Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

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Kumar, M. Suresh; Aruna, P.; Ganesan, S.

2018-03-01

One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

Up-Regulation of the Inflammatory Response by Ovariectomy in Collagen-Induced Arthritis. Effects of Tin Protoporphyrin IX.

NARCIS (Netherlands)

Ibanez, L.; Alcaraz, M.J.; Maicas Blasco, N.; Guede, D.; Caeiro, J.R.; Koenders, M.I.; Berg, W.B. van den; Ferrandiz, M.L.

2011-01-01

We have studied the influence of ovariectomy on the inflammatory response and bone metabolism on CIA as a model of postmenopausal arthritis as well as the effects of tin protoporphyrin IX (SnPP), a heme oxygenase inhibitor. Ovariectomy in non-arthritic mice produced increased serum PGD(2) levels and

Egg-Citing! Isolation of Protoporphyrin IX from Brown Eggshells and Its Detection by Optical Spectroscopy and Chemiluminescence

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Dean, Michelle L.; Miller, Tyson A.; Bruckner, Christian

2011-01-01

A simple and cost-effective laboratory experiment is described that extracts protoporphyrin IX from brown eggshells. The porphyrin is characterized by UV-vis and fluorescence spectroscopy. A chemiluminescence reaction (peroxyoxalate ester fragmentation) is performed that emits light in the UV region. When the porphyrin extract is added as a fluor…

Syntheses of protoporphyrin-IX regioselectivity carbon-13 labelled at the alpha-vinyl carbons

International Nuclear Information System (INIS)

Smith, K.M.; Fujinari, E.M.

1986-01-01

A method for transformation of readily available beta-vinyl 99% carbon-13 enriched derivatives of protoporphyrin-IX dimethyl ester into the less accessible alpha-vinyl labelled isomers is described. The procedure involves thallium(III) promoted vinyl carbon rearrangement, and proceeds through 2,2-dimethoxyethyl, formylmethyl, 2-hydroxyethyl and 2-chloroethyl porphyrins; the rearranged vinyl groups are regenerated from 2-chloroethyl in the last step by treatment with base. No evidence of vinyl carbon scrambling in the sequence is observed, and spectroscopic data of the products are given. (author)

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

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Qing Li

2013-09-01

Full Text Available Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX, a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180 cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl-2, 5-diphenyltetrazoliumbromide (MTT assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore. Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

Modulation of the endogenous production of protoporphyrin IX in a yeast-based model organism

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Joniová, Jaroslava; Gerelli, Emmanuel; Wagnières, Georges

2017-02-01

The main aim of this study was to assess conditions at which simple yeast-based model organism produces maximal levels of protoporphyrin IX (PpIX) after an exogenous administration of its precursor, 5-aminolevulinic acid (ALA), and the ferrous-ion chelator 2,2'-bipyridyl. We observed that the fluorescing porphyrin, produced after these administrations, was likely to be PpIX since fluorescence spectroscopy of the porphyrins produced endogenously in yeast cells resembles that of PpIX in DMSO and in vivo in the chick's chorioallantoic membrane model. Also, fluorescence lifetimes of these porphyrins are very similar to that of PpIX in vitro and in vivo. This suggests that PpIX is the main fluorescent compound produced by yeast in our conditions. We found that the conditions at which yeast produces the maximal PpIX were a synchronous administration of 5 μM ALA and 1 mM 2,2'-bipyridyl for yeast incubated in aqueous glucose and 1 mM 2,2'-bipyridyl in the presence of YPD medium. Such a simple model is of high interest to study basic mechanisms involved in the mitochondrial respiration since PpIX, which is produced in this organelle, can be used as an oxygen sensor, or to perform photodynamic therapy and photodiagnosis. Since the absorption and scattering coefficients of this model are much smaller than those of soft tissues over the visible part of the spectrum, a version of this model loaded with appropriated amounts of light absorbing and scattering particles could be designed as a phantom to mimic tumors containing PpIX, a useful tool to optimize certain cancer photodetection set-ups.

Quantitative model calculation of the time-dependent protoporphyrin IX concentration in normal human epidermis after delivery of ALA by passive topical application or lontophoresis

NARCIS (Netherlands)

Star, Willem M.; Aalders, Maurice C. G.; Sac, Arnoldo; Sterenborg, Henricus J. C. M.

2002-01-01

We present a mathematical layer model to quantitatively calculate the diffusion of 5-aminolevulinic acid (ALA) in the skin in vivo, its uptake into the cells and its conversion to protoporphyrin IX (PpIX) and subsequently to heme. The model is a modification and extension of a recently presented

Singlet oxygen feedback delayed fluorescence of protoporphyrin IX in organic solutions.

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Vinklárek, Ivo S; Scholz, Marek; Dědic, Roman; Hála, Jan

2017-04-12

Delayed fluorescence (DF) of protoporphyrin IX (PpIX) has been recently proposed as a tool for monitoring of mitochondrial oxygen tension in vivo as well as for observation of the effectiveness of photodynamic therapy (PDT) [E. G. Mik, Anesth. Analg., 2013, 117, 834-346; F. Piffaretti et al., J. Biomed. Opt., 2012, 17, 115007]. However, the efficiency of the mechanism of thermal activation (E-type DF), which was considered in the papers, is limited due to a large energy gap between the first excited singlet and the first triplet state of PpIX at room or body temperatures. Moreover, the energy gap is roughly equal to other porphyrinoid photosensitizers that generate DF mostly through the Singlet Oxygen Feedback-Induced mechanism (SOFDF) under certain conditions [M. Scholz and R. Dědic, Singlet Oxygen: Applications in Biosciences and Nanosciences, 2016, vol. 2, pp. 63-81]. The mechanisms of delayed fluorescence of PpIX dissolved either in dimethylformamide (DMF) or in the mixture of DMF with ethylene glycol (EG) were investigated at atmospheric partial pressure of oxygen by means of a simultaneous time-resolved detection of 1 O 2 phosphorescence and PpIX DF which makes a direct comparison of the kinetics and lifetimes of both the luminescence channels possible. Samples of PpIX (100 μM) exhibit concave DF kinetics, which is a typical footprint of the SOFDF mechanism. The dramatic decrease in the DF intensity after adding a selective 1 O 2 quencher sodium azide (NaN 3 , 10 mM) proves that >90% of DF is indeed generated through SOFDF. Moreover, the analysis of the DF kinetics in the presence of NaN 3 implies that the second significant mechanism of DF generation is the triplet-triplet annihilation (P-type DF). The bimolecular mechanism of DF was further confirmed by the decrease of the DF intensity in the more viscous mixture DMF/EG and by the increase of the ratio of DF to the prompt fluorescence (PF) intensity with the increasing excitation intensity. These results

High overexpression of dye decolorizing peroxidase TfuDyP leads to the incorporation of heme precursor protoporphyrin IX

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Colpa, Dana I.; Fraaije, Marco W.

2016-01-01

Highlights • Dye decolorizing peroxidase TfuDyP binds heme and protoporphyrin IX in vivo. • The activity of TfuDyP is dependent on the expression level in E. coli. • Expression of fully functional DyPs can be tuned by the type of expression host and expression conditions. The heterologous

Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma

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Wang M

2017-05-01

Full Text Available Mian Wang,1 Benjamin M Geilich,2 Michael Keidar,3 Thomas J Webster1,4 1Department of Chemical Engineering, 2Department of Bioengineering, Northeastern University, Boston, MA, 3Department of Mechanical and Aerospace Engineering, George Washington University, Washington, DC, USA; 4Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX, an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed. With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed compared to not using a light source (45% were killed or using a UV light source (65% were killed. In summary, these results indicated for the

Evaluation of Sonochemiluminescence in a Phantom in the Presence of Protoporphyrin IX Conjugated to Nanoparticles

International Nuclear Information System (INIS)

Shanei, A.; Sazgarnia, A.; Hassanzadeh-Kayyat, M.; Eshghi, H.; Soudmand, S.; Attaran Kakhki, N.

2012-01-01

When a liquid is irradiated with high-intensity and low-frequency ultrasound, acoustic cavitation occurs and there are some methods to determine and quantify this phenomenon. The existing methods for performing these experiments include sonochemiluminescence and chemical dosimetric methods. The particles in a liquid decrease the ultrasonic intensity threshold needed for cavitation onset. In this study, a new nano conjugate made up of Protoporphyrin IX and gold nanoparticles, i.e., Au-PpIX was used to provide nucleation sites for cavitation. The nonradiative relaxation time of PpIX in the presence of GNPs is longer than the similar time for PpIX without GNPs. This effect can be used in medical diagnostic and therapeutic applications. The acoustic cavitation activity was investigated studying integrated sonochemiluminescence signal in the wavelength range of 400-500 nm in polyacrylamide gel phantom containing luminol using a cooled CCD spectrometer at different intensities of 1 MHz ultrasound. In order to confirm these results, a chemical dosimetric method was utilized, too. sonochemiluminescence signal level in gel phantom containing Au-PpIX was higher than the other phantoms. These results have been confirmed by the chemical dosimetric data. This finding can be related to the existence of PpIX as a sensitizer and GNPs as cavitation nuclei. In other words, nanoparticles have acted as the sites for cavitation and have increased the cavitation rate. Another theory is that activation of PpIX has produced more free radicals and has enhanced the sonochemiluminescence signal level.

Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas: standardization and quantitative comparison with histology

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Wei, Linpeng; Chen, Ye; Yin, Chengbo; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T. C.

2017-04-01

Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image contrast in many tumors due to the increased accumulation of protoporphyrin IX (PpIX), a fluorescent porphyrin that is associated with tumor burden and proliferation. The value of PpIX-guided resection of malignant gliomas has been demonstrated in prospective randomized clinical studies in which a twofold greater extent of resection and improved progression-free survival have been observed. In low-grade gliomas and at the diffuse infiltrative margins of all gliomas, PpIX fluorescence is often too weak to be detected with current low-resolution surgical microscopes that are used in operating rooms. However, it has been demonstrated that high-resolution optical-sectioning microscopes are capable of detecting the sparse and punctate accumulations of PpIX that are undetectable via conventional low-power surgical fluorescence microscopes. To standardize the performance of high-resolution optical-sectioning devices for future clinical use, we have developed an imaging phantom and methods to ensure that the imaging of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging studies with a dual-axis confocal microscope demonstrate that these methods enable the acquisition of images from unsectioned human brain tissues that quantitatively and consistently correlate with images of histologically processed tissue sections.

Evaluation of Sonochemiluminescence in a Phantom in the Presence of Protoporphyrin IX Conjugated to Nanoparticles

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Ahmad Shanei

2012-03-01

Full Text Available Introduction When a liquid is irradiated with high-intensity and low-frequency ultrasound, acoustic cavitation occurs and there are some methods to determine and quantify this phenomenon. The existing methods for performing these experiments include sonochemiluminescence (SCL and chemical dosimetric methods. The particles in a liquid decrease the ultrasonic intensity threshold needed for cavitation onset. In this study, a new nanoconjugate made up of Protoporphyrin IX (PpIX and gold nanoparticles (GNP, i.e., Au-PpIX was used to provide nucleation sites for cavitation. The nonradiative relaxation time of PpIX in the presence of GNPs is longer than the similar time for PpIX without GNPs. This effect can be used in medical diagnostic and therapeutic applications. Materials and Methods The acoustic cavitation activity was investigated studying integrated SCL signal in the wavelength range of 400-500 nm in polyacrylamide gel phantom containing luminol using a cooled CCD spectrometer at different intensities of 1 MHz ultrasound. In order to confirm these results, a chemical dosimetric method was utilized, too. Results SCL signal level in gel phantom containing Au-PpIX was higher than the other phantoms. These results have been confirmed by the chemical dosimetric data. Conclusion This finding can be related to the existence of PpIX as a sensitizer and GNPs as cavitation nuclei. In other words, nanoparticles have acted as the sites for cavitation and have increased the cavitation rate. Another theory is that activation of PpIX has produced more free radicals and has enhanced the SCL signal level.

Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX

NARCIS (Netherlands)

Jonker, Johan W.; Musters, Sandra; Vlaming, Maria L. H.; Plosch, Torsten; Gooijert, Karin E. R.; Hillebrand, Michel J.; Rosing, Hilde; Beijnen, Jos H.; Verkade, Henkjan J.; Schinkel, Alfred H.

Proper regulation of intracellular levels of protoporphyrin IX (PPIX), the direct precursor of heme, is important for cell survival. A deficiency in ferrochelatase, which mediates the final step in heme biosynthesis, leads to erythropoietic protoporphyria (EPP), a photosensitivity syndrome caused by

Hierarchical coassembly of DNA–triptycene hybrid molecular building blocks and zinc protoporphyrin IX

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Rina Kumari

2016-05-01

Full Text Available Herein, we describe the successful construction of composite DNA nanostructures by the self-assembly of complementary symmetrical 2,6,14-triptycenetripropiolic acid (TPA–DNA building blocks and zinc protoporphyrin IX (Zn PpIX. DNA–organic molecule scaffolds for the composite DNA nanostructure were constructed through covalent conjugation of TPA with 5′-C12-amine-terminated modified single strand DNA (ssDNA and its complementary strand. The repeated covalent conjugation of TPA with DNA was confirmed by using denaturing polyacrylamide gel electrophoresis (PAGE, reverse-phase high-performance liquid chromatography (RP-HPLC and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF. The biologically relevant photosensitizer Zn PpIX was used to direct the hybridization-mediated self-assembly of DNA–TPA molecular building blocks as well as a model guest molecule within the DNA–TPA supramolecular self-assembly. The formation of fiber-like composite DNA nanostructures was observed. Native PAGE, circular dichroism (CD and atomic force microscopy (AFM have been utilized for analyzing the formation of DNA nanofibers after the coassembly. Computational methods were applied to discern the theoretical dimension of the DNA–TPA molecular building block of the nanofibers. A notable change in photocatalytic efficiency of Zn PpIX was observed when it was inside the TPA–DNA scaffold. The significant increase in ROS generation by Zn PpIX when trapped in this biocompatible DNA–TPA hybrid nanofiber may be an effective tool to explore photodynamic therapy (PDT applications as well as photocatalytic reactions.

Computational study of the solvation of protoporphyrin IX and its Fe2+ complex

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Guizado, Teobaldo Cuya; Pita, Samuel Da Rocha; Louro, Sonia R. Wanderley; Pascutti, Pedro Geraldo

Molecular dynamics (MD) simulations of a well known hydrophobic structure, the heme (ferroprotoporphyrin IX) and its precursor in the heme synthesis, protoporphyrin IX (PPIX) are presented. The objective of the present study is to determine the stability of both structures in an aqueous medium, as well as the structure-solvent relation, hydration shells, and discuss their implications for biological processes. The density functional theory (DFT) is used for the electronic and structural characterization of both PPIX and its Fe2+ complex. A classical approach based on the Gromacs package is used for the MD. The radial distribution function g(r) is used to examine the allocation of water molecules around different regions of the porphyrins. The calculations demonstrate the heterogeneous character of the porphyrins with respect to the affinity with water molecules, the general hydrophobic character of the porphyrin ring bonded or not to the ion Fe, the hydrophilic character of the carboxylic oxygen that is unchanged upon iron binding, and the low hydrophilicity of Fe2+ in the heme.

Effect of PpIX photoproducts formation on pO2 measurement by time-resolved delayed fluorescence spectroscopy of PpIX in solution and in vivo.

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Huntosova, Veronika; Gerelli, Emmanuel; Zellweger, Matthieu; Wagnières, Georges

2016-11-01

The measurement of Protoporphyrin IX delayed fluorescence lifetime is a minimally invasive method for monitoring the levels of oxygen in cells and tissues. The excitation of Protoporphyrin IX during this measurement can lead to the formation of photoproducts in vitro and in vivo. The influence of their luminescence on the measured Protoporphyrin IX delayed fluorescence lifetimes was studied in solution and in vivo on the Chick's chorioallantoic membrane (CAM) model under various oxygen enriched air conditions (0mmHg, 37mmHg and 155mmHg). The presence of photoproducts disturbs such measurements since the delayed fluorescence emission of some of them spectrally overlaps with that of Protoporphyrin IX. One possible way to avoid this obstacle is to detect Protoporphyrin IX's delayed fluorescence lifetime in a very specific spectral range (620-640nm). Another possibility is to excite Protoporphyrin IX with light doses much lower than 10J/cm 2 , quite possibly as low as a fraction 1J/cm 2 at 405nm. This leads to an increased accuracy of pO 2 detection. Furthermore, this method allows combination of diagnosis and therapy in one step. This helps to improve detection systems and real-time identification of tissue respiration, which is tuned for the detection of PpIX luminescence and not its photoproducts. Copyright © 2016 Elsevier B.V. All rights reserved.

Action of the protoporphyrin-Ix (Pp-Ix) in the life period of Drosophila mutants deficient in endogenous antioxidants

International Nuclear Information System (INIS)

Vidal E, L. M.

2012-01-01

The human being is daily exposed to free radicals or reactive oxygen species (Ros), as a result of the breathing and the interactions with xenobiotics that can cause irreversible lesions in molecules and cellular structures and that they are associated to diseases like the cancer, neuro degenerative and to the acceleration of the normal process of aging. Fortunately, to reduce the damaging effect of the Ros the cell has endogenous antioxidant systems constituted by antioxidant enzymes as: the superoxide dismutase (Sod), the catalase (Cat), and the glutathione peroxidase and reductase. Even, when these systems are not enough, we find to the exogenous antioxidants that cooperate in the balance of the Ros, as the porphyrins that include to the chlorophyllin, the hemin and the bilirubin among others. The protoporphyrin-Ix (Pp-Ix) is a tetra pyrrole without metallic center with antimutagenic and antioxidant activity similar to that of the chlorophyllin. However, is also known that their over-expression has toxic effects, because induces Ros. In Drosophila melanogaster, recently was found that the Pp-Ix have dual action anti and persistent mutagenic. One of their possible mechanism to act like mutagen is through the Ros induction. To evaluate this possibility and based in that the increase in the Ros levels can accelerate the aging process, in the present work the Pp-Ix role was evaluated, in the life period of Drosophila melanogaster strains deficient in Sod and Cat, sensitive to radiation or oxidative stress (rad, whd and flr 3 ) and a wild one as control (C-S). Females and males of each strain were treated chronically for separate with sucrose or Pp-Ix and every 15 days a group of each sex was irradiated with 10 Gy of gamma rays. The results indicated that the chronic treatment with Pp-Ix and in combination with radiation, increased the life period of the C-S strain. The Sod strain had a contrary effect and this effect was pronounced with the combined treatment of Pp-Ix

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

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Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

2016-10-12

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

Topical application of 5-aminolevulinic acid hexyl ester and 5-aminolevulinic acid to normal nude mouse skin: Differences in protoporphyrin IX fluorescence kinetics and the role of the stratum corneum

NARCIS (Netherlands)

van den Akker, J. T.; Iani, V.; Star, W. M.; Sterenborg, H. J.; Moan, J.

2000-01-01

An important limitation of topical 5-aminolevulinic acid (ALA)-based photodetection and photodynamic therapy is that the amount of the fluorescing and photosensitizing product protoporphyrin IX (PpIX) formed is limited. The reason for this Is probably the limited diffusion of ALA through the stratum

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

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Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-07-01

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

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Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

2017-03-01

Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

Fiber-optic filter fluorometer for emission detection of Protoporphyrin IX and its direct precursors – A preliminary study for improved Photodynamic Therapy applications

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Rainer Landes

2018-03-01

Full Text Available In this work we present first results of a laboratory manufactured filter-fluorometer to study differences in intensity and position of the main peaks of three porphyrins that appear during the Heme-Synthesis. Porphyrins play a major role in Photodynamic Therapy (PDT for cancer treatment. Within the Heme-Synthesis, Porphyrins such as Protoporphyrin IX (PPIX and its two precursors Coproporphyrin III (CPIII and Uroporphyrin III (UPIII represent photochemical agents that can interact with light to show fluorescence or generate Reactive Oxygen Species (ROS to destroy cells. A major problem that arises is determining the ideal time slot to begin treatment after drug application. Our work is meant to show a way to solve this problem by looking at concentration changes of precursors appearing in Heme-Synthesis and using these changes to predict the occurence of PPIX inside the mitochondria. 2000 MSC: 41A05, 41A10, 65D05, 65D17, Keywords: Photodynamic Therapy, Drug light interval, Protoporphyrin IX, Coproporphyrin III, Uroporphyrin III

Formation of zinc protoporphyrin IX in Parma-like ham without nitrate or nitrite.

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Wakamatsu, Jun-ichi; Uemura, Juichi; Odagiri, Hiroko; Okui, Jun; Hayashi, Nobutaka; Hioki, Shoji; Nishimura, Takanori; Hattori, Akihito

2009-04-01

Zinc protoporphyrin IX (ZPP) is a characteristic red pigment in meat products that are manufactured without the addition of a curing agent such as nitrate or nitrite. To examine the effects of impurities such as mineral components in sea salt on the formation of ZPP, we manufactured Parmatype dry-cured hams that were salted with refined salt or sea salt and examined the involvement of oxidation-reduction potential (ORP) in the formation of ZPP. The content of ZPP was increased drastically after 40 weeks. Microscopic observation showed strong fluorescence caused by ZPP muscle fiber after 40 weeks. Conversely, heme content varied considerably during processing. ORP increased during processing. However, there was no obvious difference between ham salted with refined salt and that salted with sea salt. Therefore, it was concluded that impurities in sea salt were not involved in the formation of ZPP.

Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

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Fidanzi-Dugas, Chloë; Liagre, Bertrand; Chemin, Guillaume; Perraud, Aurélie; Carrion, Claire; Couquet, Claude-Yves; Granet, Robert; Sol, Vincent; Léger, David Yannick

2017-07-01

Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE 2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the potential inhibitor of Ix (Pp-Ix) protoporphyrin of the genetic damage induced by gamma rays administered to different dose reasons in Drosophila melanogaster

International Nuclear Information System (INIS)

Flores A, J. A.

2016-01-01

Ionizing radiation can damage in DNA directly or indirectly by free radicals (Rl), characterized by unstable and highly reactive. To avoid damage by Rl the cell has endogenous antioxidants such as Sod, Cat, GSH or exogenous as some vitamins, but if with these mechanisms does not reach the cell homeostasis, the consequence may be the generation of chronic-disease degenerative such as cancer. This study was conducted in order to test the inhibitory role of Rl protoporphyrin Ix (Pp-Ix), induced by 20 Gy of gamma rays administered at different dose ratios using the assay of somatic mutation and recombination in the Drosophila wing. The results indicated that 20 Gy delivered at a rate of low dose (6.659 Gy/h), caused elevated frequencies of genetic damage (p <0.001), compared with those that induced a high dose reason (1111.42 Gy/h) in larvae of 48 h old. The difference is probably due to an indirect damage by Rl; when this hypothesis was approved with the possible inhibitor role of Pp-Ix (0.69 m M), damage was increased with the two reasons of tested doses. This result may be due to: 1) the Pp-Ix is not a good inhibitor of Rl, 2) the difference in the frequency of mutation found with both dose reasons, not due to Rl so that this compound did not reduce the genetic damage, and 3) that Pp-Ix acts as pro oxidant. (Author)

Influence of meat source, pH and production time on zinc protoporphyrin IX formation as natural colouring agent in nitrite-free dry fermented sausages.

Science.gov (United States)

De Maere, Hannelore; Chollet, Sylvie; De Brabanter, Jos; Michiels, Chris; Paelinck, Hubert; Fraeye, Ilse

2018-01-01

Nitrite is commonly used in meat products due to its plural technological advantages. However, it is controversial because of its detrimental side effects on health. Within the context of nitrite reduction, zinc protoporphyrin IX (Zn(II)PPIX) formation in meat products as natural red colouring agent has been suggested. This investigation presents the evaluation of naturally occurring pigments, namely Zn(II)PPIX, protoporphyrin IX (PPIX) and heme in nitrite-free dry fermented sausages in function of time, meat source (pork, horsemeat and a combination of both meat sources) and pH condition. In function of time, Zn(II)PPIX and PPIX were formed and heme content decreased. Higher pH conditions promoted Zn(II)PPIX and PPIX formation, whereas the influence of pH on heme was less clear. The use of horsemeat also promoted Zn(II)PPIX formation. Moreover, even similar amounts were formed when it was combined with pork. Product redness, however, could not be related to Zn(II)PPIX formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time, in vivo measurement of tissular pO2 through the delayed fluorescence of endogenous protoporphyrin IX during photodynamic therapy.

Science.gov (United States)

Piffaretti, Filippo; Novello, Anna Maria; Kumar, Rajendran Senthil; Forte, Eddy; Paulou, Cédric; Nowak-Sliwinska, Patrycja; van den Bergh, Hubert; Wagnières, Georges

2012-11-01

Tissular oxygen concentration plays a key role during photodynamic therapy (PDT). Therefore, monitoring its local oxygen partial pressure (pO2) may help predict and/or control the outcome of a PDT treatment. The first real-time, in vivo measurements of the pO2 in the chicken egg’s chorioallantoic membrane, using the delayed fluorescence of photoactivable porphyrins (PAPs), including protoporphyrin IX (PpIX), as monitored with a dedicated optical, fiber-based, time-resolved spectrometer, are reported here. The formation of PAPs/PpIX, photosensitizers of extensive clinical use, was induced in the chicken egg’s chorioallantoic membrane (CAM) with aminolevulinic acid. An excellent correlation between the vascular damage induced by PDT and the reduction in tissular pO2 is found. This study suggests that clinical measurement of the pO2 using the PAPs’/PpIX’s delayed fluorescence (DF) may be used to individualize in real time the PDT light dose applied.

Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy

Science.gov (United States)

Dong, Jiancheng; Ghiladi, Reza A.; Wang, Qingqing; Cai, Yibing; Wei, Qufu

2018-06-01

Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been ‘photo-aged’ with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.

Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs.

Science.gov (United States)

Li, Guangqi; Chen, Sirui; Duan, Zhongyi; Qu, Lujiang; Xu, Guiyun; Yang, Ning

2013-12-01

Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland.

Interaction of Human Serum Albumin with Metal Protoporphyrins

Science.gov (United States)

Hu, Jie; Brancaleon, Lorenzo

2015-03-01

Fluorescence spectroscopy is widely used in biotechnology, nanotechnology, and molecular biophysics, since it can provide information on a wide range of molecular processes, e.g. the interactions of solvent molecules with fluorophores, conformational changes, and binding interactions etc. In this study, we present the photophysical properties of the interaction of human serum albumin (HSA) with a series of metal compound of Protoporphyrin IX (PPIX), including ZnPPIX, FePPIX, MgPPIX, MnPPIX and SnPPIX respectively, as well as the free base PPIX. Binding constants were retrieved independently using the Benesi-Hildebrand analysis of the porphyrin emission or absorption spectra and the fluorescence quenching (i.e. Stern-Volmer analysis) and reveal that the two methods yield a difference of approximately one order or magnitude between the two. Fluorescence lifetimes was used to probe whether binding of the porphyrin changes the conformation of the protein or if the interaction places the porphyrin at a location that can prompt resonance energy transfer with the lone Tryptophan residue. In recent years it has been discovered that HSA provides a specific binding site for metal-chelated protoporphyrins in subdomain IA. This has opened a novel field of study over the importance of this site for biomedical applications but it has also created the potential for a series of biotechnological applications of the HSA/protoporphyrin complexes. Our study provides a preliminary investigation of the interaction with metal-chelated protoporphyrins that had not been previously investigated.

Prolactin-stimulated mitogenesis in the Nb2 rat lymphoma cell: Lack of protoporphyrin IX effects

Energy Technology Data Exchange (ETDEWEB)

Gerrish, K.E.; Putnam, C.W.; Laird, H.E. II (Univ. of Arizona, Tucson (USA))

1990-01-01

Pharmacological characterization of the Nb2 cell peripheral-type benzodiazepine receptor (PBR) was determined using selected 1,4-benzodiazepines, PK 11195, and protoporphyrin IX (PPIX) to compete for specific ({sup 3}H) Ro5-4864 binding. These data suggest that PPIX possesses an affinity for the Nb2 cell PBR. We have previously reported that the peripheral benzodiazepine ligands, Ro5-4864 and PK 11195, modulate prolactin-stimulated mitogenesis in the Nb2 cell. In contrast, PPIX, a putative endogenous ligand for the PBR had no effect on prolactin-stimulated mitogenesis in the Nb2 cell over the concentration range from 10{sup {minus}15} M to 10{sup {minus}6} M. Taken together these data show that PPIX has an affinity for the Nb2 cell PBR but does not modulate prolactin-stimulated mitogenesis at concentrations which should bind to the Nb2 cell PBR.

Monte Carlo modeling of in vivo protoporphyrin IX fluorescence and singlet oxygen production during photodynamic therapy for patients presenting with superficial basal cell carcinomas

Science.gov (United States)

Valentine, Ronan M.; Brown, C. Tom A.; Moseley, Harry; Ibbotson, Sally; Wood, Kenny

2011-04-01

We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 +/- 1 J/cm2. Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm2 could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.

Action of the protoporphyrin-Ix (Pp-Ix) in the life period of Drosophila mutants deficient in endogenous antioxidants; Accion de la protoporfirina-IX (PP-IX) en el periodo de vida de mutantes de Drosophila deficientes en antioxidantes endogenos

Energy Technology Data Exchange (ETDEWEB)

Vidal E, L. M.

2012-07-01

The human being is daily exposed to free radicals or reactive oxygen species (Ros), as a result of the breathing and the interactions with xenobiotics that can cause irreversible lesions in molecules and cellular structures and that they are associated to diseases like the cancer, neuro degenerative and to the acceleration of the normal process of aging. Fortunately, to reduce the damaging effect of the Ros the cell has endogenous antioxidant systems constituted by antioxidant enzymes as: the superoxide dismutase (Sod), the catalase (Cat), and the glutathione peroxidase and reductase. Even, when these systems are not enough, we find to the exogenous antioxidants that cooperate in the balance of the Ros, as the porphyrins that include to the chlorophyllin, the hemin and the bilirubin among others. The protoporphyrin-Ix (Pp-Ix) is a tetra pyrrole without metallic center with antimutagenic and antioxidant activity similar to that of the chlorophyllin. However, is also known that their over-expression has toxic effects, because induces Ros. In Drosophila melanogaster, recently was found that the Pp-Ix have dual action anti and persistent mutagenic. One of their possible mechanism to act like mutagen is through the Ros induction. To evaluate this possibility and based in that the increase in the Ros levels can accelerate the aging process, in the present work the Pp-Ix role was evaluated, in the life period of Drosophila melanogaster strains deficient in Sod and Cat, sensitive to radiation or oxidative stress (rad, whd and flr{sup 3}) and a wild one as control (C-S). Females and males of each strain were treated chronically for separate with sucrose or Pp-Ix and every 15 days a group of each sex was irradiated with 10 Gy of gamma rays. The results indicated that the chronic treatment with Pp-Ix and in combination with radiation, increased the life period of the C-S strain. The Sod strain had a contrary effect and this effect was pronounced with the combined treatment of

Kinetics and comparison of δ-aminolevulinic-acid-induced endogenous protoporphyrin-IX in single cell by steady state and multiphoton fluorescence imaging

Science.gov (United States)

Ganesan, Singaravelu; Elangovan, Masilamani; Periasamy, Ammasi

2001-04-01

Photodynamic Therapy has emerged as a new modality in the treatment of various nonmalignant and malignant diseases. It involves the systemic administration of tumor specific photo-sensitizers with the subsequent application of visible light. This combination causes the generation of cytotoxic species, which damage sensitive targets, producing cell injury and tumor destruction. Although, photofrin is the only photosensitizer currently approved for PDT and tumor detection, its concomitant cutaneous photosensitization poses a significant problem. Hence, δ-aminoleuvulinic acid (δ-ALA) a precursor for the endogenous production of Protoporphyrin IX, through heme biosynthesis pathway, has gained significant importance in the Photodynamic Therapy. Though δ-ALA is present naturally in the cells, exogenous δ-ALA helps to synthesis more of PpIX in the tumor cells, as the fast growing tumor cells take up the administered δ-ALA more than the normal cells. Based on these facts, many invasive studies have been reported on the kinetics of δ-ALA at cellular level by chemical extraction of PpIX from the cells. In the present study we have studied the kinetics of δ-ALA induced PpIX fluorescence from Hela cells by perchloric/Methanol extraction method. However, the amount of PpIX synthesized in the cells at different point of incubation time by noninvasive methods has not been reported. Hence we have also used a noninvasive technique of measuring the kinetics δ-ALA induced PPIX fluorescence from Hela, an epithelial cell derived from human cervical cancer by both single photon (steady state) and multi photon excitation. From the studies it is observed that the δ-ALA induced PpIX is more at 2 hours incubation time for 2 mM of δ-ALA concentration. Further, it is observed that with steady state fluorescence imaging method, the excitation light itself cause the Photodynamic damage, due to the prolonged exposure of the cells than in multi photon excitation, leading to the rounding

Color formation in nitrite-free dried hams as related to Zn-protoporphyrin IX and Zn-chelatase activity.

Science.gov (United States)

Parolari, Giovanni; Benedini, Riccardo; Toscani, Tania

2009-08-01

The development of red pigment Zn-protoporphyrin IX (ZPP) in nitrite-free Parma hams was investigated in 5 leg muscles at several stages of processing and the activity of muscle Zn-chelatase was concurrently assayed for its potential role in ZPP formation. A steady increase of the pigment was observed throughout the manufacturing stages at mild temperatures while no development was observed during the prior cold resting phase. The enzyme was partly inactivated according to a muscle-dependent pattern, resulting in similar ZPP contents, hence color, in finished hams. It is concluded that enzyme-dependent synthesis of ZPP in nitrite-free dried hams contributes to color development, enabling muscles in dried hams to become more similar in redness than in green thighs. Therefore, checking raw meat for the enzyme content may be a means to control color formation in nitrite-free dry-cured meat derivatives.

Seleção de genótipos de cana-de-açúcar para acúmulo de protoporfirina ix com uso de herbicidas inibidores da protox Selection of Sugarcane Genotypes for Protoporphyrin IX Accumulation using Protox-Inhibiting Herbicides

Directory of Open Access Journals (Sweden)

L.R.M. Barberis

2009-01-01

of protoporphyrin IX (PROTO IX, or its precursors in plants. Such compounds can be used as sensitizing agents in photodynamic therapy (PDT, being considered a low cost source for the treatment of malignancies. The experiment was set up on a temperature-controlled chamber, with 9 treatments being applied: (1. oxyfluorfen + monosodium glutamate + vitamin C and E; 2. oxyfluorfen + monosodium glutamate + vitamin C and E + levulenic acid; 3. oxyfluorfen; 4. carfentrazone + monosodium glutamate + vitamin C and E; 5. carfentrazone + monosodium glutamate + vitamin C and E + levulenic acid; 6. carfentrazone; 7. control + vitamin C and E; 8. control + vitamin C and E + levulenic acid; 9. control without spraying in 8 sugarcane genotypes (PO933499, RB806043, RB470355, PO830698, SP701143, PO901387, PO894414 and 8.SP903414; arranged in a factorial 9 x 8, with 4 repetitions. The repetitions were constituted by specific leaves (20 cm from each genotype, which were sprayed with the appropriate treatments in a stationary simulator. Visual evaluations of the control were carried out at 2 DAA (Days After Application, and at the end of the study, analytical determinations were conducted via fresh biomass extraction to verify the protoporphyrin IX contents by high performance liquid chromatography. The results showed that significant short-term increases were observed in the PROTO IX concentrations for the genotypes RB470355, SP903414 submitted to treatment 2 and for genotype SP701143 submitted to treatment 8, indicating that they can be used as accumulating sources of protoporphyrin IX.

Evaluation of the potential inhibitor of Ix (Pp-Ix) protoporphyrin of the genetic damage induced by gamma rays administered to different dose reasons in Drosophila melanogaster; Evaluacion del potencial inhibidor de la protoporfirina IX (PP-IX) del dano genetico inducido por rayos gama administrados a diferentes razones de dosis en Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Flores A, J. A.

2016-10-01

Ionizing radiation can damage in DNA directly or indirectly by free radicals (Rl), characterized by unstable and highly reactive. To avoid damage by Rl the cell has endogenous antioxidants such as Sod, Cat, GSH or exogenous as some vitamins, but if with these mechanisms does not reach the cell homeostasis, the consequence may be the generation of chronic-disease degenerative such as cancer. This study was conducted in order to test the inhibitory role of Rl protoporphyrin Ix (Pp-Ix), induced by 20 Gy of gamma rays administered at different dose ratios using the assay of somatic mutation and recombination in the Drosophila wing. The results indicated that 20 Gy delivered at a rate of low dose (6.659 Gy/h), caused elevated frequencies of genetic damage (p <0.001), compared with those that induced a high dose reason (1111.42 Gy/h) in larvae of 48 h old. The difference is probably due to an indirect damage by Rl; when this hypothesis was approved with the possible inhibitor role of Pp-Ix (0.69 m M), damage was increased with the two reasons of tested doses. This result may be due to: 1) the Pp-Ix is not a good inhibitor of Rl, 2) the difference in the frequency of mutation found with both dose reasons, not due to Rl so that this compound did not reduce the genetic damage, and 3) that Pp-Ix acts as pro oxidant. (Author)

Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

Science.gov (United States)

Jiang, Ching-Fen; Wang, Chih-Yu; Chiang, Chun-Ping

2011-07-01

Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R/B ratio, and R/G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R/G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

AcEST: BP912238 [AcEST

Lifescience Database Archive (English)

Full Text Available za... 219 1e-55 tr|A6N1H0|A6N1H0_ORYSI Magnesium-protoporphyrin ix monomethyl es... 219 1e-55 tr|Q40093|Q40093_IPONI PNIL34...LAEFEPQLVY 429 Y M P++SGSVD AEFEPQLVY Sbjct: 134 AYLMPPIESGSVDFAEFEPQLVY 156 >tr|Q40093|Q40093_IPONI PNIL34

Modifier activity of the protoporphyrin IX of the clastogenic damage induced by gamma radiation in Drosophila melanogaster

International Nuclear Information System (INIS)

Martinez A, G.

