isosbestic points at around 336 and 412 nm, with a blue shift in the position of the maxima absorption of mangiferin were observed, suggesting their conversion into one oxidation product. Glutathione abolished this decrease of absorbance, suggesting that the oxidation product of mangiferin forms adducts with GSH. We propose that Ca(2+) increases levels of mitochondria-generated ROS, which reacts with mangiferin producing quinoid derivatives, which in turn react with the most accessible mitochondrial thiol groups, thus triggering MPT. It seems probable that the free radical scavenging activity of mangiferin shifts its anti-oxidant protection to the thiol arylation. An interesting proposition is that accumulation of mangiferin quinoid products would take place in cells exposed to an overproduction of ROS, such as cancer cells, where the occurrence of MPT-mediated apoptosis may be a cellular defence mechanism against excessive ROS formation.

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

PubMed

Smith, James M; Moss, John A; Srinivasan, Priya; Butkyavichene, Irina; Gunawardana, Manjula; Fanter, Rob; Miller, Christine S; Sanchez, Debbie; Yang, Flora; Ellis, Shanon; Zhang, Jining; Marzinke, Mark A; Hendrix, Craig W; Kapoor, Amita; Baum, Marc M

2017-01-01

Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2) to prevent HIV, acyclovir (ACV) to prevent HSV, and etonogestrel (ENG) in combination with ethinyl estradiol (EE), FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6) over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1) for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing) 0.63; and ENG (low releasing) 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1) may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high-risk populations.

A procyanidin type A trimer from cinnamon extract attenuates glial cell swelling and the reduction in glutamate uptake following ischemia-like injury in vitro.

PubMed

Panickar, K S; Polansky, M M; Graves, D J; Urban, J F; Anderson, R A

2012-01-27

Dietary polyphenols exert neuroprotective effects in ischemic injury. The protective effects of a procyanidin type A trimer (trimer 1) isolated from a water soluble cinnamon extract (CE) were investigated on key features of ischemic injury, including cell swelling, increased free radical production, increased intracellular calcium ([Ca(2+)](i)), mitochondrial dysfunction, and the reduction in glutamate uptake. Astrocyte (glial) swelling is a major component of cytotoxic brain edema in ischemia and, along with vasogenic edema, may contribute to increased intracranial pressure, brain herniation, and additional ischemic injuries. C6 glial cultures were exposed to oxygen-glucose deprivation (OGD) for 5 h, and cell swelling was determined at 90 min after the end of OGD. OGD-induced increases in glial swelling were significantly blocked by trimer 1, but not by the major nonpolyphenol fractions of CE including cinnamaldehyde and coumarin. Increased free radical production, a contributing factor in cell swelling following ischemic injury, was also significantly reduced by trimer 1. Mitochondrial dysfunction, another key feature of ischemic injury, is hypothesized to contribute to glial swelling. Depolarization of the inner mitochondrial membrane potential (ΔΨ(m)) was assessed using a fluorescent dye (tetramethylrhodamine ethyl ester [TMRE]), and was significantly attenuated by trimer 1 as was OGD-induced increased [Ca(2+)](i). Taken together with our previous observation that blockers of [Ca(2+)](i) reduce cell swelling, our results indicate that trimer 1 may attenuate cell swelling by regulating [Ca(2+)](i). Trimer 1 also significantly attenuated the OGD-induced decrease in glutamate uptake. In addition, cyclosporin A, a blocker of the mitochondrial permeability pore (mPT), but not FK506 (that does not block the mPT), reduced the OGD-induced decline in glutamate uptake indicating a role of the mPT in such effects. Thus, the effects of trimer 1 in attenuating the reduction in glutamate uptake are likely mediated through their action on the mitochondria. Published by Elsevier Ltd on behalf of IBRO.

A random approach of test macro generation for early detection of hotspots

NASA Astrophysics Data System (ADS)

Lee, Jong-hyun; Kim, Chin; Kang, Minsoo; Hwang, Sungwook; Yang, Jae-seok; Harb, Mohammed; Al-Imam, Mohamed; Madkour, Kareem; ElManhawy, Wael; Kwan, Joe

2016-03-01

Multiple-Patterning Technology (MPT) is still the preferred choice over EUV for the advanced technology nodes, starting the 20nm node. Down the way to 7nm and 5nm nodes, Self-Aligned Multiple Patterning (SAMP) appears to be one of the effective multiple patterning techniques in terms of achieving small pitch of printed lines on wafer, yet its yield is in question. Predicting and enhancing the yield in the early stages of technology development are some of the main objectives for creating test macros on test masks. While conventional yield ramp techniques for a new technology node have relied on using designs from previous technology nodes as a starting point to identify patterns for Design of Experiment (DoE) creation, these techniques are challenging to apply in the case of introducing an MPT technique like SAMP that did not exist in previous nodes. This paper presents a new strategy for generating test structures based on random placement of unit patterns that can construct more meaningful bigger patterns. Specifications governing the relationships between those unit patterns can be adjusted to generate layout clips that look like realistic SAMP designs. A via chain can be constructed to connect the random DoE of SAMP structures through a routing layer to external pads for electrical measurement. These clips are decomposed according to the decomposition rules of the technology into the appropriate mandrel and cut masks. The decomposed clips can be tested through simulations, or electrically on silicon to discover hotspots. The hotspots can be used in optimizing the fabrication process and models to fix them. They can also be used as learning patterns for DFM deck development. By expanding the size of the randomly generated test structures, more hotspots can be detected. This should provide a faster way to enhance the yield of a new technology node.

N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting.

PubMed

Lin, Pei-Hsuan; Lin, Hsien-Yi; Kuo, Cheng-Chin; Yang, Liang-Tung

2015-06-24

The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3's action remain unanswered. We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria.

Extraction and characterization of beta-D-glucan from oat for industrial utilization.

PubMed

Ahmad, Asif; Anjum, Faqir Muhammad; Zahoor, Tahir; Nawaz, Haq; Ahmed, Zaheer

2010-04-01

Oat beta-D-glucan is a valuable functional ingredient having numerous industrial, nutritional and health benefits. Its extraction needs careful attention as extraction process may affect the physiochemical and functional properties of extracted beta-D-glucan. The present study aimed at analyzing the effect of extraction of beta-D-glucan gum pellets from oat cultivar followed by detailed chemical and functional analysis. Enzymatic extraction process resulted in highest yield and recovery. Chemical analysis revealed protein as a dominating impurity. The water binding capacity of the beta-D-glucan ranged between 3.14 and 4.52 g g(-1) of sample. beta-D-Glucan exhibited ideal foaming stability when appropriate extraction technique was used. The viscosity of beta-D-glucan gum ranged between 35.6 and 56.16 cp. The color analysis showed L* value of beta-D-glucan gum pellet ranged between 72.18 and 83.54. Phosphorus, potassium and calcium appeared as major minerals in beta-D-glucan gum whereas iron, manganese and copper appeared as minor minerals. FTIR spectroscopy also confirms the presence of beta-D-glucan, protein and other components in extracted beta-D-glucan gum pellets. Overall, extracted beta-D-glucan showed a good potential for industrial usage. Copyright 2010 Elsevier B.V. All rights reserved.

Proteolytic processing of the pro beta chain of beta-hexosaminidase occurs at basic residues contained within an exposed disulfide loop structure.

PubMed

Sagherian, C; Poroszlay, S; Vavougios, G; Mahuran, D

1993-01-01

Lysosomal beta-hexosaminidase (EC 3.2.1.52) occurs as two major isozymes, Hex A (alpha beta) and Hex B (beta beta). The alpha and beta subunits are encoded by the HEXA and HEXB genes, respectively. Extensive homology in both the gene structures and deduced primary sequences demonstrate their common evolutionary origin. While undergoing similar proteolytic modifications in the lysosome, the pro beta polypeptide is additionally cleaved internally to produce the mature 24-30 kilodalton beta b and beta a chains. Previous data have suggested that this processing event occurs somewhere between residues Ser311 and Lys315. In this report we demonstrate that this area is located in a hydrophilic disulfide-loop structure (between Cys309 and Cys360). The cleavage event is prevented by the deletion through in vitro mutagenesis of the Arg312-Gln-Asn-Lys tetrapeptide or by its substitution with the aligned alpha residues (Gly-Ser-Glu-Pro). Reintroduction of either Arg312 or Lys315 reinstates the processing. Furthermore, we show that this area is not involved in lysosomal targeting of pro-Hex B, or in the increased stability or the variation in substrate specificity of the beta as compared with the alpha subunit. Our data suggest the presence of a novel lysosomal endoprotease. Like other endoproteases it is specific for basic amino acids; however, it cleaves on the amino-terminal side rather than the conventional carboxy-terminal side of such residues and then only if they are fully exposed to the lysosomal environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficient "sensory" beta synchronization in Parkinson's disease.

PubMed

Degardin, A; Houdayer, E; Bourriez, J-L; Destée, A; Defebvre, L; Derambure, P; Devos, D

2009-03-01

Beta rhythm movement-related synchronization (beta synchronization) reflects motor cortex deactivation and sensory afference processing. In Parkinson's disease (PD), decreased beta synchronization after active movement reflects abnormal motor cortex idling and may be involved in the pathophysiology of akinesia. The objectives of the present study were to (i) compare event-related synchronization after active and passive movement and electrical nerve stimulation in PD patients and healthy, age-matched volunteers and (ii) evaluate the effect of levodopa. Using a 128-electrode EEG system, we studied beta synchronization after active and passive index finger movement and electrical median nerve stimulation in 13 patients and 12 control subjects. Patients were recorded before and after 150% of their usual morning dose of levodopa. The peak beta synchronization magnitude in the contralateral primary sensorimotor (PSM) cortex was significantly lower in PD patients after active movement, passive movement and electrical median nerve stimulation, compared with controls. Levodopa partially reversed the drop in beta synchronization after active movement but not after passive movement or electrical median nerve stimulation. If one considers that beta synchronization reflects sensory processing, our results suggest that integration of somaesthetic afferences in the PSM cortex is abnormal in PD during active and passive movement execution and after simple electrical median nerve stimulation. Better understanding of the mechanisms involved in the deficient beta synchronization observed here could prompt the development of new therapeutic approaches aimed at strengthening defective processes. The lack of full beta synchronization restoration by levodopa might be related to the involvement of non-dopaminergic pathways.

Physicochemical properties of beta-glucan in differently processed oat foods influence glycemic response.

PubMed

Regand, Alejandra; Tosh, Susan M; Wolever, Thomas M S; Wood, Peter J

2009-10-14

To assess the effect of food processing on the capacity of oat beta-glucan to attenuate postprandial glycemia, isocaloric crisp bread, granola, porridge, and pasta containing 4 g of beta-glucan as well as control products with low beta-glucan content were prepared. The physicochemical properties (viscosity, peak molecular weight (M(p)), and concentration (C)) of beta-glucan in in-vitro-digestion extracts were evaluated, and fasting and postprandial blood glucose concentrations were measured in human subjects. Porridge and granola had the highest efficacy in attenuating the peak blood glucose response (PBGR) because of their high M(p) and viscosity. beta-Glucan depolymerization in bread and pasta reduced beta-glucan bioactivity. Pastas, known to have low glycemic responses, showed the lowest PBGR. The analyses of these products with previously reported data indicated that 73% of the bioactivity in reducing PBGR can be explained by M(p) x C. Characterizing the physicochemical properties of beta-glucan in bioactive foods aids functional food development.