2007-01-01

It has been demonstrated that the copper sodium chlorophyllin (CCS) it is a potent inhibitor of the one genetic damage induced by physical or chemical agents in systems like: bacteria, Drosophila, rainbow trout and mammals. Nevertheless it has been observed that under certain conditions it promotes it. In the laboratory of Drosophila of the ININ evidences have been obtained that the CCS increases the percentage of lethal embryonic dominant and post-embryonic induced by gamma radiation. One of the probable causes of this effect promoter, is the oxidizer stress that it could cause the metallic center of the CCS. The objective of this investigation it was the evaluation of the inhibitory action of the protoporphyrin IX (PP-IX) of the genetic damage induced by gamma radiation in the germinal line of Drosophila melanogaster. For such effect it was used the lethal dominant test by means of two protocols: one in the one that the PP-IX or CCS was administered to the females and the other one to the males. Females of genotype y/y and males of the canton-S stump were used. In both cases the males were treated with 40 Gy of gamma radiation. Its were count the embryonic lethal dominant (L-E) and those post-embryonic (L-PE) of the F1. The results indicated that after the one pretreatment with PP-IX to the crossed females with males treaties increase the percentage of L-E (P ≤ 0.001) and it diminished that of L-PE (P ≤ 0.001) compared with the sucrose control more radiation, however when it was pretreated with CCS also it was observed an increment in the percentage of L-E (P ≤ 0.001), but it doesn't present effect on that of L-PE. In contrast, when the males were pretreated, it was observed that the PP-IX tends to increase those L-E, but diminished the L-PE (P ≤ 0.05), however when it was pretreated with CCS was observed that increased the percentage of L-E (P ≤ 0.001) but diminished that of L-PE (P ≤ 0.001). It was concluded that none of the two pigments act as

Redox transitions of chromium, manganese, iron, cobalt and nickel protoporphyrins in aqueous solution

NARCIS (Netherlands)

de Groot, M.T.; Koper, M.T.M.

2008-01-01

The electrochemical redox behavior of immobilized chromium, manganese, iron, cobalt, and nickel protoporphyrins IX has been investigated over the pH 0–14 range. In the investigated potential domain the metalloporphyrins were observed in four different oxidation states (MI, MII, MIII and MIV). The

Probing the Highly Efficient Electron Transfer Dynamics between Zinc Protoporphyrin IX and Sodium Titanate Nanosheets.

Science.gov (United States)

Biswas, Sudipta; Mukherjee, Debdyuti; De, Swati; Kathiravan, Arunkumar

2016-09-15

Sodium titanate nanosheets (NaTiO2 NS) have been prepared by a new method and completely characterized by TEM, SEM, XRD, EDX, and XPS techniques. The sensitization of nanosheets is carried out with Zn protoporphyrin IX (ZnPPIX). The emission intensity of ZnPPIX is quenched by NaTiO2 NS, and the dominant process for this quenching has been attributed to the process of photoinduced electron injection from excited ZnPPIX to the nanosheets. Time resolved fluorescence measurement was used to elucidate the process of electron injection from the singlet state of ZnPPIX to the conduction band of NaTiO2 NS. Electron injection from the dye to the semiconductor is very fast (ket ≈ 10(11) s(-1)), much faster than previously reported rates. The large two-dimensional surface offered by the NaTiO2 NS for interaction with the dye and the favorable driving force for electron injection from ZnPPIX to NaTiO2 NS (ΔGinj = -0.66 V) are the two important factors responsible for such efficient electron injection. Thus, NaTiO2 NS can serve as an effective alternative to the use of TiO2 nanoparticles in dye sensitized solar cells (DSSCs).

Fluorescence detection of DNA, adenosine-5'-triphosphate (ATP), and telomerase activity by zinc(II)-protoporphyrin IX/G-quadruplex labels.

Science.gov (United States)

Zhang, Zhanxia; Sharon, Etery; Freeman, Ronit; Liu, Xiaoqing; Willner, Itamar

2012-06-05

The zinc(II)-protoporphyrin IX (ZnPPIX) fluorophore binds to G-quadruplexes, and this results in the enhanced fluorescence of the fluorophore. This property enabled the development of DNA sensors, aptasensors, and a sensor following telomerase activity. The DNA sensor is based on the design of a hairpin structure that includes a "caged" inactive G-quadruplex sequence. Upon opening the hairpin by the analyte DNA, the resulting fluorescence of the ZnPPIX/G-quadruplex provides the readout signal for the sensing event (detection limit 5 nM). Addition of Exonuclease III to the system allows the recycling of the analyte and its amplified analysis (detection limit, 200 pM). The association of the ZnPPIX to G-quadruplex aptamer-substrate complexes allowed the detection of adenosine-5'-triphosphate (ATP, detection limit 10 μM). Finally, the association of ZnPPIX to the G-quadruplex repeat units of telomers allowed the detection of telomerase activity originating from 380 ± 20 cancer 293T cell extract.

Intracellular localization analysis of npAu-PpIX in HeLa cells using specific dyes and confocal microscopy

Science.gov (United States)

Roblero-Bartolón, Victoria Gabriela; Maldonado-Alvarado, Elizabeth; Galván-Mendoza, José Iván; Ramón-Gallegos, Eva

2012-10-01

Cervical carcinoma (CC) represents the second leading cause of cancer death in Mexican women. No conventional treatments are being developed such as photodynamic therapy (PDT), involving the simultaneous presence of a photosensitizer (Ps), light of a specific wavelength and tissue oxygen. On the other hand, it has seen that the use of gold nanoparticles coupled to protoporphyrin IX increases the effectiveness of PDT. The aim of this study was to determine the site of accumulation of the conjugate npAu-PpIX in cells of cervical cancer by the use of specific dyes and confocal microscopy. The results indicate that the gold nanoparticles coupled to protoporphyrin IX are accumulated in both the cytoplasm and nucleus of HeLa cells.

Iron(III) protoporphyrin IX-single-wall carbon nanotubes modified electrodes for hydrogen peroxide and nitrite detection

International Nuclear Information System (INIS)

Turdean, Graziella L.; Popescu, Ionel Catalin; Curulli, Antonella; Palleschi, Giuseppe

2006-01-01

Iron(III) protoporphyrin IX (Fe(III)P), adsorbed either on single-walled carbon nanotubes (SWCNT) or on hydroxyl-functionalized SWCNT (SWCNT-OH), was incorporated within a Nafion matrix immobilized on the surface of a graphite electrode. From cyclic voltammetric measurements, performed under different experimental conditions (pH and potential scan rate), it was established that the Fe(III)P/Fe(II)P redox couple involves 1e - /1H + . The heterogeneous electron transfer process occurred faster when Fe(III)P was adsorbed on SWCNT-OH (∼11 s -1 ) than on SWCNT (∼4.9 s -1 ). Both the SWCNT-Fe(III)P- and SWCNT-OH-Fe(III)P-modified graphite electrodes exhibit electrocatalytic activity for H 2 O 2 and nitrite reduction. The modified electrodes sensitivities were found varying in the following sequences: S SWCNT-OH-Fe(III)P = 2.45 mA/M ∼ S SWCNT-Fe(III)P = 2.95 mA/M > S Fe(III)P = 1.34 mA/M for H 2 O 2 , and S SWCNT-Fe(III)P = 3.54 mA/M > S Fe(III)P 1.44 mA/M > S SWCNT-OH-Fe(III)P = 0.81 mA/M for NO 2 -

Fiber-optic filter fluorometer for emission detection of Protoporphyrin IX and its direct precursors - A preliminary study for improved Photodynamic Therapy applications

Science.gov (United States)

Landes, Rainer; Illanes, Alfredo; van Oepen, Alexander; Goeppner, Daniela; Gollnick, Harald; Friebe, Michael

2018-03-01

In this work we present first results of a laboratory manufactured filter-fluorometer to study differences in intensity and position of the main peaks of three porphyrins that appear during the Heme-Synthesis. Porphyrins play a major role in Photodynamic Therapy (PDT) for cancer treatment. Within the Heme-Synthesis, Porphyrins such as Protoporphyrin IX (PPIX) and its two precursors Coproporphyrin III (CPIII) and Uroporphyrin III (UPIII) represent photochemical agents that can interact with light to show fluorescence or generate Reactive Oxygen Species (ROS) to destroy cells. A major problem that arises is determining the ideal time slot to begin treatment after drug application. Our work is meant to show a way to solve this problem by looking at concentration changes of precursors appearing in Heme-Synthesis and using these changes to predict the occurence of PPIX inside the mitochondria.

Study of cell killing effect on S180 by ultrasound activating protoporphyrin IX.

Science.gov (United States)

Wang, Xiao Bing; Liu, Quan Hong; Wang, Pan; Tang, Wei; Hao, Qiao

2008-04-01

The present study was initiated to investigate the potential biological mechanism of cell killing effect on isolate sarcoma 180 (S180) cells induced by ultrasound activating protoporphyrin IX (PPIX). S180 cells were exposed to ultrasound for 30s duration, at a frequency of 2.2 MHz and an acoustic power of 3 W/cm(2) in the presence of 120 microM PPIX. The viability of cells was evaluated using trypan blue staining. The generation of oxygen free radicals in cell suspensions was detected immediately after treatment using a reactive oxygen detection kit. A copper reagent colorimetry method was used to measure the level of FFAs released into cell suspensions by the process of cell damage induced by ultrasound and PPIX treatment. Oxidative stress was assessed by measuring the activities of key antioxidant enzymes (i.e., SOD, CAT, GSH-PX) in S180 tumor cells. Treatment with ultrasound and PPIX together increased the cell damage rate to 50.91%, while treatment with ultrasound alone gave a cell damage rate to 24.24%, and PPIX alone kept this rate unchanged. Colorimetry and enzymatic chemical methods showed that the level of FFAs in cell suspension increased significantly after the treatment, while the activity of all the above enzymes decreased in tumor cells at different levels, and were associated with the generation of oxygen free radicals in cell suspension after treatment. The results indicate that oxygen free radicals may play an important role in improving the membrane lipid peroxidation, degrading membrane phospholipids to release FFAs, and decreasing the activities of the key antioxidant enzymes in cells. This biological mechanism might be involved in mediating the effects on S180 cells and resulting in the cell damage seen with SDT.

Protoporphyrin IX formation and photobleaching in different layers of normal human skin

DEFF Research Database (Denmark)

Togsverd-Bo, Katrine; Idorn, Luise W; Philipsen, Peter A

2012-01-01

human skin was tape-stripped and incubated with 20% methylaminolevulinate (MAL) or 20% hexylaminolevulinate (HAL) for 3 h. Fluorescence microscopy quantified PpIX accumulation in epidermis, superficial, mid and deep dermis, down to 2 mm. PpIX photobleaching by light-emitting diode (LED, 632 nm, 18......Topical photodynamic therapy (PDT) is used for various skin disorders, and selective targeting of specific skin structures is desirable. The objective was to assess accumulation of PpIX fluorescence and photobleaching within skin layers using different photosensitizers and light sources. Normal...... and 37 J/cm(2)), intense pulsed light (IPL, 500-650 nm, 36 and 72 J/cm(2)) and long-pulsed dye laser (LPDL, 595 nm, 7.5 and 15 J/cm(2)) was measured using fluorescence photography and microscopy. We found higher PpIX fluorescence intensities in epidermis and superficial dermis in HAL-incubated skin than...

Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

Science.gov (United States)

Maytin, Edward V.; Anand, Sanjay

2016-03-01

In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

Modifier activity of the protoporphyrin IX of the clastogenic damage induced by gamma radiation in Drosophila melanogaster; Actividad modificadora de la protoporfirina IX del dano clastogenico inducido por radiacion gamma en Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Martinez A, G. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

2007-07-01

It has been demonstrated that the copper sodium chlorophyllin (CCS) it is a potent inhibitor of the one genetic damage induced by physical or chemical agents in systems like: bacteria, Drosophila, rainbow trout and mammals. Nevertheless it has been observed that under certain conditions it promotes it. In the laboratory of Drosophila of the ININ evidences have been obtained that the CCS increases the percentage of lethal embryonic dominant and post-embryonic induced by gamma radiation. One of the probable causes of this effect promoter, is the oxidizer stress that it could cause the metallic center of the CCS. The objective of this investigation it was the evaluation of the inhibitory action of the protoporphyrin IX (PP-IX) of the genetic damage induced by gamma radiation in the germinal line of Drosophila melanogaster. For such effect it was used the lethal dominant test by means of two protocols: one in the one that the PP-IX or CCS was administered to the females and the other one to the males. Females of genotype y/y and males of the canton-S stump were used. In both cases the males were treated with 40 Gy of gamma radiation. Its were count the embryonic lethal dominant (L-E) and those post-embryonic (L-PE) of the F1. The results indicated that after the one pretreatment with PP-IX to the crossed females with males treaties increase the percentage of L-E (P {<=} 0.001) and it diminished that of L-PE (P {<=} 0.001) compared with the sucrose control more radiation, however when it was pretreated with CCS also it was observed an increment in the percentage of L-E (P {<=} 0.001), but it doesn't present effect on that of L-PE. In contrast, when the males were pretreated, it was observed that the PP-IX tends to increase those L-E, but diminished the L-PE (P {<=} 0.05), however when it was pretreated with CCS was observed that increased the percentage of L-E (P {<=} 0.001) but diminished that of L-PE (P {<=} 0.001). It was concluded that none of the two pigments

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

Science.gov (United States)

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and photochemical properties of a novel iron-sulfur-nitrosyl cluster derivatized with the pendant chromophore protoporphyrin IX.

Science.gov (United States)

Conrado, Christa L; Wecksler, Stephen; Egler, Christian; Magde, Douglas; Ford, Peter C

2004-09-06

The novel Roussin red-salt ester (PPIX-RSE) with a pendant porphyrin chromophore was prepared and investigated as a precursor for the photochemical generation of nitric oxide. PPIX-RSE has the general formula Fe(2)(NO)(4)[(mu-S,mu-S')P] (where (S,S')P is the bis(2-thiolatoethyl) diester of protoporphyrin IX. The photoexcitation of PPIX-RSE with 436- or 546-nm light in an aerated chloroform solution led to the photodecomposition of the cluster with the respective quantum yields (5.2 +/- 0.7) x 10(-4) and (2.5 +/- 0.5 x 10(-4)) and the concomitant release of NO. PPIX-RSE is a significantly more effective NO generator at longer wavelength excitation than are other Fe(2)(mu-SR)(2)(NO)(4) esters for which R is a simple alkyl group such as CH(3)CH(2)- because of the much higher absorptivity of the pendant PPIX chromophore at these wavelengths and a modestly higher quantum yield. Fluorescence intensity and lifetime data indicate that the photoexcited porphyrin of PPIX-RSE is largely quenched by the energy transfer to the Fe(2)S(2)(NO)(4) cluster's core. However, a small fraction of this emission is not quenched, and it is proposed that PPIX-RSE may exist in solution as two conformers.

Transition properties of the Be-like X-ray from Mg IX

Indian Academy of Sciences (India)

Feng Hu

2017-11-23

Nov 23, 2017 ... Transition properties of the Be-like Kα X-ray from Mg IX. FENG HU1,3,∗ ... 1. Introduction. Magnesium is one of the most abundant elements in the. Universe, and its .... sion coefficients for the configuration state functions are optimized to ..... The absorption oscillator strengths ( fij) and radiative rate Aji for a ...

A comparative study of zinc protoporphyrin IX-forming properties of animal by-products as sources for improving the color of meat products.

Science.gov (United States)

Wakamatsu, Jun-ichi; Murakami, Naoko; Nishimura, Takanori

2015-05-01

The objective of this study was to obtain fundamental data for improving the color of meat products by using animal by-products. We investigated zinc protoporphyrin IX (ZnPP)-forming properties of various internal organs from pigs and chickens. ZnPP was formed in the liver, heart and kidney, whereas the porcine spleen and bile, which are involved in the metabolism of heme, did not have ZnPP-forming properties. The optimum pH values were different among the internal organs and the ZnPP-forming properties of porcine organs were better than those of chicken organs. The porcine liver showed the greatest ZnPP-forming properties among all of the internal organs investigated in this study. The optimum pH value for ZnPP formation in the liver was lower than that of skeletal muscle. Oxygen did not inhibit the formation of ZnPP in the liver, unlike in skeletal muscle. Animal by-products such as the liver have good ability for the formation of ZnPP and might be useful for improving the color of meat products. © 2014 Japanese Society of Animal Science.

Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

Science.gov (United States)

Gibbs-Strauss, Summer L.; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2008-02-01

Aminolevulinic Acid (ALA) is a prodrug which can be administered to cells, animals or patients after which it is transformed via the Heme synthesis pathway into the fluorescent molecule Protoporphyrin IX (PpIX). PpIX has been shown to be useful as both a photosensitizer for photodynamic therapy (PDT) and as a fluorescence imaging contrast agent. The ALA-PpIX system not only provides contrast for fluorescence imaging but also gives information about the metabolic activity of the imaged tissue and thus could be useful for monitoring cancer therapy. In the current study skin photobleaching was examined to determine if PpIX fluorescence contrast in malignant brain tumors could be better visualized noninvasively. Red light photobleaching decreased skin PpIX fluorescence and increased the ability to noninvasively quantify PpIX fluorescence in murine gliomas, as in vivo measurements of mean PpIX fluorescence more closely matched ex vivo quantification following skin photobleaching. Three doses of blue light photobleaching (4 J/cm2, 8 J/cm2 and 12 J/cm2) were tested and determined to give similar levels of skin photobleaching as well as a similar window of decreased skin PpIX fluorescence for noninvasive fluorescence imaging following the photobleaching dose administration.

Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

Science.gov (United States)

Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

2013-04-01

5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic gamma-glutamyl transpeptidase.

Science.gov (United States)

Kawamoto, T; Matsuno, K; Kayama, F; Arashidani, K; Yoshikawa, M; Kodama, Y

1992-11-22

In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl transpeptidase activity. Male adult Wistar rats weighing 220 g were used as experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000 mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the 4-week study, experimental animals were administered EGME or diEGME once a day orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl transpeptidase (GGT) level significantly, however, diEGME did not. The activities of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or diEGME treatment and thus there was no biochemical indices of hepatic damage by EGME or diEGME. EGME treatment increased the GGT activities in the liver and lungs. Of the organs examined, the induction of GGT was the greatest in the liver. The inducibility in the liver was 216% for the 5-day treatment and 460% for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT activity by EGME was observed. On the other hand, renal GGT activities were declined to 72% and 60% of control by the 5-day and 4-week EGME treatments, respectively. DiEGME did not affect the GGT activities in any of the tissues except those of the brain. In the histochemical study, most hepatocytes at the periportal zones were stained with GGT staining after the 4-week treatment. However, the hepatocytes at the central zones were negative.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells. Spectrophotometric studies reveal that protoporphyrin IX interacts with ...

In vitro assay of the chlorophyll biosynthetic enzyme Mg-chelatase: Resolution of the activity into soluble and membrane-bound fractions

Energy Technology Data Exchange (ETDEWEB)

Walker, C.J.; Weinstein, J.D. (Clemson Univ., SC (United States))

1991-07-01

The first committed step in chlorophyll synthesis is the Mg-chelatase-catalyzed insertion of magnesium into protoporphyrin IX. Since iron insertion into protoporphyrin leads to heme formation, Mg-chelatase lies at the branch point of heme and chlorophyll synthesis in chloroplasts. Little is known about the enzymology or regulation of Mg-chelatase, as it has been assayed only in intact cucumber chloroplasts. In this report we describe an in vitro assay for Mg-chelatase. Mg-chelatase activity in intact pea chloroplasts was 3- to 4-fold higher than in cucumber chloroplasts. This activity survived chloroplast lysis and could be fractionated by centrifugation into supernatant and pellet components. Both of these fractions were required to reconstitute Mg-chelatase activity, and both were inactivated by boiling indicating that the enzyme is composed of soluble and membrane-bound protein(s). The product of the reaction was confirmed fluorometrically as the magnesium chelate of the porphyrin substrate. The specific activity of the reconstituted system was typically 1 nmol of Mg-deuteroporphyrin per h per mg of protein, and activity was linear for at least 60 min under our assay conditions. ATP and magnesium were required for Mg-chelatase activity and the enzymen was sensitive to the sulfhydryl reagent N-ethylmaleimide (I{sub 50}, 20 {mu}M). Broken and reconstituted cucumber chloroplasts were unable to maintain Mg-chelatase activity. However, the cucumber supernatant fraction was active when combined with the pellet fraction of peas; the converse was not true, which suggested that the cucumber pellet was the component that lost activity during lysis.

Light-Emitting Photon-Upconversion Nanoparticles in the Generation of Transdermal Reactive-Oxygen Species.

Science.gov (United States)

Prieto, Martin; Rwei, Alina Y; Alejo, Teresa; Wei, Tuo; Lopez-Franco, Maria Teresa; Mendoza, Gracia; Sebastian, Victor; Kohane, Daniel S; Arruebo, Manuel

2017-12-06

Common photosensitizers used in photodynamic therapy do not penetrate the skin effectively. In addition, the visible blue and red lights used to excite such photosensitizers have shallow penetration depths through tissue. To overcome these limitations, we have synthesized ultraviolet- and visible-light-emitting, energy-transfer-based upconversion nanoparticles and coencapsulated them inside PLGA-PEG (methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)) nanoparticles with the photosensitizer protoporphyrin IX. Nd 3+ has been introduced as a sensitizer in the upconversion nanostructure to allow its excitation at 808 nm. The subcytotoxic doses of the hybrid nanoparticles have been evaluated on different cell lines (i.e., fibroblasts, HaCaT, THP-1 monocytic cell line, U251MG (glioblastoma cell line), and mMSCs (murine mesenchymal stem cells). Upon NIR (near infrared)-light excitation, the upconversion nanoparticles emitted UV and VIS light, which consequently activated the generation of reactive-oxygen species (ROS). In addition, after irradiating at 808 nm, the resulting hybrid nanoparticles containing both upconversion nanoparticles and protoporphyrin IX generated 3.4 times more ROS than PLGA-PEG nanoparticles containing just the same dose of protoporphyrin IX. Their photodynamic effect was also assayed on different cell cultures, demonstrating their efficacy in selectively killing treated and irradiated cells. Compared to the topical application of the free photosensitizer, enhanced skin permeation and penetration were observed for the nanoparticulate formulation, using an ex vivo human-skin-permeation experiment. Whereas free protoporphyrin IX remained located at the outer layer of the skin, nanoparticle-encapsulated protoporphyrin IX was able to penetrate through the epidermal layer slightly into the dermis.

In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

Science.gov (United States)

LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

2017-02-01

Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

Science.gov (United States)

Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

2013-07-01

Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular PpIX

Relationship between zinc protoporphyrin (ZPP) and free erythrocyte protoporphyrin (FEP) in lead-exposed individuals

Energy Technology Data Exchange (ETDEWEB)

Karacic, V.; Pripic-Majic, D.; Telis, S.

1980-11-01

The relationship between zinc protoporphyrin (ZPP) and total erythrozyte protoporphyrin, measured as free erythrozyte protoporphyrin (FEP), was determined in 194 adult subjects with different occupational and non-occupational lead exposures. Furthermore, the ZPP-FEP comparison was considered with respect to the dose-effect relationship of ZPP and FEP with blood lead (PbB) for males and females, Bilirubin (Bil.) interferences in ZPP analysis were taken into account. A very close and highly significant relationship was established between ZPP and FEP values. A significant correlation between log ZPP or log FEP and PbB was also found. It was established, by both in vitro and in vivo studies, that Bil. interferes with the ZPP fluorescence readings; the relationship between false positive ZPP concentrations and Bil. concentrations was highly significant. A small but highly significant influence of increased carboxyhemoglobin (COHb) concentrations on the decrease in hermatofluorometer ZPP readings, due to inadequate oxygenation of the blood, was found. The results obtained confirm the usefulness of ZPP determinations using hematofluorometers for surveillance of increased lead absorption but stress that the interfering effect of Bil. and to a lesser extent of COHb, cannot be ignored.

Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

Science.gov (United States)

Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2015-06-01

The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

Theoretical analysis of the binding of iron(III) protoporphyrin IX to 4-methoxyacetophenone thiosemicarbazone via DFT-D3, MEP, QTAIM, NCI, ELF, and LOL studies.

Science.gov (United States)

Nkungli, Nyiang Kennet; Ghogomu, Julius Numbonui

2017-07-01

Thiosemicarbazones display diverse pharmacological properties, including antimalarial activities. Their pharmacological activities have been studied in depth, but little of this research has focused on their antimalarial mode of action. To elucidate this antimalarial mechanism, we investigated the nature of the interactions between iron(III) protoporphyrin IX (Fe(III)PPIX) and the thione-thiol tautomers of 4-methoxyacetophenone thiosemicarbazone (MAPTSC). Dispersion-corrected density functional theory (DFT-D3), the quantum theory of atoms in molecules (QTAIM), the noncovalent interaction (NCI) index, the electron localization function (ELF), the localized orbital locator (LOL), and thermodynamic calculations were employed in this work. Fe(III)PPIX-MAPTSC binding is expected to inhibit hemozoin formation, thereby preventing Fe(III)PPIX detoxification in plasmodia. Preliminary studies geared toward the identification of atomic binding sites in the thione-thiol tautomers of MAPTSC were carried out using molecular electrostatic potential (MEP) maps and conceptual DFT-based local reactivity indices. The thionic sulfur and the 2 N-azomethine nitrogen/thiol sulfur of, respectively, the thione and thiol tautomers of MAPTSC were identified as the most favorable nucleophilic sites for electrophilic attack. The negative values of the computed Fe(III)PPIX-MAPTSC binding energies, enthalpies, and Gibbs free energies are indicative of the existence and stability of Fe(III)PPIX-MAPTSC complexes. MAPTSC-Fe(III) coordinate bonds and strong hydrogen bonds (N-H···O) between the NH 2 group in MAPTSC and the C=O group in one propionate side chain of Fe(III)PPIX are crucial to Fe(III)PPIX-MAPTSC binding. QTAIM, NCI, ELF, and LOL analyses revealed a subtle interplay of weak noncovalent interactions dominated by dispersive-like van der Waals interactions between Fe(III)PPIX and MAPTSC that stabilize the Fe(III)PPIX-MAPTSC complexes.

Arabidopsis CDS blastp result: AK062262 [KOME

Lifescience Database Archive (English)

Full Text Available AK062262 001-047-H04 At5g13630.1 magnesium-chelatase subunit chlH, chloroplast, put...ative / Mg-protoporphyrin IX chelatase, putative (CHLH) nearly identical to magnesium chelatase subunit GI:1...154627 from [Arabidopsis thaliana]; contains Pfam profile: PF02514 CobN/magnesium chelatase family protein 0.0 ...

Arabidopsis CDS blastp result: AK069545 [KOME

Lifescience Database Archive (English)

Full Text Available AK069545 J023025I06 At5g13630.1 magnesium-chelatase subunit chlH, chloroplast, puta...tive / Mg-protoporphyrin IX chelatase, putative (CHLH) nearly identical to magnesium chelatase subunit GI:11...54627 from [Arabidopsis thaliana]; contains Pfam profile: PF02514 CobN/magnesium chelatase family protein 0.0 ...

Arabidopsis CDS blastp result: AK067323 [KOME

Lifescience Database Archive (English)

Full Text Available AK067323 J013106B16 At5g13630.1 magnesium-chelatase subunit chlH, chloroplast, puta...tive / Mg-protoporphyrin IX chelatase, putative (CHLH) nearly identical to magnesium chelatase subunit GI:11...54627 from [Arabidopsis thaliana]; contains Pfam profile: PF02514 CobN/magnesium chelatase family protein 0.0 ...

Arabidopsis CDS blastp result: AK060612 [KOME

Lifescience Database Archive (English)

Full Text Available AK060612 001-025-F03 At5g13630.1 magnesium-chelatase subunit chlH, chloroplast, put...ative / Mg-protoporphyrin IX chelatase, putative (CHLH) nearly identical to magnesium chelatase subunit GI:1...154627 from [Arabidopsis thaliana]; contains Pfam profile: PF02514 CobN/magnesium chelatase family protein 0.0 ...

Inhibition of human peripheral blood lymphocyte function by protoporphyrin and longwave ultraviolet light

International Nuclear Information System (INIS)

Barrett, K.E.; Yen, A.; Montisano, D.; Gigli, I.; Bigby, T.D.

1994-01-01

Modulation of immunologic effector cells by exogenous photoactive substances has been advanced as an underlying mechanism for the efficacy of various photochemotherapeutic regimens. It is also possible that endogenous photosensitizers, such as protoporphyrin, could similarly modify the function of immune cell types. The authors examined the effects of protoporphyrin plus longwave UV light on the ability of human PBL to proliferate in response to mitogens. Noncytotoxic dosages of protoporphyrin plus UV light suppressed PHA-stimulated proliferation of both PBMC and enriched T cells. CD8 + cells were more sensitive to this inhibitory effect than CD4 + cells. The inhibitory effect was also observed when proliferation was induced by the combination of a phorbol ester and ionomycin. Inhibition of PBMC proliferation was associated with inhibition of IL-2 secretion but proliferation was not restored with exogenous IL-2. Instead, the effect of protoporphyrin plus UV light may be on IL-2R. Cells treated with protoporphyrin and UV light did not display the increase in CD25 and β-chain of the IL-2R induced by PHA in control cells. In contrast to the effects of protoporphyrin and UV light on IL-2 and IL-2R α-chain protein expression, the accumulation of mRNA for these proteins induced by PHA was unaffected. None of the effects of protoporphyrin plus UV light on lymphocytes were observed in control experiments where cells were treated with either protoporphyrin or UV light alone. They conclude that biologically relevant dosages of protoporphyrin and UV light modify the function of circulating lymphocytes. 26 refs., 8 figs., 1 tab

Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

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Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

2005-08-01

Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

Arabidopsis CDS blastp result: AK065420 [KOME

Lifescience Database Archive (English)

Full Text Available AK065420 J013022D10 At5g13630.1 magnesium-chelatase subunit chlH, chloroplast, puta...tive / Mg-protoporphyrin IX chelatase, putative (CHLH) nearly identical to magnesium chelatase subunit GI:11...54627 from [Arabidopsis thaliana]; contains Pfam profile: PF02514 CobN/magnesium chelatase family protein 1e-166 ...

Ablative fractional laser enhances MAL-induced PpIX accumulation

DEFF Research Database (Denmark)

Haak, C S; Christiansen, K; Erlendsson, Andrés M

2016-01-01

BACKGROUND AND OBJECTIVES: Pretreatment of skin with ablative fractional laser enhances accumulation of topical provided photosensitizer, but essential information is lacking on the interaction between laser channel densities and pharmacokinetics. Hence our objectives were to investigate how...... (range 46-133min) induced fluorescence levels similar to curettage and 180min incubation. Furthermore, MAL 80 and 160mg/g induced similar fluorescence intensities in skin exposed to laser densities of 1, 2 and 5% (p>0.0537, 30-180min). CONCLUSION: MAL-induced protoporphyrin accumulation is augmented...... protoporphyrin accumulation was affected by laser densities, incubation time and drug concentration. METHODS: We conducted the study on the back of healthy male volunteers (n=11). Test areas were pretreated with 2940nm ablative fractional Er:YAG laser, 11.2mJ per laser channel using densities of 1, 2, 5, 10...

Efficiency Of The Photodynamic Therapy Using Gold Nanoparticles (np-Au) And PpIX Induced And Not Induced

International Nuclear Information System (INIS)

Maldonado-Alvarado, Elizabeth; Ramon-Gallegos, Eva; Arenas-Huertero, Francisco jesus; Reyes-Arellano, Alicia; Tanori-Cordova, Judith; Sanchez-Espindola, Maria Esther; Jimenez-Perez, Jose Luis; Cruz-Orea, Alfredo

2008-01-01

The use of gold nanoparticles (np-Au) to eliminate cancer has proved to be very effective due to the fact that cancerous cells accumulate it 600% more than healthy cells. In addition they have a high capacity of absorption and dispersion of light. Therefore, the effectiveness of photodynamic therapy (PDT) could be improved by the simultaneous use of np-Au and photosensitizes (Ps), emphasizing the high efficiency of the PDT to diagnose and to treat pre-malignant and malignant processes. The aim of this work was to determine the efficiency of PDT using np-Au and protoporphyrin IX (PpIX) induced and not induced by the δ-aminolevulinic acid (ALA). It were found the conditions of synthesis of hydrosoluble np-Au, and were characterized by transmission electronic microscopy (TEM) and UV-VIS spectroscopy. It was realized a kinetic by TEM to determine the cellular incorporation time of np-Au, the maximum incorporation of np-Au was of 16 h. PDT was applied using different doses of np-Au and photosensitizers. It was observed that the use of PDT simultaneously with np-Au did not increase the mortality of HeLa cells. In the case of C33, when PpIX not induced is used as photosensitizer simultaneously with np-Au, the mortality increased 20%

Differential Proteomic Analysis Using iTRAQ Reveals Alterations in Hull Development in Rice (Oryza sativa L.).

Science.gov (United States)

Wang, Shuzhen; Chen, Wenyue; Xiao, Wenfei; Yang, Changdeng; Xin, Ya; Qiu, Jieren; Hu, Weimin; Ying, Wu; Fu, Yaping; Tong, Jianxin; Hu, Guocheng; Chen, Zhongzhong; Fang, Xianping; Yu, Hong; Lai, Wenguo; Ruan, Songlin; Ma, Huasheng

2015-01-01

Rice hull, the outer cover of the rice grain, determines grain shape and size. Changes in the rice hull proteome in different growth stages may reflect the underlying mechanisms involved in grain development. To better understand these changes, isobaric tags for relative and absolute quantitative (iTRAQ) MS/MS was used to detect statistically significant changes in the rice hull proteome in the booting, flowering, and milk-ripe growth stages. Differentially expressed proteins were analyzed to predict their potential functions during development. Gene ontology (GO) terms and pathways were used to evaluate the biological mechanisms involved in rice hull at the three growth stages. In total, 5,268 proteins were detected and characterized, of which 563 were differentially expressed across the development stages. The results showed that the flowering and milk-ripe stage proteomes were more similar to each other (r=0.61) than either was to the booting stage proteome. A GO enrichment analysis of the differentially expressed proteins was used to predict their roles during rice hull development. The potential functions of 25 significantly differentially expressed proteins were used to evaluate their possible roles at various growth stages. Among these proteins, an unannotated protein (Q7X8A1) was found to be overexpressed especially in the flowering stage, while a putative uncharacterized protein (B8BF94) and an aldehyde dehydrogenase (Q9FPK6) were overexpressed only in the milk-ripe stage. Pathways regulated by differentially expressed proteins were also analyzed. Magnesium-protoporphyrin IX monomethyl ester [oxidative] cyclase (Q9SDJ2), and two magnesium-chelatase subunits, ChlD (Q6ATS0), and ChlI (Q53RM0), were associated with chlorophyll biosynthesis at different developmental stages. The expression of Q9SDJ2 in the flowering and milk-ripe stages was validated by qRT-PCR. The 25 candidate proteins may be pivotal markers for controlling rice hull development at various

Perturbed porphyrin biosynthesis contributes to differential herbicidal symptoms in photodynamically stressed rice (Oryza sativa) treated with 5-aminolevulinic acid and oxyfluorfen.

Science.gov (United States)

Phung, Thu-Ha; Jung, Sunyo

2014-11-01

This paper focuses on the molecular mechanism of deregulated porphyrin biosynthesis in rice plants under photodynamic stress imposed by an exogenous supply of 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). Plants treated with 5 mM ALA or 50 µM OF exhibited differential herbicidal symptoms as characterized by white and brown necrosis, respectively, with substantial increases in cellular leakage and malondialdehyde production. Protoporphyrin IX accumulated to higher levels after 1 day of ALA and OF treatment, whereas it decreased to the control level after 2 days of ALA treatment. Plants responded to OF by greatly decreasing the levels of Mg-protoporphyrin IX (MgProto IX), MgProto IX methyl ester, and protochlorophyllide to levels lower than control, whereas their levels drastically increased 1 day after ALA treatment and then disappeared 2 days after the treatment. Enzyme activity and transcript levels of HEMA1, GSA and ALAD for ALA synthesis greatly decreased in ALA- and OF-treated plants. Transcript levels of PPO1, CHLH, CHLI, and PORB genes involving Mg-porphyrin synthesis continuously decreased in ALA- and OF-treated plants, with greater decreases in ALA-treated plants. By contrast, up-regulation of FC2 and HO2 genes in Fe-porphyrin branch was noticeable in ALA and OF-treated plants 1 day and 2 days after the treatments, respectively. Decreased transcript levels of nuclear-encoded genes Lhcb1, Lhcb6, and RbcS were accompanied by disappearance of MgProto IX in ALA- and OF-treated plants after 2 days of the treatments. Under photodynamic stress imposed by ALA and OF, tight control of porphyrin biosynthesis prevents accumulation of toxic metabolic intermediates not only by down-regulation of their biosynthesis but also by photodynamic degradation. The up-regulation of FC2 and HO2 also appears to compensate for the photodynamic stress-induced damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Degradation of the Alternaria mycotoxins alternariol, alternariol monomethyl ether, and altenuene upon bread baking.

Science.gov (United States)

Siegel, David; Feist, Michael; Proske, Matthias; Koch, Matthias; Nehls, Irene

2010-09-08

The stability of the Alternaria mycotoxins alternariol, alternariol monomethyl ether, and altenuene upon bread baking was investigated by model experiments using a spiked wholemeal wheat flour matrix. For alternariol and alternariol monomethyl ether, but not for altenuene, degradation products, formed through a sequence of hydrolysis and decarboxylation, could be identified in pilot studies. The simultaneous quantification of alternariol, alternariol monomethyl ether, altenuene, and the degradation products was achieved by a newly developed high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) multimethod. The obtained quantitative data indicate that the Alternaria mycotoxins are barely degraded during wet baking, while significant degradation occurs upon dry baking, with the stability decreasing in the order alternariol monomethyl ether>alternariol>altenuene. The novel degradation products could be detected after the wet baking of flour spiked with alternariol and in a sample survey of 24 commercial cereal based baking products.

Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

Science.gov (United States)

Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

2015-12-29

Salinity-alkalinity stress is known to adversely affect a variety of processes in plants, thus inhibiting growth and decreasing crop yield. Polyamines protect plants against a variety of environmental stresses. However, whether exogenous spermidine increases the tolerance of tomato seedlings via effects on chloroplast antioxidant enzymes and chlorophyll metabolism is unknown. In this study, we examined the effect of exogenous spermidine on chlorophyll synthesis and degradation pathway intermediates and related enzyme activities, as well as chloroplast ultrastructure, gene expression, and antioxidants in salinity-alkalinity-stressed tomato seedlings. Salinity-alkalinity stress disrupted chlorophyll metabolism and hindered uroorphyrinogen III conversion to protoporphyrin IX. These effects were more pronounced in seedlings of cultivar Zhongza No. 9 than cultivar Jinpengchaoguan. Under salinity-alkalinity stress, exogenous spermidine alleviated decreases in the contents of total chlorophyll and chlorophyll a and b in seedlings of both cultivars following 4 days of stress. With extended stress, exogenous spermidine reduced the accumulation of δ-aminolevulinic acid, porphobilinogen, and uroorphyrinogen III and increased the levels of protoporphyrin IX, Mg-protoporphyrin IX, and protochlorophyllide, suggesting that spermidine promotes the conversion of uroorphyrinogen III to protoporphyrin IX. The effect occurred earlier in cultivar Jinpengchaoguan than in cultivar Zhongza No. 9. Exogenous spermidine also alleviated the stress-induced increases in malondialdehyde content, superoxide radical generation rate, chlorophyllase activity, and expression of the chlorophyllase gene and the stress-induced decreases in the activities of antioxidant enzymes, antioxidants, and expression of the porphobilinogen deaminase gene. In addition, exogenous spermidine stabilized the chloroplast ultrastructure in stressed tomato seedlings. The tomato cultivars examined exhibited different

GUN4-Porphyrin Complexes Bind the ChlH/GUN5 Subunit of Mg-Chelatase and Promote Chlorophyll Biosynthesis in Arabidopsis[W

Science.gov (United States)

Adhikari, Neil D.; Froehlich, John E.; Strand, Deserah D.; Buck, Stephanie M.; Kramer, David M.; Larkin, Robert M.