Anti-aggregatory effect of cyclodextrins in the refolding process of recombinant growth hormones from Escherichia coli inclusion bodies.

PubMed

Bajorunaite, Egle; Cirkovas, Andrejus; Radzevicius, Kostas; Larsen, Kim Lambertsen; Sereikaite, Jolanta; Bumelis, Vladas-Algirdas

2009-06-01

Cyclodextrins with different ring size and ring substituents were tested for recombinant mink and porcine growth hormones aggregation suppression in the refolding process from Escherichia coli inclusion bodies. Methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin show a positive effect on the aggregation suppression of both proteins. The influence of different methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin concentrations on the renaturation yield of both growth hormones was investigated. Moreover, methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin suppress not only folding-related, but also temperature-related aggregates formation of both proteins. Circular dichroism experiments (monitoring of protein solution turbidity by registering high tension voltage) showed that the onset temperature of aggregation of both growth hormones increased with increasing 2-hydroxypropyl-beta-cyclodextrin concentration. In conclusion, cyclodextrins have perspectives in biotechnology of veterinary growth hormones not only for protein production, but also for its storage.

Arsenic exposure and oral cavity lesions in Bangladesh.

PubMed

Syed, Emdadul H; Melkonian, Stephanie; Poudel, Krishna C; Yasuoka, Junko; Otsuka, Keiko; Ahmed, Alauddin; Islam, Tariqul; Parvez, Faruque; Slavkovich, Vesna; Graziano, Joseph H; Ahsan, Habibul; Jimba, Masamine

2013-01-01

To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh. We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study, which is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions. Participants with high urinary arsenic levels (286.1 to 5000.0 μg/g) were more likely to develop arsenical lesions of the gums (multinomial odds ratio = 2.90; 95% confidence interval, 1.11 to 7.54), and tongue (multinomial odds ratio = 2.79; 95% confidence interval, 1.51 to 5.15), compared with those with urinary arsenic levels of 7.0 to 134.0 μg/g. Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue.

Top-down beta oscillatory signaling conveys behavioral context in early visual cortex.

PubMed

Richter, Craig G; Coppola, Richard; Bressler, Steven L

2018-05-03

Top-down modulation of sensory processing is a critical neural mechanism subserving numerous important cognitive roles, one of which may be to inform lower-order sensory systems of the current 'task at hand' by conveying behavioral context to these systems. Accumulating evidence indicates that top-down cortical influences are carried by directed interareal synchronization of oscillatory neuronal populations, with recent results pointing to beta-frequency oscillations as particularly important for top-down processing. However, it remains to be determined if top-down beta-frequency oscillations indeed convey behavioral context. We measured spectral Granger Causality (sGC) using local field potentials recorded from microelectrodes chronically implanted in visual areas V1/V2, V4, and TEO of two rhesus macaque monkeys, and applied multivariate pattern analysis to the spatial patterns of top-down sGC. We decoded behavioral context by discriminating patterns of top-down (V4/TEO-to-V1/V2) beta-peak sGC for two different task rules governing correct responses to identical visual stimuli. The results indicate that top-down directed influences are carried to visual cortex by beta oscillations, and differentiate task demands even before visual stimulus processing. They suggest that top-down beta-frequency oscillatory processes coordinate processing of sensory information by conveying global knowledge states to early levels of the sensory cortical hierarchy independently of bottom-up stimulus-driven processing.

How Should Beta-Diversity Inform Biodiversity Conservation?

PubMed

Socolar, Jacob B; Gilroy, James J; Kunin, William E; Edwards, David P

2016-01-01

To design robust protected area networks, accurately measure species losses, or understand the processes that maintain species diversity, conservation science must consider the organization of biodiversity in space. Central is beta-diversity--the component of regional diversity that accumulates from compositional differences between local species assemblages. We review how beta-diversity is impacted by human activities, including farming, selective logging, urbanization, species invasions, overhunting, and climate change. Beta-diversity increases, decreases, or remains unchanged by these impacts, depending on the balance of processes that cause species composition to become more different (biotic heterogenization) or more similar (biotic homogenization) between sites. While maintaining high beta-diversity is not always a desirable conservation outcome, understanding beta-diversity is essential for protecting regional diversity and can directly assist conservation planning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Process for reducing beta activity in uranium

DOEpatents

Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

1986-10-07

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

Process for reducing beta activity in uranium

DOEpatents

Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

1986-01-01

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

Process for reducing beta activity in uranium

DOEpatents

Briggs, G.G.; Kato, T.R.; Schonegg, E.

1985-04-11

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

Construction of moment-matching multinomial lattices using Vandermonde matrices and Gröbner bases

NASA Astrophysics Data System (ADS)

Lundengârd, Karl; Ogutu, Carolyne; Silvestrov, Sergei; Ni, Ying; Weke, Patrick

2017-01-01

In order to describe and analyze the quantitative behavior of stochastic processes, such as the process followed by a financial asset, various discretization methods are used. One such set of methods are lattice models where a time interval is divided into equal time steps and the rate of change for the process is restricted to a particular set of values in each time step. The well-known binomial- and trinomial models are the most commonly used in applications, although several kinds of higher order models have also been examined. Here we will examine various ways of designing higher order lattice schemes with different node placements in order to guarantee moment-matching with the process.

Method for conversion of .beta.-hydroxy carbonyl compounds

DOEpatents

Lilga, Michael A.; White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Muzatko, Danielle S.; Orth, Rick J.

2010-03-30

A process is disclosed for conversion of salts of .beta.-hydroxy carbonyl compounds forming useful conversion products including, e.g., .alpha.,.beta.-unsaturated carbonyl compounds and/or salts of .alpha.,.beta.-unsaturated carbonyl compounds. Conversion products find use, e.g., as feedstock and/or end-use chemicals.

Local-scale Partitioning of Functional and Phylogenetic Beta Diversity in a Tropical Tree Assemblage.

PubMed

Yang, Jie; Swenson, Nathan G; Zhang, Guocheng; Ci, Xiuqin; Cao, Min; Sha, Liqing; Li, Jie; Ferry Slik, J W; Lin, Luxiang

2015-08-03

The relative degree to which stochastic and deterministic processes underpin community assembly is a central problem in ecology. Quantifying local-scale phylogenetic and functional beta diversity may shed new light on this problem. We used species distribution, soil, trait and phylogenetic data to quantify whether environmental distance, geographic distance or their combination are the strongest predictors of phylogenetic and functional beta diversity on local scales in a 20-ha tropical seasonal rainforest dynamics plot in southwest China. The patterns of phylogenetic and functional beta diversity were generally consistent. The phylogenetic and functional dissimilarity between subplots (10 × 10 m, 20 × 20 m, 50 × 50 m and 100 × 100 m) was often higher than that expected by chance. The turnover of lineages and species function within habitats was generally slower than that across habitats. Partitioning the variation in phylogenetic and functional beta diversity showed that environmental distance was generally a better predictor of beta diversity than geographic distance thereby lending relatively more support for deterministic environmental filtering over stochastic processes. Overall, our results highlight that deterministic processes play a stronger role than stochastic processes in structuring community composition in this diverse assemblage of tropical trees.

Double Charge Exchange Reactions and Double Beta Decay

NASA Astrophysics Data System (ADS)

Auerbach, N.

2018-05-01

The subject of this presentation is at the forefront of nuclear physics, namely double beta decay. In particular one is most interested in the neutrinoless process of double beta decay, when the decay proceeds without the emission of two neutrinos. The observation of such decay would mean that the lepton conservation symmetry is violated and that the neutrinos are of Majorana type, meaning that they are their own anti-particles. The life time of this process has two unknowns, the mass of the neutrino and the nuclear matrix element. Determining the nuclear matrix element and knowing the cross-section well will set limits on the neutrino mass. There is a concentrated effort among the nuclear physics community to calculate this matrix element. Usually these matrix elements are a very small part of the total strength of the transition operators involved in the process. There is no simple way to “calibrate” the nuclear double beta decay matrix element. The double beta decay is a double charge exchange process, therefore it is proposed that double charge exchange reactions using ion projectiles on nuclei that are candidates for double beta decay, will provide additional necessary information about the nuclear matrix elements.

Three-Dimensional Bioreactor Technologies for the Cocultivation of Human Mesenchymal Stem/Stromal Cells and Beta Cells

PubMed Central

Petry, Florian; Weidner, Tobias; Salzig, Denise

2018-01-01

Diabetes is a prominent health problem caused by the failure of pancreatic beta cells. One therapeutic approach is the transplantation of functional beta cells, but it is difficult to generate sufficient beta cells in vitro and to ensure these cells remain viable at the transplantation site. Beta cells suffer from hypoxia, undergo apoptosis, or are attacked by the host immune system. Human mesenchymal stem/stromal cells (hMSCs) can improve the functionality and survival of beta cells in vivo and in vitro due to direct cell contact or the secretion of trophic factors. Current cocultivation concepts with beta cells are simple and cannot exploit the favorable properties of hMSCs. Beta cells need a three-dimensional (3D) environment to function correctly, and the cocultivation setup is therefore more complex. This review discusses 3D cultivation forms (aggregates, capsules, and carriers) for hMSCs and beta cells and strategies for large-scale cultivation. We have determined process parameters that must be balanced and considered for the cocultivation of hMSCs and beta cells, and we present several bioreactor setups that are suitable for such an innovative cocultivation approach. Bioprocess engineering of the cocultivation processes is necessary to achieve successful beta cell therapy. PMID:29731775

The egasyn gene affects the processing of oligosaccharides of lysosomal beta-glucuronidase in liver.

PubMed Central

Swank, R T; Pfister, K; Miller, D; Chapman, V

1986-01-01

The accumulation of the relatively large amounts of beta-glucuronidase in microsomal fractions of normal mice depends on formation of complexes with the protein egasyn. Unexpectedly, it was found that the egasyn gene also affects the processing of beta-glucuronidase, which is segregated to lysosomes. In egasyn-positive mice lysosomal beta-glucuronidase from liver has a mean pI of 5.9 with a minor proportion at pI 5.4, whereas in egasyn-negative mice the proportion of the two lysosomal forms is reversed. Combined experiments measuring susceptibility to neuraminidase and to endoglycosidase H and specific binding to Ricinus communis lectin-agarose columns showed that the alterations in isoelectric point were associated with a decrease in complex oligosaccharides of lysosomal beta-glucuronidase in egasyn-positive mice. Since this alteration occurs not only in a congenic strain carrying the Eg0 gene but also in several other inbred strains that are homozygous for this gene, it is considered to be a genuine effect of the Eg gene rather than other genes that might regulate oligosaccharide processing. Also, the alteration is likely to be a result of direct physical interaction of the egasyn protein and lysosomal beta-glucuronidase, since a second lysosomal enzyme, beta-galactosidase, which does not form complexes with egasyn, is unaffected. The results suggest a model in which egasyn not only causes accumulation of beta-glucuronidase in the microsomal compartment but also acts upon the precursor to lysosomal beta-glucuronidase to alter its interaction with trans-Golgi-apparatus processing enzymes. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 6. Fig. 7. Fig. 8. PMID:3101673

Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

1995-01-01

The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a protein.

Application of the HARDMAN methodology to the single channel ground-airborne radio system (SINCGARS)

NASA Astrophysics Data System (ADS)

Balcom, J.; Park, J.; Toomer, L.; Feng, T.