2011-01-01

The GENOMES UNCOUPLED4 (GUN4) protein stimulates chlorophyll biosynthesis by activating Mg-chelatase, the enzyme that commits protoporphyrin IX to chlorophyll biosynthesis. This stimulation depends on GUN4 binding the ChlH subunit of Mg-chelatase and the porphyrin substrate and product of Mg-chelatase. After binding porphyrins, GUN4 associates more stably with chloroplast membranes and was proposed to promote interactions between ChlH and chloroplast membranes—the site of Mg-chelatase activity. GUN4 was also proposed to attenuate the production of reactive oxygen species (ROS) by binding and shielding light-exposed porphyrins from collisions with O2. To test these proposals, we first engineered Arabidopsis thaliana plants that express only porphyrin binding–deficient forms of GUN4. Using these transgenic plants and particular mutants, we found that the porphyrin binding activity of GUN4 and Mg-chelatase contribute to the accumulation of chlorophyll, GUN4, and Mg-chelatase subunits. Also, we found that the porphyrin binding activity of GUN4 and Mg-chelatase affect the associations of GUN4 and ChlH with chloroplast membranes and have various effects on the expression of ROS-inducible genes. Based on our findings, we conclude that ChlH and GUN4 use distinct mechanisms to associate with chloroplast membranes and that mutant alleles of GUN4 and Mg-chelatase genes cause sensitivity to intense light by a mechanism that is potentially complex. PMID:21467578

A Zn-porphyrin complex contributes to bright red color in Parma ham.

Science.gov (United States)

Wakamatsu, J; Nishimura, T; Hattori, A

2004-05-01

The Italian traditional dry-cured ham (Parma ham) shows a stable bright red color that is achieved without the use of nitrite and/or nitrate. In this study we examined the pigment spectroscopically, fluoroscopically and by using HPLC and ESI-HR-MASS analysis. Porphyrin derivative other than acid hematin were contained in the HCl-containing acetone extract from Parma ham. A strong fluorescence peak at 588 nm and a weak fluorescence peak at 641 nm were observed. By HPLC analysis the acetone extract of Parma ham was observed at the single peak, which eluted at the same time as Zn-protoporphyrin IX and emitted fluorescence. The results of ESI-HR-MS analysis showed both agreement with the molecular weight of Zn-protoporphyrin IX and the characteristic isotope pattern caused by Zn isotopes. These results suggest that the bright red color in Parma ham is caused by Zn-protoporphyrin IX.

In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

Science.gov (United States)

Limentani, S A; Gowell, K P; Deitcher, S R

1995-04-01

This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Photodynamic therapy using aminolevulinic acid (ALA)

Science.gov (United States)

Bachor, Ruediger; Reich, Ella D.; Miller, Kurt; Hautmann, Richard E.

1994-03-01

Photodynamic therapy (PDT) is a treatment modality for a variety of cancers. Since no ideal photosensitizer is available yet, new photosensitizers are being sought. A new concept of PDT is the use of endogenous photosensitizers. ALA is a metabolite in heme synthesis. It is a precursor of protoporphyrin IX, a potent photosensitizer. After administration of ALA it is transformed by the cells to protoporphyrin IX. The goal of our study was to examine dark toxicity of ALA and its phototoxic potential in two different human cell lines.

A subchronic dermal exposure study of diethylene glycol monomethyl ether and ethylene glycol monomethyl ether in the male guinea pig.

Science.gov (United States)

Hobson, D W; D'Addario, A P; Bruner, R H; Uddin, D E

1986-02-01

Diethylene glycol monomethyl ether (DEGME) has been selected as a replacement anti-icing additive for ethylene glycol monomethyl ether (EGME) in Navy jet aircraft fuel. This experiment was performed to determine whether DEGME produced similar toxicity to EGME following dermal exposure. Male guinea pigs were dermally exposed to 1.00, 0.20, 0.04, or 0 (control) g/kg/day DEGME for 13 weeks, 5 days/week, 6 hr/day. Another group of animals was similarly exposed to 1.00 g/kg/day EGME. Body weights as well as testicular and splenic weights were reduced as a result of exposure to EGME, DEGME-exposed animals exhibited decreased splenic weight in the high- and medium-dose (1.00 and 0.20 g/kg/day) exposure groups only. Hematologic changes in EGME-exposed animals included mild anemia with increased erythrocytic mean corpuscular volumes and a lymphopenia with increased neutrophils. Similar hematological changes were not observed in any animals exposed to DEGME. Serum creatine kinase activity was increased in animals exposed to EGME, and serum lactate dehydrogenase activity was increased in EGME and 1.00 g/kg/day DEGME-exposed animals. In general, DEGME produced minimal toxicological changes following dermal exposure, whereas the toxicological changes observed following similar exposure to EGME were much more profound.

Fluorescent Endoscopy of Tumors in Upper Part of Gastrointestinal Tract

Science.gov (United States)

Borisova, E.; Vladimirov, B.; Angelov, I.; Avramov, L.

2007-04-01

In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The 5-ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for LED to use the light guide of standard video-endoscopic system (Olimpus Corp.). Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer (USB4000, OceanOptics Inc.). Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Cutaneous respirometry as novel technique to monitor mitochondrial function: A feasibility study in healthy volunteers

NARCIS (Netherlands)

F.A. Harms (Floor A.); R.J. Stolker (Robert); E.G. Mik (Egbert)

2016-01-01

textabstractBackground: The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of

In vitro evaluation of photodynamic therapy using redox-responsive nanoparticles carrying PpIX

Science.gov (United States)

Souza Leite, Ilaiáli; Vivero-Escoto, Juan L.; Lyles, Zachary; Salvador Bagnato, Vanderlei; Mayumi Inada, Natalia

2018-02-01

Photodynamic therapy (PDT) is a technique that combines light's interaction with a photoactive substance to promote cellular death and that has been used to treat a wide range of maladies. Cancer is among the leading causes of death worldwide and has been a central issue assessed by PDT research and clinical trials over the last 35 years, but its efficiency has been hampered by photosensitizer buildup at treatment site. Nanotechnology has been addressing drug delivery problems by the development of distinct nanostructured platforms capable of increasing pharmacological properties of molecules. The association of nanotechnology's potential to enhance photosensitizer delivery to target tissues with PDT's oxidative damage to induce cell death has been rising as a prospect to optimize cancer treatment. In this study, we aim to verify and compare the efficiency of PDT using redox-responsive silica-based nanoparticles carrying protoporphyrin IX (PpIX) in vitro, in both tumor and healthy cells. Dose-response experiments revealed the higher susceptibility of murine melanoma cells (B16-F10 cell line) to PDT (630 nm, 50 J/cm2) when compared to human dermal fibroblasts (HDFn): after 24 h of incubation with 50 μg/mL nanoparticles solutions, approximately 80 % of B16- F10 cells were killed, while similar results were obtained in HDFn cultures when solutions over 150 μg/mL were used. Uptake and ROS generation assays suggest increased nanoparticle internalization in the tumor cell line, in comparison with the healthy cells, and greater ROS levels were observed in B16-F10 cells.

Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

Science.gov (United States)

Stolker, Robert Jan; Mik, Egbert

2016-01-01

Background The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. This study describes the first use of a clinical prototype in skin of humans. Methods The clinical prototype was tested in 30 healthy volunteers. A self-adhesive patch containing 2 mg 5-aminolevulinic acid (ALA) was applied on the skin of the anterior chest wall (sternal) for induction of mitochondrial protoporphyrin IX and was protected from light for 5 h. MitoPO2 was measured by means of oxygen-dependent delayed fluorescence of protoporphyrin IX. MitoVO2 was determined by dynamic mitoPO2 measurements on the primed skin, while locally blocking oxygen supply by applying local pressure with the measurement probe. MitoPO2 was recorded before and during a 60-s period of compression of the microcirculation, at an interval of 1 Hz. Oxygen consumption (i.e. the local oxygen disappearance rate) was calculated from the decay of the mitoPO2 slope. Results Oxygen-dependent delayed fluorescence measurements were successfully performed in the skin of 27 volunteers. The average value (± SD) of mitoPO2 was 44 ± 17 mmHg and mean mitoVO2 values were 5.8 ± 2.3 and 6.1 ± 1.6 mmHg s-1 at a skin temperature of 34°C and 40°C, respectively. No major discomfort during measurement and no long-term dermatological abnormalities were reported in a survey performed 1 month after measurements. Conclusion These results show that the clinical prototype allows measurement of mitochondrial oxygenation and oxygen consumption in humans. The development of this clinically applicable device offers opportunities for further evaluation of the technique in humans and the start of first clinical studies. PMID:27455073

Title IX Resource Guide

Science.gov (United States)

Office for Civil Rights, US Department of Education, 2015

2015-01-01

Title IX of the Education Amendments of 1972 (Title IX) prohibits discrimination based on sex in education programs and activities in federally funded schools at all levels. If any part of a school district or college receives any Federal funds for any purpose, all of the operations of the district or college are covered by Title IX. The essence…

Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX.

Science.gov (United States)

Kobayashi, Koichi; Masuda, Tatsuru; Tajima, Naoyuki; Wada, Hajime; Sato, Naoki

2014-08-01

Tetrapyrroles such as heme and chlorophyll are essential for biological processes, including oxygenation, respiration, and photosynthesis. In the tetrapyrrole biosynthesis pathway, protoporphyrinogen IX oxidase (Protox) catalyzes the formation of protoporphyrin IX, the last common intermediate for the biosynthesis of heme and chlorophyll. Three nonhomologous isofunctional enzymes, HemG, HemJ, and HemY, for Protox have been identified. To reveal the distribution and evolution of the three Protox enzymes, we identified homologs of each along with other heme biosynthetic enzymes by whole-genome clustering across three domains of life. Most organisms possess only one of the three Protox types, with some exceptions. Detailed phylogenetic analysis revealed that HemG is mostly limited to γ-Proteobacteria whereas HemJ may have originated within α-Proteobacteria and transferred to other Proteobacteria and Cyanobacteria. In contrast, HemY is ubiquitous in prokaryotes and is the only Protox in eukaryotes, so this type may be the ancestral Protox. Land plants have a unique HemY homolog that is also shared by Chloroflexus species, in addition to the main HemY homolog originating from Cyanobacteria. Meanwhile, organisms missing any Protox can be classified into two groups; those lacking most heme synthetic genes, which necessarily depend on external heme supply, and those lacking only genes involved in the conversion of uroporphyrinogen III into heme, which would use a precorrin2-dependent alternative pathway. However, hemN encoding coproporphyrinogen IX oxidase was frequently found in organisms lacking Protox enzyme, which suggests a unique role of this gene other than in heme biosynthesis. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

iTRAQ-Based Quantitative Proteomics Identifies Potential Regulatory Proteins Involved in Chicken Eggshell Brownness.

Directory of Open Access Journals (Sweden)

Guangqi Li

Full Text Available Brown eggs are popular in many countries and consumers regard eggshell brownness as an important indicator of egg quality. However, the potential regulatory proteins and detailed molecular mechanisms regulating eggshell brownness have yet to be clearly defined. In the present study, we performed quantitative proteomics analysis with iTRAQ technology in the shell gland epithelium of hens laying dark and light brown eggs to investigate the candidate proteins and molecular mechanisms underlying variation in chicken eggshell brownness. The results indicated 147 differentially expressed proteins between these two groups, among which 65 and 82 proteins were significantly up-regulated in the light and dark groups, respectively. Functional analysis indicated that in the light group, the down-regulated iron-sulfur cluster assembly protein (Iba57 would decrease the synthesis of protoporphyrin IX; furthermore, the up-regulated protein solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 5 (SLC25A5 and down-regulated translocator protein (TSPO would lead to increased amounts of protoporphyrin IX transported into the mitochondria matrix to form heme with iron, which is supplied by ovotransferrin protein (TF. In other words, chickens from the light group produce less protoporphyrin IX, which is mainly used for heme synthesis. Therefore, the exported protoporphyrin IX available for eggshell deposition and brownness is reduced in the light group. The current study provides valuable information to elucidate variation of chicken eggshell brownness, and demonstrates the feasibility and sensitivity of iTRAQ-based quantitative proteomics analysis in providing useful insights into the molecular mechanisms underlying brown eggshell pigmentation.

Continuous ultra-low-intensity artificial daylight is not as effective as red LED light in photodynamic therapy of multiple actinic keratoses

DEFF Research Database (Denmark)

Wiegell, Stine Regin; Heydenreich, Jakob; Fabricius, Susanne

2011-01-01

Daylight-mediated photodynamic therapy (PDT) is a simple and tolerable treatment of nonmelanoma skin cancer. It is of interest which light intensity is sufficient to prevent accumulation of protoporphyrin IX (PpIX) and effectively treat actinic keratoses (AKs). We compared the efficacy of PDT...

Physiological oxygen concentration alters glioma cell malignancy and responsiveness to photodynamic therapy in vitro.

Science.gov (United States)

Albert, Ina; Hefti, Martin; Luginbuehl, Vera

2014-11-01

The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to 15%. Nevertheless, the majority of in vitro experiments with glioblastoma multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to 21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy. GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX accumulation and localization were investigated, and cell survival and cell death were observed following in vitro PDT. A physiological pO2 of 9% stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha levels, and elevated resistance to camptothecin in U-87 MG cells compared to cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced intracellular PpIX accumulation. However, physiological pO2 changed the responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20% more irradiation light was required to kill U-87 MG cells at physiological pO2, resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and inhibition of caspase 3 activation. Reduction of oxygen concentration from atmospheric to a more physiological level can influence the malignant behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise oxygen concentration control should be considered when designing and performing experiments with GBM cells.

Electrophoretic characterization of D. melanogaster strains deficient in endogenous anti-oxidants in combination with gamma radiation; Caracterizacion electroforetica de cepas de D. melanogaster deficientes en antioxidantes endogenos en combinacion con radiacion gamma

Energy Technology Data Exchange (ETDEWEB)

Gomar A, S.

2012-07-01

The free radicals derived of the oxygen and other reactive species are generated by endogenous processes as sub-products of the aerobic metabolism or by exogenous factors as the environmental pollution, the biological half life of these free radicals is of microseconds, but they have the capacity of reacting with any atom or molecule to its around causing oxidant stress and damage to molecules, cellular membranes and tissues. To counteract them, there is endogenous and exogenous anti-oxidants, the first ones are synthesized by the organism for maintaining the cellular homeostasis as the superoxide dismutase and catalase. There are recent evidences that indicate that the sodium cooper chlorophyllin (SCC) presents a dual effect reducing and/or increasing the induced genetic damage by different mutagenic agents. One hypothesis for this effect is that the SCC can act as oxidant per se or through some of their metabolites. Results more recent indicated that a similar of the SCC, the protoporphyrin-Ix, can produce genetic damage. In this work exogenous anti-oxidants were used, as the SCC, protoporphyrin-Ix or the bilirubin in the induction of endogenous anti-oxidants enzymes to evaluate the supposed oxidant activity of the SCC and/or their metabolites. Drosophila melanogaster strains deficient in superoxide dismutase, catalase and withered were used and a rustic strain Canton-S as control. In the three experiments were treated 60 males of 1 day of age, with SCC, protoporphyrin-Ix or bilirubin to one concentration of 69 m M during 12 days. Every 4 days 10 males were isolated to measure them the induction of superoxide dismutase and catalase. The results showed that the SCC, protoporphyrin-Ix and bilirubin considered like anti-oxidants, were able to increase the induction of the superoxide dismutase and catalase enzymes. This result maybe is because they are able to generate reactive species of oxygen, as the anion superoxide and the hydrogen peroxide. Among the three

Electrophoretic characterization of D. melanogaster strains deficient in endogenous anti-oxidants in combination with gamma radiation

International Nuclear Information System (INIS)

Gomar A, S.

2012-01-01

The free radicals derived of the oxygen and other reactive species are generated by endogenous processes as sub-products of the aerobic metabolism or by exogenous factors as the environmental pollution, the biological half life of these free radicals is of microseconds, but they have the capacity of reacting with any atom or molecule to its around causing oxidant stress and damage to molecules, cellular membranes and tissues. To counteract them, there is endogenous and exogenous anti-oxidants, the first ones are synthesized by the organism for maintaining the cellular homeostasis as the superoxide dismutase and catalase. There are recent evidences that indicate that the sodium cooper chlorophyllin (SCC) presents a dual effect reducing and/or increasing the induced genetic damage by different mutagenic agents. One hypothesis for this effect is that the SCC can act as oxidant per se or through some of their metabolites. Results more recent indicated that a similar of the SCC, the protoporphyrin-Ix, can produce genetic damage. In this work exogenous anti-oxidants were used, as the SCC, protoporphyrin-Ix or the bilirubin in the induction of endogenous anti-oxidants enzymes to evaluate the supposed oxidant activity of the SCC and/or their metabolites. Drosophila melanogaster strains deficient in superoxide dismutase, catalase and withered were used and a rustic strain Canton-S as control. In the three experiments were treated 60 males of 1 day of age, with SCC, protoporphyrin-Ix or bilirubin to one concentration of 69 m M during 12 days. Every 4 days 10 males were isolated to measure them the induction of superoxide dismutase and catalase. The results showed that the SCC, protoporphyrin-Ix and bilirubin considered like anti-oxidants, were able to increase the induction of the superoxide dismutase and catalase enzymes. This result maybe is because they are able to generate reactive species of oxygen, as the anion superoxide and the hydrogen peroxide. Among the three

Two-Photon Irradiation of an Intracellular Singlet Oxygen Photosensitizer: Achieving Localized Sub-Cellular Excitation in Spatially-Resolved Experiments

DEFF Research Database (Denmark)

Pedersen, Brian Wett; Breitenbach, Thomas; Redmond, Robert W.

2010-01-01

The response of a given cell to spatially-resolved sub-cellular irradiation of a singlet oxygen photosensitizer (protoporphyrin IX, PpIX) using a focused laser was assessed. In these experiments, incident light was scattered over a volume greater than that defi ned by the dimensions of the laser...

Eggshell pigmentation has no evident effects on offspring viability in common kestrels

Czech Academy of Sciences Publication Activity Database

Fargallo, J. A.; López-Rull, I.; Mikšík, Ivan; Eckhardt, Adam; Peralta-Sánchez, J. M.

2014-01-01

Roč. 28, č. 4 (2014), s. 627-637 ISSN 0269-7653 R&D Projects: GA ČR(CZ) GA13-17224S Institutional support: RVO:67985823 Keywords : biliverdin IX * egg colouration * eggshell proteins * falco tinnunculus * protoporphyrin IX Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.517, year: 2014

METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL

Science.gov (United States)

METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL ADMINISTRATION IN MICEM F Hughes1, V Devesa2, B M Adair1, M Styblo2, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hi...

Mutation of Gly195 of the ChlH subunit of Mg-chelatase reduces chlorophyll and further disrupts PS II assembly in a Ycf48-deficient strain of Synechocystis sp. PCC 6803

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Tim Crawford

2016-07-01

Full Text Available Biogenesis of the photosystems in oxygenic phototrophs requires co-translational insertion of chlorophyll a. The first committed step of chlorophyll a biosynthesis is the insertion of a Mg2+ ion into the tetrapyrrole intermediate protoporphyrin IX, catalyzed by Mg-chelatase. We have identified a Synechocystis sp. PCC 6803 strain with a spontaneous mutation in chlH that results in a Gly195 to Glu substitution in a conserved region of the catalytic subunit of Mg-chelatase. Mutant strains containing the ChlH Gly195 to Glu mutation were generated using a two-step protocol that introduced the chlH gene into a putative neutral site in the chromosome prior to deletion of the native gene. The Gly195 to Glu mutation resulted in strains with decreased chlorophyll a. Deletion of the PS II assembly factor Ycf48 in a strain carrying the ChlH Gly195 to Glu mutation did not grow photoautotrophically. In addition, the ChlH-G195E:ΔYcf48 strain showed impaired PS II activity and decreased assembly of PS II centers in comparison to a ΔYcf48 strain. We suggest decreased chlorophyll in the ChlH-G195E mutant provides a background to screen for the role of assembly factors that are not essential under optimal growth conditions.

Linoleic acid, thymine, and tryptophan radiosensitization by protoporphyrin in presence of oxygene

International Nuclear Information System (INIS)

Champel, P.; Mignot, M.A.; Pillement, B.; Fontenil, L.; Rocquet, G.

Sensitizing effect induced by protoporphyrin, an active molecule in photooxidation is studied. Studied substances are tryptophan, thymine, linoleic acid, each component representing one of the great groups of biological components, nucleic acid, proteins, lipids [fr

Tissue-specific expression of type IX collagen

International Nuclear Information System (INIS)

Nishimura, I.; Muragaki, Y.; Ninomiya, Y.; Olsen, B.R.; Hayashi, M.

1990-01-01

This paper reports on the tissue-specific expression of type IX collagen, a major component of cartilage fibrils. It contains molecules with three genetically distinct subunits. The subunits form three triple-helical (CO) domains separated by non-triple-helical (NC) sequences. One of the subunits in cartilage, α1(IX), contains a large amino-terminal globular domain, NC4, while a second subunit, α2(IX), contains a covalently attached chondroitin sulfate chain. The site of attachment for this chain is located within the non-triple-helical sequence NC3, which separates the amino-terminal and central triple-helical domains of the type IX molecules. The NC3 region is 5 amino acid residues longer in the α2(IX) chain than in the α1(IX) and α3(IX) chains. This may explain why type IX molecules tend to show a sharp angle in the NC3 region, and why monoclonal antibody molecules that are specific for the stub left after chondroitinase ABC digestion of the chondroitin sulfate side chain always are located on the outside of the angle

Equivalent chain lengths of all C4-C23 saturated monomethyl branched fatty acid methyl esters on methylsilicone OV-1 stationary phase.

Science.gov (United States)

Kubinec, Róbert; Blaško, Jaroslav; Górová, Renáta; Addová, Gabriela; Ostrovský, Ivan; Amann, Anton; Soják, Ladislav

2011-04-01

Isomer mixtures of monomethyl branched saturated C7-C23 fatty acid methyl esters (FAME) were prepared by performing a methylene insertion reaction to the straight chain FAME and this study model was completed by using commercially available standards of C4-C7 FAME. The equivalent chain lengths (ECL) of all 220 C4-C23 monomethyl branched FAME on OV-1 stationary phase were measured, achieving an average repeatability of ±0.0004 ECL units. The monomethyl branched FAME was identified by GC on the basis of regularity of the fractional chain lengths (FCL) dependence on the number of carbon atoms (C(z)) of individual homologous series of methyl 2-, 3-, …, 21-FAME. The prediction of retention of the first homologues, having the new position of methyl group beginning at higher carbon atoms number, and analogously for the second, third, fourth, and other members of the homologous series, allowed the dependence FCL=f(C(z)) for the first and subsequent members of beginning homologous of monomethyl derivatives of FAME. The identification was confirmed by mass spectrometry. All of the methyl isomers of FAME, which could not be completely separated by gas chromatography due to having a methyl group in surroundings of the middle of the carbon chain, were resolved by mass spectrometry using deconvolution in a SIM-mode. Measured gas chromatographic and mass spectrometric data were applied for identification of the monomethyl branched saturated FAME in tongue coating. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification and molecular characterization of the second Chlamydomonas gun4 mutant, gun4-II [v2; ref status: indexed, http://f1000r.es/1id

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Phillip B Grovenstein

2013-07-01

Full Text Available The green micro-alga Chlamydomonas reinhardtii is an elegant model organism to study oxygenic photosynthesis. Chlorophyll (Chl and heme are major tetrapyrroles that play an essential role in photosynthesis and respiration. These tetrapyrroles are synthesized via a common branched pathway that involves mainly enzymes, encoded by nuclear genes. One of the enzymes in the pathway is Mg chelatase (MgChel. MgChel catalyzes insertion of Mg2+ into protoporphyrin IX (PPIX, proto to form Magnesium-protoporphyrin IX (MgPPIX, Mgproto, the first biosynthetic intermediate in the Chl branch. The GUN4 (genomes uncoupled 4 protein is not essential for the MgChel activity but has been shown to significantly stimulate its activity. We have isolated a light sensitive mutant, 6F14, by random DNA insertional mutagenesis. 6F14 cannot tolerate light intensities higher than 90-100 μmol photons m-2 s-1. It shows a light intensity dependent progressive photo-bleaching. 6F14 is incapable of photo-autotrophic growth under light intensity higher than 100 μmol photons m-2 s-1. PCR based analyses show that in 6F14 the insertion of the plasmid outside the GUN4 locus has resulted in a genetic rearrangement of the GUN4 gene and possible deletions in the genomic region flanking the GUN4 gene. Our gun4 mutant has a Chl content very similar to that in the wild type in the dark and is very sensitive to fluctuations in the light intensity in the environment unlike the earlier identified Chlamydomonas gun4 mutant. Complementation with a functional copy of the GUN4 gene restored light tolerance, Chl biosynthesis and photo-autotrophic growth under high light intensities in 6F14. 6F14 is the second gun4 mutant to be identified in C. reinhardtii. Additionally, we show that our two gun4 complements over-express the GUN4 protein and show a higher Chl content per cell compared to that in the wild type strain.

Eggshell Biliverdin and Protoporphyrin Pigments in a Songbird: Are They Derived from Erythrocytes, Blood Plasma, or the Shell Gland?

Science.gov (United States)

Hargitai, Rita; Boross, Nóra; Hámori, Susanne; Neuberger, Eszter; Nyiri, Zoltán

Biliverdin and protoporphyrin pigments are deposited into the eggshell when the developing egg is in the shell gland. However, the site of synthesis of eggshell pigments is still uncertain, although it may influence the possible costs and potential functions of eggshell coloration in avian species. Eggshell pigments may be derived from red blood cells or be produced in other organs and then transferred to the shell gland, or they may be synthesized de novo in the shell gland. We studied in the canary (Serinus canaria) whether eggshell blue-green and brown pigmentations are associated with experimentally elevated anemia, female hematocrit level, immature erythrocyte percentage, and feces and plasma pigment levels during egg laying to find out the possible origin of eggshell pigments. We found no significant effects of hematocrit level or experimentally elevated anemia on intensity of eggshell blue-green and brown pigmentations; therefore, we consider it less likely that eggshell pigments are derived from erythrocytes. In addition, we found no significant associations between female feces biliverdin concentration during egg laying and intensity of eggshell blue-green pigmentation, suggesting that eggshell biliverdin may not originate from the spleen or liver. We found a negative association between plasma and feces protoporphyrin concentrations during egg laying and eggshell brown chroma. This result suggests that an increased production of protoporphyrin in the liver, which could have elevated plasma and feces protoporphyrin concentrations, could inhibit eggshell protoporphyrin pigmentation, probably through affecting enzymatic activities. We suggest that both pigments are produced de novo in the shell gland in the canary, but circulating pigment levels may influence shell gland pigment synthesis, thus connecting the physiological status of the female to eggshell coloration.

Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation for use in photodynamic therapy of lesions of the gastrointestinal tract.

Science.gov (United States)

Bourre, Ludovic; Thibaut, Sonia; Briffaud, Amelie; Lajat, Youenn; Patrice, Thierry

2002-02-01

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX may play a role in the treatment of dysplastic Barrett's oesophagus. An ALA thermosetting gel Pluronic F-127) was developed and evaluated in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro studies of the influence of Pluronic F-127 percentage on thermosetting gel temperature, followed by the influence of ALA concentration on thermosetting temperature and ALA-gel stability as a function of time or temperature were studied. In vivo relationships between ALA doses and fluorescence were studied to determine the optimal concentration. Fluorescence measurement in vivo showed that ALA concentration and time had a nonlinear influence on protoporphyrin IX synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was reached, the maximum fluorescence being obtained after 4 h whatever the time of contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1) ALA-gel, and fluorescence intensities differed with time, reaching a maximum after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of Barrett's oesophagus, allowing easy application in liquid form at 4 degrees C and good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into treated mucosa. Copyright 2002 Elsevier Science Ltd.

Endogenous and exogenous fluorescence of gastrointestinal tumors: initial clinical observations

Science.gov (United States)

Borisova, Ekaterina; Plamenova, Lilia; Keremedchiev, Momchil; Vladimirov, Borislav; Avramov, Latchezar

2013-03-01

The limitations of standard endoscopy for detection and evaluation of cancerous changes in gastrointestinal tract (GIT) are significant challenge and initiate development of new diagnostic modalities. Therefore many spectral and optical techniques are applied recently into the clinical practice for obtaining qualitatively and quantitatively new data from gastrointestinal neoplasia with different level of clinical applicability and diagnostic success. One of the most promising approaches is fluorescence detection using naturally existing fluorescent molecules or added fluorescent markers. Deltaaminolevulinic acid / protoporphyrin IX is applied for exogenous fluorescent tumor detection in the upper part of gastrointestinal tract. The 5-ALA is administered per os six hours before measurements at dose 20mg/kg weight. Highpower light-emitting diode at 405 nm is used as a source and the excitation light is passed through the light-guide of standard video-endoscopic system to obtain 2-D visualization. Both kinds of spectra - autofluorescence signals and protoporphyrin IX signal are recorded and stored using a fiber-optic microspectrometer, as in endoscopy instrumental channel a fiber is applied to return information about fluorescence signals. In such way 1-D detection and 2-D visualization of the lesions' fluorescence are received. The results from in vivo detection show significant differentiation between normal and abnormal tissues in 1-D spectroscopic regime, but only moderate discrimination in 2-D imaging.

TMEM14C is required for erythroid mitochondrial heme metabolism.

Science.gov (United States)

Yien, Yvette Y; Robledo, Raymond F; Schultz, Iman J; Takahashi-Makise, Naoko; Gwynn, Babette; Bauer, Daniel E; Dass, Abhishek; Yi, Gloria; Li, Liangtao; Hildick-Smith, Gordon J; Cooney, Jeffrey D; Pierce, Eric L; Mohler, Kyla; Dailey, Tamara A; Miyata, Non; Kingsley, Paul D; Garone, Caterina; Hattangadi, Shilpa M; Huang, Hui; Chen, Wen; Keenan, Ellen M; Shah, Dhvanit I; Schlaeger, Thorsten M; DiMauro, Salvatore; Orkin, Stuart H; Cantor, Alan B; Palis, James; Koehler, Carla M; Lodish, Harvey F; Kaplan, Jerry; Ward, Diane M; Dailey, Harry A; Phillips, John D; Peters, Luanne L; Paw, Barry H

2014-10-01

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.

The histone H4 lysine 20 monomethyl mark, set by PR-Set7 and stabilized by L(3mbt, is necessary for proper interphase chromatin organization.

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Ayako Sakaguchi

Full Text Available Drosophila PR-Set7 or SET8 is a histone methyltransferase that specifically monomethylates histone H4 lysine 20 (H4K20. L(3MBT has been identified as a reader of methylated H4K20. It contains several conserved domains including three MBT repeats binding mono- and dimethylated H4K20 peptides. We find that the depletion of PR-Set7 blocks de novo H4K20me1 resulting in the immediate activation of the DNA damage checkpoint, an increase in the size of interphase nuclei, and drastic reduction of cell viability. L(3mbt on the other hand stabilizes the monomethyl mark, as L(3mbt-depleted S2 cells show a reduction of more than 60% of bulk monomethylated H4K20 (H4K20me1 while viability is barely affected. Ploidy and basic chromatin structure show only small changes in PR-Set7-depleted cells, but higher order interphase chromatin organization is significantly affected presumably resulting in the activation of the DNA damage checkpoint. In the absence of any other known functions of PR-Set7, the setting of the de novo monomethyl mark appears essential for cell viability in the presence or absence of the DNA damage checkpoint, but once newly assembled chromatin is established the monomethyl mark, protected by L(3mbt, is dispensable.

Laser-induced fluorescence studies of premalignant and benign lesions in the female genital tract

Science.gov (United States)

af Klinteberg, Claes; Wang, Ingrid; Lindquist, Charlotta; Vaitkuviene, Aurelija; Svanberg, Katarina

1997-12-01

Laser-induced fluorescence (LIF) was studied in vivo from premalignant and benign lesions in the female genital tract, in particular the cervix. The aim of the study was to investigate the possibilities to differentiate cervical intraepithelial neoplasia (CIN) from normal tissue by means of two different fluorescence modalities. Most of the patients were given a low dose (5 mg/kg bw) of (delta) -amino levulinic acid (ALA). The ALA was orally administered 2 - 4 hours prior to the investigation. During this time, the ALA is transformed to the strongly fluorescent protoporphyrin IX (PpIX) via the haem cycle. Excitation light with a wavelength of 405 nm was used to excite the PpIX fluorescence. Excess amounts of PpIX were accumulated preferentially in diseased tissue. However, the variability in the PpIX accumulation from patient to patient was large. By using excitation light at 337 nm, the endogenous fluorophores are more efficiently excited. Therefore, this excitation modality was exploited for studying spectral characteristics of the autofluorescence in different tissue types. The spectra obtained were evaluated by forming fluorescence intensity ratios. The tissue types were grouped according to the histopathological examination. A correlation with the fluorescence ratios was performed. Some problems with the classification remain, mostly due to the difficulties in obtaining histopathologic evaluation of the biopsies at the exact location of the LIF measurements.

Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.

Science.gov (United States)

Verma, Dheeraj; Moghimi, Babak; LoDuca, Paul A; Singh, Harminder D; Hoffman, Brad E; Herzog, Roland W; Daniell, Henry

2010-04-13

To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.

Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

Science.gov (United States)

Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

2013-05-10

Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

IBM PC/IX operating system evaluation plan

Science.gov (United States)

Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros

1984-01-01

An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.

Sequence Classification: 751792 [

Lifescience Database Archive (English)

Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB TMB >gi|30686748|ref|NP_849438.1| magnesium-protopo...rphyrin O-methyltransferase, putative / magnesium-protoporphyrin IX methyltransferase, putative || http://www.ncbi.nlm.nih.gov/protein/30686748 ...

Sequence Classification: 751793 [

Lifescience Database Archive (English)

Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB TMB >gi|30686750|ref|NP_849439.1| magnesium-protopo...rphyrin O-methyltransferase, putative / magnesium-protoporphyrin IX methyltransferase, putative || http://www.ncbi.nlm.nih.gov/protein/30686750 ...

Sequence Classification: 751791 [

Lifescience Database Archive (English)

Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB TMB >gi|15234905|ref|NP_194238.1| magnesium-protopo...rphyrin O-methyltransferase, putative / magnesium-protoporphyrin IX methyltransferase, putative || http://www.ncbi.nlm.nih.gov/protein/15234905 ...

Title IX: With New Opportunities, Girls' Interest Rises

Science.gov (United States)

Toporek, Bryan

2012-01-01

On June 23, 1972, President Richard M. Nixon signed into law Title IX of the Education Amendments of 1972, which prohibits gender discrimination in any federally financed education program or activity. Title IX is far-reaching, but the law is most often associated with school and college athletics. Title IX allows schools to prove their athletic…

Effects of tin-protoporphyrin administration on hepatic xenobiotic metabolizing enzymes in the juvenile rat

International Nuclear Information System (INIS)

Stout, D.L.; Becker, F.F.

1988-01-01

The heme analogue tin-protoporphyrin IX (SnP) is a potent inhibitor of microsomal heme oxygenase. Administration of SnP to neonatal rats can prevent hyperbilirubinemia by blocking the postnatal increase of heme oxygenase activity. Apparently innocuous at therapeutic doses, it is of potential clinical value for chemoprevention of neonatal jaundice. We found that when 50-g male Sprague-Dawley rats were treated daily with 50 mumol of SnP/kg sc for 6 days, hepatic microsomal cytochromes b5 and P-450 were significantly diminished. Cytochrome P-450 reductase, two P-450-dependent monooxygenases, aminopyrine demethylase and benzo(a)pyrene hydroxylase, and catalase, a peroxisomal hemoprotein, were also significantly diminished. These results suggested that SnP might significantly affect the metabolism of other xenobiotics. This possibility was confirmed by the finding that hexobarbital-induced sleep lasted 4 times longer in SnP-treated rats than in controls. Inhibition of protein synthesis by SnP was ruled out as the cause of hemoprotein loss when administration of [ 3 H]leucine to SnP-treated and control rats demonstrated that proteins of the microsomal, cytosolic, and plasma membrane fractions of the livers from both groups incorporated similar levels of leucine. When 55 FeCl 3 and [2- 14 C]glycine were administered to measure heme synthesis, heme extract from the livers of SnP-treated rats contained 4 times more label from iron and glycine than did heme from control livers. Despite the apparent increased rate of heme synthesis in SnP-treated rats, each of the three cell fractions demonstrated a significant loss of heme but contained sizable amounts of SnP. These findings suggest that SnP causes a decrease of functional hemoprotein and partial loss of enzymic activity by displacing intracellular heme

Perturbations in the Photosynthetic Pigment Status Result in Photooxidation-Induced Crosstalk between Carotenoid and Porphyrin Biosynthetic Pathways

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Joon-Heum Park

2017-11-01

Full Text Available Possible crosstalk between the carotenoid and porphyrin biosynthetic pathways under photooxidative conditions was investigated by using their biosynthetic inhibitors, norflurazon (NF and oxyfluorfen (OF. High levels of protoporphyrin IX (Proto IX accumulated in rice plants treated with OF, whereas Proto IX decreased in plants treated with NF. Both NF and OF treatments resulted in greater decreases in MgProto IX, MgProto IX methyl ester, and protochlorophyllide. Activities and transcript levels of most porphyrin biosynthetic enzymes, particularly in the Mg-porphyrin branch, were greatly down-regulated in NF and OF plants. In contrast, the transcript levels of GSA, PPO1, and CHLD as well as FC2 and HO2 were up-regulated in NF-treated plants, while only moderate increases in FC2 and HO2 were observed in the early stage of OF treatment. Phytoene, antheraxanthin, and zeaxanthin showed high accumulation in NF-treated plants, whereas other carotenoid intermediates greatly decreased. Transcript levels of carotenoid biosynthetic genes, PSY1 and PDS, decreased in response to NF and OF, whereas plants in the later stage of NF treatment exhibited up-regulation of BCH and VDE as well as recovery of PDS. However, perturbed porphyrin biosynthesis by OF did not noticeably influence levels of carotenoid metabolites, regardless of the strong down-regulation of carotenoid biosynthetic genes. Both NF and OF plants appeared to provide enhanced protection against photooxidative damage, not only by scavenging of Mg-porphyrins, but also by up-regulating FC2, HO2, and Fe-chelatase, particularly with increased levels of zeaxanthin via up-regulation of BCH and VDE in NF plants. On the other hand, the up-regulation of GSA, PPO1, and CHLD under inhibition of carotenogenic flux may be derived from the necessity to recover impaired chloroplast biogenesis during photooxidative stress. Our study demonstrates that perturbations in carotenoid and porphyrin biosynthesis coordinate

Perturbations in the Photosynthetic Pigment Status Result in Photooxidation-Induced Crosstalk between Carotenoid and Porphyrin Biosynthetic Pathways.