1984-12-01

The HARDMAN methodology is designed to assess the human resource requirements early in the weapon system acquisition process. In this case, the methodology was applied to the family of radios known as SINCGARS (Single Channel Ground-Airborne Radio System). At the time of the study, SINCGARS was approaching the Full-Scale Development phase, with 2 contractors in competition. Their proposed systems were compared with a composite baseline comparison (reference) system. The systems' manpower, personnel and training requirements were compared. Based on RAM data, the contractors' MPT figures showed a significant reduction from the figures derived for the baseline comparison system. Differences between the two contractors were relatively small. Impact and some tradeoff analyses were hindered by data access problems. Tactical radios, manpower and personnel requirements analysis, impact and tradeoff analysis, human resource sensitivity, training requirements analysis, human resources in LCSMM, and logistics analyses are discussed.

Development of a wheat-Aegilops searsii substitution line with positively affecting Chinese steamed bread quality

PubMed Central

Du, Xuye; Ma, Xin; Min, Jingzhi; Zhang, Xiaocun; Jia, Zhenzhen

2018-01-01

A wheat-Aegilops searsii substitution line GL1402, in which chromosome 1B was substituted with 1Ss from Ae. searsii, was developed and detected using SDS-PAGE and GISH. The SDS-PAGE analysis showed that the HMW-GS encoded by the Glu-B1 loci of Chinese Spring was replaced by the HMW-GS encoded by the Glu-1Ss loci of Ae. searsii. Glutenin macropolymer (GMP) investigation showed that GL1402 had a much higher GMP content than Chinese Spring did. A dough quality comparison of GL1402 and Chinese Spring indicated that GL1402 showed a significantly higher protein content and middle peak time (MPT), and a smaller right peak slope (RPS). Quality tests of Chinese steamed bread (CSB) showed that the GL1402 also produced good steamed bread quality. These results suggested that the substitution line is a valuable breeding material for improving the wheat processing quality.

Deconvolution of the relaxations associated with local and segmental motions in poly(methacrylate)s containing dichlorinated benzyl moieties in the ester residue.

PubMed

Dominguez-Espinosa, Gustavo; Díaz-Calleja, Ricardo; Riande, Evaristo; Gargallo, Ligia; Radic, Deodato

2005-09-15

The relaxation behavior of poly(2,3-dichlorobenzyl methacrylate) is studied by broadband dielectric spectroscopy in the frequency range of 10(-1)-10(9) Hz and temperature interval of 303-423 K. The isotherms representing the dielectric loss of the glassy polymer in the frequency domain present a single absorption, called beta process. At temperatures close to Tg, the dynamical alpha relaxation already overlaps with the beta process, the degree of overlapping increasing with temperature. The deconvolution of the alpha and beta relaxations is facilitated using the retardation spectra calculated from the isotherms utilizing linear programming regularization parameter techniques. The temperature dependence of the beta relaxation presents a crossover associated with a change in activation energy of the local processes. The distance between the alpha and beta peaks, expressed as log(fmax;beta/fmax;alpha) where fmax is the frequency at the peak maximum, follows Arrhenius behavior in the temperature range of 310-384 K. Above 384 K, the distance between the peaks remains nearly constant and, as a result, the a onset temperature exhibited for many polymers is not reached in this system. The fraction of relaxation carried out through the alpha process, without beta assistance, is larger than 60% in the temperature range of 310-384 K where the so-called Williams ansatz holds.

Mapping CHU9D Utility Scores from the PedsQLTM 4.0 SF-15.

PubMed

Mpundu-Kaambwa, Christine; Chen, Gang; Russo, Remo; Stevens, Katherine; Petersen, Karin Dam; Ratcliffe, Julie

2017-04-01

The Pediatric Quality of Life Inventory™ 4.0 Short Form 15 Generic Core Scales (hereafter the PedsQL) and the Child Health Utility-9 Dimensions (CHU9D) are two generic instruments designed to measure health-related quality of life in children and adolescents in the general population and paediatric patient groups living with specific health conditions. Although the PedsQL is widely used among paediatric patient populations, presently it is not possible to directly use the scores from the instrument to calculate quality-adjusted life-years (QALYs) for application in economic evaluation because it produces summary scores which are not preference-based. This paper examines different econometric mapping techniques for estimating CHU9D utility scores from the PedsQL for the purpose of calculating QALYs for cost-utility analysis. The PedsQL and the CHU9D were completed by a community sample of 755 Australian adolescents aged 15-17 years. Seven regression models were estimated: ordinary least squares estimator, generalised linear model, robust MM estimator, multivariate factorial polynomial estimator, beta-binomial estimator, finite mixture model and multinomial logistic model. The mean absolute error (MAE) and the mean squared error (MSE) were used to assess predictive ability of the models. The MM estimator with stepwise-selected PedsQL dimension scores as explanatory variables had the best predictive accuracy using MAE and the equivalent beta-binomial model had the best predictive accuracy using MSE. Our mapping algorithm facilitates the estimation of health-state utilities for use within economic evaluations where only PedsQL data is available and is suitable for use in community-based adolescents aged 15-17 years. Applicability of the algorithm in younger populations should be assessed in further research.

Think twice before you book? Modelling the choice of public vs private dentist in a choice experiment.

PubMed

Kiiskinen, Urpo; Suominen-Taipale, Anna Liisa; Cairns, John

2010-06-01

This study concerns the choice of primary dental service provider by consumers. If the health service delivery system allows individuals to choose between public-care providers or if complementary private services are available, it is typically assumed that utilisation is a three-stage decision process. The patient first makes a decision to seek care, and then chooses the service provider. The final stage, involving decisions over the amount and form of treatment, is not considered here. The paper reports a discrete choice experiment (DCE) designed to evaluate attributes affecting individuals' choice of dental-care provider. The feasibility of the DCE approach in modelling consumers' choice in the context of non-acute need for dental care is assessed. The aim is to test whether a separate two-stage logit, a multinomial logit, or a nested logit best fits the choice process of consumers. A nested logit model of indirect utility functions is estimated and inclusive value (IV) constraints are tested for modelling implications. The results show that non-trading behaviour has an impact on the choice of appropriate modelling technique, but is to some extent dependent on the choice of scenarios offered. It is concluded that for traders multinomial logit is appropriate, whereas for non-traders and on average the nested logit is the method supported by the analyses. The consistent finding in all subgroup analyses is that the traditional two-stage decision process is found to be implausible in the context of consumer's choice of dental-care provider.

Acquisition Management for System of Systems: Requirement Evolution and Acquisition Strategy Planning

DTIC Science & Technology

2013-01-29

of modern portfolio and control theory . The reformulation allows for possible changes in estimated quantities (e.g., due to market shifts in... Portfolio Theory (MPT). Final Report: NPS award N00244-11-1-0003 5 Extending CEM and Markov: Agent-Based Modeling Approach Research conducted in the...integration and acquisition from a robust portfolio theory standpoint. Robust portfolio management methodologies have been widely used by financial

Dynamic Nanocomposite Self-Deactivating Fabrics for the Individual and Collective Protection

DTIC Science & Technology

2006-11-01

poly-ß-cyclodextrins (PCDs) and poly- trehalose (PTH) as polymeric supports, the incorporated enzymes will be able to repair themselves through a re...POLY- TREHALOSE (PTH) In a similar manner, polymeric trehalose (PTH) was also prepared in a different molar ratio optimized to maximize...MPT), polymeric trehalose (PTH) particles were prepared as a complementary substrate to poly-ß- CD particles in various aspects serving as an

FBIS report. Science and technology: Japan, February 20, 1996

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

NONE

1996-02-20

;Partial Contents: Energy (Japan: MHI Discovers Maritime Photo Plankton that Produces Ethanol from CO2, Japan: Tokyo Electric Power Co.`s PAFC Development); Telecommunications (Japan: Report on 1st Asian Telecommunications Industry Exchange, Japan: MPT Reports Test Evaluation Results for PHS); Defense Industries (Japan: Expert on Shipbuilding, Welding Technology, Japan: Komatsu R&D Chief on Dream of Ground Robots; Japan: Defense Simulator Series, Part 7: Torpedo Simulator).

A Preliminary Analysis of Human Factors Affecting the Recognition Accuracy of a Discrete Word Recognizer for C3 Systems.

DTIC Science & Technology

1983-03-01

acoustic wave pattern and, if so, word recognitios would be a sliple matter of the voice recogniticn system scanning the pattern, comparing the slmple...TRAINING WEEL - EEK#1 ORD# UTTERANCE CRT PRCtMPT (co0THREE THREE (Oe1EUROPE ERP V)r;_ OVE IT LEFT MCV7 IT LEFT 01 !CARRIAGE RETURN CAER RETURN LOGOLT LOGO UT

PARP1-mediated necrosis is dependent on parallel JNK and Ca2+/calpain pathways

PubMed Central

Douglas, Diana L.; Baines, Christopher P.

2014-01-01

ABSTRACT Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme that can trigger caspase-independent necrosis. Two main mechanisms for this have been proposed: one involving RIP1 and JNK kinases and mitochondrial permeability transition (MPT), the other involving calpain-mediated activation of Bax and mitochondrial release of apoptosis-inducing factor (AIF). However, whether these two mechanisms represent distinct pathways for PARP1-induced necrosis, or whether they are simply different components of the same pathway has yet to be tested. Mouse embryonic fibroblasts (MEFs) were treated with either N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or β-Lapachone, resulting in PARP1-dependent necrosis. This was associated with increases in calpain activity, JNK activation and AIF translocation. JNK inhibition significantly reduced MNNG- and β-Lapachone-induced JNK activation, AIF translocation, and necrosis, but not calpain activation. In contrast, inhibition of calpain either by Ca2+ chelation or knockdown attenuated necrosis, but did not affect JNK activation or AIF translocation. To our surprise, genetic and/or pharmacological inhibition of RIP1, AIF, Bax and the MPT pore failed to abrogate MNNG- and β-Lapachone-induced necrosis. In conclusion, although JNK and calpain both contribute to PARP1-induced necrosis, they do so via parallel mechanisms. PMID:25052090

In vivo characterization of structural changes after topical application of glucocorticoids in healthy human skin

NASA Astrophysics Data System (ADS)

Jung, Sora; Lademann, Jürgen; Darvin, Maxim E.; Richter, Claudia; Pedersen, Claus Bang; Richter, Heike; Schanzer, Sabine; Kottner, Jan; Blume-Peytavi, Ulrike; Røpke, Mads Almose

2017-07-01

Topical glucocorticoids (GC) are known to induce changes in human skin with the potential to develop skin atrophy. Here, atrophogenic effects and subsequent structural changes in the skin after topical application of GC were investigated in vivo. Sixteen healthy volunteers were topically treated daily on the forearms with clobetasol propionate, betamethasone dipropionate, and the petrolatum vehicle for 4 weeks. All treated skin areas and a nontreated control area were examined by ultrasound, optical coherence tomography, confocal laser scanning microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at baseline 1 day after last application and 1 week after last application. Investigated parameters included stratum corneum thickness, epidermal, and full skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm ratio, skin surface classification, relative collagen and elastin signal intensity, second-harmonic generation-to-autofluorescence aging index of dermis (SAAID), and the antioxidant status of the skin. A reduction in epidermal and dermal skin thickness was observed in GC treated as well as in vehicle-treated and untreated skin areas on the volar forearm. MPT analysis showed an increased epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a significant increase of SAAID after GC treatment indicating a restructuring or compression of collagen fibers clinically being observed as atrophic changes.

Some Rare Earth Elements Analysis by Microwave Plasma Torch Coupled with the Linear Ion Trap Mass Spectrometry

PubMed Central

Xiong, Xiaohong; Jiang, Tao; Qi, Wenhao; Zuo, Jun; Yang, Meiling; Fei, Qiang; Xiao, Saijin; Yu, Aimin; Zhu, Zhiqiang; Chen, Huanwen

2015-01-01

A sensitive mass spectrometric analysis method based on the microwave plasma technique is developed for the fast detection of trace rare earth elements (REEs) in aqueous solution. The plasma was produced from a microwave plasma torch (MPT) under atmospheric pressure and was used as ambient ion source of a linear ion trap mass spectrometer (LTQ). Water samples were directly pneumatically nebulized to flow into the plasma through the central tube of MPT. For some REEs, the generated composite ions were detected in both positive and negative ion modes and further characterized in tandem mass spectrometry. Under the optimized conditions, the limit of detection (LOD) was at the level 0.1 ng/mL using MS2 procedure in negative mode. A single REE analysis can be completed within 2~3 minutes with the relative standard deviation ranging between 2.4% and 21.2% (six repeated measurements) for the 5 experimental runs. Moreover, the recovery rates of these REEs are between the range of 97.6%–122.1%. Two real samples have also been analyzed, including well and orange juice. These experimental data demonstrated that this method is a useful tool for the field analysis of REEs in water and can be used as an alternative supplement of ICP-MS. PMID:26421013

Impacts and limitations of medialization thyroplasty on swallowing function of patients with unilateral vocal fold paralysis.

PubMed

Tateya, Ichiro; Hirano, Shigeru; Kishimoto, Yo; Suehiro, Atsushi; Kojima, Tsuyohi; Ohno, Satoshi; Ito, Juichi

2010-11-01

Medialization thyroplasty was effective in improving swallowing function as well as vocal function in most cases with unilateral vocal fold paralysis. The impact of medialization thryoplasty was insufficient for the case with severe atrophy and that in which the vocal fold was fixed in the lateral position. To evaluate the impacts and limitations of medialization thyroplasty on swallowing function of the patients with unilateral vocal fold paralysis. Eight cases (mean age 68.5 years) with unilateral vocal fold paralysis chiefly complaining of swallowing disturbance were studied. All patients underwent thyroplasty type I. The causes of the paralysis were lung cancer in four cases, esophageal cancer in one case, aortic aneurysm in one case, subarachnoid hemorrhage in one case, and unknown in one case. Subjective swallowing function score, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), and pitch perturbation quotient (PPQ) were examined pre- and postoperatively. The swallowing score improved in all except two cases. However, bilateral thryoplasty was necessary for the case with severe vocal fold atrophy and arytenoid adduction was needed for the case in which the vocal fold was fixed in the lateral position. The swallowing score, MPT, and MFR showed significant improvement after surgery.

High-efficiency and low-background multi-segmented proportional gas counter for β-decay spectroscopy

NASA Astrophysics Data System (ADS)

Mukai, M.; Hirayama, Y.; Watanabe, Y. X.; Schury, P.; Jung, H. S.; Ahmed, M.; Haba, H.; Ishiyama, H.; Jeong, S. C.; Kakiguchi, Y.; Kimura, S.; Moon, J. Y.; Oyaizu, M.; Ozawa, A.; Park, J. H.; Ueno, H.; Wada, M.; Miyatake, H.

2018-03-01

A multi-segmented proportional gas counter (MSPGC) with high detection efficiency and low-background event rate has been developed for β-decay spectroscopy. The MSPGC consists of two cylindrically aligned layers of 16 counters (32 counters in total). Each counter has a long active length and small trapezoidal cross-section, and the total solid angle of the 32 counters is 80% of 4 π. β-rays are distinguished from the background events including cosmic-rays by analyzing the hit patterns of independent counters. The deduced intrinsic detection efficiency of each counter was almost 100%. The measured background event rate was 0.11 counts per second using the combination of veto counters for cosmic-rays and lead block shields for background γ-rays. The MSPGC was applied to measure the β-decay half-lives of 198Ir and 199mPt. The evaluated half-lives of T1/2 = 9 . 8(7) s and 12.4(7) s for 198Ir and 199mPt, respectively, were in agreement with previously reported values. The estimated absolute detection efficiency of the MSPGC from GEANT4 simulations was consistent with the evaluated efficiency from the analysis of the β- γ spectroscopy of 199Pt, saturating at approximately 60% for Qβ > 4 MeV.

Cephalometric risk factors of obstructive sleep apnea.

PubMed

Bayat, Mohamad; Shariati, Mahsa; Rakhshan, Vahid; Abbasi, Mohsen; Fateh, Ali; Sobouti, Farhad; Davoudmanesh, Zeinab

2017-09-01

Previous studies on risk factors of obstructive sleep apnea (OSA) are highly controversial and mostly identifying a few cephalometric risk factors. OSA diagnosis was made according to the patients' apnea-hypopnea index (AHI). Included were 74 OSA patients (AHI > 10) and 52 control subjects (AHI ≤ 10 + free of other OSA symptoms). In both groups, 18 cephalometric parameters were traced (SNA, SNB, ANB, the soft palate's length (PNS-P), inferior airway space, the distance from the mandibular plane to the hyoid (MP-H), lengths of mandible (Go-Gn) and maxilla (PNS-ANS), vertical height of airway (VAL), vertical height of the posterior maxilla (S-PNS), superior posterior airway space (SPAS), middle airway space, distances from hyoid to third cervical vertebra and retrognathion (HH1), C3 (C3H), and RGN (HRGN), the maximum thickness of soft palate (MPT), tongue length (TGL), and the maximum height of tongue). These parameters were compared using t-test. Significant variables were SPAS (p = 0.027), MPT, TGL, HH1, C3H, HRGN, PNS-P, S-PNS, MP-H, VAL, and Go-Gn (all p values ≤ 0.006). OSA patients exhibited thicker and longer soft palates, hyoid bones more distant from the vertebrae, retrognathion, and mandibular plane, higher posterior maxillae, longer mandibles, and smaller superior-posterior airways.

Enhancement of magnetocaloric effect by external hydrostatic pressure in MnNi0.75Fe0.25Ge alloy

NASA Astrophysics Data System (ADS)

Mandal, K.; Dutta, P.; Dasgupta, P.; Pramanick, S.; Chatterjee, S.

2018-06-01

A systematic investigation on the structural and magnetic properties of an Fe-doped MnNiGe alloy with nominal composition MnNi0.75Fe0.25Ge has been performed. Temperature dependent x-ray diffraction studies indicate a clear structural phase transition (martensitic type) from the high temperature hexagonal austenite phase (space group P63/mmc) to the low temperature orthorhombic martensite phase (space group Pnma). Interestingly, about 1.4% of the high temperature hexagonal phase has been observed at 15 K, which is well below the martensitic phase transition (MPT) temperature. The studied alloy is found to be ferromagnetic in nature at the lowest temperature of measurement and the saturation moment increases in the presence of external hydrostatic pressure (P). In addition, it shows a significantly large conventional (negative) magnetocaloric effect with an adiabatic entropy change () of about ‑16.2 J kg‑1 K‑1 around the MPT for a magnetic field changing from 0  →  5 T. The most interesting observation is the  ∼40.1% increase in the peak value of on application of 6 kbar of external P. A considerable increment in the refrigeration capacity has also been noted with the applied P.

Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress.

PubMed

Li, Tsyregma; Brustovetsky, Tatiana; Antonsson, Bruno; Brustovetsky, Nickolay

2008-11-01

In the present study, we investigated the mechanism of cytochrome c release from isolated brain mitochondria induced by recombinant oligomeric BAX (BAX(oligo)). We found that BAX(oligo) caused a complete release of cytochrome c in a concentration- and time-dependent manner. The release was similar to those induced by alamethicin, which causes maximal mitochondrial swelling and eliminates barrier properties of the OMM. BAX(oligo) also produced large amplitude mitochondrial swelling as judged by light scattering assay and transmission electron microscopy. In addition, BAX(oligo) resulted in a strong mitochondrial depolarization. ATP or a combination of cyclosporin A and ADP, inhibitors of the mPT, suppressed BAX(oligo)-induced mitochondrial swelling and depolarization as well as cytochrome c release but did not influence BAX(oligo) insertion into the OMM. Both BAX(oligo)- and alamethicin-induced cytochrome c releases were accompanied by inhibition of ROS generation, which was assessed by measuring mitochondrial H(2)O(2) release with an Amplex Red assay. The mPT inhibitors antagonized suppression of ROS generation caused by BAX(oligo) but not by alamethicin. Thus, BAX(oligo) resulted in a complete cytochrome c release from isolated brain mitochondria in the mPT-dependent manner without involvement of oxidative stress by the mechanism requiring mitochondrial remodeling and permeabilization of the OMM.

Integrating medical, assistive, and universal design products and technologies: Assistive Technology Service Method (ATSM).

PubMed

Elsaesser, Linda-Jeanne; Bauer, Stephen

2012-07-01

ISO26000 provides guidance on effective organizational performance that recognizes social responsibility (including rights of persons with disabilities (PWD)), engages stakeholders, and contributes to sustainable development [1]. Millennium Development Goals 2010 state: while progress has been made, insufficient dedication to sustainable development, and inequalities to the most vulnerable people require attention [2]. World Report on Disability 2011 recommendations includes improved data collection and removal of barriers to rehabilitation that empower PWD [3]. The Assistive Technology Service Method (ATSM), Assistive Technology Device Classification (ATDC) and Matching Person and Technology (MPT) provide an evidence-based, standardized, internationally comparable framework to improve rehabilitation interventions [4-6]. The ATSM and ATDC support universal design (UD) principles and provision of universal technology. The MPT assures interventions are effective and satisfactory to end-users [7]. The ICF conceptual framework and common language are used throughout [8]. Research findings on healthcare needs are translated. ATSM applications in support of these findings are presented. National initiatives demonstrate the need and value of the ATSM as an evidence-based, user-centric, interdisciplinary method to improve individual and organizational performance for rehabilitation [including AT] services. Two Disability & Rehabilitation: Assistive Technology articles demonstrate ATSM and ATDC use to strengthen rehabilitation services and integrate Universal Design principles for socially responsible behavior.

Acoustic changes in student actors' voices after 12 months of training.

PubMed

Walzak, Peta; McCabe, Patricia; Madill, Cate; Sheard, Christine

2008-05-01

This study was to evaluate acoustic changes in student actors' voices after 12 months of actor training. The design used was a longitudinal study. Eighteen students enrolled in an Australian tertiary 3-year acting program (nine male and nine female) were assessed at the beginning of their acting course and again 12 months later using a questionnaire, interview, maximum phonation time (MPT), reading, spontaneous speaking, sustained phonation tasks, and a pitch range task. Samples were analyzed for MPT, fundamental frequency across tasks, pitch range for speaking and reading, singing pitch range, noise-to-harmonic ratio, shimmer, and jitter. After training, measures of shimmer significantly increased for both male and female participants. Female participants' pitch range significantly increased after training, with a significantly lower mean frequency for their lowest pitch. The finding of limited or negative changes for some measures indicate that further investigation is required into the long-term effects of actor voice training and which parameters of voicing are most targeted and valued in training. Particular investigation into the relationship between training targets and outcomes could more reliably inform acting programs about changes in teaching methodologies. Further research into the relationship between specific training techniques, physiological changes, and vocal changes may also provide information on implementing more evidence-based training methods.