Science.gov (United States)

Park, Joon-Heum; Tran, Lien H; Jung, Sunyo

2017-01-01

Possible crosstalk between the carotenoid and porphyrin biosynthetic pathways under photooxidative conditions was investigated by using their biosynthetic inhibitors, norflurazon (NF) and oxyfluorfen (OF). High levels of protoporphyrin IX (Proto IX) accumulated in rice plants treated with OF, whereas Proto IX decreased in plants treated with NF. Both NF and OF treatments resulted in greater decreases in MgProto IX, MgProto IX methyl ester, and protochlorophyllide. Activities and transcript levels of most porphyrin biosynthetic enzymes, particularly in the Mg-porphyrin branch, were greatly down-regulated in NF and OF plants. In contrast, the transcript levels of GSA, PPO1 , and CHLD as well as FC2 and HO2 were up-regulated in NF-treated plants, while only moderate increases in FC2 and HO2 were observed in the early stage of OF treatment. Phytoene, antheraxanthin, and zeaxanthin showed high accumulation in NF-treated plants, whereas other carotenoid intermediates greatly decreased. Transcript levels of carotenoid biosynthetic genes, PSY1 and PDS , decreased in response to NF and OF, whereas plants in the later stage of NF treatment exhibited up-regulation of BCH and VDE as well as recovery of PDS . However, perturbed porphyrin biosynthesis by OF did not noticeably influence levels of carotenoid metabolites, regardless of the strong down-regulation of carotenoid biosynthetic genes. Both NF and OF plants appeared to provide enhanced protection against photooxidative damage, not only by scavenging of Mg - porphyrins, but also by up-regulating FC2, HO2 , and Fe-chelatase, particularly with increased levels of zeaxanthin via up-regulation of BCH and VDE in NF plants. On the other hand, the up-regulation of GSA, PPO1 , and CHLD under inhibition of carotenogenic flux may be derived from the necessity to recover impaired chloroplast biogenesis during photooxidative stress. Our study demonstrates that perturbations in carotenoid and porphyrin biosynthesis coordinate the

Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death.

Science.gov (United States)

Wang, Yan; Cordewener, Jan H G; America, Antoine H P; Shan, Weixing; Bouwmeester, Klaas; Govers, Francine

2015-09-01

L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

The xantha Marker Trait Is Associated with Altered Tetrapyrrole Biosynthesis and Deregulated Transcription of PhANGs in Rice

Directory of Open Access Journals (Sweden)

Rui-Qing Li

2017-05-01

Full Text Available The xantha marker trait, which is controlled by a down-regulating epi-mutation of OsGUN4, has been applied to the production of hybrid rice. However, the molecular basis for the ability of xantha mutants to attain high photosynthetic capacity even with decreased chlorophyll contents has not been characterized. In the present study, we observed that the total chlorophyll content of the xantha mutant was only 27.2% of that of the wild-type (WT plants. However, the xantha mutant still accumulated 59.9% of the WT δ-aminolevulinic acid content, 72.8% of the WT Mg-protoporphyrin IX content, and 63.0% of the WT protochlorophyllide a content. Additionally, the protoporphyrin IX and heme contents in the mutant increased to 155.0 and 160.0%, respectively, of the WT levels. A search for homologs resulted in the identification of 124 rice genes involved in tetrapyrrole biosynthesis and photosynthesis. With the exception of OsGUN4, OsHO-1, and OsHO-2, the expression levels of the genes involved in tetrapyrrole biosynthesis were significantly higher in the xantha mutant than in the WT plants, as were all 72 photosynthesis-associated nuclear genes. In contrast, there were no differences between the xantha mutant and WT plants regarding the expression of all 22 photosynthesis-associated chloroplast genes. Furthermore, the abundance of 1O2 and the expression levels of 1O2-related genes were lower in the xantha mutant than in the WT plants, indicating 1O2-mediated retrograde signaling was repressed in the mutant plants. These results suggested that the abundance of protoporphyrin IX used for chlorophyll synthesis decreased in the mutant, which ultimately decreased the amount of chlorophyll in the xantha mutant. Additionally, the up-regulated expression of photosynthesis-associated nuclear genes enabled the mutant to attain a high photosynthetic capacity. Our findings confirm that OsGUN4 plays an important role in tetrapyrrole biosynthesis and photosynthesis in

Hematoporphyrin monomethyl ether-mediated photodynamic therapy selectively kills sarcomas by inducing apoptosis.

Directory of Open Access Journals (Sweden)

Hui Zeng

Full Text Available We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7 was time- and dose-dependent, while this was not observed for myoblast cells (C2C12 and fibroblast cells (NIH/3T3. HMME-PDT markedly inhibited the proliferation of sarcoma cell lines (LM8, MG63, Saos-2, SW1353, TC71, and RD (P<0.05, and the killing effect was improved with increased HMME concentration and energy intensity. Flow cytometry analysis revealed that LM8, MG63, and Saos-2 cells underwent apoptosis after treatment with HMME-PDT. Additionally, apoptosis was induced after HMME-PDT in a three-dimensional culture of osteosarcoma cells. Hoechst 33342 staining confirmed apoptosis. Cell death caused by PDT was rescued by an irreversible inhibitor (Z-VAD-FMK of caspase. However, cell viability was not markedly decreased compared with the HMME-PDT group. Expression levels of caspase-1, caspase-3, caspase-6, caspase-9, and poly (ADP-ribose polymerase (PARP proteins were markedly up-regulated in the treatment groups and increased with HMME concentration as determined by western blot analysis. In vivo, tumor volume markedly decreased at 7-16 days post-PDT. Hematoxylin and eosin staining revealed widespread necrotic and infiltrative inflammatory cells in the HMME-PDT group. Immunohistochemistry analysis also showed that caspase-1, caspase-3, caspase-6, caspase-9, and PARP proteins were significantly increased in the HMME-PDT group. These results indicate that HMME-PDT has a potent killing effect on osteosarcoma cells in vitro and significantly inhibits tumor growth in vivo, which is associated with the caspase-dependent pathway.

Synthesis of indium-111 mesoprotoporphyrin IX

International Nuclear Information System (INIS)

Lee, K.M.; Marshall, A.G.

1981-01-01

Indium-111 mesoprotoporphyrin IX has been prepared by refluxing suitable proportions of InCl 3 , sodium acetate, and mesoprotoporphyrin IX in glacial acetic acid. The labeled metalloporphyrin is sufficiently water-soluble for use as a scanning agent, and can also be incorporated into heme apoproteins for perturbed gamma-gamma angular correlation measurements. (author)

Labeled factor IX kinetics in patients with hemophilia-B

International Nuclear Information System (INIS)

Smith, K.J.; Thompson, A.R.

1981-01-01

Labeled factor IX was infused five time into four patients with hemophilia-B. Ten-minute plasma recovery average 35% (SD +/- 2) and the mean T 1/2 beta-phase elimination was 23 hr (+/- 5). No alteration in the postinfusion 125I-factor-IX could be detected by radioautography of plasma samples run on polyacrylamide gels or on crossed-immunoelectrophoresis. Label was excreted into the urine as free 125I-iodide. Kinetics were similar when the labeled preparation was infused alone or with a commercial concentrate containing unlabeled factor IX. Infusion of factor IX in man is best described by a two-compartment open pharmacokinetic model where factor IX is distributed in a space larger than the plasma volume

Factor IX assay

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/003679.htm Factor IX assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources

DEFF Research Database (Denmark)

Lerche, Catharina; Heerfordt, Ida M; Heydenreich, Jakob

2016-01-01

to photobleach protoporphyrin IX (PpIX). Furthermore, we measured the amount of PpIX activating daylight available in a glass greenhouse, which can be an alternative when it is uncomfortable for patients to be outdoors. The lamps investigated were: halogen lamps (overhead and slide projector), white light...... was suitable for daylight PDT since the effect of solar light is lowered only by 25%. In conclusion, we found four of the five light sources and the greenhouse usable for indoor daylight PDT. The greenhouse is beneficial when the weather outside is rainy or windy. Only insignificant ultraviolet B radiation...

Mg IX emission lines in an active region spectrum obtained with the Solar EUV Rocket Telescope and Spectrograph (SERTS)

Science.gov (United States)

Keenan, F. P.; Thomas, R. J.; Neupert, W. M.; Conlon, E. S.

1994-01-01

Theoretical electron-temperature-sensitive Mg IX emission line ratios are presented for R(sub 1) = I(443.96 A)/I(368.06 A), R(sub 2) = I(439.17 A)/I(368.06 A), R(sub 3) = I(443.37 A)/I(368.06 A), R(sub 4) = I(441.22 A)/I(368.06 A), and R(sub 5) = I(448.28 A)/I(368.06 A). A comparison of these with observational data for a solar active region, obtained during a rocket flight by the Solar EUV Rocket Telescope and Spectrograph (SERTS), reveals excellent agreement between theory and observation for R(sub 1) through R(sub 4), with discrepancies that average only 9%. This provides experimental support for the accuracy of the atomic data adopted in the line ratio calculations, and also resolves discrepancies found previously when the theoretical results were compared with solar data from the S082A instrument on board Skylab. However in the case of R(sub 5), the theoretical and observed ratios differ by almost a factor of 2. This may be due to the measured intensity of the 448.28 A line being seriously affected by instrumental effects, as it lies very close to the long wavelength edge of the SERTS spectral coverage (235.46-448.76 A).

Photoacoustic spectroscopy as a non-invasive tool for farmacokinetic studies in blood

International Nuclear Information System (INIS)

Stolik, S.; Tomas, S. A.; Ramon-Gallegos, E.; Delgado-Atencio, J. A.

2002-01-01

Photodynamic Therapy (PDT) has become a successful method in the treatment of cancerous tumours. This therapy is based on the interaction of light of appropriate wavelength with a photosensitiser located in tumorous tissue. It is well known that the administration of aminolevulinic acid (ALA) induces the production of protoporphyrin IX (PpIX) in different organs at characteristic times. For instance, a maximum content of PpIX is observed in skin nearly 2-3 h after exposition to ALA, whereas in blood this process usually takes place in shorter times. In this work, a comparison has been made between the conventional fluorometric measurement of PpIX in mice blood and the determination of this compound by photoacoustic spectroscopy

Evaluation of factor IX deficiency by interdigitated electrode (IDE)

Science.gov (United States)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

Electrocatalytic reduction of carbon dioxide to carbon monoxide and methane at an immobilized cobalt protoporphyrin

NARCIS (Netherlands)

Shen, J.; Kortlever, R.; Kas, Recep; Mul, Guido; Koper, M.T.M.

2015-01-01

The electrochemical conversion of carbon dioxide and water into useful products is a major challenge in facilitating a closed carbon cycle. Here we report a cobalt protoporphyrin immobilized on a pyrolytic graphite electrode that reduces carbon dioxide in an aqueous acidic solution at relatively low

Intricate Conformational Tunneling in Carbonic Acid Monomethyl Ester.

Science.gov (United States)

Linden, Michael M; Wagner, J Philipp; Bernhardt, Bastian; Bartlett, Marcus A; Allen, Wesley D; Schreiner, Peter R

2018-04-05

Disentangling internal and external effects is a key requirement for understanding conformational tunneling processes. Here we report the s- trans/ s- cis tunneling rotamerization of carbonic acid monomethyl ester (1) under matrix isolation conditions and make comparisons to its parent carbonic acid (3). The observed tunneling rate of 1 is temperature-independent in the 3-20 K range and accelerates when using argon instead of neon as the matrix material. The methyl group increases the effective half life (τ eff ) of the energetically disfavored s- trans-conformer from 3-5 h for 3 to 11-13 h for 1. Methyl group deuteration slows the rotamerization further (τ eff ≈ 35 h). CCSD(T)/cc-pVQZ//MP2/aug-cc-pVTZ computations of the tunneling probability suggest that the rate should be almost unaffected by methyl substitution or its deuteration. Thus the observed relative rates are puzzling, and they disagree with previous explanations involving fast vibrational relaxation after the tunneling event facilitated by the alkyl rotor.

Assembly of Highly Standardized Gene Fragments for High-Level Production of Porphyrins in E. coli

DEFF Research Database (Denmark)

Nielsen, Morten Thrane; Madsen, Karina Marie; Seppala, Susanna

2015-01-01

to formulate a molecular cloning pipeline and iteratively assemble and optimize a six-gene pathway for protoporphyrin IX synthesis in Escherichia coli. State of the art production levels were achieved through two simple cycles of engineering and screening. The principles defined here are generally applicable...

77 FR 64401 - Order of Succession for HUD Region IX

Science.gov (United States)

2012-10-19

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [FR-5550-D-12] Order of Succession for HUD Region IX... Field Offices (Region IX). This Order of Succession supersedes all previous Orders of Succession for HUD Region IX. DATES: Effective Date: October 9, 2012. FOR FURTHER INFORMATION CONTACT: Lawrence D. Reynolds...

Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

Science.gov (United States)

Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

2016-04-01

Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group.

Science.gov (United States)

White, G C; Shapiro, A D; Kurczynski, E M; Kim, H C; Bergman, G E

1995-05-01

Monoclonal antibody purified factor IX concentrate, Mononine (Armour Pharmaceutical Company, Kankakee, Illinois, USA), is a recently developed replacement factor concentrate for the treatment of patients with hemophilia B. The pharmacokinetic properties of monoclonal antibody purified factor IX concentrate (MAb Factor IX concentrate) have been evaluated in only small samples of patients, and little is known about those factors that might influenced in vivo recovery of factor IX after infusion is a larger patient population. In vivo recovery of factor IX was therefore evaluated for 80 different indications in 72 patients who received MAb Factor IX concentrate for the management of spontaneous or trauma-induced bleeding, or as prophylaxis with surgery. The average recovery after infusions for presurgical pharmacokinetic analysis (mean +/- standard deviation) was 1.28 +/- 0.56 U/dl rise per U/kg infused (range 0.41-2.80), and the average recovery after all infusions for treatment was 1.23 +/- 0.49 U/dl rise per U/kg infused (range - 0.35-2.92). Recovery values for multiple MAb Factor IX doses in a given patient were also variable; the average recovery was 1.22 +/- 0.53 U/dl rise per U/kg given, and standard deviations ranged from 0.03 to 1.26. Patient age, weight, and MAb Factor IX concentrate dose minimally but significantly influenced factor IX recovery. There was no significant effect of either race, history of previous thrombotic complications during treatment with other replacement factor concentrates, or bleeding state on recovery. All of the patients treated with this preparation experienced excellent hemostasis, and no thrombotic complications were observed.

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

Directory of Open Access Journals (Sweden)

Justina Kazokaitė

2017-11-01

Full Text Available The expression of carbonic anhydrase (CA IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors.

Effect of IX dosing on polypropylene and PVDF membrane fouling control

KAUST Repository

Myat, Darli Theint

2013-07-01

The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA) and fluorescence spectroscopy (Method A), and UV254, organic carbon and organic nitrogen detectors (Method B), was undertaken on wastewater before and after magnetic IX treatment. Results showed partial removal of the biopolymer fraction at high IX doses. With increasing concentration of IX, evidence for nitrogen-containing compounds such as proteins and amino acids disappeared from the LC-OND chromatogram, complementary to the fluorescence response. A greater fluorescence response of tryptophan-like proteins (278nm/343nm) for low IX concentrations was consistent with aggregation of tryptophan-like compounds into larger aggregates, either by self-aggregation or with polysaccharides. Recycling of IX resin through multiple adsorption steps without regeneration maintained the high level of humics removal but there was no continued removal of biopolymer. Subsequent membrane filtration of the IX treated waters resulted in complex fouling trends. Filtration tests with either polypropylene (PP) or polyvinylidene fluoride (PVDF) membranes showed higher rates of initial fouling following treatment with high IX doses (10mL/L) compared to filtration of untreated water, while treatment with lower IX doses resulted in decreased fouling rates relative to the untreated water. However, at longer filtration times the rate of fouling of IX treated waters was lower than untreated water and the relative fouling rates corresponded to the amount of biopolymer material in the feed. It was proposed that the mode of fouling changed from pore constriction during the initial filtration period to filter cake build up at longer filtration times. The organic composition strongly influenced the rate of fouling during the initial filtration period due to

The feasibility of using concentrates containing factor IX for continuous infusion.

Science.gov (United States)

Schulman, S; Gitel, S; Zivelin, A; Katsarou, O; Mandalaki, T; Varon, D; Martinowitz, U

1995-04-01

We have investigated the feasibility of continuous infusion of undiluted factor IX (F IX) over several days using minipumps. The stabilities of seven different reconstituted F IX products were substantially better than those declared by the manufacturers. Several concentrates maintained factor activities 80% of baseline for the entire period of 4 weeks at 4-8d̀C as did one product at 20-23d̀A. At 37d̀C the latter concentrate was stable for at least 1 week. The stability seemed to correlate with the purity of the product. Analysis of two prothrombin comples concentrates by gel electrophoresis demonstrated degradation of prothrombin to prethrombin-1 and fragment 1 at 37d̀C and in one of the concentrates also at 20-23d̀C. In two F IX concentrates the corresponding analysis did not reveal any degradation. Four patients were treated with continuous infusion with a pure F IX concentrate (Mononine™, Armour) after surgery or for serious haemorrhage (two each) with good haemostatic effect, an initial progressive decrease of the F IX clearance, and no side-effects. Continuous infusion with F IX, using a minipump and undiluted reconstituted factor, is therefore feasible and effective, and can be conveniently prepared for several days at a time. Pure F IX products are more stable and probably safer for this purpose.

Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment

Czech Academy of Sciences Publication Activity Database

Závadová, Zuzana; Závada, Jan

2005-01-01

Roč. 13, č. 5 (2005), s. 977-982 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA203/02/0405 Institutional research plan: CEZ:AV0Z50520514 Keywords : carbonic anhydrase IX * cell adhesion * microenvironment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.572, year: 2005

Specific acid catalyzed deuteration of the acetyl groups of 2,4-diacetyldeuterohemin-OMe

International Nuclear Information System (INIS)

Oster, O.; Neireiter, G.W.; Gurd, F.R.N.

1975-01-01

The methyl group of the acetyl groups in 2,4-diacetyldeuterohemin-OMe has been selectively deuterated. After removal of the iron, D 6 -2,4-diacetyl-deuteroporphyrin-OMe can be reduced to the corresponding hematoporphyrin and subsequent dehydration gives deuterated vinylic groups for protoporphyrin IX-OMe. (orig.) [de

Factor IX gene haplotypes in Amerindians.

Science.gov (United States)

Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

1997-02-01

We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

5-ALA/PpIX fluorescence detection of gastrointestinal neoplasia

Science.gov (United States)

Borisova, Ekaterina G.; Vladimirov, Borislav; Terziev, Ivan; Ivanova, Radina; Avramov, Latchezar

2009-07-01

In the recent study delta-ALA/PpIX is used as fluorescent marker for dysplasia and tumor detection in esophagus, stomach and colon. ALA is administered per os six to eight (depending on the lesion location) hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for the LED to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to re-absorption of oxy-hemoglobin in this spectral area. Endogenous and exogenous fluorescence spectra are used to develop simple but effective algorithm, based on dimensionless ratio of the signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues. Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo.

Science.gov (United States)

Monroe, D M; McCord, D M; Huang, M N; High, K A; Lundblad, R L; Kasper, C K; Roberts, H R

1989-05-01

Factor IX Hilo is a variant factor IX molecule that has no detectable coagulant activity. The defect in factor IX Hilo arises from a point mutation in the gene such that in the protein Arg180 is converted to a Gln. Activation of factor IX Hilo by factor Xla was monitored using the fluorescent active site probe p-aminobenzamidine. Normal factor IX showed complete activation in one hour as determined by measuring the increase in fluorescence when p-aminobenzamidine bound to activated factor IX. Factor IX Hilo showed no increase in fluorescence even after 24 hours, indicating that the active site was not exposed. Polyacrylamide gel electrophoresis showed that factor IX Hilo was cleaved to a light chain plus a larger peptide with a molecular weight equivalent to a heavy chain covalently linked to an activation peptide. Amino terminal amino acid sequencing of factor IX Hilo cleaved by factor Xla showed cleavage only at Arg145-Ala146, indicating that the Gln180-Val181 bond was not cleaved and that the active site was thus not exposed. The presence of factor IX Hilo in patient plasma was responsible for the patient having a very long ox brain prothrombin time characteristic of severe hemophilia Bm. Patient plasma had an ox brain prothrombin time of 100 seconds using a Thrombotest kit, significantly prolonged over the normal control value of 45 seconds. When factor IX Hilo was depleted from patient plasma using an immunoaffinity column, the ox brain prothrombin time decreased to 41 seconds. When factor IX Hilo was added back to depleted patient plasma, to normal plasma depleted of factor IX by the same affinity column, or to plasma from a CRM- hemophilia B patient, the ox brain prothrombin time was significantly prolonged. We conclude that the Arg180 to Gln mutation in factor IX Hilo results in a molecule that cannot be activated by factor Xla. Further, our data suggest that the mutation results in a molecule that interacts with components of the extrinsic pathway to give

4p-5s transitions in YVII, VIII, ZrVIII, IX, NbIX, X and MoX, XI

International Nuclear Information System (INIS)

Rahimullah, K.; Chaghtai, M.S.Z.; Khatoon, S.

1976-01-01

The spectra of Y VII, VIII, Zr VIII, IX, Nb X and Mo X, XI are studied for the first time and the 1971 analysis of Nb IX is improved. By analyses of the transitions 4s 2 4psup(k)-4s 2 4psup(k-1)5s all the levels of the configurations 4p 3 , 4p 2 5s, 4p 2 and 4p5s are established in the spectra concerned. (Auth.)

The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

Science.gov (United States)

Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

2016-08-23

Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

ALA-based fluorescent diagnosis of malignant oral lesions in the presence of bacterial porphyrin formation

Science.gov (United States)

Schleier, P.; Berndt, A.; Zinner, K.; Zenk, W.; Dietel, W.; Pfister, W.

2006-02-01

The aminolevulinic acid (5-ALA) -based fluorescence diagnosis has been found to be promising for an early detection and demarcation of superficial oral squamous cell carcinomas (OSCC). This method has previously demonstrated high sensitivity, however this clinical trial showed a specificity of approximately 62 %. This specificity was mainly restricted by tumor detection in the oral cavity in the presence of bacteria. After topical ALA application in the mouth of patients with previously diagnosed OSSC, red fluorescent areas were observed which did not correlate to confirm histological findings. Swabs and plaque samples were taken from 44 patients and cultivated microbiologically. Fluorescence was investigated (OMA-system) from 32 different bacteria strains found naturally in the oral cavity. After ALA incubation, 30 of 32 strains were found to synthesize fluorescent porphyrins, mainly Protoporphyrin IX. Also multiple fluorescent spectra were obtained having peak wavelengths of 636 nm and around 618 nm - 620 nm indicating synthesis of different porphyrins, such as the lipophylic Protoporphyrin IX (PpIX) and hydrophylic porphyrins (water soluble porphyrins, wsp). Of the 32 fluorescent bacterial strains, 18 produced wsp, often in combination with PpIX, and 5 produced solely wsp. These results clarify that ALA-based fluorescence diagnosis without consideration or suppression of bacteria fluorescence may lead to false-positive findings. It is necessary to suppress bacteria fluorescence with suitable antiseptics before starting the procedure. In this study, when specific antiseptic pre-treatment was performed bacterial associated fluorescence was significantly reduced.

Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic treatment enhances proliferation at the single cell level.

Science.gov (United States)

Blázquez-Castro, Alfonso; Breitenbach, Thomas; Ogilby, Peter R

2014-09-01

Two-photon excitation of a sensitizer with a focused laser beam was used to create a spatially-localized subcellular population of reactive oxygen species, ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX, endogenously derived from 5-aminolevulinic acid delivered to the cells. Although we infer that singlet oxygen, O2(a(1)Δg), is one ROS produced upon irradiation of PpIX under these conditions, it is possible that the superoxide ion, O2(-˙), may also play a role in this system. With a "high" dose of PpIX-sensitized ROS, the expected death of the cell was observed. However, under "low dose" conditions, clear signs of cell proliferation were observed. The present results facilitate studies of ROS-mediated signalling in imaging-based single cell experiments.

Effects of light irradiation upon photodynamic therapy based on 5-aminolevulinic acid–gold nanoparticle conjugates in K562 cells via singlet oxygen generation

Directory of Open Access Journals (Sweden)

Xu H

2012-09-01

Full Text Available Hao Xu, Chen Liu, Jiansheng Mei, Cuiping Yao, Sijia Wang, Jing Wang, Zheng Li, Zhenxi ZhangKey Laboratory of Biomedical Information Engineering of Education Ministry, Institute of Biomedical Analytical Technology and Instrumentation, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi, People’s Republic of ChinaPurpose: As a precursor of the potent photosensitizer protoporphyrin IX (PpIX, 5-aminolevulinic acid (5-ALA, was conjugated onto cationic gold nanoparticles (GNPs to improve the efficacy of photodynamic therapy (PDT.Methods: Cationic GNPs reduced by branched polyethyleneimine and 5-ALA were conjugated onto the cationic GNPs by creating an electrostatic interaction at physiological pH. The efficacy of ALA-GNP conjugates in PDT was investigated under irradiation with a mercury lamp (central wavelength of 395 nm and three types of light-emitting diode arrays (central wavelengths of 399, 502, and 621 nm, respectively. The impacts of GNPs on PDT were then analyzed by measuring the intracellular PpIX levels in K562 cells and the singlet oxygen yield of PpIX under irradiation.Results: The 2 mM ALA-GNP conjugates showed greater cytotoxicity against K562 cells than ALA alone. Light-emitting diode (505 nm irradiation of the conjugates caused a level of K562 cell destruction similar to that with irradiation by a mercury lamp, although it had no adverse effects on drug-free control cells. These results may be attributed to the singlet oxygen yield of PpIX, which can be enhanced by GNPs.Conclusion: Under irradiation with a suitable light source, ALA-GNP conjugates can effectively destroy K562 cells. The technique offers a new strategy of PDT.Keywords: nonradiative energy transfer, photodamage, protoporphyrin IX, selective destruction, singlet oxygen sensor green reagent, surface plasmon resonance

The Nature of the intermediates in the reactions of Fe(III)- and Mn(III)-microperoxidase-8 with H2O2 : a rapid kinetic study

NARCIS (Netherlands)

Primus, J.L.; Grunenwald, S.; Hagedoorn, P.L.; Albrecht-Gary, A.M.; Mandon, D.; Veeger, C.

2002-01-01

Kinetic studies were performed with microperoxidase-8 (Fe(III)MP-8), the proteolytic breakdown product of horse heart cytochrome c containing an octapeptide linked to an iron protoporphyrin IX. Mn(III) was substituted for Fe(III) in Mn(III)MP-8.The mechanism of formation of the reactive metal-oxo

5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies

Science.gov (United States)

Babič, Andrej; Herceg, V.; Bastien, E.; Lassalle, H.-P.; Bezdetnaya, L.; Lange, Norbert

2018-01-01

Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was used to covalently conjugate 5-ALA to squalene, a natural precursor of cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The nanoassemblies were monodisperse with average size of 70 nm, polydispersity index of 0.12, and ζ-potential of + 36 mV. They showed good stability over several weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in vitro upon the incubation with nanoassemblies. They were more efficient in generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0 to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ presents a novel nano-delivery platform with great potential for the systemic administration of 5-ALA.

Fluorescence detection of esophageal neoplasia

Science.gov (United States)

Borisova, E.; Vladimirov, B.; Avramov, L.

2008-06-01

White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

Science.gov (United States)

Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

2016-01-01

Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

Water containing explosive for big diameter use. [Slurry of ammonium nitrate and monomethyl lamine

Energy Technology Data Exchange (ETDEWEB)

Sunakawa, Tomoji; Fujita, Koichi; Kodama, Taro; Suzuki, Masahiro; Ono, Naoki

1988-05-11

This is a report concerning the design and experiment of water containing explosive which can be used as a substitute of ANFO. As the water containing explosive, slurry type was taken which consists of ammonium nitrate and monomethyl amine as main components and density of which was more than 1.2, explosion speed 4880 m/s, F value 7790 atm*L/Kg. Experiments were conducted for variuous loading length. From the result, it was recognized that at least 4.5 m of loading length was neccessary for achieving better result than the case whlen only ANFO was used. (1 fig, 1 tab)

MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

International Nuclear Information System (INIS)

Detappe, A; Rottmann, J; Kunjachan, S; Berbeco, R; Tillement, O

2015-01-01

Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM of nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy

Novel applications of photoacoustic spectroscopy in life sciences

Science.gov (United States)

Stolik, S.

2004-10-01

The Photoacoustic Spectroscopy, based on the generation of acoustic waves following the absorption of the modulated light by an enclosed material, was discovered in 1880 by Alexander Graham Bell. There are a lot of remarkable achievements in this topic since those days. It has been intended to present a relatively new tool to the researchers in biological areas and, simultaneously, to propose new fields of investigation to those who have been attracted by physics. The application of Photoacoustic trace gas detection to the determination of ethylene content in mice exhalation is described as a biomarker of free radicals production. It has been demonstrated the feasibility of studying the lipid peroxidation in vivo by this technique. Specifically, the results of δ-aminolevulinic acid administration in mice are presented. This drug has been used to induce Protoporphyrin IX production and ultimately to apply the Photodynamic Therapy, a recent method in cancer treatment. A kinetic study of Protoporphyrin IX production in mice skin and blood after δ-aminolevulinic acid administration in different doses is also shown. This study was performed using Photoacoustic Spectroscopy in solids.

Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

Science.gov (United States)

Nair, Lakshmi V; Nazeer, Shaiju S; Jayasree, Ramapurath S; Ajayaghosh, Ayyappanpillai

2015-06-23

Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 μg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

Porphyrin involvement in redshift fluorescence in dentin decay

Science.gov (United States)

Slimani, A.; Panayotov, I.; Levallois, B.; Cloitre, T.; Gergely, C.; Bec, N.; Larroque, C.; Tassery, H.; Cuisinier, F.

2014-05-01

The aim of this study was to evaluate the porphyrin involvement in the red fluorescence observed in dental caries with Soprolife® light-induced fluorescence camera in treatments mode (SOPRO, ACTEON Group, La Ciotat, France) and Vistacam® camera (DÜRR DENTAL AG, Bietigheim-Bissingen, Germany). The International Caries Detection and Assessment System (ICDAS) was used to rand the samples. Human teeth cross-sections, ranked from ICDAS score 0 to 6, were examined by epi-fluorescence microscopy and Confocal Raman microscopy. Comparable studies were done with Protoporphyrin IX, Porphyrin I and Pentosidine solutions. An RGB analysis of Soprolife® images was performed using ImageJ Software (1.46r, National Institutes of Health, USA). Fluorescence spectroscopy and MicroRaman spectroscopy revealed the presence of Protoporphyrin IX, in carious enamel, dentin and dental plaque. However, the presence of porphyrin I and pentosidine cannot be excluded. The results indicated that not only porphyrin were implicated in the red fluorescence, Advanced Glygation Endproducts (AGEs) of the Maillard reaction also contributed to this phenomenon.

Title IX--Beyond Compliance to Personal Commitment and Leadership

Science.gov (United States)

Peterson, Barbara

1976-01-01

In order to move beyond legal compliance to real equality of opportunity, every educational leader must develop some systematic means of extending his or her personal knowledge and skills with respect to Title IX. Provides a check list for self evaluation of educational leaders and a guide for developing an implementation plan for Title IX.…

Stability of O/W Emulsion with Synthetic Perfumes Oxidized by Singlet Oxygen

Directory of Open Access Journals (Sweden)

Naoki Watabe

2013-01-01

Full Text Available We prepared O/W emulsion composed of a synthetic perfume, n-dodecane, protoporphyrin IX disodium salt (PpIX-2Na, sodium dodecyl sulfate, and water and investigated oxidative decomposition of the synthetic perfume in the emulsion and change in the stability of the emulsion by singlet oxygen (1O2 generated by photosensitization of PpIX-2Na. We used eugenol, linalool, benzyl acetate, α-ionone, α-hexylcinnamaldehyde, and d-limonene as a synthetic perfume. The stability of the O/W emulation including eugenol and linalool significantly decreased with increasing light irradiation time. The decrease in the emulsion stability may be attributable to oxidative decomposition of eugenol and linalool by 1O2 and enlargement of the oil droplet size.

A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung D. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Seo, Kwang W. [Department of Internal Medicines, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Lee, Eun A.; Quang, Nguyen N. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Cho, Hong R. [Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Kwon, Byungsuk, E-mail: bskwon@mail.ulsan.as.kr [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of)

2011-07-01

Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

Effect of IX dosing on polypropylene and PVDF membrane fouling control

KAUST Repository

Myat, Darli Theint; Mergen, Max R D; Zhao, Oliver; Stewart, Matthew B.; Orbell, John D.; Merle, Tony; Croue, Jean-Philippe; Gray, Stephen R.

2013-01-01

The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA

IX : An OS for datacenter applications with aggressive networking requirements

CERN Multimedia

CERN. Geneva

2014-01-01

The conventional wisdom is that aggressive networking requirements, such as high packet rates for small messages and microsecond-scale tail latency, are best addressed outside the kernel, in a user-level networking stack. We present IX, a dataplane operating system designed to support low-latency, high-throughput and high-connection count applications.  Like classic operating systems such as Linux, IX provides strong protection guarantees to the networking stack.  However, and unlike classic operating systems, IX is designed for the ground up to support applications with aggressive networking requirements on dense multi-core platforms with 10GbE and 40GbE Ethernet NICs.  IX outperforms Linux by an order of magnitude on micro benchmarks, and by up to 3.6x when running an unmodified memcached, a popular key-value store. The presentation is based on the joint work with Adam Belay, George Prekas, Ana Klimovic, Sam Grossman and Christos Kozyrakis, published at OSDI 2014; Best P...

Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

NARCIS (Netherlands)

Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

2010-01-01

The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

Science.gov (United States)

Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

2018-01-01

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

19.-25. IX toimub Rüütelkonna hoones Kumu pärlite nädal...

Index Scriptorium Estoniae

2005-01-01

23. IX kõneleb Anu Allikvee teemal "Eestlane baltisaksa kunstnike vaatepiiris"; 24. IX tutvustab Mai Levin Eugen Dückeri maale, 25. IX Ene Lamp Konrad Mäge. Vt. ka lk. 24 Tähtede nädal 26. IX-2. X - kohtumisõhtutel esinevad Marika ja Heinz Valk, Jüri Kuuskemaa, Sirje Helme, Pekka Vapaavuori, Inge Teder, Rain Lõhmus

Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

International Nuclear Information System (INIS)

Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

1984-01-01

The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble 3 H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl 2 (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of 3 H preceded the appearance of Factor IXa activity, and the percentage of 3 H released remained constant when the mole fraction of 3 H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of 3 H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant

Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts

International Nuclear Information System (INIS)

Ditte, Zuzana; Ditte, Peter; Labudova, Martina; Simko, Veronika; Iuliano, Filippo; Zatovicova, Miriam; Csaderova, Lucia; Pastorekova, Silvia; Pastorek, Jaromir

2014-01-01

Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1α and CA IX and/or altered CA IX function. The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1α and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Carnosine increased the expression levels of HIF-1α and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the

Enhancer-associated H3K4 monomethylation by trithorax-related, the drosophila homolog of mammalian MLL3/MLL4

NARCIS (Netherlands)

H.-M. Herz (Hans-Martin); M. Mohan (Man); A.S. Garruss (Alexander); K. Liang (Kaiwei); Y.-H. Takahashi (Yoh-hei); K. Mickey (Kristen); O. Voets (Olaf); C.P. Verrijzer (Peter); A. Shilatifard (Ali)

2012-01-01

textabstractMonomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are

Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors.

Science.gov (United States)

Ditte, Peter; Dequiedt, Franck; Svastova, Eliska; Hulikova, Alzbeta; Ohradanova-Repic, Anna; Zatovicova, Miriam; Csaderova, Lucia; Kopacek, Juraj; Supuran, Claudiu T; Pastorekova, Silvia; Pastorek, Jaromir

2011-12-15

In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment.

Fluorescence spectroscopy of gastrointestinal tumors using δ-ALA

Science.gov (United States)

Borisova, E. G.; Vladimirov, B. G.; Angelov, I. G.; Avramov, L. A.

2007-03-01

In the recent study delta-aminolevulinic acid/Protoporphyrin IX (δ-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ-ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system (Olimpus Corp.). Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer (USB4000, OceanOptics Inc.). The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors neovascularisation and it is clearly pronounced in all dysplastic and tumor sites investigated. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of δ-ALA/PpIX only in abnormal sites and gives high contrast when lesion borders are determined from clinicians during video observation in the process of diagnostic procedure. Very good correlation between fluorescence signals and histology examination results of the lesions investigated is achieved.

Effect of IX column maintenance on carbon-14 concentration in moderator systems

International Nuclear Information System (INIS)

Gallagher, C.L.; Tripple, A.W.