Automatic Trading Agent. RMT Based Portfolio Theory and Portfolio Selection

NASA Astrophysics Data System (ADS)

Snarska, M.; Krzych, J.

2006-11-01

Portfolio theory is a very powerful tool in the modern investment theory. It is helpful in estimating risk of an investor's portfolio, arosen from lack of information, uncertainty and incomplete knowledge of reality, which forbids a perfect prediction of future price changes. Despite of many advantages this tool is not known and not widely used among investors on Warsaw Stock Exchange. The main reason for abandoning this method is a high level of complexity and immense calculations. The aim of this paper is to introduce an automatic decision-making system, which allows a single investor to use complex methods of Modern Portfolio Theory (MPT). The key tool in MPT is an analysis of an empirical covariance matrix. This matrix, obtained from historical data, biased by such a high amount of statistical uncertainty, that it can be seen as random. By bringing into practice the ideas of Random Matrix Theory (RMT), the noise is removed or significantly reduced, so the future risk and return are better estimated and controlled. These concepts are applied to the Warsaw Stock Exchange Simulator {http://gra.onet.pl}. The result of the simulation is 18% level of gains in comparison with respective 10% loss of the Warsaw Stock Exchange main index WIG.

Neurofeedback of SMR and Beta1 Frequencies: An Investigation of Learning Indices and Frequency-Specific Effects.

PubMed

Pimenta, Miguel G; van Run, Chris; de Fockert, Jan W; Gruzelier, John H

2018-05-15

Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have distinct cognitive enhancement effects, it remains unclear whether their amplitudes can be independently enhanced. Furthermore, demands for top-down attention control, postural restraint and maintenance of cognitive set processes, all requiring low-beta frequencies, might masquerade as learning and confound interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes was investigated with the addition of a random frequency control condition that also requires the potentially confounding cognitive processes. A comprehensive approach to assessing neurofeedback learning was undertaken through the calculation of learning indices within- and across-session and pre-to-post baseline. Herein we provide the first demonstration of beta1 within-session amplitude learning that was not attributable to extraneous cognitive processes, for it was not found with random frequency training. On the other hand, within-session SMR learning might have been obscured by high interindividual variability and methodological limitations such as the type of feedback screen, the insufficient number of sessions, and the exclusion of simultaneous theta and high-beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions in the three groups suggesting unspecific effects of neurofeedback in the low beta frequency band. Moreover, there was no clear evidence of frequency specificity associated with either SMR or beta1 training. Some methodological limitations may underpin the divergent results with previous studies. Copyright © 2017 IBRO. All rights reserved.

Noradrenergic innervation of the hypothalamus of rhesus monkeys: distribution of dopamine-beta-hydroxylase immunoreactive fibers and quantitative analysis of varicosities in the paraventricular nucleus.

PubMed

Ginsberg, S D; Hof, P R; Young, W G; Morrison, J H

1993-01-22

The distribution of noradrenergic processes within the hypothalamus of rhesus monkeys (Macaca mulatta) was examined by immunohistochemistry with an antibody against dopamine-beta-hydroxylase. The results revealed that the pattern of dopamine-beta-hydroxylase immunoreactivity varied systematically throughout the rhesus monkey hypothalamus. Extremely high densities of dopamine-beta-hydroxylase-immunoreactive processes were observed in the paraventricular and supraoptic nuclei, while relatively lower levels were found in the arcuate and dorsomedial nuclei and in the medial preoptic, perifornical, and suprachiasmatic areas. Moderate levels of dopamine-beta-hydroxylase immunoreactivity were found throughout the lateral hypothalamic area and in the internal lamina of the median eminence. Very few immunoreactive processes were found in the ventromedial nucleus or in the mammillary complex. Other midline diencephalic structures were found to have high densities of dopamine-beta-hydroxylase immunoreactivity, including the paraventricular nucleus of the thalamus and a discrete subregion of nucleus reuniens, the magnocellular subfascicular nucleus. A moderate density of dopamine-beta-hydroxylase immunoreactive processes were found in the rhomboid nucleus and zona incerta whereas little dopamine-beta-hydroxylase immunoreactivity was found in the fields of Forel, nucleus reuniens, or subthalamic nucleus. The differential distribution of dopamine-beta-hydroxylase-immunoreactive processes may reflect a potential role of norepinephrine as a regulator of a variety of functions associated with the nuclei that are most heavily innervated, e.g., neuroendocrine release from the paraventricular and supraoptic nuclei, and gonadotropin release from the medial preoptic area and mediobasal hypothalamus. Additionally, quantitative analysis of dopamine-beta-hydroxylase-immunoreactive varicosities was performed on a laser scanning microscope in both magnocellular and parvicellular regions of the paraventricular nucleus of the hypothalamus. The methodology employed in this study allowed for the high resolution of immunoreactive profiles through the volume of tissue being analyzed, and was more accurate than conventional light microscopy in terms of varicosity quantification. Quantitatively, a significant difference in the density of dopamine-beta-hydroxylase-immunoreactive varicosities was found between magnocellular and parvicellular regions, suggesting that parvicellular neurons received a denser noradrenergic input. These differential patterns may reflect an important functional role for norepinephrine in the regulation of anterior pituitary secretion through the hypothalamic-pituitary-adrenal stress axis.

Shared Sulfur Mobilization Routes for tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Prokaryotes and Eukaryotes

PubMed Central

Leimkühler, Silke; Bühning, Martin; Beilschmidt, Lena

2017-01-01

Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm5s2U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure. The trafficking and delivery of sulfur nucleosides is a complex process carried out by sulfur relay systems involving numerous proteins, which not only deliver sulfur to the specific tRNAs but also to other sulfur-containing molecules including iron–sulfur clusters, thiamin, biotin, lipoic acid and molybdopterin (MPT). Among the biosynthesis of these sulfur-containing molecules, the biosynthesis of the molybdenum cofactor (Moco) and the synthesis of thio-modified tRNAs in particular show a surprising link by sharing protein components for sulfur mobilization in pro- and eukaryotes. PMID:28098827

Role of ROS-mediated TGF beta activation in laser photobiomodulation

NASA Astrophysics Data System (ADS)

Arany, Praveen R.; Chen, Aaron Chih-Hao; Hunt, Tristan; Mooney, David J.; Hamblin, Michael

2009-02-01

The ability of laser light to modulate specific biological processes has been well documented but the precise mechanism mediating these photobiological interactions remains an area of intense investigation. We recently published the results of our clinical trial with 30 patients in an oral tooth-extraction wound healing model using a 904nm GaAs laser (Oralaser 1010, Oralia, Konstnaz, Germany), assessing healing parameters using routine histopathology and immunostaining (Arany et al Wound Rep Regen 2007, 15, 866). We observed a better organized healing response in laser irradiated oral tissues that correlated with an increased expression of TGF-beta1 immediately post laser irradiation. Our data suggested the source of latent TGF-beta1 might be from the degranulating platelets in the serum, an abundant source of in vivo latent TGF-beta, in the freshly wounded tissues. Further, we also demonstrated the ability of the low power near-infrared laser irradiation to activate the latent TGF-beta complexes in vitro at varying fluences from 10sec (0.1 J/cm2) to 600secs (6 J/cm2). Using serum we observed two isoforms, namely TGF-beta1 and TGF-beta3, were capable of being activated by laser irradiation using an isoform-specific ELISA and a reporter based (p3TP) assay system. We are presently pursuing the precise photomolecular mechanisms focusing on potential chromophores, wavelength and fluence parameters affecting the Latent TGF-beta activation process in serum. As ROS mediated TGF-beta activation has been previously demonstrated and we are also exploring the role of Laser generated-ROS in this activation process. In summary, we present evidence of a potential molecular mechanism for laser photobiomodulation in its ability to activate latent TGF-beta complexes.

Improved simultaneous determination method of beta-carotene and retinol with saponification in human serum and rat liver.

PubMed

Hosotani, Keisuke; Kitagawa, Masahiro

2003-07-05

Among the many simultaneous determination methods for carotenoid and retinoid, there are only a few reports including the saponification process. However, the yields of beta-carotene and retinol were higher when using this process. In this study, the analytical conditions, including saponification, were investigated. The extraction solvent was n-hexane and the sample solvent was HPLC mobile phase in the beta-carotene and retinol analysis. BHT as an antioxidant was added at concentrations of 0.125 and 0.025%, respectively, to ethanol and n-hexane phase in the extraction process for serum. The recovery rates were 99.7, 93.7 and 98.3% for beta-carotene, retinol and retinyl palmitate in serum, respectively, and 107.1, 92.8 and 98.8% for beta-carotene, retinol and retinyl palmitate in liver, respectively. The within-day coefficients of variation (C.V.) were 6.0% for serum and 4.7% for liver in the case of beta-carotene, 7.1% for serum, and 5.1% for liver in the case of retinol. The between-day coefficients of variation were 2.7% for serum and 2.7% for liver in the case of beta-carotene, and for retinol, 6.4% for serum and 2.7% for liver.

Ultrafast Unzipping of a Beta-Hairpin Peptide

NASA Astrophysics Data System (ADS)

Zinth, W.; Schrader, T. E.; Schreier, W. J.; Koller, F. O.; Cordes, T.; Babitzki, G.; Denschlag, R.; Tavan, P.; Löweneck, M.; Dong, Shou-Liang; Moroder, L.; Renner, C.

Light induced switching of a beta-hairpin structure is investigated by femtosecond IR spectroscopy. While the unzipping process comprises ultrafast kinetics and is finished within 1 ns, the folding into the hairpin structure is a much slower process.

Effect of processing on fracture toughness of silicon carbide as determined by Vickers indentations

NASA Technical Reports Server (NTRS)

Dannels, Christine M.; Dutta, Sunil

1989-01-01

Several alpha-SiC materials were processed by hot isostatic pressing (HIPing) and by sintering an alpha-SiC powder containing boron and carbon. Several beta-SiC materials were processed by HIPing a beta-SiC powder with boron and carbon additions. The fracture toughnesses K(sub 1c) of these beta- and alpha-SiC materials were estimated from measurements of Vickers indentations. The three formulas used to estimate K(sub 1c) from the indentation fracture patterns resulted in three ranges of K(sub 1c) estimates. Furthermore, each formula measured the effects of processing differently. All three estimates indicated that fine-grained HIPed alpha-SiC has a higher K(sub 1c) than coarsed-grained sintered alpha-SiC. Hot isostatically pressed beta-SiC, which had an ultrafine grain structure, exhibited a K(sub 1c) comparable to that of HIPed alpha-SiC.

Multinomial Logistic Regression & Bootstrapping for Bayesian Estimation of Vertical Facies Prediction in Heterogeneous Sandstone Reservoirs

NASA Astrophysics Data System (ADS)

Al-Mudhafar, W. J.