2006-01-01

The radionuclide 14 C is produced in CANDU reactors primarily by the (n,α) reaction with 17 O. Because of high neutron fluxes in the core, the majority of the 14 C (94.5%) is produced in the moderator. In the moderator system, 14 C is present mainly as CO 2 in the cover gas in dynamic equilibrium with dissolved carbonates, bicarbonates and CO 2 in the moderator water. Emissions of 14 C from reactors occur through venting or leakage of the cover gas. By controlling the dissolved carbonates in the moderator water with an ion exchange (IX) purification system, the amount of 14 C in the cover gas is minimized and thus the emissions of 14 C can be reduced. A study was conducted to measure the 14 C concentrations in the moderator system at Gentilly 2 in order to determine the effectiveness of the purification system in removing 14 C. Moderator water samples were obtained from the inlet and outlet of the purification system from 2004 January 14 to July 12, covering the operation of two IX columns (IX-1 and IX-3). The moderator water samples contained high levels of tritium (∼2 TBq·L -1 ). As both tritium and 14 C are β-radiation emitters, direct counting of moderator water for 14 C is impossible as the signal due to tritium dominates over that of other β-emitters. Therefore, a procedure developed by Caron et al. was used in this study, which involved acidifying the sample to release the dissolved 14 CO 2 as gas and collecting the 14 CO 2 in a base (NaOH), which could then be measured by liquid scintillation counting to determine the 14 C concentration. Both of the IX columns started with 14 C removal efficiencies of about 95%. The efficiency began to decrease almost immediately with the IX-1 column dropping to 80% efficiency after ∼1115 hours. This drop in efficiency also led to an increase in the inlet concentration over time. IX-1 column was removed from service after ∼1745 hours with a 14 C removal efficiency of ∼31%. IX-3 column was then placed in service

On the role of type IX collagen in the extracellular matrix of cartilage: type IX collagen is localized to intersections of collagen fibrils

OpenAIRE

1986-01-01

The tissue distribution of type II and type IX collagen in 17-d-old chicken embryo was studied by immunofluorescence using polyclonal antibodies against type II collagen and a peptic fragment of type IX collagen (HMW), respectively. Both proteins were found only in cartilage where they were co-distributed. They occurred uniformly throughout the extracellular matrix, i.e., without distinction between pericellular, territorial, and interterritorial matrices. Tissues that undergo endochondral bo...

The magnesium chelation step in chlorophyll biosynthesis

Energy Technology Data Exchange (ETDEWEB)

Weinstein, J.D.

1991-01-01

The biogenesis of energy transducing membranes requires the coordinate synthesis of prosthetic groups, proteins and lipids. Two of the major prosthetic groups, chlorophyll and heme, share a common biosynthetic pathway that diverges at the point of metal insertion into protoporphyrin IX. Insertion of iron leads to heme, while insertion of magnesium leads to chlorophyll. The Mg-chelatase from intact cucumber chloroplasts has been characterized with regard to substrate specificity, regulation, ATP requirement, and a requirement for intact chloroplasts. Mg-chelatase was isolated from maize, barley and peas and characterized in order to circumvent the intact chloroplast requirement of cucumber Mg-chelatase. Pea Mg-chelatase activity is higher than cucumber Mg-chelatase activity, and lacks the requirement for intact chloroplasts. Studies on isolated pea Mg-chelatase have shown more cofactors are required for the reaction than are seen with ferrochelatase, indicating a greater opportunity for regulatory control of this pathway. Two of the cofactors are proteins, and there appears to be a requirement for a protease-sensitive component which is outside the outer envelope. We are developing a continuous spectrophotometric assay for Mg-chelatase activity, and an assay for free heme which has shown heme efflux from intact chloroplasts. 18 refs. (MHB)

Influence of food tannins on certain aspects of iron metabolism : Part 3 -- Heme synthesis and haematopoiesis in normal and anemic rats

International Nuclear Information System (INIS)

Roy, S.N.; Mukherjee, S.

1979-01-01

Tannin from various fruits and vegetables at a dose level of 0.5 mg/kg wt/day helps approximately 65% recovery of the blood hemoglobin concentration in hemolytic anemic rats within 7 days resulting in normal levels of haematological parameters. While in vitro tannin at low doses (5-10 μg/mg protein) stimulates iron incorporation into protoporphyrin IX by rat liver subcellular fractions, at higher doses (15-40 μg/mg protein) it inhibits the heme synthesis in liver, the inhibition being complete at 40 μg/mg protein. In vivo studies indicate that the administration of tannin (0.5 mg/kg) exhibits significant increase in incorporation of label into hemin of anemic rats compared to that of anemic control and tannin-fed normal groups. In rats receiving supplements of tannin (0.5 mg/k.o.), incorporation of the label into hemin of anemic ones is comparatively greater when 59 Fe is given by intravenous route instead of oral administration of radio-iron. The total labelling of 59 Fe in red blood cells is significantly greater in tannin-fed anemic rats than anemic control. These results suggest that tannin (0.5 mg/kg) from fruits and vegetables may help iron utilization more effectively for greater haematopoiesis in hemolytic anemia. (auth.)

Influence of food tannins on certain aspects of iron metabolism : Part 3 -- Heme synthesis and haematopoiesis in normal and anemic rats

Energy Technology Data Exchange (ETDEWEB)

Roy, S N [Albert Einstein Coll. of Medicine, Bronx, NY (USA); Mukherjee, S [Calcutta Univ. (India). Dept. of Applied Chemistry

1979-06-01

Tannin from various fruits and vegetables at a dose level of 0.5 mg/kg wt/day helps approximately 65% recovery of the blood hemoglobin concentration in hemolytic anemic rats within 7 days resulting in normal levels of haematological parameters. While in vitro tannin at low doses (5-10 ..mu..g/mg protein) stimulates iron incorporation into protoporphyrin IX by rat liver subcellular fractions, at higher doses (15-40 ..mu..g/mg protein) it inhibits the heme synthesis in liver, the inhibition being complete at 40 ..mu..g/mg protein. In vivo studies indicate that the administration of tannin (0.5 mg/kg) exhibits significant increase in incorporation of label into hemin of anemic rats compared to that of anemic control and tannin-fed normal groups. In rats receiving supplements of tannin (0.5 mg/k.o.), incorporation of the label into hemin of anemic ones is comparatively greater when /sup 59/Fe is given by intravenous route instead of oral administration of radio-iron. The total labelling of /sup 59/Fe in red blood cells is significantly greater in tannin-fed anemic rats than anemic control. These results suggest that tannin (0.5 mg/kg) from fruits and vegetables may help iron utilization more effectively for greater haematopoiesis in hemolytic anemia.

A License for Bias: Sex Discrimination, Schools, and Title IX.

Science.gov (United States)

Morse, Susan Ed.

This report discusses non-sports-related Title IX complaints filed with the Department of Education's Office for Civil Rights (OCR) from 1993-1997. Its purpose is to dispel the popular belief that Title IX is a sports-equity law and to determine the effectiveness of the legislation. The document examines the kinds of complaints filed, the status…

The History, Uses, and Abuses of Title IX. 2016 Bulletin

Science.gov (United States)

American Association of University Professors, 2016

2016-01-01

This report, an evaluation of the history and current uses of Title IX, is the result of a joint effort by a subcommittee that included members of the AAUP's Committee A on Academic Freedom and Tenure and the Committee on Women in the Academic Profession. The report identifies tensions between current interpretations of Title IX and the academic…

Synthesis of [119mSn]-mesoporphyrin IX dichloride

International Nuclear Information System (INIS)

Denissen, J.F.

1990-01-01

Tin mesoporphyrin IX dichloride (Sn-MPCl 2 ) is a heme oxygenase inhibitor of current clinical interest for the treatment of neonatal hyperbilirubinemia. The synthesis of [ 119m Sn]-MPCl 2 for drug metabolism and disposition studies is reported. [ 119m Sn]-MPCl 2 was prepared in 60% radiochemical yield by metalation of the porphyrin nucleus of mesoporphyrin IX dihydrochloride with tin(II)-119m acetate. The product had a specific activity of 43.4 mCi/mmol and a radiochemical purity of 99%, as determined by radio-HPLC analysis. (author)

Natural occurrence of alternariol and alternariol monomethyl ether in soya beans.

Science.gov (United States)

Oviedo, M S; Barros, G G; Chulze, S N; Ramirez, M L

2012-08-01

The natural occurrence of alternariol (AOH) and alternariol monomethyl ether (AME) in soya beans harvested in Argentina was evaluated. Both toxins were simultaneously detected by using HPLC analysis coupled with a solid phase extraction column clean-up. Characteristics of this in-house method such as accuracy, precision and detection and quantification limits were defined by means of recovery test with spiked soya bean samples. Out of 50 soya bean samples, 60% showed contamination with the mycotoxins analyzed; among them, 16% were only contaminated with AOH and 14% just with AME. Fifteen of the positive samples showed co-occurrence of both mycotoxins analyzed. AOH was detected in concentrations ranging from 25 to 211 ng/g, whereas AME was found in concentrations ranging from 62 to 1,153 ng/g. Although a limited number of samples were evaluated, this is the first report on the natural occurrence of Alternaria toxins in soya beans and is relevant from the point of view of animal public health.

Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

Science.gov (United States)

Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

2015-03-01

Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

Spectral action for Bianchi type-IX cosmological models

International Nuclear Information System (INIS)

Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

2015-01-01

A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w_1(t),w_2(t),w_3(t), and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a_0,a_2,a_4 of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki’s noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

Bovine adenovirus type 3 containing heterologous protein in the C-terminus of minor capsid protein IX

International Nuclear Information System (INIS)

Zakhartchouk, Alexander; Connors, Wayne; Van Kessel, Andrew; Tikoo, Suresh Kumar

2004-01-01

Earlier, we detected pIX of BAdV-3 as a 14-kDa protein in purified virions. Analysis of BAdV-3 pIX using different region antibodies revealed that the N-terminus and central domain of the pIX contain immunogenic sites and are not exposed on the surface of BAdV-3 virion. This suggested that the C-terminus of BAdV-3 pIX (125 amino acid) may be exposed on the virion and may be used as a site for incorporation of heterologous peptides or proteins. We constructed recombinant BAV950 containing a small peptide (21 amino acid), including the RGD motif or recombinant BAV951 containing enhanced yellow-green fluorescent protein (EYFP) fused to the C-terminus of pIX. Western blot analysis demonstrated that the chimeric pIX-RGD was incorporated into virion capsids. Incorporation of the RGD motif into the pIX resulted in significant augmentation of BAdV-3 fiber knob-independent infection of the integrin-positive cells, suggesting that RGD motifs are displayed on the surface of virion capsids and are accessible for binding to integrins. Analysis of BAV951 revealed that the chimeric pIX is incorporated into virion capsids and EYFP containing the C-terminus of pIX is exposed on the surface of the virion. Moreover, insertion of chimeric pIXs was maintained without change through successive rounds of viral replication. These results suggested that in contrast to major capsid proteins (hexon, penton, fiber), the minor capsid protein IX can be use for the incorporation of targeting ligands based on either small peptides or longer polypeptides

The H IX galaxy survey - II. H I kinematics of H I eXtreme galaxies

Science.gov (United States)

Lutz, K. A.; Kilborn, V. A.; Koribalski, B. S.; Catinella, B.; Józsa, G. I. G.; Wong, O. I.; Stevens, A. R. H.; Obreschkow, D.; Dénes, H.

2018-05-01

By analysing a sample of galaxies selected from the H I Parkes All Sky Survey (HIPASS) to contain more than 2.5 times their expected H I content based on their optical properties, we investigate what drives these H I eXtreme (H IX) galaxies to be so H I-rich. We model the H I kinematics with the Tilted Ring Fitting Code TiRiFiC and compare the observed H IX galaxies to a control sample of galaxies from HIPASS as well as simulated galaxies built with the semi-analytic model DARK SAGE. We find that (1) H I discs in H IX galaxies are more likely to be warped and more likely to host H I arms and tails than in the control galaxies, (2) the average H I and average stellar column density of H IX galaxies is comparable to the control sample, (3) H IX galaxies have higher H I and baryonic specific angular momenta than control galaxies, (4) most H IX galaxies live in higher spin haloes than most control galaxies. These results suggest that H IX galaxies are H I-rich because they can support more H I against gravitational instability due to their high specific angular momentum. The majority of the H IX galaxies inherits their high specific angular momentum from their halo. The H I content of H IX galaxies might be further increased by gas-rich minor mergers. This paper is based on data obtained with the Australia Telescope Compact Array through the large program C 2705.

Ares I-X: First Flight of a New Generation

Science.gov (United States)

Davis, Stephan R.; Askins, Bruce R.

2010-01-01

The Ares I-X suborbital development flight test demonstrated NASA s ability to design, develop, launch and control a new human-rated launch vehicle (Figure 14). This hands-on missions experience will provide the agency with necessary skills and insights regardless of the future direction of space exploration. The Ares I-X team, having executed a successful launch, will now focus on analyzing the flight data and extracting lessons learned that will be used to support the development of future vehicles.

Not Second-Class: Title IX, Equity, and Girls' High School Sports

Science.gov (United States)

Stader, David L.; Surface, Jeanne L.

2014-01-01

Title IX is designed to protect students from discrimination based on sex in any educational institution that receives financial assistance. This article focuses on Title IX as it applies to high school athletic programs by considering the trial of a high school district in California. A federal court found considerable inequalities between boys…

Embryonic chicken cornea and cartilage synthesize type IX collagen molecules with different amino-terminal domains.

OpenAIRE

Svoboda, K K; Nishimura, I; Sugrue, S P; Ninomiya, Y; Olsen, B R

1988-01-01

We have analyzed embryonic chicken cornea for the presence of type IX collagen mRNA and protein. Using RNA transfer blot analysis, we demonstrate that alpha 1(IX) and alpha 2(IX) mRNAs are expressed by corneal epithelial cells at the time that the primary stromal components are synthesized. The levels of the mRNAs decrease with increasing developmental age and are barely detectable at day 11 of development. In contrast, type IX collagen protein is detectable by immunofluorescence at days 5 an...

Fluorescence diagnosis of pre-tumor and tumor pathology of endometrium

Directory of Open Access Journals (Sweden)

E. V. Filonenko

2014-01-01

Full Text Available The technique of fluorescence hysteroscopy with Alasens includes visual assessment of fluorescence of Alasens-induced protoporphyrin IX and local fluorescence spectroscopy. The technique allows to improve the efficacy of early diagnosis for endometrial pathology including early endometrial cancer, to assess definitely an extent of pre-tumor and tumor process. The sensitivity of fluorescence hysteroscopy accounts for 100%, the specificity – 98%. 

Why, What and Where To? Title IX, Educational Amendment of 1972.

Science.gov (United States)

Perry-Miller, Mitzi

Three years after Title IX of the Education Amendments of 1972 became law, the U. S. Department of Health, Education, and Welfare provided regulations for the implementation of Title IX. This report reviews the implications of these regulations as well as several of the court cases in which discrimination on the basis of sex has been declared…

Spectral action for Bianchi type-IX cosmological models

Energy Technology Data Exchange (ETDEWEB)

Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde [Division of Physics, Mathematics and Astronomy, California Institute of Technology,1200 E. California Blvd., Pasadena, CA 91125 (United States)

2015-10-13

A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w{sub 1}(t),w{sub 2}(t),w{sub 3}(t), and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a{sub 0},a{sub 2},a{sub 4} of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki’s noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol-chitosan copolymer for photodynamic therapy

Directory of Open Access Journals (Sweden)

Chung CW

2013-02-01

Full Text Available Chung-Wook Chung,1,* Kyu-Don Chung,2,* Young-Il Jeong,1 Dae Hwan Kang,1 1National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University, Seoul, Republic of Korea*These authors contributed equally to this workPurpose: The aim of this study was to make 5-aminolevulinic acid (5-ALA-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito copolymer for application in photodynamic therapy for colon cancer cells.Methods: 5-ALA-incorporated (PEG-Chito-5-ALA nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.Results: PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles. 1H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone.Conclusion: PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA

Star formation rate in Holmberg IX dwarf galaxy

Directory of Open Access Journals (Sweden)

Anđelić M.M.

2011-01-01

Full Text Available In this paper we use previously determined Hα fluxes for dwarf galaxy Holmberg IX (Arbutina et al. 2009 to calculate star formation rate (SFR in this galaxy. We discuss possible contaminations of Hα flux and, for the first time, we take into account optical emission from supernova remnants (SNRs as a possible source of contamination of Hα flux. Derived SFR for Holmberg IX is 3:4 x 10-4M.yr-1. Our value is lower then in previous studies, due to luminous shock-heated source M&H 9-10, possible hypernova remnant, which we excluded from the total Hα flux in our calculation of SFR.

Prevention and Reversal of Antibody Responses Against Factor IX in Gene Therapy for Hemophilia B

Directory of Open Access Journals (Sweden)

Sushrusha eNayak

2011-12-01

Full Text Available Intramuscular (IM administration of an adeno-associated viral (AAV vector represents a simple and safe method of gene transfer for treatment of the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency. However, the approach is hampered by an increased risk of immune responses against F.IX. Previously, we demonstrated that the drug cocktail of immune suppressants rapamycin, IL-10, and a specific peptide (encoding a dominant CD4+ T cell epitope caused an induction of regulatory T cells (Treg with a concomitant apoptosis of antigen-specific effector T cells (J. Thromb. Haemost. 7:1523, 2009. This protocol was effective in preventing inhibitory antibody formation against human F.IX (hF.IX in muscle gene transfer to C3H/HeJ hemophilia B mice (with targeted F9 gene deletion. Here, we show that this protocol can also be used to reverse inhibitor formation. IM injection of AAV1-hF.IX vector resulted in inhibitors of on average 8-10 BU within 1 month. Subsequent treatment with the tolerogenic cocktail accomplished a rapid reduction of hF.IX-specific antibodies to <2 BU, which lasted for >4.5 months. Systemic hF.IX expression increased from undetectable to >200 ng/ml, and coagulation times improved. In addition, we developed an alternative prophylactic protocol against inhibitor formation that did not require knowledge of T cell epitopes, consisting of daily oral administration of rapamycin for 1-month combined with frequent, low-dose intravenous injection of hF.IX protein. Experiments in T cell receptor transgenic mice showed that the route and dosing schedule of drug administration substantially affected Treg induction. When combined with intravenous antigen administration, oral delivery of rapamycin had to be performed daily in order to induce Treg, which were suppressive and phenotypically comparable to natural Treg.

Photodynamic therapy with 5-aminolevulinic acid: basic principles and applications

Science.gov (United States)

Pottier, Roy H.; Kennedy, James C.

1996-01-01

Numerous photosensitizing pigments that absorb visible light and are selectively retained in neoplastic tissue are being investigated as potential photochemotherapeutic agents. While much emphasis is being placed on the synthesis of new, far-red absorbing photosensitizers, an alternative approach has been to stimulate the human body to produce its own natural photosensitizer, namely protoporphyrin IX (PpIX). Exogenous 5-aminolevulinic acid (ALA) is rapidly bioconverted into PP by mitochondria, the process being particularly efficient in tumor cells. Since PpIX has a natural and rapid clearing mechanism (via the capture of iron in the process of being converted into heme), ALA-PDT does not suffer from lingering skin phototoxicity. ALA may be introduced orally, intravenously, or topically, and ALA-PDT has been shown to be effective in the treatment of both malignant and non-malignant lesions.

Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

Czech Academy of Sciences Publication Activity Database

Závada, Jan; Závadová, Zuzana; Zaťovičová, M.; Hyršl, L.; Kawaciuk, I.

2003-01-01

Roč. 89, - (2003), s. 1067-1071 ISSN 0007-0920 R&D Projects: GA ČR GA301/99/0356 Institutional research plan: CEZ:AV0Z5052915 Keywords : carbonic anhydrase IX * tumor antigens * cancer diagnostics Subject RIV: EC - Immunology Impact factor: 3.894, year: 2003

A Place on the Team: The Triumph and Tragedy of Title IX

Science.gov (United States)

Suggs, Welch

2006-01-01

"A Place on the Team" is the inside story of how Title IX revolutionized American sports. The federal law guaranteeing women's rights in education, Title IX opened gymnasiums and playing fields to millions of young women previously locked out. Journalist Welch Suggs chronicles both the law's successes and failures-the exciting…

Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)

International Nuclear Information System (INIS)

Taylor, S.A.M.; Deugau, K.V.; Lillicrap, D.P.

1991-01-01

Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which >95% are single nulceotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. The authors used differential termination of primer extension to confirm and measure the degree of mosaicism. The study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factor IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male

Loop quantum cosmology of Bianchi IX: effective dynamics

International Nuclear Information System (INIS)

Corichi, Alejandro; Montoya, Edison

2017-01-01

We study solutions to the effective equations for the Bianchi IX class of spacetimes within loop quantum cosmology (LQC). We consider Bianchi IX models whose matter content is a massless scalar field, by numerically solving the loop quantum cosmology effective equations, with and without inverse triad corrections. The solutions are classified using certain geometrically motivated classical observables. We show that both effective theories—with lapse N   =   V and N   =  1—resolve the big bang singularity and reproduce the classical dynamics far from the bounce. Moreover, due to the positive spatial curvature, there is an infinite number of bounces and recollapses. We study the limit of large field momentum and show that both effective theories reproduce the same dynamics, thus recovering general relativity. We implement a procedure to identify amongst the Bianchi IX solutions, those that behave like k   =  0,1 FLRW as well as Bianchi I, II, and VII 0 models. The effective solutions exhibit Bianchi I phases with Bianchi II transitions and also Bianchi VII 0 phases, which had not been studied before. We comment on the possible implications of these results for a quantum modification to the classical BKL behaviour. (paper)

Loop quantum cosmology of Bianchi IX: effective dynamics

Science.gov (United States)

Corichi, Alejandro; Montoya, Edison

2017-03-01

We study solutions to the effective equations for the Bianchi IX class of spacetimes within loop quantum cosmology (LQC). We consider Bianchi IX models whose matter content is a massless scalar field, by numerically solving the loop quantum cosmology effective equations, with and without inverse triad corrections. The solutions are classified using certain geometrically motivated classical observables. We show that both effective theories—with lapse N  =  V and N  =  1—resolve the big bang singularity and reproduce the classical dynamics far from the bounce. Moreover, due to the positive spatial curvature, there is an infinite number of bounces and recollapses. We study the limit of large field momentum and show that both effective theories reproduce the same dynamics, thus recovering general relativity. We implement a procedure to identify amongst the Bianchi IX solutions, those that behave like k  =  0,1 FLRW as well as Bianchi I, II, and VII0 models. The effective solutions exhibit Bianchi I phases with Bianchi II transitions and also Bianchi VII0 phases, which had not been studied before. We comment on the possible implications of these results for a quantum modification to the classical BKL behaviour.

Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes

OpenAIRE

Chiabrando, Deborah; Vinchi, Francesca; Fiorito, Veronica; Mercurio, Sonia; Tolosano, Emanuela

2014-01-01

Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multi...

Operational Lessons Learned from the Ares I-X Flight Test

Science.gov (United States)

Davis, Stephan R.

2010-01-01

The Ares I-X flight test, launched in 2009, is the first test of the Ares I crew launch vehicle. This development flight test evaluated the flight dynamics, roll control, and separation events, but also provided early insights into logistical, stacking, launch, and recovery operations for Ares I. Operational lessons will be especially important for NASA as the agency makes the transition from the Space Shuttle to the Constellation Program, which is designed to be less labor-intensive. The mission team itself comprised only 700 individuals over the life of the project compared to the thousands involved in Shuttle and Apollo missions; while missions to and beyond low-Earth orbit obviously will require additional personnel, this lean approach will serve as a model for future Constellation missions. To prepare for Ares I-X, vehicle stacking and launch infrastructure had to be modified at Kennedy Space Center's Vehicle Assembly Building (VAB) as well as Launch Complex (LC) 39B. In the VAB, several platforms and other structures designed for the Shuttle s configuration had to be removed to accommodate the in-line, much taller Ares I-X. Vehicle preparation activities resulted in delays, but also in lessons learned for ground operations personnel, including hardware deliveries, cable routing, transferred work and custodial paperwork. Ares I-X also proved to be a resource challenge, as individuals and ground service equipment (GSE) supporting the mission also were required for Shuttle or Atlas V operations at LC 40/41 at Cape Canaveral Air Force Station. At LC 39B, several Shuttle-specific access arms were removed and others were added to accommodate the in-line Ares vehicle. Ground command, control, and communication (GC3) hardware was incorporated into the Mobile Launcher Platform (MLP). The lightning protection system at LC 39B was replaced by a trio of 600-foot-tall towers connected by a catenary wire to account for the much greater height of the vehicle. Like Shuttle

Mercury, monomethyl mercury, and dissolved organic carbon concentrations in surface water entering and exiting constructed wetlands treated with metal-based coagulants, Twitchell Island, California

Science.gov (United States)

Stumpner, Elizabeth B.; Kraus, Tamara E.C.; Fleck, Jacob A.; Hansen, Angela M.; Bachand, Sandra M.; Horwath, William R.; DeWild, John F.; Krabbenhoft, David P.; Bachand, Philip A.M.

2015-09-02

Coagulation with metal-based salts is a practice commonly employed by drinking-water utilities to decrease particle and dissolved organic carbon concentrations in water. In addition to decreasing dissolved organic carbon concentrations, the effectiveness of iron- and aluminum-based coagulants for decreasing dissolved concentrations both of inorganic and monomethyl mercury in water was demonstrated in laboratory studies that used agricultural drainage water from the Sacramento–San Joaquin Delta of California. To test the effectiveness of this approach at the field scale, nine 15-by-40‑meter wetland cells were constructed on Twitchell Island that received untreated water from island drainage canals (control) or drainage water treated with polyaluminum chloride or ferric sulfate coagulants. Surface-water samples were collected approximately monthly during November 2012–September 2013 from the inlets and outlets of the wetland cells and then analyzed by the U.S. Geological Survey for total concentrations of mercury and monomethyl mercury in filtered (less than 0.3 micrometers) and suspended-particulate fractions and for concentrations of dissolved organic carbon.

Wide-field spectrally resolved quantitative fluorescence imaging system: toward neurosurgical guidance in glioma resection

Science.gov (United States)

Xie, Yijing; Thom, Maria; Ebner, Michael; Wykes, Victoria; Desjardins, Adrien; Miserocchi, Anna; Ourselin, Sebastien; McEvoy, Andrew W.; Vercauteren, Tom

2017-11-01

In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary. We developed a wide-field spectrally resolved fluorescence imaging system utilizing a Generation II scientific CMOS camera and an improved computational model for the precise reconstruction of the PpIX concentration map. In our model, the tissue's optical properties and illumination geometry, which distort the fluorescent emission spectra, are considered. We demonstrate that the CMOS-based system can detect low PpIX concentration at short camera exposure times, while providing high-pixel resolution wide-field images. We show that total variation regularization improves the contrast-to-noise ratio of the reconstructed quantitative concentration map by approximately twofold. Quantitative comparison between the estimated PpIX concentration and tumor histopathology was also investigated to further evaluate the system.

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX

NARCIS (Netherlands)

Mik, Egbert G.; Stap, Jan; Sinaasappel, Michiel; Beek, Johan F.; Aten, Jacob A.; van Leeuwen, Ton G.; Ince, Can

2006-01-01

Molecular oxygen is the primary oxidant in biological systems. The ultimate destination of oxygen in vivo is the mitochondria where it is used in oxidative phosphorylation. The ability of this process to produce an amount of high-energy phosphates adequate to sustain life highly depends on the

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

Science.gov (United States)

Sibai, Mira; Fisher, Carl; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Roberts, David W.; Wilson, Brian C.

2017-07-01

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for in vivo imaging on an RG2 rat brain tumor model. Despite the moderate errors in retrieving the absorption and reduced scattering coefficients in the subdiffusive regime of 14% and 19%, respectively, the recovered [PpIX] maps agree within 10% of the point [PpIX] values measured by the fiber-optic probe, validating its potential as an extension or an alternative to point sampling during glioma resection.

Red Yeast Rice Protects Circulating Bone Marrow-Derived Proangiogenic Cells against High-Glucose-Induced Senescence and Oxidative Stress: The Role of Heme Oxygenase-1

Directory of Open Access Journals (Sweden)

Jung-Tung Liu

2017-01-01

Full Text Available The inflammation and oxidative stress of bone marrow-derived proangiogenic cells (PACs, also named endothelial progenitor cells, triggered by hyperglycemia contributes significantly to vascular dysfunction. There is supporting evidence that the consumption of red yeast rice (RYR; Monascus purpureus-fermented rice reduces the vascular complications of diabetes; however, the underlying mechanism remains unclear. This study aimed to elucidate the effects of RYR extract in PACs, focusing particularly on the role of a potent antioxidative enzyme, heme oxygenase-1 (HO-1. We found that treatment with RYR extract induced nuclear factor erythroid-2-related factor nuclear translocation and HO-1 mRNA and protein levels in PACs. RYR extract inhibited high-glucose-induced (30 mM PAC senescence and the development of reactive oxygen species (ROS in a dose-dependent manner. The HO-1 inducer cobalt protoporphyrin IX also decreased high-glucose-induced cell senescence and oxidative stress, whereas the HO-1 enzyme inhibitor zinc protoporphyrin IX and HO-1 small interfering RNA significantly reversed RYR extract-caused inhibition of senescence and reduction of oxidative stress in high-glucose-treated PACs. These results suggest that RYR extract serves as alternative and complementary medicine in the treatment of these diseases, by inducing HO-1, thereby decreasing the vascular complications of diabetes.

Effects of Processing Temperature on Color Properties of Dry-Cured Hams Made without Nitrite

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Giovanni Parolari

2016-04-01

Full Text Available Dry cured hams were investigated for their ability to develop red color even at low temperature (3–4 °C and in the absence of added nitrites; results were compared with those obtained from nitrite-free hams made at conventional warm maturing temperatures. Colorimetric parameters (L*, a*, b*, and hue and concentration of the main pigments Zn protoporphyrin IX (ZnPP and heme were measured at three stages of preparation (six, nine, and 12 months, showing that red color was successfully formed at low temperatures, though at a slower rate and less intensively than under warm conditions. Major differences in the pattern of color development were found with the two processing temperatures. While the typical features of an enzyme-dependent mechanism, with a progressive drop in enzyme activity paralleling the synthesis of Zn protoporphyrin IX, were observed at warm temperatures, the same did not occur in cold-made hams, where the enzyme activity was almost unchanged throughout the process. These results, along with data from a descriptive sensory analysis, are supportive of a non-enzymatic mechanism leading to ZnPP (hence the red color under cold conditions, with an estimated three-month delay compared with nitrite-free hams manufactured in a warm maturing regimen.

Effects of Processing Temperature on Color Properties of Dry-Cured Hams Made without Nitrite.

Science.gov (United States)

Parolari, Giovanni; Aguzzoni, Agnese; Toscani, Tania

2016-04-29

Dry cured hams were investigated for their ability to develop red color even at low temperature (3-4 °C) and in the absence of added nitrites; results were compared with those obtained from nitrite-free hams made at conventional warm maturing temperatures. Colorimetric parameters (L*, a*, b*, and hue) and concentration of the main pigments Zn protoporphyrin IX (ZnPP) and heme were measured at three stages of preparation (six, nine, and 12 months), showing that red color was successfully formed at low temperatures, though at a slower rate and less intensively than under warm conditions. Major differences in the pattern of color development were found with the two processing temperatures. While the typical features of an enzyme-dependent mechanism, with a progressive drop in enzyme activity paralleling the synthesis of Zn protoporphyrin IX, were observed at warm temperatures, the same did not occur in cold-made hams, where the enzyme activity was almost unchanged throughout the process. These results, along with data from a descriptive sensory analysis, are supportive of a non-enzymatic mechanism leading to ZnPP (hence the red color) under cold conditions, with an estimated three-month delay compared with nitrite-free hams manufactured in a warm maturing regimen.

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

Science.gov (United States)

Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

2017-05-01

We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene expression pattern at different time points following ALA-PDT

International Nuclear Information System (INIS)

Verwanger, T.; Sanovic, R.; Ruhdorfer, S.; Aberger, F.; Frischauf, A.; Krammer, B.

2003-01-01

Full text: The photo sensitizer protoporphyrin IX, endogenously accumulated from the precursor aminolevulinic acid (ALA), is a successful agent in photodynamic tumor therapy. In spite of encouraging clinical results, the basic mechanisms leading to cell death are not fully understood. We therefore set out to analyze the alteration of the gene expression pattern in the squamous cell carcinoma cell line A-431 at different time points after photodynamic treatment with endogenous protoporphyrin IX by cDNA-array technique. Cells were incubated for 16 hours with 100 μg/ml ALA and irradiated with a fluence of 3.5 J/cm 2 resulting in 50 % survival until 8 hours post treatment. RNA was isolated at 1.5, 3, 5 and 8 hours post treatment as well as of 3 controls (untreated, light only and dark), radioactively labelled by reverse transcription with 33P-dCTP and hybridized onto macroarray PCR filters containing PCR products of 2135 genes, which were selected for relevance in tumors, stress response and signal transduction. Verification of observed expression changes was carried out by real time PCR. We found a strong induction of expression of immediate early genes like c-fos as well as decreased expression of genes involved in proliferation like myc and the proliferating cell nuclear antigen (PCNA). (author)

Effects of Processing Temperature on Color Properties of Dry-Cured Hams Made without Nitrite

Science.gov (United States)

Parolari, Giovanni; Aguzzoni, Agnese; Toscani, Tania

2016-01-01

Dry cured hams were investigated for their ability to develop red color even at low temperature (3–4 °C) and in the absence of added nitrites; results were compared with those obtained from nitrite-free hams made at conventional warm maturing temperatures. Colorimetric parameters (L*, a*, b*, and hue) and concentration of the main pigments Zn protoporphyrin IX (ZnPP) and heme were measured at three stages of preparation (six, nine, and 12 months), showing that red color was successfully formed at low temperatures, though at a slower rate and less intensively than under warm conditions. Major differences in the pattern of color development were found with the two processing temperatures. While the typical features of an enzyme-dependent mechanism, with a progressive drop in enzyme activity paralleling the synthesis of Zn protoporphyrin IX, were observed at warm temperatures, the same did not occur in cold-made hams, where the enzyme activity was almost unchanged throughout the process. These results, along with data from a descriptive sensory analysis, are supportive of a non-enzymatic mechanism leading to ZnPP (hence the red color) under cold conditions, with an estimated three-month delay compared with nitrite-free hams manufactured in a warm maturing regimen. PMID:28231128

Platelet Glycoprotein Ib-IX and Malignancy

Science.gov (United States)

2010-09-01

provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin - rich network produced by coagulation...process and can initiate the formation of a platelet - rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib... Platelet Glycoprotein Ib-IX and Malignancy PRINCIPAL INVESTIGATOR: Jerry Ware, Ph.D

The hydroxypyridinone iron chelator CP94 increases methyl-aminolevulinate-based photodynamic cell killing by increasing the generation of reactive oxygen species

Directory of Open Access Journals (Sweden)

Yuktee Dogra

2016-10-01

Full Text Available Methyl-aminolevulinate-based photodynamic therapy (MAL-PDT is utilised clinically for the treatment of non-melanoma skin cancers and pre-cancers and the hydroxypyridinone iron chelator, CP94, has successfully been demonstrated to increase MAL-PDT efficacy in an initial clinical pilot study. However, the biochemical and photochemical processes leading to CP94-enhanced photodynamic cell death, beyond the well-documented increases in accumulation of the photosensitiser protoporphyrin IX (PpIX, have not yet been fully elucidated. This investigation demonstrated that MAL-based photodynamic cell killing of cultured human squamous carcinoma cells (A431 occurred in a predominantly necrotic manner following the generation of singlet oxygen and ROS. Augmenting MAL-based photodynamic cell killing with CP94 co-treatment resulted in increased PpIX accumulation, MitoSOX-detectable ROS generation (probably of mitochondrial origin and necrotic cell death, but did not affect singlet oxygen generation. We also report (to our knowledge, for the first time the detection of intracellular PpIX-generated singlet oxygen in whole cells via electron paramagnetic resonance spectroscopy in conjunction with a spin trap.

Adenine nucleotide translocator transports haem precursors into mitochondria.

Directory of Open Access Journals (Sweden)

Motoki Azuma

2008-08-01

Full Text Available Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT, the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

Elevation of blood levels of zinc protoporphyrin by radiomimetic drugs and friend leukemia virus

International Nuclear Information System (INIS)

Walden, T.L.; Al-Ansari, H.M.; Farkas, W.R.; Tennessee Univ., Knoxville; Tennessee Univ., Knoxville

1987-01-01

Sublethal doses of whole-body irradiation induced the elevation of zinc protoporphyrin (ZPP). Experiments were conducted to determine if recovery from radiomimetic drugs also resulted in elevation of ZPP. Daily injections with hydroxyurea and other cytotoxic drugs for 10 days caused ZPP elevation and a dose of radiation too low to cause ZPP elevation by itself caused ZPP elevation when hydroxyurea was administered prior to irradiation. Friend leukemia virus also brought about an elevation of ZPP. However, not all factors that increased erythropoiesis brought about ZPP elevation. The elevated erythropoiesis in response to hypoxia and the enhanced erythropoiesis that followed administration of folic acid to folic acid-deficient mice was not accompanied by ZPP elevation. (orig.)

Elevation of blood levels of zinc protoporphyrin by radiomimetic drugs and friend leukemia virus

Energy Technology Data Exchange (ETDEWEB)

Walden, T.L.; Al-Ansari, H.M.; Farkas, W.R.

1987-01-01

Sublethal doses of whole-body irradiation induced the elevation of zinc protoporphyrin (ZPP). Experiments were conducted to determine if recovery from radiomimetic drugs also resulted in elevation of ZPP. Daily injections with hydroxyurea and other cytotoxic drugs for 10 days caused ZPP elevation and a dose of radiation too low to cause ZPP elevation by itself caused ZPP elevation when hydroxyurea was administered prior to irradiation. Friend leukemia virus also brought about an elevation of ZPP. However, not all factors that increased erythropoiesis brought about ZPP elevation. The elevated erythropoiesis in response to hypoxia and the enhanced erythropoiesis that followed administration of folic acid to folic acid-deficient mice was not accompanied by ZPP elevation.

Crystal structures of eight mono-methyl alkanes (C26–C32 via single-crystal and powder diffraction and DFT-D optimization

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Lee Brooks

2015-09-01

Full Text Available The crystal structures of eight mono-methyl alkanes have been determined from single-crystal or high-resolution powder X-ray diffraction using synchrotron radiation. Mono-methyl alkanes can be found on the cuticles of insects and are believed to act as recognition pheromones in some social species, e.g. ants, wasps etc. The molecules were synthesized as pure S enantiomers and are (S-9-methylpentacosane, C26H54; (S-9-methylheptacosane and (S-11-methylheptacosane, C28H58; (S-7-methylnonacosane, (S-9-methylnonacosane, (S-11-methylnonacosane and (S-13-methylnonacosane, C30H62; and (S-9-methylhentriacontane, C32H66. All crystallize in space group P21. Depending on the position of the methyl group on the carbon chain, two packing schemes are observed, in which the molecules pack together hexagonally as linear rods with terminal and side methyl groups clustering to form distinct motifs. Carbon-chain torsion angles deviate by less than 10° from the fully extended conformation, but with one packing form showing greater curvature than the other near the position of the methyl side group. The crystal structures are optimized by dispersion-corrected DFT calculations, because of the difficulties in refining accurate structural parameters from powder diffraction data from relatively poorly crystalline materials.

New polymorphic variants of human blood clotting factor IX

Energy Technology Data Exchange (ETDEWEB)

Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

1995-04-01

The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

Screening for occupational vitiligo in workers exposed to hydroquinone monomethyl ether and to paratertiary-amyl-phenol

Energy Technology Data Exchange (ETDEWEB)

O' Sullivan, J.J.; Stevenson, C.J.