2013-12-01

Precisely prediction of rock facies leads to adequate reservoir characterization by improving the porosity-permeability relationships to estimate the properties in non-cored intervals. It also helps to accurately identify the spatial facies distribution to perform an accurate reservoir model for optimal future reservoir performance. In this paper, the facies estimation has been done through Multinomial logistic regression (MLR) with respect to the well logs and core data in a well in upper sandstone formation of South Rumaila oil field. The entire independent variables are gamma rays, formation density, water saturation, shale volume, log porosity, core porosity, and core permeability. Firstly, Robust Sequential Imputation Algorithm has been considered to impute the missing data. This algorithm starts from a complete subset of the dataset and estimates sequentially the missing values in an incomplete observation by minimizing the determinant of the covariance of the augmented data matrix. Then, the observation is added to the complete data matrix and the algorithm continues with the next observation with missing values. The MLR has been chosen to estimate the maximum likelihood and minimize the standard error for the nonlinear relationships between facies & core and log data. The MLR is used to predict the probabilities of the different possible facies given each independent variable by constructing a linear predictor function having a set of weights that are linearly combined with the independent variables by using a dot product. Beta distribution of facies has been considered as prior knowledge and the resulted predicted probability (posterior) has been estimated from MLR based on Baye's theorem that represents the relationship between predicted probability (posterior) with the conditional probability and the prior knowledge. To assess the statistical accuracy of the model, the bootstrap should be carried out to estimate extra-sample prediction error by randomly drawing datasets with replacement from the training data. Each sample has the same size of the original training set and it can be conducted N times to produce N bootstrap datasets to re-fit the model accordingly to decrease the squared difference between the estimated and observed categorical variables (facies) leading to decrease the degree of uncertainty.

The beta-diversity of species interactions: Untangling the drivers of geographic variation in plant-pollinator diversity and function across scales.

PubMed

Burkle, Laura A; Myers, Jonathan A; Belote, R Travis

2016-01-01

Geographic patterns of biodiversity have long inspired interest in processes that shape the assembly, diversity, and dynamics of communities at different spatial scales. To study mechanisms of community assembly, ecologists often compare spatial variation in community composition (beta-diversity) across environmental and spatial gradients. These same patterns inspired evolutionary biologists to investigate how micro- and macro-evolutionary processes create gradients in biodiversity. Central to these perspectives are species interactions, which contribute to community assembly and geographic variation in evolutionary processes. However, studies of beta-diversity have predominantly focused on single trophic levels, resulting in gaps in our understanding of variation in species-interaction networks (interaction beta-diversity), especially at scales most relevant to evolutionary studies of geographic variation. We outline two challenges and their consequences in scaling-up studies of interaction beta-diversity from local to biogeographic scales using plant-pollinator interactions as a model system in ecology, evolution, and conservation. First, we highlight how variation in regional species pools may contribute to variation in interaction beta-diversity among biogeographic regions with dissimilar evolutionary history. Second, we highlight how pollinator behavior (host-switching) links ecological networks to geographic patterns of plant-pollinator interactions and evolutionary processes. Third, we outline key unanswered questions regarding the role of geographic variation in plant-pollinator interactions for conservation and ecosystem services (pollination) in changing environments. We conclude that the largest advances in the burgeoning field of interaction beta-diversity will come from studies that integrate frameworks in ecology, evolution, and conservation to understand the causes and consequences of interaction beta-diversity across scales. © 2016 Botanical Society of America.

Direct Initiation Through Detonation Branching in a Pulsed Detonation Engine

DTIC Science & Technology

2008-03-01

important features noted ................................. 33  Figure 20. GM Quad 4 engine head used as the PDE research engine with the detonation tube...Deflagration to Detonation Transition EF – Engine Frequency FF – Fill Fraction NPT – National Pipe Thread MPT – Male National Pipe Thread PDE – Pulsed... Detonation Engines ( PDE ) has increased greatly in recent years due in part to the potential for increased thermal efficiency derived from constant

Handbook for Conducting Analysis of the Manpower, Personnel, and Training Elements for a MANPRINT Assessment

DTIC Science & Technology

1991-04-01

Traditional LCSMM and the Streamlined LCSMM. The Traditional LCSMM is divided into four phases: Concept Exploration, Demonstration and Validation, Full-Scale...to go faster. Whether that person is a typist, pianist or rifleman, his accuracy is nearly always decreased.) Figure 11 provides a graphic...each). Organizations are divided into two levels: primary and secondary. 44 Table 4 EXAMPLES OF MPT QUESTIONS USED FOR ANALYSIS OF RPV MANPOWER

The Reliability and Concurrent Validity of the Figure-of-Eight Method of Measuring Hand Edema in Patients with Burns

DTIC Science & Technology

2007-02-01

Travis L. Hedman, MPT, OCS, Ted T. Chapman, OTR/L, Steven E. Wolf, MD, FACS, John B. Holcomb, MD, FACS Objective: Water volumetry is considered the...hand, using the figure-of-eight technique. A third tester per- formed two measurements, using water volumetry . An independent investigator recorded...all measurements. Intratester and intertester reliability were analyzed. Concurrent validity was examined and compared with water volumetry

A beta-galactosidase gene is expressed during mature fruit abscission of 'Valencia' orange (Citrus sinensis).

PubMed

Wu, Zhencai; Burns, Jacqueline K

2004-07-01

beta-galactosidases have been detected in a wide range of plants and are characterized by their ability to hydrolyse terminal non-reducing beta-D-galactosyl residues from beta-D-galactosides. These enzymes have been detected in a wide range of plant organs and tissues. In a search for differentially expressed genes during the abscission process in citrus, sequences encoding beta-galactosidase were identified. Three cDNA fragments of a beta-galactosidase gene were isolated from a cDNA subtraction library constructed from mature fruit abscission zones 48 h after the application of a mature fruit-specific abscission agent, 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMN-pyrazole). Based on sequence information derived from these fragments, a full-length cDNA of 2847 nucleotides (GenBank accession number AY029198) encoding beta-galactosidase was isolated from mature fruit abscission zones by 5'- and 3'-RACE approaches. The beta-galactosidase cDNA encoded a protein of 737 amino acid residues with a calculated molecular weight of 82 kDa. The deduced protein was highly homologous to plant beta-galactosidases expressed in fruit ripening. Southern blot analysis demonstrated that at least two closely related beta-galactosidase genes were present in 'Valencia' orange. Temporal expression patterns in mature fruit abscission zones indicated beta-galactosidase mRNA was detected 48 h after treatment of CMN-pyrazole and ethephon in mature fruit abscission zones. beta-galactosidase transcripts were detected in leaf abscission zones only after ethephon application. The citrus beta-galactosidase was expressed in stamens and petals of fully opened flowers and young fruitlets. The results suggest that this beta-galactosidase may play a role during abscission as well as early growth and development processes in flowers and fruitlets.

Public funding of pharmaceuticals in The Netherlands: investigating the effect of evidence, process and context on CVZ decision-making.

PubMed

Cerri, Karin H; Knapp, Martin; Fernandez, Jose-Luis

2014-09-01

The College Voor Zorgverzekeringen (CVZ) provides guidance to the Dutch healthcare system on funding and use of new pharmaceutical technologies. This study examined the impact of evidence, process and context factors on CVZ decisions in 2004-2009. A data set of CVZ decisions pertaining to pharmaceutical technologies was created, including 29 variables extracted from published information. A three-category outcome variable was used, defined as the decision to 'recommend', 'restrict' or 'not recommend' a technology. Technologies included in list 1A/1B or on the expensive drug list were considered recommended; those included in list 2 or for which patient co-payment is required were considered restricted; technologies not included on any reimbursement list were classified as 'not recommended'. Using multinomial logistic regression, the relative contribution of explanatory variables on CVZ decisions was assessed. In all, 244 technology appraisals (256 technologies) were analysed, with 51%, of technologies recommended, 33% restricted and 16% not recommended by CVZ for funding. The multinomial model showed significant associations (p ≤ 0.10) between CVZ outcome and several variables, including: (1) use of an active comparator and demonstration of statistical superiority of the primary endpoint in clinical trials, (2) pharmaceutical budget impact associated with introduction of the technology, (3) therapeutic indication and (4) prevalence of the target population. Results confirm the value of a comprehensive and multivariate approach to understanding CVZ decision-making.

Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing.

PubMed

Sakurai, Takashi; Kaneko, Kumi; Okuno, Misako; Wada, Koji; Kashiyama, Taku; Shimizu, Hideaki; Akagi, Takumi; Hashikawa, Tsutomu; Nukina, Nobuyuki

2008-10-20

Neuronal activity has an impact on beta cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-beta peptide (Abeta). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of beta cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1-containing microdomains through X11-Munc18, which inhibits the APP-BACE1 interaction and beta cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Abeta overproduction, promotes the switching of APP microdomain association as well as beta cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons.

Species replacement dominates megabenthos beta diversity in a remote seamount setting.

PubMed

Victorero, Lissette; Robert, Katleen; Robinson, Laura F; Taylor, Michelle L; Huvenne, Veerle A I

2018-03-07

Seamounts are proposed to be hotspots of deep-sea biodiversity, a pattern potentially arising from increased productivity in a heterogeneous landscape leading to either high species co-existence or species turnover (beta diversity). However, studies on individual seamounts remain rare, hindering our understanding of the underlying causes of local changes in beta diversity. Here, we investigated processes behind beta diversity using ROV video, coupled with oceanographic and quantitative terrain parameters, over a depth gradient in Annan Seamount, Equatorial Atlantic. By applying recently developed beta diversity analyses, we identified ecologically unique sites and distinguished between two beta diversity processes: species replacement and changes in species richness. The total beta diversity was high with an index of 0.92 out of 1 and was dominated by species replacement (68%). Species replacement was affected by depth-related variables, including temperature and water mass in addition to the aspect and local elevation of the seabed. In contrast, changes in species richness component were affected only by the water mass. Water mass, along with substrate also affected differences in species abundance. This study identified, for the first time on seamount megabenthos, the different beta diversity components and drivers, which can contribute towards understanding and protecting regional deep-sea biodiversity.

Electrophysiological spatiotemporal dynamics during implicit visual threat processing.

PubMed

DeLaRosa, Bambi L; Spence, Jeffrey S; Shakal, Scott K M; Motes, Michael A; Calley, Clifford S; Calley, Virginia I; Hart, John; Kraut, Michael A

2014-11-01

Numerous studies have found evidence for corticolimbic theta band electroencephalographic (EEG) oscillations in the neural processing of visual stimuli perceived as threatening. However, varying temporal and topographical patterns have emerged, possibly due to varying arousal levels of the stimuli. In addition, recent studies suggest neural oscillations in delta, theta, alpha, and beta-band frequencies play a functional role in information processing in the brain. This study implemented a data-driven PCA based analysis investigating the spatiotemporal dynamics of electroencephalographic delta, theta, alpha, and beta-band frequencies during an implicit visual threat processing task. While controlling for the arousal dimension (the intensity of emotional activation), we found several spatial and temporal differences for threatening compared to nonthreatening visual images. We detected an early posterior increase in theta power followed by a later frontal increase in theta power, greatest for the threatening condition. There was also a consistent left lateralized beta desynchronization for the threatening condition. Our results provide support for a dynamic corticolimbic network, with theta and beta band activity indexing processes pivotal in visual threat processing. Published by Elsevier Inc.

A kinetic comparison of the processing and secretion of the alpha beta dimer and the uncombined alpha and beta subunits of chorionic gonadotropin synthesized by human choriocarcinoma cells.