1981-11-01

Two men reported previously with vitiligo after occupational exposure to hydroquinone monomethyl ether (HMME) have been reviewed after eight years. Repigmentation of significant degree was found in one man and of limited degree in the other. One hundred and sixty-nine men in the same works have been screened with Wood's light for evidence of vitiligo. No cases were found in the 148 men exposed to HMME (colleagues who screened 100 men exposed to HMME in two other factories also found no case) or in the 129 who had been exposed to paratertiary-amyl-phenol. Loss of light reflection on Wood's light examination was observed in 13 men due to scars or to other skin disorders.

Effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic metabolizing enzymes.

Science.gov (United States)

Kawamoto, T; Matsuno, K; Kayama, F; Hirai, M; Arashidani, K; Yoshikawa, M; Kodama, Y

1990-06-01

Glycol ethers have been extensively used in industry over the past 40-50 years. Numerous studies on the toxicity of glycol ethers have been performed, however, the effects of glycol ethers on the hepatic drug metabolizing enzymes are still unknown. We studied the changes of the putative metabolic enzymes, that is, the hepatic microsomal mixed function oxidase system and cytosolic alcohol dehydrogenase, by the oral administration of diEGME and EGME. Adult male Wistar rats were used. DiEGME was administered orally; 500, 1000, 2000 mg/kg for 1, 2, 5 or 20 days and EGME was 100, 300 mg/kg for 1, 2, 5 or 20 days. Decreases in liver weights were produced by highest doses of diEGME (2000 mg/kg body wt/day for 20 days) and EGME (300 mg/kg body wt/day for 20 days). DiEGME increased hepatic microsomal protein contents and induced cytochrome P-450, but not cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was not affected by diEGME administration. On the other hand, EGME did not change cytochrome P-450, cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was increased by repeated EGME treatment. Therefore it is suspected that the enzyme which takes part in the metabolism of diEGME is different from that of EGME, although diEGME is a structural homologue of EGME.

Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

International Nuclear Information System (INIS)

Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

2011-01-01

We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: → We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. → Cre/loxP recombination was used to modify the adenovirus genome. → A targeting ligand present on capsid protein IX was removed or replaced using recombination. → Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

An explorative study of non-invasive ultra-weak photon emission and the anti-oxidative influence of oral zinc sulphate in light-sensitive patients with erythropoietic protoporphyria

DEFF Research Database (Denmark)

Petersen, Anita Birgit; Philipsen, Peter Alshede; Wulf, Hans Christian

2011-01-01

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, inherited disorder of haem biosynthesis owing to deficient ferrochelatase (FECH) and accumulation of protoporphyrin IX (PPIX). This results in acute cutaneous photosensitivity upon light exposure with production of reactive oxygen species...... correlation was found between plasma zinc concentration and the initial burst. CONCLUSION: Measurements of UPE can be used for monitoring UVA-induced oxidative processes in vivo in the skin of EPP patients....... (ROS) and ultra-weak photon emission (UPE) as a by-product. We investigated if UPE evaluated the light sensitivity in EPP patients and influence of zinc treatment. METHODS: Fourteen EPP patients took zinc sulphate (3 × 200 mg/day) during spring and summer. Using a photomultiplier (PM), UPE was measured...... from the buttock skin and dorsal hand before and after solar-simulated light (SUN) exposure. Blood samples were analysed routinely for plasma zinc, iron, ferritin, transferrin, haemoglobin, erythrocyte PPIX and Zn-PPIX. RESULTS: UPE in EPP patients resembled that seen in healthy individuals. Without...

Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX

Energy Technology Data Exchange (ETDEWEB)

Winship, P.R. (Univ. of Oxford (England))

1990-03-11

Haemophilia B is a blood coagulation disorder caused by mutations in the factor IX gene giving functionally defective or reduced levels of factor IX protein circulating in the plasma. The mutation in the Caucasian patient under investigation, Haemophilia B Oxford h5 (Oxh5), was characterized at the DNA level by constructing a genomic library using leucocyte-derived DNA from the patient. Overlapping recombinant clones spanning the entire factor IX locus were isolated which then allowed the generation of a series of sub-clones across all eight exons (a-h) plus the 5{prime} and 3{prime} flanking sequences known to be important in regulation of the gene and polyadenylation of the mRNA species.

Dual-channel (green and red) fluorescence microendoscope with subcellular resolution

Science.gov (United States)

de Paula D'Almeida, Camila; Fortunato, Thereza Cury; Teixeira Rosa, Ramon Gabriel; Romano, Renan Arnon; Moriyama, Lilian Tan; Pratavieira, Sebastião.

2018-02-01

Usually, tissue images at cellular level need biopsies to be done. Considering this, diagnostic devices, such as microendoscopes, have been developed with the purpose of do not be invasive. This study goal is the development of a dual-channel microendoscope, using two fluorescent labels: proflavine and protoporphyrin IX (PpIX), both approved by Food and Drug Administration. This system, with the potential to perform a microscopic diagnosis and to monitor a photodynamic therapy (PDT) session, uses a halogen lamp and an image fiber bundle to perform subcellular image. Proflavine fluorescence indicates the nuclei of the cell, which is the reference for PpIX localization on image tissue. Preliminary results indicate the efficacy of this optical technique to detect abnormal tissues and to improve the PDT dosimetry. This was the first time, up to our knowledge, that PpIX fluorescence was microscopically observed in vivo, in real time, combined to other fluorescent marker (Proflavine), which allowed to simultaneously observe the spatial localization of the PpIX in the mucosal tissue. We believe this system is very promising tool to monitor PDT in mucosa as it happens. Further experiments have to be performed in order to validate the system for PDT monitoring.

Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources

Directory of Open Access Journals (Sweden)

Catharina M. Lerche

2016-02-01

Full Text Available Daylight-mediated photodynamic therapy (daylight PDT is a simple and pain free treatment of actinic keratoses. Weather conditions may not always allow daylight PDT outdoors. We compared the spectrum of five different lamp candidates for indoor “daylight PDT” and investigated their ability to photobleach protoporphyrin IX (PpIX. Furthermore, we measured the amount of PpIX activating daylight available in a glass greenhouse, which can be an alternative when it is uncomfortable for patients to be outdoors. The lamps investigated were: halogen lamps (overhead and slide projector, white light-emitting diode (LED lamp, red LED panel and lamps used for conventional PDT. Four of the five light sources were able to photobleach PpIX completely. For halogen light and the red LED lamp, 5000 lux could photobleach PpIX whereas 12,000 lux were needed for the white LED lamp. Furthermore, the greenhouse was suitable for daylight PDT since the effect of solar light is lowered only by 25%. In conclusion, we found four of the five light sources and the greenhouse usable for indoor daylight PDT. The greenhouse is beneficial when the weather outside is rainy or windy. Only insignificant ultraviolet B radiation (UVB radiation passes through the greenhouse glass, so sun protection is not needed.

Providing Transparency to the Title IX Process

Science.gov (United States)

Hartle, Terry

2017-01-01

When U.S. Secretary of Education Betsy DeVos announced Sept. 7, 2017, that her department would revisit how Title IX rules are enforced with respect to campus sexual assault, she said the first step would be a "transparent notice and comment process" to replace the 2011 "guidance" (and follow up 2014 guidance) that has been…

Medicinal Flowers. XXXII. Structures of oleanane-type triterpene saponins, perennisosides VIII, IX, X, XI, and XII, from the flowers of Bellis perennis.

Science.gov (United States)

Morikawa, Toshio; Li, Xuezheng; Nishida, Eriko; Nakamura, Seikou; Ninomiya, Kiyofumi; Matsuda, Hisashi; Hamao, Makoto; Muraoka, Osamu; Hayakawa, Takao; Yoshikawa, Masayuki

2011-01-01

Five new triterpene saponins perennisosides VIII (1), IX (2), X (3), XI (4), and XII (5) were isolated from the MeOH-eluated fraction of the methanolic extract from the flowers of Bellis perennis. The MeOH-eluted fraction of the methanolic extract from the flowers of B. perennis was found to inhibit gastric emptying in olive oil-loaded mice at a dose of 200 mg/kg, per os (p.o.). The stereostructures of 1-5 were elucidated on the basis of chemical and spectroscopic evidence.

The antimalarial activities of methylene blue and the 1,4-naphthoquinone 3-[4-(trifluoromethyl)benzyl]-menadione are not due to inhibition of the mitochondrial electron transport chain.

Science.gov (United States)

Ehrhardt, Katharina; Davioud-Charvet, Elisabeth; Ke, Hangjun; Vaidya, Akhil B; Lanzer, Michael; Deponte, Marcel

2013-05-01

Methylene blue and a series of recently developed 1,4-naphthoquinones, including 3-[4-(substituted)benzyl]-menadiones, are potent antimalarial agents in vitro and in vivo. The activity of these structurally diverse compounds against the human malaria parasite Plasmodium falciparum might involve their peculiar redox properties. According to the current theory, redox-active methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione are "subversive substrates." These agents are thought to shuttle electrons from reduced flavoproteins to acceptors such as hemoglobin-associated or free Fe(III)-protoporphyrin IX. The reduction of Fe(III)-protoporphyrin IX could subsequently prevent essential hemoglobin digestion and heme detoxification in the parasite. Alternatively, owing to their structures and redox properties, methylene blue and 1,4-naphthoquinones might also affect the mitochondrial electron transport chain. Here, we tested the latter hypothesis using an established system of transgenic P. falciparum cell lines and the antimalarial agents atovaquone and chloroquine as controls. In contrast to atovaquone, methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione do not inhibit the mitochondrial electron transport chain. A systematic comparison of the morphologies of drug-treated parasites furthermore suggests that the three drugs do not share a mechanism of action. Our findings support the idea that methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione exert their antimalarial activity as redox-active subversive substrates.

Legal Forum: Title IX: Does It Apply to Employees?

Science.gov (United States)

McCarthy, Martha

1981-01-01

Briefly reviews a number of Federal court cases that have dealt with Title IX, considering the issue of whether the 1974 regulations prohibiting sex discrimination in employment practices accurately reflect the intent of the 1972 law. (GC)

Title IX and Sexual Harassment of Student Athletes.

Science.gov (United States)

Wolohan, John T.

1995-01-01

This article reviews what constitutes sexual harassment in sports by examining Title IX of the Education Amendments of 1972 and the effect it has had on charges of sexual harrassment in educational institutions. Athletic administrators are provided with strategies and recommendations to help schools and athletic departments develop sexual…

Significant performance enhancement of inverted organic light-emitting diodes by using ZnIx as a hole-blocking layer

Science.gov (United States)

Cheng, Chuan-Hui; Zhang, Bi-Long; Sun, Chao; Li, Ruo-Xuan; Wang, Yuan; Tian, Wen-Ming; Zhao, Chun-Yi; Jin, Sheng-Ye; Liu, Wei-Feng; Luo, Ying-Min; Du, Guo-Tong; Cong, Shu-Lin

2017-06-01

A highly efficient inverted organic light emitting diode using 1.0 nm-thick ZnIx as a hole-blocking layer is developed. We fabricate devices with the configuration ITO/ZnIx (1.0 nm)/Alq3 (50 nm)/NPB (50 nm)/MoO3 (6.0 nm)/Al (100 nm). The deposition of a ZnIx layer increases the maximum luminance by two orders of magnitude from 13.4 to 3566.1 cd/m2. In addition, the maximum current efficiency and power efficiency are increased by three orders of magnitude, and the turn-on voltage to reach 1 cd/m2 decreases from 13 to 8 V. The results suggest that the electron injection efficiency is not improved by introducing a ZnIx layer. Instead, the improved device performance originates from the strong hole-blocking ability of ZnIx. This work indicates that layered materials may lead to novel applications in optoelectronic devices.

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

Directory of Open Access Journals (Sweden)

Shi J

2013-07-01

Full Text Available Jinjin Shi,* Rourou Ma,* Lei Wang, Jing Zhang, Ruiyuan Liu, Lulu Li, Yan Liu, Lin Hou, Xiaoyuan Yu, Jun Gao, Zhenzhong Zhang School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People's Republic of China*These authors contributed equally to this workAbstract: Carbon nanotubes (CNTs have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME, was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy.Keywords: photodynamic therapy, photothermal therapy, HA-derivatized carbon nanotubes, tumor targeting, synergistic effect, hematoporphyrin monomethyl ether

Hubungan Gaya Kepemimpinan Orang Tua terhadap Hasil Belajar IPA Siswa Kelas IX SMPN 2 Batang Anai

Directory of Open Access Journals (Sweden)

Nelfi Erlinda

2017-02-01

Full Text Available AbstractPenelitian ini dilatarbelakangi oleh rendahnya hasil belajar IPA siswa kelas IX SMPN 2 Batang Anai. Faktor penyebabnya ada yang berasal dari dalam diri siswa dan dari luar diri siswa. Faktor yang berasal dari dalam diri siswa seperti malas belajar. Faktor luar diri siswa seperti faktor lingkungan keluarga yang terdiri dari faktor orang tua, suasana keluarga, lingkungan keluarga, kondisi keluarga yang tidak sehat atau broken home. Hal ini berpengaruh dalam proses belajar dan hasil belajar siswa di sekolah. Penelitian ini bertujuan untuk mengetahui hubungan gaya kepemimpinan orang tua terhadap hasil belajar IPA siswa kelas IX SMPN 2 Batang Anai. Jenis penelitian ini adalah penelitian deskriptif. Populasi penelitian adalah semua siswa kelas IX SMPN 2 Batang Anai yang terdaftar dalam tahun ajaran  2016/2017. Sampel penelitian adalah semua kelas IX SMPN 2 Batang Anai. Teknik pengambilan sampel menggunakan total sampling. Instrumen penelitian yang digunakan berupa angket atau kuesioner yang diberikan ke siswa. Teknik analisis data yang digunakan untuk menguji hipotesis adalah analisis korelasi dengan menggunakan uji chi kuadrat untuk melihat antara hubungan gaya kepemimpinan oramg tua dengan hasil belajar IPA siswa kelas IX SMPN 2 Batang Anai. Berdasarkan analisis data didapatkan dua gaya kepemimpimam yaitu otoriter dan demokratis. Hasil uji hipotesis diperoleh X2hitung < X2tabel = 0,004 < 3,841  sehingga hipotesis Ho diterima pada taraf nyata 0,05 dan hipotesis Hi ditolak. Jadi tidak ada hubungan yang berarti antara gaya kepemimpinan orang tua terhadap hasil belajar IPA siswa kelas IX SMPN 2 Batang Anai. Kata kunci :  Gaya kepemimpinan orang tua, hasil belajar.

An organelle-free assay for pea chloroplast Mg-chelatase: Resolution of the activity into soluble and membrane bound fractions

Energy Technology Data Exchange (ETDEWEB)

Walker, C.J.; Weinstein, J.D. (Clemson Univ, SC (United States))

1991-05-01

Mg-chelatase, which catalyzes the insertion of magnesium into protoporphyrin, lies at the branchpoint of heme and chlorophyll biosynthesis in chloroplasts. Since magnesium chelation is the first step unique to chlorophyll synthesis, one would expect this step to be highly regulated. However, to date little is known about the enzymology or regulation of Mg-chelatase due mostly to an inability to assay it's activity outside of the intact plastid. Here the authors report the first truly in vitro i.e. organelle-free, assay for Mg-chelatase. Mg-chelatase activity in intact pea chloroplasts which is 3 to 4 fold higher than in cucumber chloroplasts, survived chloroplast lysis and could be fractionated, by centrifugation, into supernatant and pellet components. Both of these fractions were required to reconstitute Mg-chelatase activity and both were inactivated by boiling; indicating that the enzyme is composed of soluble and membrane bound protein(s). The specific activity of the reconstituted system was typically 1 nmol Mg-Deuteroporphyrin/h/mg protein and activity was linear for at least 60 min under our assay conditions. ATP and magnesium were required for Mg-chelatase activity. The soluble component could be fractionated with ammonium sulfate. The product of the reaction was confirmed fluorometrically as the magnesium chelate of the porphyrin substrate. Crude separation of chloroplast membranes into thylakoids and envelopes, suggested that the membrane-bound component of Mg-chelatase is probably located in the envelope.

Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

International Nuclear Information System (INIS)

Morrison, S.A.; Jesty, J.

1984-01-01

A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

23. IX korraldab Vaala galerii kunstioksjoni "Väliseesti eri"

Index Scriptorium Estoniae

2004-01-01

Oksjonil on esindatud Eerik Haamer, Jaan Grünberg, Arno Vihalemm, Eduard Wiiralt, Ruth Tulving, Endel Kõks, Harald Jürissaar, Otto Paas, Ville Tops, Otto Puusta. Töödega saab tutvuda alates 18. IX, traditsiooniline sügisoksjon toimub 18. XI

Efficacy of a high-purity factor IX concentrate in hemophilia B patients undergoing surgery Eficácia do concentrado de alta pureza do fator IX em pacientes cirúrgicos portadores de hemofilia B

Directory of Open Access Journals (Sweden)

Vesa Rasi

2002-04-01

Full Text Available A plasma derived, high purity, solvent-detergent treated and subsequently nanofiltered factor IX concentrate (BEMOFIL was evaluated in 19 hemophilia B patients, including four with severe, thirteen with mild or moderate type of disease and two hemophilia B carriers undergoing 31 surgical procedures. The mean in vivo recovery was 52 %, range 36 - 76 %. The mean preoperative plasma factor IX activity after the initial loading dose was 0.86 IU mL-1, range 0.59 - 1.32 IU mL-1. In eight major orthopedic procedures, the mean usage of factor IX was 44600 IU or 574 IU kg-1 during the hospital stay, mean 11.6 days. Thromboprophylaxis was not used. The hemostatic efficacy was evaluated good in all cases and there were no thromboembolic complications. In conclusion, BEMOFIL used as bolus dosing was found to be safe and effective in achieving hemostasis in subjects with hereditary F IX deficiency undergoing surgery.O concentrado de fator IX ( Bemofil , um derivado plasmático de alta pureza tratado com solventes- detergente e nano-filtrado , foi avaliado em 19 pacientes portadores de Hemofilia B .Quatro pacientes apresentavam a forma grave da moléstia, 13 a forma leve e moderada e dois portadores em um total de 31 atos cirúrgicos.A recuperação média "in vivo" foi de 52% (36-76%. A atividade plasmática média pré-operatória do fator IX após a dose inicial foi de 0,86 UI ml -1 , média de 0,59 - 1,32 UI ml-1. Em oito procedimentos ortopédicos extensos , a média de utilização do fator IX foi de 44.600 UI ou 574 UI kg -1 durante a hospitalização que teve a média de 11,6 dias. A tromboprofilaxia não foi utilizada. A eficácia hemostática avaliada em todos os casos foi boa ,e não ocorreu nenhum tipo de complicação tromboembólica. Concluímos que o Bemofil em bolus foi considerado seguro e eficaz para a hemostasia em pacientes portadores de hemofilia B que necessitam de um procedimento cirúrgico.

Ares I-X Ground Diagnostic Prototype

Science.gov (United States)

Schwabacher, Mark A.; Martin, Rodney Alexander; Waterman, Robert D.; Oostdyk, Rebecca Lynn; Ossenfort, John P.; Matthews, Bryan

2010-01-01

The automation of pre-launch diagnostics for launch vehicles offers three potential benefits: improving safety, reducing cost, and reducing launch delays. The Ares I-X Ground Diagnostic Prototype demonstrated anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage Thrust Vector Control and for the associated ground hydraulics while the vehicle was in the Vehicle Assembly Building at Kennedy Space Center (KSC) and while it was on the launch pad. The prototype combines three existing tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool from Qualtech Systems Inc. for fault isolation and diagnostics. The second tool, SHINE (Spacecraft Health Inference Engine), is a rule-based expert system that was developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification, and used the outputs of SHINE as inputs to TEAMS. The third tool, IMS (Inductive Monitoring System), is an anomaly detection tool that was developed at NASA Ames Research Center. The three tools were integrated and deployed to KSC, where they were interfaced with live data. This paper describes how the prototype performed during the period of time before the launch, including accuracy and computer resource usage. The paper concludes with some of the lessons that we learned from the experience of developing and deploying the prototype.

IX Jornadas de educación emocional. Educación emocional y valores

OpenAIRE

Barredo Gutiérrez, Blanca; Bisquerra Alzina, Rafael; Blanco Cuch, Aida; Giner, Antoni; Pérez Escoda, Núria; Tey, Amèlia

2013-01-01

Barredo Gutierrez, B.; Bisquerra Alzina, R.; Blanco Cuch, A.; Giner Tarrida, A.; Perez Escoda, N.; Tey Teijón, A. (eds.) IX Jornades d’educació emocional. Educació emocional i valors / IX Jornadas de educación emocional. Educación emocional y valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic.valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic

Absence of collagen IX accelerates hypertrophic differentiation in the embryonic mouse spine through a disturbance of the Ihh-PTHrP feedback loop.

Science.gov (United States)

Kamper, Matthias; Paulsson, Mats; Zaucke, Frank

2017-02-01

Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice. Histological staining was used to show tissue morphology at different time points. Localization of extracellular matrix proteins as well as components of signaling pathways were analyzed by immunohistochemistry. Developing vertebral bodies of Col IX -/- mice were smaller and already appeared more compact at E12.5. At E15.5, vertebral bodies of Col IX -/- mice revealed an increased number of hypertrophic chondrocytes as well as enhanced staining for the terminal differentiation markers alkaline phosphatase and collagen X. This correlates with an imbalance in the Ihh-PTHrP signaling pathway at this time point, reflected by an increase of Ihh and a concomitant decrease of PTHrP expression. An accelerated hypertrophic differentiation caused by a disturbed Ihh-PTHrP signaling pathway may lead to a higher bone mineral density in the vertebral bodies of newborn Col IX -/- mice and, as a result, to the early onset of disc degeneration.

Metallation of protoporphyrins used as fluorescent chemo sensor for imidazole recognition

International Nuclear Information System (INIS)

Panpae, Kornvalai; Krikrutthee, Chaiwat; Porntaweethum, Phumthan; Weerachiwcharnchai, Panya; Chenwittayayos, Aekapoj

2008-01-01

Metalloporphyrin Complexes play significant roles in many biological and catalytic systems. The diversity of their functions is due in part to the variety of metals that bind in the pocket of the porphyrin ring system. Two kinds of metalloporphyrin derivatives, Cu (II) and Zn (II) protoporphyrins (PP) were microscale synthesized and characterized by spectroscopic methods and magnetic measurements. A PP ligand bound to each metal center in a tetradentate fashion including four amine nitrogen atoms in the equatorial planes. These complexes were found to recognize imidazolyl groups of histidine and histamine derivatives as guest molecules by coordination and additional non-covalent interactions. These added analytes displace the selective fluorescent indicator, which when released to the solution displays its full fluorescence. Thus, analyte recognition is signaled by the sharp appearance of the fluorescence of the indicators. The binding affinities to histidine and histamine were investigated and accounted for different complexation properties. Moreover, we demonstrated that careful choice of a fluorescent indicator with tuned affinity toward the receptor can provide discrimination in sensing of a desired substrate and the role that the metal coordination plays on the hypochromic shift and loss of fluorescence distincted characteristics of hypsoporphyrins were also discussed. (author)

Elevation of blood levels of zinc protoporphyrin in mice following whole-body irradiation

International Nuclear Information System (INIS)

Walden, T.L. Jr.

1983-01-01

Elevation of zinc protoporphyrin (ZPP) levels in the blood has served as an indicator of lead poisoning and iron deficiency anemia for many years. The author has discovered that sublethal doses of whole body irradiation with X-rays also elevates ZPP two- to three-fold over normal levels. The ZPP level does not begin to increase until days 12 to 14 post-irradiation and peaks between days 18 to 20 before returning to normal levels between days 28 to 35. Increasing the radiation dose delays the onset of the rise in ZPP but does not affect the magnitude of the elevation. At lethal doses, ZPP elevation is not observed. Neither of the two previously described mechanisms which cause elevations of ZPP, namely iron deficiency and inhibition of ferrochelatase, are responsible for the radiation induced elevation of ZPP. The elevation of ZPP appears to be correlated with the recovery of the hematopoietic system from radiation injury

Evaluation of photodynamic treatment efficiency on glioblastoma cells received from malignant lesions: initial studies

Science.gov (United States)

Borisova, Ekaterina; Kyurkchiev, Dobroslav; Tumangelova-Yuzeir, Kalina; Angelov, Ivan; Genova-Hristova, Tsanislava; Semyachkina-Glushkovskaya, Oxana; Minkin, Krassimir

2018-04-01

Photodynamic therapy is well-established and extensively used method in treatment of different cancer types. This research reveals its potential in the treatment of cultivated human glioblastoma cells with adherent morphology. As the blood-brain barrier (BBB) permeability of the drugs is a significant problem that could not be solved easily for large biomolecules, we search for an appropriate low-molecular weight photosensitizer that could be applied for photodynamic treatment of glioblastoma cells. We used delta-aminolevulinic acid (5-ALA), which could pass BBB and plays the role of precursor of a protoporphyrin IX (PpIX) - photosensitizer, that is accumulated selectively in the tumour cells and could be a proper tool in PDT of glioblastoma. However, differences from patient to patient and between the cell activities could also lead to different effectiveness of the PDT treatment of the tumour areas. Therefore in our study we investigated not only the effect of using different fluence rates and light doses, but aims to establish more efficient values for further clinical applications for each sub-type of the GBM lesions. For the needs of PDT application an illumination device was developed in Laboratory of Biophotonics, BAS based on light-emitting diode (LED) matrix light sources for therapeutic application emitting at 635 nm. The device is optimized for PDT in combination with aminolevulinic acid/protoporphyrin IX applied as a photosensitizer drug. By the means of FACSCalibur flow cytometer (Becton Dickinson, USA) and Cell Quest Software was made evaluation of PDT effect on used human glioblastoma cells. Treatment of glioblastoma tumours continues to be a very serious issue and there is growing need in development of new concepts, methods and cancer-fighting strategies. PDT may contribute in accomplishing better results in cancer treatment and can be applied as well in combination with other techniques.

Phase-space dynamics of Bianchi IX cosmological models

International Nuclear Information System (INIS)

Soares, I.D.

1985-01-01

The complex phase-space dynamical behaviour of a class of Biachi IX cosmological models is discussed, as the chaotic gravitational collapse due Poincare's homoclinic phenomena, and the n-furcation of periodic orbits and tori in the phase space of the models. Poincare maps which show this behaviour are constructed merically and applications are discussed. (Author) [pt

Factor IX[sub Madrid 2]: A deletion/insertion in Facotr IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site

Energy Technology Data Exchange (ETDEWEB)

Solera, J. (Unidades de Genetica Molecular, Madrid (Spain)); Magallon, M.; Martin-Villar, J. (Hemofilia Hospital, Madrid (Spain)); Coloma, A. (Departamento deBioquimica de la Facultad de Medicina de la Universidad Autonoma, Madrid (Spain))

1992-02-01

DNA from a patient with severe hemophilia B was evaluated by RFLP analysis, producing results which suggested the existence of a partial deletion within the factor IX gene. The deletion was further localized and characterized by PCR amplification and sequencing. The altered allele has a 4,442-bp deletion which removes both the donor splice site located at the 5[prime] end of intron d and the two last coding nucleotides located at the 3[prime] end of exon IV in the normal factor IX gene; this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment.

In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

Science.gov (United States)

Rollakanti, K.; Anand, S.; Maytin, E. V.

2013-03-01

Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

Thioredoxin and NADPH-Dependent Thioredoxin Reductase C Regulation of Tetrapyrrole Biosynthesis.

Science.gov (United States)

Da, Qingen; Wang, Peng; Wang, Menglong; Sun, Ting; Jin, Honglei; Liu, Bing; Wang, Jinfa; Grimm, Bernhard; Wang, Hong-Bin

2017-10-01

In chloroplasts, thioredoxin (TRX) isoforms and NADPH-dependent thioredoxin reductase C (NTRC) act as redox regulatory factors involved in multiple plastid biogenesis and metabolic processes. To date, less is known about the functional coordination between TRXs and NTRC in chlorophyll biosynthesis. In this study, we aimed to explore the potential functions of TRX m and NTRC in the regulation of the tetrapyrrole biosynthesis (TBS) pathway. Silencing of three genes, TRX m1 , TRX m2 , and TRX m4 ( TRX ms ), led to pale-green leaves, a significantly reduced 5-aminolevulinic acid (ALA)-synthesizing capacity, and reduced accumulation of chlorophyll and its metabolic intermediates in Arabidopsis ( Arabidopsis thaliana ). The contents of ALA dehydratase, protoporphyrinogen IX oxidase, the I subunit of Mg-chelatase, Mg-protoporphyrin IX methyltransferase (CHLM), and NADPH-protochlorophyllide oxidoreductase were decreased in triple TRX m- silenced seedlings compared with the wild type, although the transcript levels of the corresponding genes were not altered significantly. Protein-protein interaction analyses revealed a physical interaction between the TRX m isoforms and CHLM. 4-Acetoamido-4-maleimidylstilbene-2,2-disulfonate labeling showed the regulatory impact of TRX ms on the CHLM redox status. Since CHLM also is regulated by NTRC (Richter et al., 2013), we assessed the concurrent functions of TRX m and NTRC in the control of CHLM. Combined deficiencies of three TRX m isoforms and NTRC led to a cumulative decrease in leaf pigmentation, TBS intermediate contents, ALA synthesis rate, and CHLM activity. We discuss the coordinated roles of TRX m and NTRC in the redox control of CHLM stability with its corollary activity in the TBS pathway. © 2017 American Society of Plant Biologists. All Rights Reserved.

Study of primitive universe in the Bianchi IX model

International Nuclear Information System (INIS)

Matsas, G.E.A.

1988-03-01

The theory of general relativity is used to study the homogeneous cosmological model Bianch IX with isometry group SO(3) near the cosmological singularity. The Bogoyavlenskii-Novikov formalism to explain the anusual behaviour of the Liapunov exponent associated with this chaotic system, is introduced. (author) [pt

The elevation of blood levels of zinc protoporphyrin in mice following whole body irradiation

International Nuclear Information System (INIS)

Walden, T.L.; Draganac, P.S.; Farkas, W.R.

1984-01-01

Elevation of zinc protoporphyrin (ZPP) levels in the blood has served as an indicator of lead poisoning and iron deficiency anemia for many years. We have discovered that sublethal doses of whole body irradiation with x-rays also elevates ZPP 2-3-fold over normal levels. The ZPP level does not begin to increase until days 12-14 postirradiation and peaks between days 18 and 20 before returning to normal levels between days 28 and 35. Increasing the radiation dose delays the onset of the rise in ZPP, but does not affect the magnitude of the elevation. At lethal doses, ZPP elevation is not observed. Neither of the two previously described mechanisms that cause elevations of ZPP, namely iron deficiency and inhibition of ferrochelatase, are responsible for the radiation-induced elevation of ZPP. The elevation of ZPP appears to be correlated with the recovery of the hematopoietic system from radiation injury

Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

Science.gov (United States)

Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

2018-03-05

Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

Counselor Education and Title IX: Current Perceptions and Questions

Science.gov (United States)

Welfare, Laura E.; Wagstaff, Jennifer; Haynes, Jenna R.

2017-01-01

This national survey of counselor educator perceptions of the Title IX requirement to report student disclosures of gender-based discrimination revealed the need for greater clarity about faculty strategies for serving counseling program students while upholding the federal law. The authors describe the recent expansion of the requirements and…

Big Men on Campus: Administrative Response to Title IX and the Development of Women's Sports in the Big Ten Conference, 1972-1982

Science.gov (United States)

Ramsey, Jeffrey T.

2014-01-01

Signed into law in 1972, Title IX of the Education Amendments was designed to eliminate gender discrimination throughout the American educational system. Title IX applied to all educational programs at any level of schooling including admissions, financial aid, academic programs, and social organizations. However, Title IX has primarily been…

Transmembrane carbonic anhydrase isozymes IX and XII in the female mouse reproductive organs

Directory of Open Access Journals (Sweden)

Tomas Eija

2004-10-01

Full Text Available Abstract Background Carbonic anhydrase (CA classically catalyses the reversible hydration of dissolved CO2 to form bicarbonate ions and protons. The twelve active CA isozymes are thought to regulate a variety of cellular functions including several processes in the reproductive systems. Methods The present study was designed to investigate the expression of transmembrane CAs, CA IX and XII, in the mouse uterus, ovary and placenta. The expression of CA IX and XII was examined by immunoperoxidase staining method and western blotting. CA II and XIII served as positive controls since they are known to be present in the mouse reproductive tract. Results The data of our study indicated that CA XII is expressed in the mouse endometrium. Only very faint signal was observed in the corpus luteum of the ovary and the placenta remained mainly negative. CA IX showed weak reaction in the endometrial epithelium, while it was completely absent in the ovary and placenta. Conclusion The conservation of CA XII expression in both mouse and human endometrium suggests a role for this isozyme in reproductive physiology.

Pattern recognition of neurotransmitters using multimode sensing.

Science.gov (United States)

Stefan-van Staden, Raluca-Ioana; Moldoveanu, Iuliana; van Staden, Jacobus Frederick

2014-05-30

Pattern recognition is essential in chemical analysis of biological fluids. Reliable and sensitive methods for neurotransmitters analysis are needed. Therefore, we developed for pattern recognition of neurotransmitters: dopamine, epinephrine, norepinephrine a method based on multimode sensing. Multimode sensing was performed using microsensors based on diamond paste modified with 5,10,15,20-tetraphenyl-21H,23H-porphyrine, hemin and protoporphyrin IX in stochastic and differential pulse voltammetry modes. Optimized working conditions: phosphate buffer solution of pH 3.01 and KCl 0.1mol/L (as electrolyte support), were determined using cyclic voltammetry and used in all measurements. The lowest limits of quantification were: 10(-10)mol/L for dopamine and epinephrine, and 10(-11)mol/L for norepinephrine. The multimode microsensors were selective over ascorbic and uric acids and the method facilitated reliable assay of neurotransmitters in urine samples, and therefore, the pattern recognition showed high reliability (RSDneurotransmitters on biological fluids at a lower determination level than chromatographic methods. The sampling of the biological fluids referees only to the buffering (1:1, v/v) with a phosphate buffer pH 3.01, while for chromatographic methods the sampling is laborious. Accordingly with the statistic evaluation of the results at 99.00% confidence level, both modes can be used for pattern recognition and quantification of neurotransmitters with high reliability. The best multimode microsensor was the one based on diamond paste modified with protoporphyrin IX. Copyright © 2014 Elsevier B.V. All rights reserved.

Methamphetamine induces heme oxygenase-1 expression in cortical neurons and glia to prevent its toxicity

International Nuclear Information System (INIS)

Huang, Y.-N.; Wu, C.-H.; Lin, T.-C.; Wang, J.-Y.

2009-01-01

The impairment of cognitive and motor functions in humans and animals caused by methamphetamine (METH) administration underscores the importance of METH toxicity in cortical neurons. The heme oxygenase-1 (HO-1) exerts a cytoprotective effect against various neuronal injures; however, it remains unclear whether HO-1 is involved in METH-induced toxicity. We used primary cortical neuron/glia cocultures to explore the role of HO-1 in METH-induced toxicity. Exposure of cultured cells to various concentrations of METH (0.1, 0.5, 1, 3, 5, and 10 mM) led to cytotoxicity in a concentration-dependent manner. A METH concentration of 5 mM, which caused 50% of neuronal death and glial activation, was chosen for subsequent experiments. RT-PCR and Western blot analysis revealed that METH significantly induced HO-1 mRNA and protein expression, both preceded cell death. Double and triple immunofluorescence staining further identified HO-1-positive cells as activated astrocytes, microglia, and viable neurons, but not dying neurons. Inhibition of the p38 mitogen-activated protein kinase pathway significantly blocked HO-1 induction by METH and aggravated METH neurotoxicity. Inhibition of HO activity using tin protoporphyrine IX significantly reduced HO activity and exacerbated METH neurotoxicity. However, prior induction of HO-1 using cobalt protoporphyrine IX partially protected neurons from METH toxicity. Taken together, our results suggest that induction of HO-1 by METH via the p38 signaling pathway may be protective, albeit insufficient to completely protect cortical neurons from METH toxicity.

Cytochrome P-450 inactivation by 3-alkylsydnones. Mechanistic implications of N-alkyl and N-alkenyl heme adduct formation

International Nuclear Information System (INIS)

Grab, L.A.; Swanson, B.A.; Ortiz de Montellano, P.R.

1988-01-01

Incubation of 3-(2-phenylethyl)-4-methylsydnone (PMS) with liver microsomes from phenobarbital-pretreated rats or with reconstituted cytochrome P-450b results in loss of the enzyme chromophore. Chromophore loss is NADPH-dependent even though the sydnone decomposes by an oxygen- but not enzyme-dependent process to give pyruvic acid and, presumably, the (2-phenylethyl)diazonium cation. N-(2-Phenylethyl)protoporphyrin IX and N-(2-phenylethenyl)protoporphyrin IX have been isolated from the livers of rats treated with PMS. Both deuteriums are retained in the N-(2-phenylethyl) adduct derived from 3-(2-phenyl[1,1- 2 H]ethyl)-4-methylsydnone, but one deuterium is lost in the N-(2-phenylethenyl) adduct. The N-(2-phenylethyl) to N-(2-phenylethenyl) adduct ratio is increased by deuterium substitution. Electron paramagnetic resonance (EPR)-spin trapping studies show that carbon radicals are formed in incubations of the sydnones with liver microsomes but by a process that is independent of chromophore destruction. It is proposed that the 2-phenylethyl radical formed by electron transfer to the sydnone-derived (2-phenylethyl)diazonium cation adds to the prosthetic heme group to give the N-(2-phenylethyl) adduct. This alkylation reaction is similar to that observed with (2-phenylethyl)hydrazine. Autoxidation of the Fe-CH(CH 2 Ph)-N bridged species expected from insertion of 2-phenyldiazoethane into one of the heme Fe-N bonds is proposed to explain the unprecedented introduction of a double bond into the N-(2-phenylethenyl)adduct

YOUNG STELLAR POPULATIONS IN MYStIX STAR-FORMING REGIONS: CANDIDATE PROTOSTARS

Energy Technology Data Exchange (ETDEWEB)

Romine, Gregory; Feigelson, Eric D.; Getman, Konstantin V. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Kuhn, Michael A. [Millennium Institute of Astrophysics, Camino El Observatorio 1515, Las Condes, Santiago (Chile); Povich, Matthew S., E-mail: edf@astro.psu.edu [Department of Physics and Astronomy, California State Polytechnic University, 3801 West Temple Ave., Pomona, CA 91768 (United States)

2016-12-20

The Massive Young Star-Forming Complex in Infrared and X-ray (MYStIX) project provides a new census on stellar members of massive star-forming regions within 4 kpc. Here the MYStIX Infrared Excess catalog and Chandra -based X-ray photometric catalogs are mined to obtain high-quality samples of Class I protostars using criteria designed to reduce extragalactic and Galactic field star contamination. A total of 1109 MYStIX Candidate Protostars (MCPs) are found in 14 star-forming regions. Most are selected from protoplanetary disk infrared excess emission, but 20% are found from their ultrahard X-ray spectra from heavily absorbed magnetospheric flare emission. Two-thirds of the MCP sample is newly reported here. The resulting samples are strongly spatially associated with molecular cores and filaments on Herschel far-infrared maps. This spatial agreement and other evidence indicate that the MCP sample has high reliability with relatively few “false positives” from contaminating populations. But the limited sensitivity and sparse overlap among the infrared and X-ray subsamples indicate that the sample is very incomplete with many “false negatives.” Maps, tables, and source descriptions are provided to guide further study of star formation in these regions. In particular, the nature of ultrahard X-ray protostellar candidates without known infrared counterparts needs to be elucidated.