PubMed

Peters, B P; Krzesicki, R F; Hartle, R J; Perini, F; Ruddon, R W

1984-12-25

Human choriocarcinoma cells (JAR) synthesize the alpha and beta subunits of the glycoprotein hormone chorionic gonadotropin (hCG) (R.W. Ruddon, C.A. Hanson, A. H. Bryan, G.J. Putterman, E.L. White, F. Perini, K. S. Meade, and P.H. Aldenderfer (1980) J. Biol. Chem. 255, 1000-1007). In addition to the hCG dimer (alpha beta), JAR cells secrete uncombined alpha and beta subunits into the culture medium (L.A. Cole, R.J. Hartle, J.A. Laferla, and R.W. Ruddon (1983) Endocrinology 113, 1176-1178). Pulse-chase studies with [35S]methionine or [3H]mannose were carried out in order to compare free alpha, free beta, and the alpha beta dimer with regard to the kinetics of synthesis, N-linked oligosaccharide processing, and secretion and to determine the kinetics of alpha-beta subunit combination. A panel of three antisera was used to immunoprecipitate directly the free subunits and the alpha beta dimer sequentially from the same cell lysates and culture media. The alpha subunit of hCG was synthesized in a slight molar excess (1.2-1.5-fold) over the beta subunit, and alpha beta dimer was rapidly formed by combination of the intracellular alpha and beta precursors. Dimer formation was already apparent in JAR cells following a 10-min biosynthetic labeling incubation with [35S]methionine. The combination of subunits ceased by 30 min of chase even though 51% of alpha and 44% of beta remained free within the cells. Combination of the alpha and beta precursors had occurred before their N-linked oligosaccharides were processed beyond the Man8GlcNAc2 structure. The initial trimming of glucosyl and mannosyl units from the high-mannose oligosaccharides of the hCG precursors occurred more rapidly for free alpha and CG-alpha than for free beta and CG-beta. JAR cells accumulated alpha precursors bearing mostly Man8GlcNAc2 units and beta precursors bearing Man8GlcNAc2 units that represent the substrates of the rate-limiting step in the secretory pathway. In spite of the fact that their N-linked oligosaccharides were trimmed at different rates, free alpha, free beta, and alpha beta dimer were all secreted into the medium at the same rate, with a half-time of 35 min. The secreted hCG forms were stable in the chase medium between 4 and 8h, indicating that extracellular degradation, combination of free subunits to form dimer, or dissociation of dimer to form free subunits did not occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Redox-mediated activation of latent transforming growth factor-beta 1

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Dix, T. A.; Chatterjee, A. (Principal Investigator)

1996-01-01

Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during disease mechanisms involving chronic ROS production.

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

Kosicek, Marko, E-mail: marko.kosicek@irb.hr; Malnar, Martina, E-mail: martina.malnar@irb.hr; Goate, Alison, E-mail: goate@icarus.wustl.edu

It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradientmore » centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.« less

Reorganization of Ice Sheet Flow Patterns in Arctic Canada Prior to the Mid-Pleistocene Transition

NASA Astrophysics Data System (ADS)

Refsnider, K. A.; Miller, G. H.

2010-12-01

The Foxe sector of the Laurentide Ice Sheet (LIS) experienced a complex and dynamic interplay between cold-based, non-erosive ice on uplands, fast-moving outlet glaciers that carved deep fiords through the Arctic Cordillera, and even more erosive ice streams that occupied larger straits and sounds, transporting ice from the Foxe Dome to calving margins in Baffin Bay and the Labrador Sea. The high topography of Baffin Island forms a broad barrier to the flow of ice to these calving margins and gradually has been dissected since the onset of Northern Hemisphere glaciation. However, evidence for the evolution of LIS erosion and basal thermal regime patterns during successive glaciations is poorly preserved in the geologic record. We use a new approach utilizing published till geochemistry and cosmogenic radionuclide (CRN) data to constrain the development of the fiorded coastline and the distribution of cold-based ice across central Baffin Island in both spatial and temporal domains over many glacial-interglacial cycles. The combination of till geochemistry data, which is used to characterize till weathering, and modeled CRN burial-exposure histories provides strong evidence for a shift in basal thermal regimes across the interior plateaux of Baffin Island between 1.9 and 1.2 Ma. While it may be coincidence that this time interval abuts the onset of the mid-Pleistocene transition (MPT), it has been hypothesized that changes in subglacial conditions were potentially an important mechanism in altering LIS dynamics across the MPT. Prior to this time, ice was likely wet-based and erosive across the majority of the Baffin Island interior, but by 1.9-1.2 Ma, some parts of the landscape became perpetually covered by cold-based ice during glaciations, a pattern that persisted through the last glacial cycle. The modern fiord system also must have developed by this time, and preferential channeling of ice flow into major fiords may have been sufficient to effectively shut off ice flow across the landscape between outlet glaciers. These results imply that there was a major shift in the basal thermal regime across the northeastern LIS, and the subsequent expansion of cold-based ice and the concentration of ice flow in fewer outlet systems across this region may help explain the cause of the MPT from 41- to 100-kyr glacial cycles.

Palaeoenvironmental conditions in the Gulf of Alaska (NE Pacific) during the Mid Pleistocene Transition

NASA Astrophysics Data System (ADS)

Müller, J.; Romero, O. E.; McClymont, E.; Stein, R. H.; Fahl, K.

2014-12-01

The Mid Pleistocene Transition (MPT) constitutes a fundamental shift in Earth's climate system from a 41 ka to a 100 ka periodicity in glacial oscillations. The exact timing and mechanism(s) that caused this change from a low- to high-amplitude glacial variability are still under debate and only recently Pena & Goldstein (2014) suggested that a disruption of the thermohaline circulation at about 900 ka BP and a subsequent change in ocean circulation might have acted as a trigger for the onset of 100 ka glacial-interglacial cycles. Most studies targeting the MPT are based on Atlantic sediment records whereas only few data sets are available from the North Pacific (see e.g. Clark et al., 2006 and McClymont et al., 2013 for reviews). IODP Expedition 341 distal deep-water site U1417 in the Gulf of Alaska (subpolar NE Pacific) now provided a continuous sediment record for reconstructing Miocene to Late Pleistocene changes in the sea surface conditions and how these relate to orbital and millennial scale climate variability. Here we present organic geochemical biomarker data covering the 1.5 Ma to 0.1 Ma time interval with special focus on the MPT. Alkenone, sterol, n-alkane and C25 highly branched isoprenoid data are used to reconstruct sea surface temperatures, primary productivity and terrigenous organic matter input (via sea ice, icebergs, meltwater discharge or aeolian transport). In addition, the diatom concentration and the species composition of the diatom assemblage deliver information on changes in palaeoproductivity and nutrient (silicate) availability. A major change in the environmental setting between 1.2 and 0.8 Ma is recorded by the biomarkers. This shift seems to be associated with a significant cooling of the surface waters in the Gulf of Alaska. Matching this shift, a significant change in the main components of the diatom community occurred between 1.2 and 0.8 Ma. References Clark, P.U., Archer, D., Pollard, D., Blum, J.D., Rial, J.A., Brovkin, V., Mix, A.C., Pisias, N.G., Roy, M., 2006. Quaternary Science Reviews, 25, (23-24), 3150-3184. McClymont, E.L., Sosdian, S.M., Rosell-Melé, A., Rosenthal, Y., 2013. Earth-Science Reviews, 123, 173-193. Pena, L.D. and Goldstein, S.L., 2014. Science, 345, 318-322.

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: prevention by thiol group protecting agents.

PubMed

Custódio, José B A; Cardoso, Carla M P; Santos, Maria S; Almeida, Leonor M; Vicente, Joaquim A F; Fernandes, Maria A S

2009-05-02

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca(2+)-induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20nmol/mg protein) induced Ca(2+)-dependent mitochondrial swelling, depolarization of membrane potential (DeltaPsi), Ca(2+) release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the DeltaPsi, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H(2)O(2) generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca(2+)-induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to H(+); (3) does not significantly affect H(2)O(2) generation by mitochondria; (4) its mitochondrial damaging effects are protected by thiol group protecting agents. Based on these conclusions, it is possible to hypothesise that small changes on the redox-status of thiol groups, affecting membrane permeability to cations (Ca(2+) and H(+)) underlie CisPt-induced liver mitochondrial damage, putatively responsible for its hepatotoxicity. Therefore, we propose that CisPt-induced mitochondrial damage and consequent hepatotoxicity could be prevented by using thiol group protecting agents as therapeutic adjuvants.

Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline.

PubMed

Hu, Jiangting; Kholmukhamedov, Andaleb; Lindsey, Christopher C; Beeson, Craig C; Jaeschke, Hartmut; Lemasters, John J

2016-08-01

Acetaminophen (APAP) overdose causes hepatotoxicity involving mitochondrial dysfunction and the mitochondrial permeability transition (MPT). Iron is a critical catalyst for ROS formation, and reactive oxygen species (ROS) play an important role in APAP-induced hepatotoxicity. Previous studies show that APAP disrupts lysosomes, which release ferrous iron (Fe(2+)) into the cytosol to trigger the MPT and cell killing. Here, our aim was to investigate whether iron released from lysosomes after APAP is then taken up into mitochondria via the mitochondrial electrogenic Ca(2+), Fe(2+) uniporter (MCFU) to cause mitochondrial dysfunction and cell death. Hepatocytes were isolated from fasted male C57BL/6 mice. Necrotic cell killing was assessed by propidium iodide fluorimetry. Mitochondrial membrane potential (ΔΨ) was visualized by confocal microscopy of rhodamine 123 (Rh123) and tetramethylrhodamine methylester (TMRM). Chelatable Fe(2+) was monitored by quenching of calcein (cytosol) and mitoferrofluor (MFF, mitochondria). ROS generation was monitored by confocal microscopy of MitoSox Red and plate reader fluorimetry of chloromethyldihydrodichlorofluorescein diacetate (cmH2DCF-DA). Administered 1h before APAP (10mM), the lysosomally targeted iron chelator, starch-desferal (1mM), and the MCFU inhibitors, Ru360 (100nM) and minocycline (4µM), decreased cell killing from 83% to 41%, 57% and 53%, respectively, after 10h. Progressive quenching of calcein and MFF began after ~4h, signifying increased cytosolic and mitochondrial chelatable Fe(2+). Mitochondria then depolarized after ~10h. Dipyridyl, a membrane-permeable iron chelator, dequenched calcein and MFF fluorescence after APAP. Starch-desferal, but not Ru360 and minocycline, suppressed cytosolic calcein quenching, whereas starch-desferal, Ru360 and minocycline all suppressed mitochondrial MFF quenching and mitochondrial depolarization. Starch-desferal, Ru360 and minocycline also each decreased ROS formation. Moreover, minocycline 1h after APAP decreased cell killing by half. In conclusion, release of Fe(2+) from lysosomes followed by uptake into mitochondria via MCFU occurs during APAP hepatotoxicity. Mitochondrial iron then catalyzes toxic hydroxyl radical formation, which triggers the MPT and cell killing. The efficacy of minocycline post-treatment shows minocycline as a possible therapeutic agent against APAP hepatotoxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Geomorphology Drives Amphibian Beta Diversity in Atlantic Forest Lowlands of Southeastern Brazil

PubMed Central

Luiz, Amom Mendes; Leão-Pires, Thiago Augusto; Sawaya, Ricardo J.

2016-01-01

Beta diversity patterns are the outcome of multiple processes operating at different scales. Amphibian assemblages seem to be affected by contemporary climate and dispersal-based processes. However, historical processes involved in present patterns of beta diversity remain poorly understood. We assess and disentangle geomorphological, climatic and spatial drivers of amphibian beta diversity in coastal lowlands of the Atlantic Forest, southeastern Brazil. We tested the hypothesis that geomorphological factors are more important in structuring anuran beta diversity than climatic and spatial factors. We obtained species composition via field survey (N = 766 individuals), museum specimens (N = 9,730) and literature records (N = 4,763). Sampling area was divided in four spatially explicit geomorphological units, representing historical predictors. Climatic descriptors were represented by the first two axis of a Principal Component Analysis. Spatial predictors in different spatial scales were described by Moran Eigenvector Maps. Redundancy Analysis was implemented to partition the explained variation of species composition by geomorphological, climatic and spatial predictors. Moreover, spatial autocorrelation analyses were used to test neutral theory predictions. Beta diversity was spatially structured in broader scales. Shared fraction between climatic and geomorphological variables was an important predictor of species composition (13%), as well as broad scale spatial predictors (13%). However, geomorphological variables alone were the most important predictor of beta diversity (42%). Historical factors related to geomorphology must have played a crucial role in structuring amphibian beta diversity. The complex relationships between geomorphological history and climatic gradients generated by the Serra do Mar Precambrian basements were also important. We highlight the importance of combining spatially explicit historical and contemporary predictors for understanding and disentangling major drivers of beta diversity patterns. PMID:27171522

Geomorphology Drives Amphibian Beta Diversity in Atlantic Forest Lowlands of Southeastern Brazil.

PubMed

Luiz, Amom Mendes; Leão-Pires, Thiago Augusto; Sawaya, Ricardo J

2016-01-01

Beta diversity patterns are the outcome of multiple processes operating at different scales. Amphibian assemblages seem to be affected by contemporary climate and dispersal-based processes. However, historical processes involved in present patterns of beta diversity remain poorly understood. We assess and disentangle geomorphological, climatic and spatial drivers of amphibian beta diversity in coastal lowlands of the Atlantic Forest, southeastern Brazil. We tested the hypothesis that geomorphological factors are more important in structuring anuran beta diversity than climatic and spatial factors. We obtained species composition via field survey (N = 766 individuals), museum specimens (N = 9,730) and literature records (N = 4,763). Sampling area was divided in four spatially explicit geomorphological units, representing historical predictors. Climatic descriptors were represented by the first two axis of a Principal Component Analysis. Spatial predictors in different spatial scales were described by Moran Eigenvector Maps. Redundancy Analysis was implemented to partition the explained variation of species composition by geomorphological, climatic and spatial predictors. Moreover, spatial autocorrelation analyses were used to test neutral theory predictions. Beta diversity was spatially structured in broader scales. Shared fraction between climatic and geomorphological variables was an important predictor of species composition (13%), as well as broad scale spatial predictors (13%). However, geomorphological variables alone were the most important predictor of beta diversity (42%). Historical factors related to geomorphology must have played a crucial role in structuring amphibian beta diversity. The complex relationships between geomorphological history and climatic gradients generated by the Serra do Mar Precambrian basements were also important. We highlight the importance of combining spatially explicit historical and contemporary predictors for understanding and disentangling major drivers of beta diversity patterns.

Multinomial logistic regression in workers' health

NASA Astrophysics Data System (ADS)

Grilo, Luís M.; Grilo, Helena L.; Gonçalves, Sónia P.; Junça, Ana

2017-11-01

In European countries, namely in Portugal, it is common to hear some people mentioning that they are exposed to excessive and continuous psychosocial stressors at work. This is increasing in diverse activity sectors, such as, the Services sector. A representative sample was collected from a Portuguese Services' organization, by applying a survey (internationally validated), which variables were measured in five ordered categories in Likert-type scale. A multinomial logistic regression model is used to estimate the probability of each category of the dependent variable general health perception where, among other independent variables, burnout appear as statistically significant.

A computer program for estimation from incomplete multinomial data

NASA Technical Reports Server (NTRS)

Credeur, K. R.

1978-01-01

Coding is given for maximum likelihood and Bayesian estimation of the vector p of multinomial cell probabilities from incomplete data. Also included is coding to calculate and approximate elements of the posterior mean and covariance matrices. The program is written in FORTRAN 4 language for the Control Data CYBER 170 series digital computer system with network operating system (NOS) 1.1. The program requires approximately 44000 octal locations of core storage. A typical case requires from 72 seconds to 92 seconds on CYBER 175 depending on the value of the prior parameter.

Categorical Data Analysis Using a Skewed Weibull Regression Model

NASA Astrophysics Data System (ADS)

Caron, Renault; Sinha, Debajyoti; Dey, Dipak; Polpo, Adriano

2018-03-01

In this paper, we present a Weibull link (skewed) model for categorical response data arising from binomial as well as multinomial model. We show that, for such types of categorical data, the most commonly used models (logit, probit and complementary log-log) can be obtained as limiting cases. We further compare the proposed model with some other asymmetrical models. The Bayesian as well as frequentist estimation procedures for binomial and multinomial data responses are presented in details. The analysis of two data sets to show the efficiency of the proposed model is performed.

Environmental Filtering Process Has More Important Roles than Dispersal Limitation in Shaping Large-Scale Prokaryotic Beta Diversity Patterns of Grassland Soils.

PubMed

Cao, Peng; Wang, Jun-Tao; Hu, Hang-Wei; Zheng, Yuan-Ming; Ge, Yuan; Shen, Ju-Pei; He, Ji-Zheng

2016-07-01

Despite the utmost importance of microorganisms in maintaining ecosystem functioning and their ubiquitous distribution, our knowledge of the large-scale pattern of microbial diversity is limited, particularly in grassland soils. In this study, the microbial communities of 99 soil samples spanning over 3000 km across grassland ecosystems in northern China were investigated using high-throughput sequencing to analyze the beta diversity pattern and the underlying ecological processes. The microbial communities were dominated by Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, and Planctomycetes across all the soil samples. Spearman's correlation analysis indicated that climatic factors and soil pH were significantly correlated with the dominant microbial taxa, while soil microbial richness was positively linked to annual precipitation. The environmental divergence-dissimilarity relationship was significantly positive, suggesting the importance of environmental filtering processes in shaping soil microbial communities. Structural equation modeling found that the deterministic process played a more important role than the stochastic process on the pattern of soil microbial beta diversity, which supported the predictions of niche theory. Partial mantel test analysis have showed that the contribution of independent environmental variables has a significant effect on beta diversity, while independent spatial distance has no such relationship, confirming that the deterministic process was dominant in structuring soil microbial communities. Overall, environmental filtering process has more important roles than dispersal limitation in shaping microbial beta diversity patterns in the grassland soils.

METHOD OF PREPARING COMPLEXES OF PLUTONIUM WITH DIKETONES

DOEpatents

Dixon, J.S.; Katz, J.J.; Orlemann, E.F.

1961-06-20

A process is described for sepsrating Pu from an aqueous alkaline solution by either precipitating with a beta -diketone or extracting into a solution of the beta -dixetone in an organic water-immiscible solvent. Acetyl acetone and benzoyl acetone are the beta -diketones used.

Synthesis of anatase TiO2 nanoparticles with beta-cyclodextrin as a supramolecular shell.

PubMed

Li, Landong; Sun, Xiaohong; Yang, Yali; Guan, Naijia; Zhang, Fuxiang

2006-11-20

We report a novel, green hydrothermal-synthesis route to well-dispersed anatase TiO2 nanoparticles with particle sizes of 9-16 nm in the presence of beta-CD (beta-cyclodextrin). During the synthesis process, the CD-containing synthesis mixture assembled in both longitudinal and latitudinal directions. Driven by the interaction between molecules, the beta-CDs assembled in the longitudinal direction to form long-chain compounds, whereas in the latitudinal direction, they tended to form regular aggregates through coordination with the Ti species from the hydrolysis of tetrabutyl titanate. In view of the effect of the coordination and the steric hindrance of beta-CDs as a supramolecular shell, homogeneous nuclei and slow growth of TiO2 crystals during the synthesis process was observed, which was responsible for the formation of uniform TiO2 nanoparticles. The low beta-CD dosage and the high product yield (>90%) demonstrated well the potential of this synthesis route in the large-scale industrial production of anatase nanoparticles.

Economic analysis of fuel ethanol production from hulled barley by the EDGE (Enhanced Dry Grind Enzymatic) process

USDA-ARS?s Scientific Manuscript database

A cost model was developed for fuel ethanol production from barley based on the EDGE (Enhanced Dry Grind Enzymatic) process (Nghiem, et al., 2008). In this process, in addition to beta-glucanases, which is added to reduce the viscosity of the barley mash for efficient mixing, another enzyme, beta-...

Role of cyclophilin D-dependent mitochondrial permeability transition in glutamate-induced calcium deregulation and excitotoxic neuronal death

PubMed Central

Li, Viacheslav; Brustovetsky, Tatiana; Brustovetsky, Nickolay

2009-01-01

In the present study we tested the hypothesis that the cyclophilin D-dependent (CyD) mitochondrial permeability transition (CyD-mPT) plays an important role in glutamate-triggered delayed calcium deregulation (DCD) and excitotoxic neuronal death. We used cultured cortical neurons from wild-type C57BL/6 and cyclophilin D knockout mice (Ppif-/-). Induction of the mPT was identified by following the rapid secondary acidification of mitochondrial matrices monitored with mitochondrially targeted pH-sensitive yellow fluorescent protein. Suppression of the CyD-mPT due to genetic CyD ablation deferred DCD and mitochondrial depolarization, and increased the survival rate after exposure of neurons to 10μM glutamate, but not to 100μM glutamate. Ca2+ influx into Ppif-/- neurons was not diminished in comparison with WT neurons judging by 45Ca accumulation. In both types of neurons, 100μM glutamate produced greater Ca2+ influx than 10μM glutamate. We hypothesize that greater Ca2+ influx produced by higher glutamate rapidly triggered the CyD-independent mPT in both WT and Ppif-/- neurons equalizing their responses to supra-physiologic excitotoxic insults. In neurons exposed to moderate but pathophysiologically-relevant glutamate concentrations, an induction of the CyD-mPT appears to play an important role in mitochondrial injury contributing to DCD and cell death. PMID:19236863

CO2 laser-assisted microsurgery for intracordal cysts: technique and results of 49 patients.

PubMed

Matar, Nayla; Amoussa, Kassira; Verduyckt, Ingrid; Nollevaux, Marie-Cecile; Jamart, Jacques; Lawson, Georges; Remacle, Marc

2010-12-01

Microsurgery for intracordal cysts is a challenging procedure, because cysts are close to the vocal ligament and the risk of inducing a scar is high. In this retrospective study, our experience with the CO(2)-laser scanning system (Acublade(®)) is reported on 49 patients. There were 41% epidermoid cysts and 59% mucous retention cysts. A quarter of the patients presented with bilateral cystic lesions and 59% had a contralateral lesion other than a cyst. The cyst was removed after a minimicroflap. It was dissected away from the lamina propria and the epithelium. Collagen was injected intraoperatively if the glottal gap was considered important. The epithelium was redraped using Tissucol (Baxter, Vienna, Austria). The mean follow-up time was 160 days. We noted a statistically significant improvement in the grade of the dysphonia according to Hirano's perceptual scale (G pre = 2, G post = 1, p = 0.002); the Vocal Handicap Index (VHI pre = 51, VHI post = 28, p = 0.001) and the maximal phonation time in milliseconds (MPT pre = 11, 1 MPT post = 12.7, p = 0.033) in all the patients. In the professional voice subgroup (20/49 patients), there was a significant improvement in the frequency range (FR pre = 310 Hz, FR post = 434 Hz, p = 0.001). The CO(2)-laser scanning system is reliable in the treatment of intracordal cysts.