YOUNG STELLAR POPULATIONS IN MYStIX STAR-FORMING REGIONS: CANDIDATE PROTOSTARS

International Nuclear Information System (INIS)

Romine, Gregory; Feigelson, Eric D.; Getman, Konstantin V.; Kuhn, Michael A.; Povich, Matthew S.

2016-01-01

The Massive Young Star-Forming Complex in Infrared and X-ray (MYStIX) project provides a new census on stellar members of massive star-forming regions within 4 kpc. Here the MYStIX Infrared Excess catalog and Chandra -based X-ray photometric catalogs are mined to obtain high-quality samples of Class I protostars using criteria designed to reduce extragalactic and Galactic field star contamination. A total of 1109 MYStIX Candidate Protostars (MCPs) are found in 14 star-forming regions. Most are selected from protoplanetary disk infrared excess emission, but 20% are found from their ultrahard X-ray spectra from heavily absorbed magnetospheric flare emission. Two-thirds of the MCP sample is newly reported here. The resulting samples are strongly spatially associated with molecular cores and filaments on Herschel far-infrared maps. This spatial agreement and other evidence indicate that the MCP sample has high reliability with relatively few “false positives” from contaminating populations. But the limited sensitivity and sparse overlap among the infrared and X-ray subsamples indicate that the sample is very incomplete with many “false negatives.” Maps, tables, and source descriptions are provided to guide further study of star formation in these regions. In particular, the nature of ultrahard X-ray protostellar candidates without known infrared counterparts needs to be elucidated.

Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.

Science.gov (United States)

Yang, Deng-Fu; Chen, Jia-Haur; Chiang, Chun-Pin; Huang, Zheng; Lee, Jeng-Woei; Liu, Chung-Ji; Chang, Junn-Liang; Hsu, Yih-Chih

2014-09-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL). Precancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots. Fluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (plevel. Topical CAL can improve the efficacy of ALA-PDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production. Copyright © 2014 Elsevier B.V. All rights reserved.

The scorpion toxin Bot IX is a potent member of the α-like family and has a unique N-terminal sequence extension.

Science.gov (United States)

Martin-Eauclaire, Marie-France; Salvatierra, Juan; Bosmans, Frank; Bougis, Pierre E

2016-09-01

We report the detailed chemical, immunological and pharmacological characterization of the α-toxin Bot IX from the Moroccan scorpion Buthus occitanus tunetanus venom. Bot IX, which consists of 70 amino acids, is a highly atypical toxin. It carries a unique N-terminal sequence extension and is highly lethal in mice. Voltage clamp recordings on oocytes expressing rat Nav1.2 or insect BgNav1 reveal that, similar to other α-like toxins, Bot IX inhibits fast inactivation of both variants. Moreover, Bot IX belongs to the same structural/immunological group as the α-like toxin Bot I. Remarkably, radioiodinated Bot IX competes efficiently with the classical α-toxin AaH II from Androctonus australis, and displays one of the highest affinities for Nav channels. © 2016 Federation of European Biochemical Societies.

Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

International Nuclear Information System (INIS)

Oesterud, B.; Rapaport, S.I.

Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

Motives and periods in Bianchi IX gravity models

Science.gov (United States)

Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

2018-05-01

We show that, when considering the anisotropic scaling factors and their derivatives as affine variables, the coefficients of the heat-kernel expansion of the Dirac-Laplacian on SU(2) Bianchi IX metrics are algebro-geometric periods of motives of complements in affine spaces of unions of quadrics and hyperplanes. We show that the motives are mixed Tate and we provide an explicit computation of their Grothendieck classes.

Compact invariant sets of the Bianchi VIII and Bianchi IX Hamiltonian systems

International Nuclear Information System (INIS)

Starkov, Konstantin E.

2011-01-01

In this Letter we prove that all compact invariant sets of the Bianchi VIII Hamiltonian system are contained in the set described by several simple linear equalities and inequalities. Moreover, we describe invariant domains in which the phase flow of this system has no recurrence property and show that there are no periodic orbits and neither homoclinic, nor heteroclinic orbits contained in the zero level set of its Hamiltonian. Similar results are obtained for the Bianchi IX Hamiltonian system. -- Highlights: → Zero level set of Hamiltonian of Bianchi VIII/IX systems contains no periodic orbits. → Similar conditions for homoclinic/heteroclinic orbits are given. → General nonexistence conditions of compact invariant sets are got.

Compact invariant sets of the Bianchi VIII and Bianchi IX Hamiltonian systems

Energy Technology Data Exchange (ETDEWEB)

Starkov, Konstantin E., E-mail: konst@citedi.mx [CITEDI-IPN, Av. del Parque 1310, Mesa de Otay, Tijuana, BC (Mexico)

2011-08-22

In this Letter we prove that all compact invariant sets of the Bianchi VIII Hamiltonian system are contained in the set described by several simple linear equalities and inequalities. Moreover, we describe invariant domains in which the phase flow of this system has no recurrence property and show that there are no periodic orbits and neither homoclinic, nor heteroclinic orbits contained in the zero level set of its Hamiltonian. Similar results are obtained for the Bianchi IX Hamiltonian system. -- Highlights: → Zero level set of Hamiltonian of Bianchi VIII/IX systems contains no periodic orbits. → Similar conditions for homoclinic/heteroclinic orbits are given. → General nonexistence conditions of compact invariant sets are got.

Immunosuppressive effects of factor IX products: an in vitro study.

Science.gov (United States)

Grosset, A B; McGregor, J R; Samlowski, W E; Rodgers, G M

1999-11-01

The effects of a recombinant factor IX product (BeneFix), and of five plasma-derived factor IX products, AlphaNine, Immunine, Konyne, Mononine and Replinine on in vitro peripheral blood mononuclear cell (PBMC) immune function were compared in a blinded study. We assessed the effects of these products on Con-A-induced lymphocyte proliferation and interleukin-2 and interleukin-10 secretion, expression of lymphocyte activation markers, and nitric oxide secretion by stimulated mouse peritoneal macrophages. At 1 mL-1 for 48 h, Konyne reduced Con-A-induced mitogenesis by 50% (P < 0.05); AlphaNine, Mononine and BeneFix had no effect. At 10 IU mL-1, Con-A-induced mi- togenesis was at control levels with Mononine and BeneFix, but was reduced to <15% (P < 0.05) with each of the other products. IL-2 and IL-10 secretion by Con-A-stimulated lymphocytes was also markedly depressed by all the products tested except Mononine and BeneFix. Dialysis of these products did not substantially affect these results. Flow cytometric analysis of lymphocyte activation markers following Con-A stimulation showed that Konyne also decreased IL-2 receptor alpha and beta chain (CD25 and CD122) induction on PBMC. Konyne also inhibited nitric oxide secretion to levels <18% of controls. These results indicate that certain factor IX products, including some of purported higher purity, substantially depress in vitro immune function. The importance of these findings to in vivo immune function in haemophilia B patients remains to be established.

Ares I-X Flight Test Philosophy

Science.gov (United States)

Davis, S. R.; Tuma, M. L.; Heitzman, K.

2007-01-01

In response to the Vision for Space Exploration, the National Aeronautics and Space Administration (NASA) has defined a new space exploration architecture to return humans to the Moon and prepare for human exploration of Mars. One of the first new developments will be the Ares I Crew Launch Vehicle (CLV), which will carry the Orion Crew Exploration Vehicle (CEV), into Low Earth Orbit (LEO) to support International Space Station (ISS) missions and, later, support lunar missions. As part of Ares I development, NASA will perform a series of Ares I flight tests. The tests will provide data that will inform the engineering and design process and verify the flight hardware and software. The data gained from the flight tests will be used to certify the new Ares/Orion vehicle for human space flight. The primary objectives of this first flight test (Ares I-X) are the following: Demonstrate control of a dynamically similar integrated Ares CLV/Orion CEV using Ares CLV ascent control algorithms; Perform an in-flight separation/staging event between an Ares I-similar First Stage and a representative Upper Stage; Demonstrate assembly and recovery of a new Ares CLV-like First Stage element at Kennedy Space Center (KSC); Demonstrate First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics and parachute performance; and Characterize the magnitude of the integrated vehicle roll torque throughout the First Stage (powered) flight. This paper will provide an overview of the Ares I-X flight test process and details of the individual flight tests.

Dynamic of exact perturbations in Bianchi IX type cosmological models

International Nuclear Information System (INIS)

Mello Neto, J.R.T. de.

1985-01-01

The dynamic of Bianchi IX type cosmological models is studied, after reducing Einstein equations to Hamiltonian system. Using the Melnikov method, the existence of chaos in the dynamic of these models is proved, and some numerical experiments are carried out. (M.C.K.) [pt

Long-sustaining response in a patient with non-resectable, distant recurrence of glioblastoma multiforme treated by interstitial photodynamic therapy using 5-ALA: case report.

Science.gov (United States)

Stummer, Walter; Beck, Tobias; Beyer, Wolfgang; Mehrkens, Jan Hendrik; Obermeier, Andreas; Etminan, Nima; Stepp, Herbert; Tonn, Jörg-Christian; Baumgartner, Reinhold; Herms, Jochen; Kreth, Friedrich Wilhelm

2008-03-01

Glioblastoma multiforme continues to be a devastating disease despite modest improvements in survival achieved at present, and there is an urgent need for innovative treatment concepts. Five-aminolevulinic acid (ALA) is a drug which induces protoporphyrin IX accumulation in malignant gliomas and has been explored for fluorescence-guided resections of these tumors. ALA is also under investigation as a photosensitizer. We report a case of a patient with prior left frontal glioblastoma multiforme treated by surgery, radiation and chemotherapy, who developed a remote lesion in the left insula, which was refractory to secondary treatments. In a compassionate use setting she was treated by oral application of ALA (20 mg/kg bodyweight), and stereotactic phototherapy achieved by positioning four laser diffusors using 3-dimensional irradiation planning, and a 633 nm diode laser. The lesion disappeared 24 h after therapy. Circumferential contrast enhancement was observed at 72 h, which disappeared in the course of subsequent months. Edema resolved completely. The patient is still free of recurrence 56 months after treatment, demonstrating an impressive and long-lasting response to this novel mode of therapy.

Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

Science.gov (United States)

Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

2005-04-01

During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

Science.gov (United States)

Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

1995-01-01

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1

Developing a New Sampling And Analysis Method For Hydrazine And Monomethyl Hydrazine: Using a Derivatizing Agent With Solid Phase Microextraction

Science.gov (United States)

Allen, John

2001-01-01

Solid phase microextraction (SPME) will be used to develop a method for detecting monomethyl hydrazine (MMH) and hydrazine (Hz). A derivatizing agent, pentafluorobenzoyl chloride (PFBCI), is known to react readily with MMH and Hz. The SPME fiber can either be coated with PFBCl and introduced into a gaseous stream containing MMH, or PFBCl and MMH can react first in a syringe barrel and after a short equilibration period a SPME is used to sample the resulting solution. These methods were optimized and compared. Because Hz and MMH can degrade the SPME, letting the reaction occur first gave better results. Only MMH could be detected using either of these methods. Future research will concentrate on constructing calibration curves and determining the detection limit.

Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy

DEFF Research Database (Denmark)

Bay, Christiane; Lerche, Catharina Margrethe; Ferrick, Bradford

2017-01-01

completed the study protocol. Interventions: Participants were each exposed to standardized skin preparation with curettage, microdermabrasion with abrasive pads, microneedling with dermarollers, ablative fractional laser (AFXL), non-AFXL, and no pretreatment, followed by 3 hours of methyl aminolevulinate...... curettage and microdermabrasion and similar vertical penetration depths for microneedling, AFXL, and non-AFXL (median, 125 μm). PPIX fluorescence reached highest intensities in skin pretreated with AFXL (median, 8661 arbitrary units [AU]) compared with microdermabrasion (median, 6731 AU), microneedling....... Conclusions and Relevance: Under standardized conditions, PPIX accumulation was most enhanced after AFXL pretreatment, followed by microdermabrasion, microneedling, and curettage. Increasing the number of pretreatment passes and laser densities did not further augment PPIX accumulation. These results may...

Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

Science.gov (United States)

Chen, Xiaoyan; Lane, Stephen

2010-02-01

We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

IX Congress of Spanish radiation protection Society (Bilbao, May-2002)

International Nuclear Information System (INIS)

2002-01-01

The present book contains the papers presented to the IX Congress of Spanish Radiation Protection Society. The main sessions were : 1.- Scientific area of Radiation Protection and Regulation, Social aspects, Radioactive waste management and Dismantling. 2.- Radiation protection in Medical applications. 3.- Physics of radiations and their measurements

The Protective Role of Carbon Monoxide (CO Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO

Directory of Open Access Journals (Sweden)

Katarzyna Magierowska

2016-03-01

Full Text Available Carbon monoxide (CO produced by heme oxygenase (HO-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II dimer (CORM-2 causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g., RuCl3 (1 mg/kg i.g., zinc protoporphyrin IX (ZnPP (10 mg/kg intraperitoneally (i.p., hemin (1–10 mg/kg i.g. and CORM-2 (1 mg/kg i.g. combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p., 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p., indomethacin (5 mg/kg i.p., SC-560 (5 mg/kg i.g., and celecoxib (10 mg/kg i.g. affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS. Gastric blood flow (GBF, the number of gastric lesions and gastric CO and nitric oxide (NO contents, blood carboxyhemoglobin (COHb level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α, tumor necrosis factor α (TNF-α, cyclooxygenase (COX-2 and inducible NO synthase (iNOS were determined. CORM-2 (1 mg/kg i.g. and hemin (10 mg/kg i.g. significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO.

"To Study the Relationship of Academic Stress and Socio-Economic Status among IX Standard Students of Raipur City"

Science.gov (United States)

Khan, Suhail Ahmed; Ayyub, Khan Farhat

2013-01-01

This paper focuses on the relationship between academic stress and socio-economic status among IX standard students. The research was carried out in Raipur City (Chhattisgarh) on a sample of 600 IX standard students of English and Hindi medium schools. Academic Stress was measured by Stress Inventory for School Students prepared by Seema Rani…

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer.

Science.gov (United States)

Buchlis, George; Podsakoff, Gregory M; Radu, Antonetta; Hawk, Sarah M; Flake, Alan W; Mingozzi, Federico; High, Katherine A

2012-03-29

In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.

Analyses of the Sn IX-Sn XII spectra in the EUV region

International Nuclear Information System (INIS)

Churilov, S S; Ryabtsev, A N

2006-01-01

The Sn IX-Sn XII spectra excited in a vacuum spark have been analysed in the 130-160 A wavelength region. The analysis was based on the energy parameter extrapolation in the isonuclear Sn VI-VIII and Sn XIII-XIV sequence. 266 spectral lines belonging to the 4d m -(4d m-1 4f+4p 5 4d m+1 ) (m=6-3) transition arrays were classified in the Sn IX-Sn XII spectra for the first time. All 18 level energies of the 4d 3 configuration and 39 level energies of the strongly interacting 4d 2 4f and 4p 5 4d 4 configurations were established in the Sn XII spectrum. The energy differences between the majority of the 4d m levels and about 40 levels of the 4d m-1 4f+4p 5 4d m+1 configurations were determined in each of the Sn IX, Sn X and Sn XI spectra (m=6-4). As a result, all intense lines were classified in the 130-140 A region relevant to the extreme ultraviolet (EUV) lithography. It was shown that the most of the intense lines in the 2% bandwidth at 135 A belong to the transitions in the Sn XI-Sn XIII spectra

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

Directory of Open Access Journals (Sweden)

Massimo Collino

2013-07-01

We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

Science.gov (United States)

Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

2013-07-01

We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

Lacerations to Zones VIII and IX: It Is Not Just a Tendon Injury

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Charla R. Fischer

2011-01-01

Full Text Available Extensor tendon injuries are widely believed to be straightforward problems that are relatively simple to manage. However, these injuries can be complex and demand a thorough understanding of anatomy to achieve the best functional outcomes. When lacerations occur in the forearm as in Zones VIII and IX injury, the repair of the extensor tendon and muscle, and posterior interosseous nerve (PIN is often challenging. A review of the literature shows little guidance and attention for these injuries. We present four patients with injuries to Zones VIII and IX as well as a review of surgical technique, postoperative rehabilitation, and pearls that may be of benefit to those managing these injuries.

Two novel mutations in the PPIB gene cause a rare pedigree of osteogenesis imperfecta type IX.

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Jiang, Yu; Pan, Jingxin; Guo, Dongwei; Zhang, Wei; Xie, Jie; Fang, Zishui; Guo, Chunmiao; Fang, Qun; Jiang, Weiying; Guo, Yibin

2017-06-01

Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder characterized by increased bone fragility and vulnerability to fractures. PPIB is identified as a candidate gene for OI-IX, here we detect two pathogenic mutations in PPIB and analyze the genotype-phenotype correlation in a Chinese family with OI. Next-generation sequencing (NGS) was used to screen the whole exome of the parents of proband. Screening of variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations. Sanger sequencing was used to confirm the candidate variants. RTQ-PCR was used to analyze the PPIB gene expression. All mutant genes screened out by NGS were excluded except PPIB. Two novel heterozygous PPIB mutations (father, c.25A>G; mother, c.509G>A) were identified in relation to osteogenesis imperfecta type IX. Both mutations were predicted to be pathogenic by bioinformatics analysis and RTQ-PCR analysis revealed downregulated PPIB expression in the two carriers. We report a rare pedigree with an autosomal recessive osteogenesis imperfecta type IX (OI-IX) caused by two novel PPIB mutations identified for the first time in China. The current study expands our knowledge of PPIB mutations and their associated phenotypes, and provides new information on the genetic defects associated with this disease for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

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Kimura, Makoto; Kashikura, Kasumi; Yokoi, Satomi; Koiwa, Yumiko; Tokuoka, Yoshikazu; Kawashima, Norimichi

We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm2, for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1-32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm2), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.

Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

Science.gov (United States)

Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

2016-03-31

There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro

Science.gov (United States)

Helander, Linda; Krokan, Hans E.; Johnsson, Anders; Gederaas, Odrun A.; Plaetzer, Kristjan

2014-08-01

Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT624 induced more apoptosis than HAL-PDT410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro.

Science.gov (United States)

Helander, Linda; Krokan, Hans E; Johnsson, Anders; Gederaas, Odrun A; Plaetzer, Kristjan

2014-08-01

Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT₆₂₄ induced more apoptosis than HAL-PDT₄₁₀ and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

Evidence of mutualism between two periodontal pathogens: co-operative haem acquisition by the HmuY haemophore of Porphyromonas gingivalis and the cysteine protease interpain A (InpA) of Prevotella intermedia.

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Byrne, D P; Potempa, J; Olczak, T; Smalley, J W

2013-06-01

Haem (iron protoporphyrin IX) is both an essential growth factor and a virulence regulator of the periodontal pathogens Porphyromonas gingivalis and Prevotella intermedia, which acquire it through the proteolytic degradation of haemoglobin and other haem-carrying plasma proteins. The haem-binding lipoprotein HmuY haemophore and the gingipain proteases of P. gingivalis form a unique synthrophic system responsible for capture of haem from haemoglobin and methaemalbumin. In this system, methaemoglobin is formed from oxyhaemoglobin by the activities of gingipain proteases and serves as a facile substrate from which HmuY can capture haem. This study examined the possibility of cooperation between HmuY and the cysteine protease interpain A (InpA) of Pr. intermedia in the haem acquisition process. Using UV-visible spectroscopy and polyacrylamide gel electrophoresis, HmuY was demonstrated to be resistant to proteolysis and so able to cooperate with InpA to extract haem from haemoglobin, which was proteolytically converted to methaemoglobin by the protease. Spectroscopic pH titrations showed that both the iron(II) and iron(III) protoporphyrin IX-HmuY complexes were stable over the pH range 4-10, demonstrating that the haemophore could function over a range of pH that may be encountered in the dental plaque biofilm. This is the first demonstration of a bacterial haemophore working in conjunction with a protease from another bacterial species to acquire haem from haemoglobin and may represent mutualism between P. gingivalis and Pr. intermedia co-inhabiting the periodontal pocket. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

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Wang X

2015-01-01

Full Text Available Xiaojie Wang,1,2,* Lei Shi,2,* Qingfeng Tu,2 Hongwei Wang,3 Haiyan Zhang,2 Peiru Wang,2 Linglin Zhang,2 Zheng Huang,4 Feng Zhao,5 Hansen Luan,5 Xiuli Wang2 1Shanghai Skin Diseases Clinical College of Anhui Medical University, 2Shanghai Skin Disease Hospital, 3Huadong Hospital, Fudan University, Shanghai, 4MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, 5National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People’s Republic of China *These authors contributed equally to this study Background: Squamous cell carcinoma (SCC is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP-assisted 5-aminolevulinic acid (ALA delivery for topical photodynamic therapy (PDT of cutaneous SCC.Materials and methods: Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.Results: PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC.Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. Keywords: 5-aminolevulinic acid (ALA, polylactic-co-glycolic acid (PLGA, nanoparticles (NPs, cutaneous squamous cell carcinoma (SCC, photodynamic therapy (PDT, microneedling

No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.

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Steinkellner, Hannes; Singh, Himanshu Narayan; Muckenthaler, Martina U; Goldenberg, Hans; Moganty, Rajeswari R; Scheiber-Mojdehkar, Barbara; Sturm, Brigitte

2017-07-20

Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported. Copyright © 2017 Elsevier B.V. All rights reserved.

Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts

Science.gov (United States)

Fakhar-E-Alam, Muhammad; Akram, M. Waseem; Iqbal, Seemab; Alimgeer, K. S.; Atif, M.; Sultana, K.; Willander, M.; Wang, Zhiming M.

2017-04-01

Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

Science.gov (United States)

Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

2015-05-01

There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

Synthesis and biological evaluation of porphyrin-polyamine conjugates as potential agents in photodynamic therapy

International Nuclear Information System (INIS)

Lamarche, Francois

2004-01-01

The synthesis of photosensitizers that specifically recognize tumoral cells constitutes a challenging step in the field of photodynamic therapy. To this end, we designed a new class of porphyrins linked to natural polyamines (spermidine, spermine). As a first step, we synthesized para and ortho-carboxy-propyl-oxy-phenyl-tritolyl-porphyrins bearing spermidine or spermine. Then, we designed two precursors, N4-aminobutyl-spermidine-Boc2 and N4-aminobutyl-spermine-Boc3. These derivatives have been fixed on carboxy-porphyrins, protoporphyrin IX and chlorin e6. These new compounds have been characterized by MALDI spectrometry, UV-Visible and 1 H NMR spectroscopy. They have been found to produce singlet oxygen. Biological activity study of these photosensitizers has been realized on K562 cell line, irradiated with fluorescent bulbs. In vitro tests of these porphyrins have shown their photo-cytotoxic activity and protoporphyrins-polyamines have been able to trigger early apoptotic events. Finally, preliminary results obtained with chlorin e6-polyamines, irradiated with red light, seem to show that these structures are good candidates for an application in PDT. (author) [fr

Sex Discrimination and Intercollegiate Athletics: Putting Some Muscle on Title IX.

Science.gov (United States)

Yale Law Journal, 1979

1979-01-01

Argues that the general language of the Title IX statute, together with certain specific features of it, strongly suggests that the Department of Health, Education, and Welfare should develop more stringent and demanding regulations based on social policy considerations concerning sex discrimination in intercollegiate sports. Available from Yale…

Aplikasi Peta Kendali p sebagai Pengendalian Kualitas Karet di PTPN IX Batujamus/Kerjoarum

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Isti Khomah

2016-03-01

Full Text Available The increasing of global rubber consumption is an opportunity as well as a challenge for Indonesian rubber produsers to increase the quantity and the quality of production. Faced the competition between countries, the quality of rubber products should be enhanced adapted to consumer demand. This study aims to determine whether the quality of the rubber produced in PTPN IX (Persero Garden Batujamus/Kerjoarum still within the control or not. This study uses time series data, in the form of rubber production data during March 2012 - February 201, that were analyzed descriptively using Control p Chart Analysis. Control p Chart describe the proportion of production damage that can be tolerated as a tool for statistical Control p Chart Application as Quality Control Tools for Rubber Production in PTPN IX Batujamus/Kerjoarum process control. This study shows that the quality of the rubber produced by PTPN IX (Persero Garden Batujamus/ Kerjoarum is out of the control. The Control p Chart proves that there are still many points that are outside the production control line. The production domination of the third RSS type (RSS 3 cause this problem, so that the profit and the efficiency of the company can be increased if the RSS 3 product can be controlled and be changed with the production of RSS 1.

Collateral patient doses in the Varian 21iX radiotherapy Linac

International Nuclear Information System (INIS)

Barquero, R.; Castillo, A. del

2008-01-01

Full text: The radiotherapy aim is to irradiate the patient tumor cells while the doses in healthy tissue remains as low as possible. Nevertheless, when high photon energy accelerators are used, collateral undesired photon and neutron doses are always implied during the treatments and became more important with the new accelerators and techniques as IMRT. To assess secondary cancer risk outside the treatment volume as a long-term medical consequence of treatments, the total doses received by each patient outside the primary field during his treatment must be estimated. To achieve this purpose photon and neutron dose equivalents Hp(10) and H*(10) has been measured in a new Varian 21iX with maximum photon energy of 15 MV placed recently in our radiotherapy department. Three devices: 1) a neutron dose rate meter BERTHOLD LB 4111 calibrated recently in the German PTB laboratory, 2) a calibrated environmental pressurized photon ionization chamber (IC) VICTOREEN 450-PI n/s 1020, and 3) a calibrated personal electronic photon dosimeter GAMMACOM 4200M, were placed above the treatment couch outside the primary field while the Varian 21iX reference test were done. In particular the photon and neutron doses in the couch were measured while a water phantom was irradiated during automatic beam data acquisition for a 15 MV beam. A complete set of measurements changing field size are made. These 15 MV results are compared with data measured previously by thermoluminescence and bubble dosimeters in the same facility for an Elekta Precise and a Siemens KDS both with maximum photon energy of 18 MV. From this the benefits in the patient collateral doses of decreasing the maximum treatment photon energy are discussed. The patient doses obtained in the Varian 21iX had values that go from 80 to 800 uSv per treatment Gray. As the Varian 21iX therapy Linac is operated in pulsed mode with short pulse length the discussion of the results includes: 1. The correction of dead time in the GM

Fe IX CALCULATIONS FOR THE SOLAR DYNAMICS OBSERVATORY

International Nuclear Information System (INIS)

Foster, Adam R.; Testa, Paola

2011-01-01

New calculations of the energy levels, radiative transition rates, and collisional excitation rates of Fe IX have been carried out using the Flexible Atomic Code, paying close attention to experimentally identified levels and extending existing calculations to higher energy levels. For lower levels, R-matrix collisional excitation rates from earlier work have been used. Significant emission is predicted by these calculations in the 5f-3d transitions, which will impact analysis of Solar Dynamics Observatory Atmospheric Imaging Assembly observations using the 94 A filter.

Bianchi Type-IX viscous fluid cosmological model in general relativity

Indian Academy of Sciences (India)

the de-Sitter universe, the Taub-NUT solutions etc. are of Bianchi Type-IX space- times. In these models, neutrino viscosity does not guarantee isotropy at the present ..... The model (2.11) starts with a big-bang at T = 0 where α > 0 and m < 2, and the expansion in the model decreases as time increases. The expansion in the ...

Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting

International Nuclear Information System (INIS)

Campos, Samuel K.; Barry, Michael A.

2006-01-01

The direct genetic modification of adenoviral capsid proteins with new ligands is an attractive means to confer targeted tropism to adenoviral vectors. Although several capsid proteins have been reported to tolerate the genetic fusion of foreign peptides and proteins, direct comparison of cell targeting efficiencies through the different capsomeres has been lacking. Likewise, direct comparison of with one or multiple ligands has not been performed due to a lack of capsid-compatible ligands available for retargeting. Here we utilize a panel of metabolically biotinylated Ad vectors to directly compare targeted transduction through the fiber, protein IX, and hexon capsomeres using a variety of biotinylated ligands including antibodies, transferrin, EGF, and cholera toxin B. These results clearly demonstrate that cell targeting with a variety of high affinity receptor-binding ligands is only effective when transduction is redirected through the fiber protein. In contrast, protein IX and hexon-mediated targeting by the same set of ligands failed to mediate robust vector targeting, perhaps due to aberrant trafficking at the cell surface or inside targeted cells. These data suggest that vector targeting by genetic incorporation of high affinity ligands will likely be most efficient through modification of the adenovirus fiber rather than the protein IX and hexon capsomeres. In contrast, single-step monomeric avidin affinity purification of Ad vectors using the metabolic biotinylation system is most effective through capsomeres like protein IX and hexon

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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Marcelo Zerati

2013-07-01

Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

Evaluation of a gadolinium-based nanoparticle (AGuIX) for contrast-enhanced MRI of the liver in a rat model of hepatic colorectal cancer metastases at 9.4 tesla

Energy Technology Data Exchange (ETDEWEB)

Fries, P.; Morr, D.; Mueller, A.; Massmann, A.; Seidel, R.; Schneider, G.; Buecker, A. [Saarland University Medical Center, Homburg (Germany). Clinic of Diagnostic and Interventional Radiology; Lux, F.; Tillement, O. [Universite Claude Bernard, Lyon (France). Laboratoire de Physico-Chimie des Materiaux Luminescents; Schaefer, T. [Saarland University Medical Center, Homburg (Germany). Dept. of General, Visceral and Pediatric Surgery; Menger, M.D. [Saarland University Medical Center, Homburg (Germany). Inst. for Clinical and Experimental Surgery

2015-12-15

The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE=45/2.5 ms, alpha = 45 , TA=1: 23 min, FOV=5.12 x 5.12 cm{sup 2}, matrix = 256 x 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 ± 0.7; AGuIX: 28.2 ± 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 ± 1.2; AGuIX: 29.6 ± 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 ± 0.7; AGuIX: 15.4 ± 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 ± 0.3; AGuIX: 14.0 ± 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 ± 0.2; AGuIX: -7.5 ± 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 ± 0.7; AGuIX: 14.9 ± 2.8, p=0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors.

Evaluation of a gadolinium-based nanoparticle (AGuIX) for contrast-enhanced MRI of the liver in a rat model of hepatic colorectal cancer metastases at 9.4 tesla

International Nuclear Information System (INIS)

Fries, P.; Morr, D.; Mueller, A.; Massmann, A.; Seidel, R.; Schneider, G.; Buecker, A.; Lux, F.; Tillement, O.; Schaefer, T.; Menger, M.D.

2015-01-01

The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE=45/2.5 ms, alpha = 45 , TA=1: 23 min, FOV=5.12 x 5.12 cm 2 , matrix = 256 x 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 ± 0.7; AGuIX: 28.2 ± 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 ± 1.2; AGuIX: 29.6 ± 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 ± 0.7; AGuIX: 15.4 ± 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 ± 0.3; AGuIX: 14.0 ± 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 ± 0.2; AGuIX: -7.5 ± 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 ± 0.7; AGuIX: 14.9 ± 2.8, p=0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

International Nuclear Information System (INIS)

Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T

2013-01-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

The Future of Electronic Power Processing and Conversion: Highlights from FEPPCON IX

DEFF Research Database (Denmark)

Enslin, Johan H.; Blaabjerg, Frede; Tan, Don F.D.

2017-01-01

Since 1991, every second year the IEEE Power Electronics Society (PELS) has organized the technical long-range planning meeting "Future of Electronic Power Processing and Conversion" (FEPPCON). FEPPCON IX was held 12-16 June 2017 in beautiful Kruger Park in South Africa (Figure 1). The overall go...

Development of nitric oxide sensor for asthma attack prevention

International Nuclear Information System (INIS)

Vilar, M. Rei; El-Beghdadi, J.; Debontridder, F.; Naaman, R.; Arbel, A.; Ferraria, A.M.; Do Rego, A.M. Botelho

2006-01-01

The aim of this work is the development of a NO sensor for asthma control and medication monitoring. The transducer is a Molecular Controlled Semiconductor Resistor (MOCSER), which is a GaAs based heterostructure. Protoporphyrins IX, containing carboxylic groups to chemisorb on GaAs, were used as sensing molecules. Characterization of the protoporphyrin monolayers was held using Attenuated Total Reflection in Multiple Internal Reflection (ATR/MIR), High Resolution Electron Energy Loss Spectroscopy (HREELS) in the vibrational and electronic domain and X-ray Photoelectron Spectroscopy (XPS). Degreasing and etching of the GaAs substrates were accomplished before adsorption. Interfacial bonding investigated by ATR/MIR shows that protoporphyrin adsorbs to the GaAs (100) through a unidentate complex and remains mostly vertically oriented. The electronic domain of the HREELS spectra exhibits the Q band with α and β components on the same position as in the UV/Vis spectrum. Soret band is blue shifted showing a face to face stacking of the protoporphyrin molecules on the GaAs substrates. XPS spectra reveal the presence of Cobalt in monolayers prepared with 8 x 10 -5 M CoPP solutions. Kinetics is best fitted by an Elovich equation, showing some hindrance due to the previous adsorbed molecules. Thickness found from XPS data ranges from 1.3 to 1.5 nm, which fits with the molecular dimensions. Using the GaAs preparation methods developed here, an NO sensor prototype was assembled and tested for NO sensitivity and repeatability. Relative to NO, tests reveal a good sensitivity between 1.6 and 200 ppb. NO sensitivity was also measured towards CO, CO 2 and O 2 . Pure nitrogen sweeps NO from the porphyrin layer, opening the possibility of the sensor reutilization

Development of nitric oxide sensor for asthma attack prevention

Energy Technology Data Exchange (ETDEWEB)

Vilar, M. Rei [ITODYS, CNRS-Universite Denis Diderot, Paris (France)]. E-mail: reivilar@paris7.jussieu.fr; El-Beghdadi, J. [ITODYS, CNRS-Universite Denis Diderot, Paris (France); Debontridder, F. [ITODYS, CNRS-Universite Denis Diderot, Paris (France); Naaman, R. [Department of Chemical Physics, Weizmann Institute, Rehovot (Israel); Arbel, A. [Chiaro Networks, Jerusalem (Israel); Ferraria, A.M. [CQFM, Instituto Superior Tecnico, Lisboa (Portugal); Do Rego, A.M. Botelho [CQFM, Instituto Superior Tecnico, Lisbon (Portugal)

2006-03-15

The aim of this work is the development of a NO sensor for asthma control and medication monitoring. The transducer is a Molecular Controlled Semiconductor Resistor (MOCSER), which is a GaAs based heterostructure. Protoporphyrins IX, containing carboxylic groups to chemisorb on GaAs, were used as sensing molecules. Characterization of the protoporphyrin monolayers was held using Attenuated Total Reflection in Multiple Internal Reflection (ATR/MIR), High Resolution Electron Energy Loss Spectroscopy (HREELS) in the vibrational and electronic domain and X-ray Photoelectron Spectroscopy (XPS). Degreasing and etching of the GaAs substrates were accomplished before adsorption. Interfacial bonding investigated by ATR/MIR shows that protoporphyrin adsorbs to the GaAs (100) through a unidentate complex and remains mostly vertically oriented. The electronic domain of the HREELS spectra exhibits the Q band with {alpha} and {beta} components on the same position as in the UV/Vis spectrum. Soret band is blue shifted showing a face to face stacking of the protoporphyrin molecules on the GaAs substrates. XPS spectra reveal the presence of Cobalt in monolayers prepared with 8 x 10{sup -5} M CoPP solutions. Kinetics is best fitted by an Elovich equation, showing some hindrance due to the previous adsorbed molecules. Thickness found from XPS data ranges from 1.3 to 1.5 nm, which fits with the molecular dimensions. Using the GaAs preparation methods developed here, an NO sensor prototype was assembled and tested for NO sensitivity and repeatability. Relative to NO, tests reveal a good sensitivity between 1.6 and 200 ppb. NO sensitivity was also measured towards CO, CO{sub 2} and O{sub 2}. Pure nitrogen sweeps NO from the porphyrin layer, opening the possibility of the sensor reutilization.

PHKA2 mutation spectrum in Korean patients with glycogen storage disease type IX: prevalence of deletion mutations.

Science.gov (United States)

Choi, Rihwa; Park, Hyung-Doo; Kang, Ben; Choi, So Yoon; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Jong-Won; Song, Junghan; Choe, Yon Ho

2016-04-21

Molecular diagnosis of glycogen storage diseases (GSDs) is important to enable accurate diagnoses and make appropriate therapeutic plans. The aim of this study was to evaluate the PHKA2 mutation spectrum in Korean patients with GSD type IX. Thirteen Korean patients were tested for PHKA2 mutations using direct sequencing and a multiplex polymerase chain reaction method. A comprehensive review of the literature on previously reported PHKA2 mutations in other ethnic populations was conducted for comparison. Among 13 patients tested, six unrelated male patients with GSD IX aged 2 to 6 years at the first diagnostic work-up for hepatomegaly with elevated aspartate transaminase (AST) and alanine transaminase (ALT) were found to have PHKA2 mutations. These patients had different PHKA2 mutations: five were known mutations (c.537 + 5G > A, c.884G > A [p.Arg295His], c.3210_3212delGAG [p.Arg1072del], exon 8 deletion, and exons 27-33 deletion) and one was a novel mutation (exons 18-33 deletion). Notably, the most common type of mutation was gross deletion, in contrast to other ethnic populations in which the most common mutation type was sequence variant. This study expands our knowledge of the PHKA2 mutation spectrum of GSD IX. Considering the PHKA2 mutation spectrum in Korean patients with GSD IX, molecular diagnostic methods for deletions should be conducted in conjunction with direct sequence analysis to enable accurate molecular diagnosis of this disease in the Korean population.

Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients.

Science.gov (United States)

Martinowitz, U; Lissitchkov, T; Lubetsky, A; Jotov, G; Barazani-Brutman, T; Voigt, C; Jacobs, I; Wuerfel, T; Santagostino, E

2015-11-01

rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated. © 2015 CSL Behring. Haemophilia published by John Wiley & Sons Ltd.

Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

Indian Academy of Sciences (India)

In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the ... The self-bound state appears to be at ρ ... The observations suggest that the Hubble expansion of the Universe ... Taking motivation from.

Protective effect of hemin against cadmium-induced testicular damage in rats

International Nuclear Information System (INIS)

Fouad, Amr A.; Qureshi, Habib A.; Al-Sultan, Ali Ibrahim; Yacoubi, Mohamed T.; Ali, Abdellah Abusrie

2009-01-01

The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium

Signal Transduction Pathways that Regulate CAB Gene Expression

Energy Technology Data Exchange (ETDEWEB)

Chory, Joanne

2004-12-31

The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

Signal Transduction Pathways that Regulate CAB Gene Expression

Energy Technology Data Exchange (ETDEWEB)

Chory, Joanne

2006-01-16

The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

Studies of porphyrin-containing specimens using an optical spectrometer connected to a confocal scanning laser microscope.

Science.gov (United States)

Trepte, O; Rokahr, I; Andersson-Engels, S; Carlsson, K

1994-12-01

A spectrometer has been developed for use with a confocal scanning laser microscope. With this unit, spectral information from a single point or a user-defined region within the microscope specimen can be recorded. A glass prism is used to disperse the spectral components of the recorded light over a linear CCD photodiode array with 256 elements. A regulated cooling unit keeps the detector at 277 K, thereby allowing integration times of up to 60 s. The spectral resolving power, lambda/delta lambda, ranges from 350 at lambda = 400 nm to 100 at lambda = 700 nm. Since the entrance aperture of the spectrometer has the same size as the detector pinhole used during normal confocal scanning, the three-dimensional spatial resolution is equivalent to that of normal confocal scanning. Light from the specimen is deflected to the spectrometer by a solenoid controlled mirror, allowing fast and easy switching between normal confocal scanning and spectrometer readings. With this equipment, studies of rodent liver specimens containing porphyrins have been made. The subcellular localization is of interest for the mechanisms of photodynamic therapy (PDT) of malignant tumours. Spectroscopic detection is necessary to distinguish the porphyrin signal from other fluorescent components in the specimen. Two different substances were administered to the tissue, Photofrin, a haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), a precursor to protoporphyrin IX and haem in the haem cycle. Both are substances under clinical trials for PDT of malignant tumours. Following administration of these compounds to the tissue, the potent photosensitizer and fluorescent compound Photofrin, or protoporphyrin IX, respectively, is accumulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

Directory of Open Access Journals (Sweden)

Eva Zilian

Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

Heme metabolism as an integral part of iron homeostasis

Directory of Open Access Journals (Sweden)

Paweł Lipiński

2014-01-01

Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

[Heme metabolism as an integral part of iron homeostasis].

Science.gov (United States)

Lipiński, Paweł; Starzyński, Rafał R; Styś, Agnieszka; Gajowiak, Anna; Staroń, Robert

2014-01-02

Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

High-resolution Laboratory Measurements of Coronal Lines near the Fe IX Line at 171 Å

Science.gov (United States)

Beiersdorfer, Peter; Träbert, Elmar

2018-02-01

We present high-resolution laboratory measurements in the spectral region between 165 and 175 Å that focus on the emission from various ions of C, O, F, Ne, S, Ar, Fe, and Ni. This wavelength region is centered on the λ171 Fe IX channel of the Atmospheric Imaging Assembly on the Solar Dynamics Observatory, and we place special emphasis on the weaker emission lines of Fe IX predicted in this region. In general, our measurements show a multitude of weak lines missing in the current databases, where the emission lines of Ni are probably most in need of further identification and reclassification. We also find that the wavelengths of some of the known lines need updating. Using the multi-reference Møller–Plesset method for wavelength predictions and collisional-radiative modeling of the line intensities, we have made tentative assignments of more than a dozen lines to the spectrum of Fe IX, some of which have formerly been identified as Fe VII, Fe XIV, or Fe XVI lines. Several Fe features remain unassigned, although they appear to be either Fe VII or Fe X lines. Further work will be needed to complete and correct the spectral line lists in this wavelength region.

SU-E-T-238: Monte Carlo Estimation of Cerenkov Dose for Photo-Dynamic Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Chibani, O; Price, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Eldib, A [Fox Chase Cancer Center, Philadelphia, PA (United States); University Cairo (Egypt); Mora, G [de Lisboa, Codex, Lisboa (Portugal)

2014-06-01

Purpose: Estimation of Cerenkov dose from high-energy megavoltage photon and electron beams in tissue and its impact on the radiosensitization using Protoporphyrine IX (PpIX) for tumor targeting enhancement in radiotherapy. Methods: The GEPTS Monte Carlo code is used to generate dose distributions from 18MV Varian photon beam and generic high-energy (45-MV) photon and (45-MeV) electron beams in a voxel-based tissueequivalent phantom. In addition to calculating the ionization dose, the code scores Cerenkov energy released in the wavelength range 375–425 nm corresponding to the pick of the PpIX absorption spectrum (Fig. 1) using the Frank-Tamm formula. Results: The simulations shows that the produced Cerenkov dose suitable for activating PpIX is 4000 to 5500 times lower than the overall radiation dose for all considered beams (18MV, 45 MV and 45 MeV). These results were contradictory to the recent experimental studies by Axelsson et al. (Med. Phys. 38 (2011) p 4127), where Cerenkov dose was reported to be only two orders of magnitude lower than the radiation dose. Note that our simulation results can be corroborated by a simple model where the Frank and Tamm formula is applied for electrons with 2 MeV/cm stopping power generating Cerenkov photons in the 375–425 nm range and assuming these photons have less than 1mm penetration in tissue. Conclusion: The Cerenkov dose generated by high-energy photon and electron beams may produce minimal clinical effect in comparison with the photon fluence (or dose) commonly used for photo-dynamic therapy. At the present time, it is unclear whether Cerenkov radiation is a significant contributor to the recently observed tumor regression for patients receiving radiotherapy and PpIX versus patients receiving radiotherapy only. The ongoing study will include animal experimentation and investigation of dose rate effects on PpIX response.

Kinetic data bank for Ramona of the Siemens 9x9-IX

International Nuclear Information System (INIS)

Alonso V, G.

1993-12-01

With the purpose of making the transitory analyses of the Laguna Verde Nuclear Power station when Siemens fuel of the type 9x9-IX is used, proposed for the cycle 2 of the Unit 2, the kinetic data bank in hot condition for the Ramona code has been generated. (Author)

The Bianchi IX model in loop quantum cosmology

International Nuclear Information System (INIS)

Bojowald, Martin; Date, Ghanashyam; Hossain, Golam Mortuza

2004-01-01

The Bianchi IX model has been used often to investigate the structure close to singularities of general relativity. Its classical chaos is expected to have, via the BKL scenario, implications even for the approach to general inhomogeneous singularities. Thus, it is a popular model to test consequences of modifications to general relativity suggested by quantum theories of gravity. This paper presents a detailed proof that modifications coming from loop quantum gravity lead to a non-chaotic effective behaviour. The way this is realized, independently of quantization ambiguities, suggests a new look at initial and final singularities

Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

Science.gov (United States)

Wu, P C; Hamaguchi, N; Yu, Y S; Shen, M C; Lin, S W

2000-10-01

Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine

Controlled Vectorial Electron Transfer and Photoelectrochemical Applications of Layered Relay/Photosensitizer-Imprinted Au Nanoparticle Architectures on Electrodes.

Science.gov (United States)

Metzger, Tzuriel S; Tel-Vered, Ran; Willner, Itamar

2016-03-23

Two configurations of molecularly imprinted bis-aniline-bridged Au nanoparticles (NPs) for the specific binding of the electron acceptor N,N'-dimethyl-4,4'-bipyridinium (MV(2+) ) and for the photosensitizer Zn(II)-protoporphyrin IX (Zn(II)-PP-IX) are assembled on electrodes, and the photoelectrochemical features of the two configurations are discussed. Configuration I includes the MV(2+) -imprinted Au NPs matrix as a base layer, on which the Zn(II)-PP-IX-imprinted Au NPs layer is deposited, while configuration II consists of a bilayer corresponding to the reversed imprinting order. Irradiation of the two electrodes in the presence of a benzoquinone/benzohydroquinone redox probe yields photocurrents of unique features: (i) Whereas configuration I yields an anodic photocurrent, the photocurrent generated by configuration II is cathodic. (ii) The photocurrents obtained upon irradiation of the imprinted electrodes are substantially higher as compared to the nonimprinted surfaces. The high photocurrents generated by the imprinted Au NPs-modified electrodes are attributed to the effective loading of the imprinted matrices with the MV(2+) and Zn(II)-PP-IX units and to the effective charge separation proceeding in the systems. The directional anodic/cathodic photocurrents are rationalized in terms of vectorial electron transfer processes dictated by the imprinting order and by the redox potentials of the photosensitizer/electron acceptor units associated with the imprinted sites in the two configurations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estado de la investigacion en enfermería IX región de la Araucania, Temuco, Chile 2002 State of the research in nursing IX th region of the Araucania, Temuco, Chile 2002

Directory of Open Access Journals (Sweden)

Edith Elina Rivas Riveros

2005-09-01

Full Text Available El desarrollo de la investigación nos proyecta en la imagen de enfermera(o que queremos para el siglo XXI y el posicionamiento que tendremos. Esta imagen debe caracterizarse por intervenciones que demuestren calidad científica y humanización del cuidado. Las prácticas del cuidado, si bien son concebidas como una actividad práctica, necesitan de la actividad intelectual y de una masa crítica de investigadores e ideólogos que orienten las acciones, situación que debe fundamentarse en la evidencia. El propósito de esta investigación fue identificar, por medio de un estudio descriptivo, exploratorio y correlacional, el estado de la investigación en enfermería en la IX Región de la Araucania, Chile. Los objetivos específicos fueron analizar las condiciones en que se desarrolló el perfeccionamiento de las enfermeras en la IX Región y contribuir a la identificación de las líneas de investigación. El estudio recoge las características de los postgrados en enfermería en la IX Región, Chile: licenciatura, magíster y doctorado hasta el año 2002. Se concluye que en materia de enfoques predomina el positivista; las enfermeras están motivadas a perfeccionarse en programas de postgrado fundamen-talmente por razones de desarrollo personal y el deseo de contribuir a mejorar la profesión; quienes realizan estudios de postgrado se desempeñan en docencia en institutos y universidades, y la temática de las in-vestigaciones está básicamente orientada hacia la enseñanza de enfermería.The development of the investigation projected us in nurse’s image that we want for the XXI Century and the positioning that we will have. This image will be characterized by interventions that demonstrate scientific quality and humanization of the care. The practices of the care, although they are conceived as a practical activity, they need of the intellectual activity and of a critical mass of investigators and ideologists that guide the actions

Comparison of Ares I-X Wind-Tunnel Derived Buffet Environment with Flight Data

Science.gov (United States)

Piatak, David J.; Sekula, Martin K.; Rausch, Russ D.

2011-01-01

The Ares I-X Flight Test Vehicle (FTV), launched in October 2009, carried with it over 243 buffet verification pressure sensors and was one of the most heavily instrumented launch vehicle flight tests. This flight test represented a unique opportunity for NASA and its partners to compare the wind-tunnel derived buffet environment with that measured during the flight of Ares I-X. It is necessary to define the launch vehicle buffet loads to ensure that structural components and vehicle subsystems possess adequate strength, stress, and fatigue margins when the vehicle structural dynamic response to buffet forcing functions are considered. Ares I-X buffet forcing functions were obtained via wind-tunnel testing of a rigid buffet model (RBM) instrumented with hundreds of unsteady pressure transducers designed to measure the buffet environment across the desired frequency range. This paper discusses the comparison of RBM and FTV buffet environments, including fluctuating pressure coefficient and normalized sectional buffet forcing function root-mean-square magnitudes, frequency content of power-spectral density functions, and force magnitudes of an alternating flow phenomena. Comparison of wind-tunnel model and flight test vehicle buffet environments show very good agreement with root-mean-square magnitudes of buffet forcing functions at the majority of vehicle stations. Spectra proved a challenge to compare because of different wind-tunnel and flight test conditions and data acquisition rates. However, meaningful and promising comparisons of buffet spectra are presented. Lastly, the buffet loads resulting from the transition of subsonic separated flow to supersonic attached flow were significantly over-predicted by wind-tunnel results.

Broadband X-ray spectra of the ultraluminous x-ray source Holmberg IX X-1 observed with NuSTAR, XMM-Newton, and Suzaku

DEFF Research Database (Denmark)

Walton, D. J.; Harrison, F. A.; Grefenstette, B. W.

2014-01-01

We present results from the coordinated broadband X-ray observations of the extreme ultraluminous X-ray source Holmberg IX X-1 performed by NuSTAR, XMM-Newton, and Suzaku in late 2012. These observations provide the first high-quality spectra of Holmberg IX X-1 above 10 keV to date, extending the...

The detection of iron protoporphyrin (heme b) in phytoplankton and marine particulate material by electrospray ionisation mass spectrometry – comparison with diode array detection

Energy Technology Data Exchange (ETDEWEB)

Gledhill, Martha, E-mail: m.gledhill@geomar.de

2014-09-02

Highlights: • Mass spectrometry was applied to the analysis of heme b in biological material. • Optimal conditions involved selective reactant monitoring of the heme b product ion. • The isotopic signature for this iron tetrapyrrole further improved selectivity. • Mass spectrometry and spectrophotometry were compared for heme b analysis. • Combining techniques made a powerful tool for analysis of heme in marine microbes. - Abstract: A mass spectrometric (MS) method for the identification of iron protoporphyrin (IX) (FePTP, heme b) in marine particulate material and phytoplankton is described. Electrospray ionisation of FePTP produced the molecular Fe(III)PTP{sup +} ion (m/z = 616) or the pseudomolecular [Fe(II)PTP + H]{sup +} ion (m/z = 617), depending on the oxidation state of the central iron ion. Collision induced dissociation (CID) in the ion trap mass spectrometer resulted in a single detected product ion (m/z = 557) indicative of loss of ethanoic acid from a carboxylic acid side chain. Widening the isolation width to 616 ± 3 resulted in production of a mass spectrum demonstrating the distinctive isotopic ratio of the iron containing fragment, further increasing the specificity of the analysis. Selective reactant monitoring (SRM) of the fragment ion (m/z = 557) was applied to the detection of FePTP after chromatography of ammoniacal OGP extracts of marine samples. The detection limit for FePTP analysed by SRM after chromatography was 1.2 ± 0.5 fmol. For phytoplankton samples, reasonably good agreement was achieved between results obtained with SRM and those obtained by monitoring absorbance at λ = 400 nm using a diode array detector (DAD). Use of SRM for analysis of particulate material obtained from the high latitude North Atlantic allowed for the analysis of FePTP in the presence of a co-eluting compound that interfered with detection by DAD. Simultaneous collection of mass spectra from m/z = 300 to 1500 resulted in identification of the

Chlorin photosensitizers sterically designed to prevent self-aggregation.

Science.gov (United States)

Uchoa, Adjaci F; de Oliveira, Kleber T; Baptista, Mauricio S; Bortoluzzi, Adailton J; Iamamoto, Yassuko; Serra, Osvaldo A

2011-11-04

The synthesis and photophysical evaluation of new chlorin derivatives are described. The Diels-Alder reaction between protoporphyrin IX dimethyl ester and substituted maleimides furnishes endo-adducts that completely prevent the self-aggregation of the chlorins. Fluorescence, resonant light scattering (RLS) and (1)H NMR experiments, as well as X-ray crystallographic have demonstrated that the configurational arrangement of the synthesized chlorins prevent π-stacking interactions between macrocycles, thus indicating that it is a nonaggregating photosensitizer with high singlet oxygen (Φ(Δ)) and fluorescence (Φ(f)) quantum yields. Our results show that this type of synthetic strategy may provide the lead to a new generation of PDT photosensitizers.

Cutaneous respirometry by dynamic measurement of mitochondrial oxygen tension for monitoring mitochondrial function in vivo.

Science.gov (United States)

Harms, Floor A; Voorbeijtel, Wilhelmina J; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

2013-09-01

Progress in diagnosis and treatment of mitochondrial dysfunction in chronic and acute disease could greatly benefit from techniques for monitoring of mitochondrial function in vivo. In this study we demonstrate the feasibility of in vivo respirometry in skin. Mitochondrial oxygen measurements by means of oxygen-dependent delayed fluorescence of protoporphyrin IX are shown to provide a robust basis for measurement of local oxygen disappearance rate (ODR). The fundamental principles behind the technology are described, together with an analysis method for retrievel of respirometry data. The feasibility and reproducibility of this clinically useful approach are demonstrated in a series of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

Suggestions for Local School District Compliance with Title IX Rules and Regulations.

Science.gov (United States)

Arizona State Dept. of Education, Phoenix.

This guidebook is designed to help local districts determine how well they comply with the spirit of the Title IX requirements against sex discrimination, which in turn could aid in compliance with the letter of the law. The document's first section presents samples of required antidiscrimination policy statements issued by two districts. The…

Optical Observations of M81 Galaxy Group in Narrow Band [SII] and H_alpha Filters: Holmberg IX

Directory of Open Access Journals (Sweden)

Arbutina, B.

2009-12-01

Full Text Available We present observations of the nearby tidal dwarf galaxy Holmberg IX in M81 galaxy group in narrow band [SII] and H$alpha$ filters, carried out in March and November 2008 with the 2m RCC telescope at NAO Rozhen, Bulgaria. Our search for resident supernova remnants (identified as sources with enhanced [SII] emission relative to their H$alpha$ emission in this galaxy yielded no sources of this kind, besides M&H 10-11 or HoIX X-1. Nevertheless, we found a number of objects with significant H$alpha$ emission that probably represent uncatalogued HII regions.

The rates and patterns of deletions in the human factor IX gene

Energy Technology Data Exchange (ETDEWEB)

Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

1994-02-01

Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

Title IX, Girls' Sports Participation, and Adult Female Physical Activity and Weight

Science.gov (United States)

Kaestner, Robert; Xu, Xin

2010-01-01

Arguably, the most important school-based intervention to increase physical activity was Title IX of the Education Amendments of 1972, which led to a 600% increase in girls' sports participation between 1972 and 1978. We studied the effect of this increase in sports participation and athletic opportunities while young on the physical activity and…

Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

Indian Academy of Sciences (India)

In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the context of general relativity are explored. To obtain deterministic solution of the Einstein's field equations, various techniques are adopted. The features of the obtained solution are discussed.

Bianchi - I, II, VIII, IX and Kantowski-Sachs-like cosmological models with perfect fluid and electromagnetic fields with conductivity current

International Nuclear Information System (INIS)

Portugal, R.

1984-01-01

Three processes of solutions of the Einstein-Maxwell equations for Bianchi - I, II, VIII, IX and Kantowski-Sachs-like cosmological models with perfect fluid in magnetohydrolodynamical regimem are presented. Diagonal Bianchi-like models are considered with two anisotropy direction in the maximum. Solutions are found for Bianchi-II and IX-like models with energy conditions to be analyzed. Solutions are found for Bianchi-IX and Kantowski-Sachs-Like models with positive electric conductivity and satisfering to the predominant energy conditions. Solutions are formed for isotropic Kantowski-Sachs-Like models satisfering to the equation of state p=λρ, 0 0, admiting, in addition to the perfect fluid, electric field only. It is shown that a class of Bertotti-Robinson-like solutions is unstable by perturbations and it is carried in Kantowski-Sachs-like models with non-null electric conductivity. (L.C.) [pt

Identification of five novel 14-3-3 isoforms interacting with the GPIb-IX complex in platelets.

Science.gov (United States)

Mangin, P H; Receveur, N; Wurtz, V; David, T; Gachet, C; Lanza, F

2009-09-01

Binding of von Willebrand factor to the platelet glycoprotein (GP)Ib-IX complex initiates a signaling cascade leading to integrin alpha(IIb)beta(3) activation, a key process in hemostasis and thrombosis. Interaction of 14-3-3zeta with the intracytoplasmic domain of GPIb appears to be a major effector of this activation pathway. The aim of our study was to determine whether other members of the 14-3-3 family bind to GPIb-IX. In this study, western blot analyses showed that platelets also contain the 14-3-3beta, 14-3-3gamma, 14-3-3epsilon, 14-3-3eta and 14-3-3theta isoforms, but lack 14-3-3sigma. Coimmunoprecipitation studies in platelets and CHO transfectants demonstrated that all six 14-3-3 isoforms expressed in platelets, including, as previously reported, 14-3-3zeta, bind to GPIb-IX. In addition, their interaction was found to critically require the same GPIbalpha domains (580-590 and 605-610) already identified as essential for 14-3-3zeta binding, in agreement with the conservation of the sequence of the I-helix among these different isoforms. Pull-down experiments indicated that all six 14-3-3 isoforms present in platelets bind to GPIbbeta. In contrast, deletion or mutation of the GPIbbeta intracytoplasmic tail did not affect the interaction of GPIb-IX with the 14-3-3 isoforms, questioning the importance of this domain. Our study suggests that, to inhibit GPIb-induced integrin alpha(IIb)beta(3) activation, a more appropriate strategy than inhibiting individual 14-3-3 isoforms would be to target the 14-3-3-binding motif on GPIb or, alternatively, the conserved 14-3-3 I-helix.

Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

Science.gov (United States)

Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

2016-03-01

Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

Revisitation of chaos in Bianchi IX Universe and in generalized scalar-tensor cosmologies

International Nuclear Information System (INIS)

Lehner, Thierry; Di Menza, Laurent

2003-01-01

We show that there is a threshold for the onset of chaos in cosmology for the Universe described as a dynamical system derived from the Einstein equations of general relativity (GR). In the case of the mixmaster model (homogeneous and anisotropic cosmology with a Bianchi IX metric) the chaos occurs precisely at the prescribed necessary value H vac =0 of the GR for the energy of the Universe while the system is found regular for H vac >0 and chaotic for H vac <0 with respect to its pure vacuum part. In the case of generalized scalar tensor theories within the Bianchi IX model we show using the ADM formalism and a conformal transformation that the energy of the dynamical system as compared to vacuum lies below the threshold thus the system is not exhibiting chaos and the conclusion still holds in the presence of ordinary matter as well. The suppression of chaos occurs in a similar way for stiff matter alone

Kinetic study of the substitution of pyridine by cyanide in the bis(pyridine)cobalt(III)hematoporphyrin-IX: distinguishing between Isub(d) and D mechanism

International Nuclear Information System (INIS)

Birush, M.; Pribanicj, M.

1977-01-01

''Mass-law (rate) retardation'' effect shows that the reaction between the cyanide ion and bis(pyridine)cobalt(III)hematoporphyrin-IX complex to give (CN) 2 cobalt(III)hematoporphyrin-IX occurs by a purely dissociative (D but not Isub(d)) mechanism in chloroform. Limiting rate constant at the excess of cyanide ion concentration at 25 deg C was found to be 2.5x10 -3 S -1 and the competition ratio of pyridine (ksub(-) 1 ) and the cyanide ion (k 2 ) for a five coordinate intermediate (pyridin) cobalt(III)hematoporphyrin-IX complex was obtained as ksub(-) 1 /k 2 =0.35. (author)

Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

Directory of Open Access Journals (Sweden)

Aikaterini Peperidou

2018-01-01

Full Text Available A series of carboxamide derivatives of 6- and 7-substituted coumarins have been prepared by an original procedure starting from the corresponding 6- or 7-hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained ester was converted to the corresponding carboxylic acids which were thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs and soy bean lipoxygenase (LOX. Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX inhibitors (KIs in the range of 30.2–30.5 nM were detected in this study. Two compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore, these coumarins did not significantly inhibit the widespread cytosolic isoforms hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX-selective inhibitors. As hCA IX and LOX are validated antitumor targets, these results are promising for the investigation of novel drug targets involved in tumorigenesis.

Venous drainage of the dorsal sector of the liver: differences between segments I and IX. A study on corrosion casts of the human liver.

Science.gov (United States)

Gadzijev, E M; Ravnik, D; Stanisavljevic, D; Trotovsek, B

1997-01-01

The aim of this study was to determine the venous drainage of the dorsal sector of the liver in order to define the differences between segments I and IX and their implications for sectorially and segmentally oriented hepatic surgery. The study was based on corrosion casts of 61 macroscopically healthy livers. The drainage pathways of veins at least 10 mm long and 1 mm wide were evaluated and statistically analysed. On average, 9 veins drained the two segments and three veins from both segments entered the inferior vena cava. In 95% of cases the veins from segment I drained predominantly into the inferior vena cava, whereas in segment IX this pathway was dominant in only 30% of cases. In 64% of cases a vein originating in segment IX entered the right hepatic v. The difference in the venous drainage of the two segments suggests that segment IX partly belongs to the neighbouring segments and may thus be only a paracaval region of the right liver.

Title IX: Does Help for Women Come at the Expense of African Americans?

Science.gov (United States)

Greenlee, Craig T.

1997-01-01

Federal law that forbids sex discrimination in educational institutions receiving federal funds (Title IX) has created opportunities for women athletes, but some say men's sports have lost ground. Since athletics provide major educational opportunities for black men, less so for black women, critics are concerned blacks may be losing. (MSE)

Delta-ALA-mediated fluorescence spectroscopy of gastrointestinal tumors: comparison of in vivo and in vitro results

Science.gov (United States)

Vladimirov, B.; Borisova, E.; Avramov, L.

2007-06-01

The limitations of standard endoscopy for detection of dysplastic changes of mucosa are significant challenge and initiate development of new photodiagnostic techniques, additional to diagnostic possibilities of standard endoscopic equipment. One of the most widely examined optical modalities is the laser- or light-induced fluorescence spectroscopy (LIFS), because of its rapid and highly sensitive response to early biochemical and morphological changes in biological tissues. In the recent study delta-aminolevulinic acid/protoporphyrin IX is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ -ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from in vivo tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors vascularization and it is clearly pronounced in all dysplastic and tumor sites investigated. After formalin conservation for in vitro samples hemoglobin absorption is strongly reduced that increases mucous fluorescence signal in green-yellow spectral region. Simultaneously the maxima at 635 nm and 720 nm are reduced.

X-RAY OUTFLOWS AND SUPER-EDDINGTON ACCRETION IN THE ULTRALUMINOUS X-RAY SOURCE HOLMBERG IX X-1

International Nuclear Information System (INIS)

Walton, D. J.; Harrison, F. A.; Miller, J. M.; Reis, R. C.; Fabian, A. C.; Roberts, T. P.; Middleton, M. J.

2013-01-01

Studies of X-ray continuum emission and flux variability have not conclusively revealed the nature of ultraluminous X-ray sources (ULXs) at the high-luminosity end of the distribution (those with L X ≥ 10 40 erg s –1 ). These are of particular interest because the luminosity requires either super-Eddington accretion onto a black hole of mass ∼10 M ☉ or more standard accretion onto an intermediate-mass black hole. Super-Eddington accretion models predict strong outflowing winds, making atomic absorption lines a key diagnostic of the nature of extreme ULXs. To search for such features, we have undertaken a long, 500 ks observing campaign on Holmberg IX X-1 with Suzaku. This is the most sensitive data set in the iron K bandpass for a bright, isolated ULX to date, yet we find no statistically significant atomic features in either emission or absorption; any undetected narrow features must have equivalent widths less than 15-20 eV at 99% confidence. These limits are far below the ∼>150 eV lines expected if observed trends between mass inflow and outflow rates extend into the super-Eddington regime and in fact rule out the line strengths observed from disk winds in a variety of sub-Eddington black holes. We therefore cannot be viewing the central regions of Holmberg IX X-1 through any substantial column of material, ruling out models of spherical super-Eddington accretion. If Holmberg IX X-1 is a super-Eddington source, any associated outflow must have an anisotropic geometry. Finally, the lack of iron emission suggests that the stellar companion cannot be launching a strong wind and that Holmberg IX X-1 must primarily accrete via Roche-lobe overflow

In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

Science.gov (United States)

Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

1993-10-01

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Hemin binding by Porphyromonas gingivalis strains is dependent on the presence of A-LPS.

Science.gov (United States)

Rangarajan, M; Aduse-Opoku, J; Paramonov, N A; Hashim, A; Curtis, M A

2017-10-01

Porphyromonas gingivalis is a Gram-negative black pigmenting anaerobe that is unable to synthesize heme [Fe(II)-protoporphyrin IX] or hemin [Fe(III)-protoporphyrin IX-Cl], which are important growth/virulence factors, and must therefore derive them from the host. Porphyromonas gingivalis expresses several proteinaceous hemin-binding sites, which are important in the binding/transport of heme/hemin from the host. It also synthesizes several virulence factors, namely cysteine-proteases Arg- and Lys-gingipains and two lipopolysaccharides (LPS), O-LPS and A-LPS. The gingipains are required for the production of the black pigment, μ-oxo-bisheme {[Fe(III)PPIX] 2 O}, which is derived from hemoglobin and deposited on the bacterial cell-surface leading to the characteristic black colonies when grown on blood agar. In this study we investigated the role of LPS in the deposition of μ-oxo-bisheme on the cell-surface. A P. gingivalis mutant defective in the biosynthesis of Arg-gingipains, namely rgpA/rgpB, produces brown colonies on blood agar and mutants defective in Lys-gingipain (kgp) and LPS biosynthesis namely porR, waaL, wzy, and pg0129 (α-1, 3-mannosyltransferase) produce non-pigmented colonies. However, only those mutants lacking A-LPS showed reduced hemin-binding when cells in suspension were incubated with hemin. Using native, de-O-phosphorylated and de-lipidated LPS from P. gingivalis W50 and porR strains, we demonstrated that hemin-binding to O-polysaccharide (PS) and to the lipid A moiety of LPS was reduced compared with hemin-binding to A-PS. We conclude that A-LPS in the outer-membrane of P. gingivalis serves as a scaffold/anchor for the retention of μ-oxo-bisheme on the cell surface and pigmentation is dependent on the presence of A-LPS. © 2017 The Authors. Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

The Application of Lean Thinking Principles and Kaizen Practices for the Successful Development and Implementation of the Ares I-X Flight Test Rocket and Mission

Science.gov (United States)

Askins, B. R.; Davis, S. R.; Heitzman, K. S.; Olsen, R. A.

2011-01-01

On October 28, 2009 the Ares I-X flight test rocket launched from Kennedy Space Center and flew its suborbital trajectory as designed. The mission was successfully completed as data from the test, and associated development activities were analyzed, transferred to stakeholders, and well documented. A positive lesson learned from Ares I-X was that the application of lean thinking principles and kaizen practices was very effective in streamlining development activities. Ares I-X, like other historical rocket development projects, was hampered by technical, cost, and schedule challenges and if not addressed boldly could have resulted in cancellation of the test. The mission management team conducted nine major meetings, referred to as lean events, across its elements to assess plans, procedures, processes, requirements, controls, culture, organization, use of resources, and anything that could be changed to optimize schedule or reduce risk. The preeminent aspect of the lean events was the focus on value added activities and the removal or at least reduction in non-value added activities. Trained Lean Six Sigma facilitators assisted the Ares I-X developers in conducting the lean events. They indirectly helped formulate the mission s own unique methodology for assessing schedule. A core team was selected to lead the events and report to the mission manager. Each activity leveraged specialized participants to analyze the subject matter and its related processes and then recommended alternatives and solutions. Stakeholders were the event champions. They empowered and encouraged the team to succeed. The keys to success were thorough preparation, honest dialog, small groups, adherence to the Ares I-X ground rules, and accountability through disciplined reporting and tracking of actions. This lean event formula was game-changing as demonstrated by Ares I-X. It is highly recommended as a management tool to help develop other complex systems efficiently. The key benefits for

The transitions 4p-5s in Y VI, Zr VII, Nb VIII and Mo IX

International Nuclear Information System (INIS)

Chaghtai, M.S.Z.; Rahimullah, K.; Khatoon, S.

1976-01-01

With the help of the spectra recorded in the Physics Department of Lund University, Y VI, Zr VII, Nb VIII and Mo IX are freshly analysed. The five 4s 2 4p 4 ground levels and the ten 4s 2 4p 3 5s levels of previous analyses are confirmed in the first three spectra, except for revising in Y VI the 4p 4 1 S 0 and 4p 3 5s( 4 Ssub(3/2)) 2 levels and interchanging 5s( 2 Dsub(3/2)) 1 with 5s( 2 Dsub(3/2)) 2 . All level values are improved due to the new measurements. A new analysis of Mo IX establishing all the 4p 4 and 4p 3 5s levels is being reported. (Auth.)

Evaluating the effect of local pH on fluorescence emissions from oral bacteria of the genus Prevotella

Science.gov (United States)

Hope, Christopher K.; Higham, Susan M.

2016-08-01

A number of anaerobic oral bacteria, notably Prevotellaceae, exhibit red fluorescence when excited by short-wavelength visible light due to their accumulation of porphyrins, particularly protoporphyrin IX. pH affects the fluorescence of abiotic preparations of porphyrins due to transformations in speciation between monomers, higher aggregates, and dimers. To elucidate whether the porphyrin speciation phenomenon could be manifested within a microbiological system, suspensions of Prevotella intermedia and Prevotella nigrescens were examined by fluorescence spectrophotometry while being titrated against NaOH. The initial pH of the samples was oral cavity could affect the fluorescence of oral bacteria in vivo, which may in turn have connotations for any clinical diagnoses that may be inferred from dental plaque fluorescence.

Low-cost photodynamic therapy devices for global health settings: Characterization of battery-powered LED performance and smartphone imaging in 3D tumor models

Science.gov (United States)

Hempstead, Joshua; Jones, Dustin P.; Ziouche, Abdelali; Cramer, Gwendolyn M.; Rizvi, Imran; Arnason, Stephen; Hasan, Tayyaba; Celli, Jonathan P.

2015-05-01

A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries. Photodynamic therapy (PDT) is a light-based treatment modality that has exhibited safety and efficacy in the clinic using wavelengths and irradiances achievable with light-emitting diodes (LEDs) operated on battery power. Here we assess low-cost enabling technology to extend the clinical benefit of PDT to regions with little or no access to electricity or medical infrastructure. We demonstrate the efficacy of a device based on a 635 nm high-output LED powered by three AA disposable alkaline batteries, to achieve strong cytotoxic response in monolayer and 3D cultures of A431 squamous carcinoma cells following photosensitization by administering aminolevulinic acid (ALA) to induce the accumulation of protoporphyrin IX (PpIX). Here we characterize challenges of battery-operated device performance, including battery drain and voltage stability specifically over relevant PDT dose parameters. Further motivated by the well-established capacity of PDT photosensitizers to serve as tumour-selective fluorescence contrast agents, we demonstrate the capability of a consumer smartphone with low-cost add-ons to measure concentration-dependent PpIX fluorescence. This study lays the groundwork for the on-going development of image-guided ALA-PDT treatment technologies for global health applications.

Resistance of a soybean cell line to oxyfluorfen by overproduction of mitochondrial protoporphyrinogen oxidase.

Science.gov (United States)

Warabi, E; Usui, K; Tanaka, Y; Matsumoto, H

2001-08-01

The diphenyl ether herbicide oxyfluorfen (2-chloro-4-trifluoromethylphenyl 3-ethoxy-4-nitrophenyl ether) inhibits protoporphyrinogen oxidase (Protox) which catalyzes the oxidation of protoporphyrinogen IX (Protogen) to protoporphyrin IX (Proto IX), the last step of the common pathway to chlorophyll and haeme biosynthesis. We have selected an oxyfluorfen-resistant soybean cell line by stepwise selection methods, and the resistance mechanism has been investigated. No growth inhibition was observed in resistant cells at a concentration of 10(-7) M oxyfluorfen, a concentration at which normal cells did not survive. While the degree of inhibition of total extractable Protox by oxyfluorfen was the same in both cell types, the enzyme activity in the mitochondrial fraction from non-treated resistant cells was about nine-fold higher than that from normal cells. Northern analysis of mitochondrial Protox revealed that the concentration of mitochondrial Protox mRNA was much higher in resistant cells than that in normal cells. There were no differences in the absorption and metabolic breakdown of oxyfluorfen. The growth of resistant cells was also insensitive to oxadiazon [5-tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-(3H)- one], the other chemical class of Protox inhibitor. Therefore, the resistance of the selected soybean cell line to oxyfluorfen is probably mainly due to the overproduction of mitochondrial Protox.

Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.

Science.gov (United States)

Anderson, Catriona M H; Jevons, Mark; Thangaraju, Muthusamy; Edwards, Noel; Conlon, Nichola J; Woods, Steven; Ganapathy, Vadivel; Thwaites, David T

2010-01-01

5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H(+)-coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H(+)-coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H(+)-coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue.

The Fourth Circuit Kicks a Hole through the Contact-Sport Exception to Title IX.

Science.gov (United States)

Puszczewicz, James

2000-01-01

Discusses a recent Fourth Circuit Court of Appeals decision that when individuals are allowed to try out for or join a team participating in a contact sport and operated for members of the other sex, then discrimination against because of their sex is prohibited by Title IX. (22 footnotes) (MLF)

The Role of Hexon Protein as a Molecular Mold in Patterning the Protein IX Organization in Human Adenoviruses.

Science.gov (United States)

Reddy, Vijay S

2017-09-01

Adenoviruses are respiratory, ocular and enteric pathogens that form complex capsids, which are assembled from seven different structural proteins and composed of several core proteins that closely interact with the packaged dsDNA genome. The recent near-atomic resolution structures revealed that the interlacing continuous hexagonal network formed by the protein IX molecules is conserved among different human adenoviruses (HAdVs), but not in non-HAdVs. In this report, we propose a distinct role for the hexon protein as a "molecular mold" in enabling the formation of such hexagonal protein IX network that has been shown to preserve the stability and infectivity of HAdVs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of invitro cytotoxic and genotoxic potential of glass ionomer cement type IX on human lymphocytes before and after electron beam irradiation

International Nuclear Information System (INIS)

Hegde, Mithra N.; Brijesh; Shetty, Shilpa S.; Hegde, Nidarsh D.; Suchetha Kumari; Sanjeev, Ganesh

2013-01-01

Glass ionomer cements are widely used in dentistry as an adhesive restorative materials. However, the results of cytotoxicity and genotoxicity studies using these materials are inconclusive in literature. The aim of this study was to examine the cytotoxic and genotoxic potential of glass ionomer cement type IX available commercially before and after irradiation. Glass ionomer cement type IX was obtained commercially. Samples were prepared as per the ISO standard size of 25x2x2 mm using polytetrafluoroethylene teflon mould and divided into two groups - non irradiated and irradiated groups. The samples in radiated category were exposed to 10 KGy of electron beam irradiation at Microtron Centre, Mangalore University, Mangalore, India. For hemolysis assay, the samples were immersed in phosphate buffer saline and incubated at 370℃ for 24 hrs, 7 days and 14 days. 200 μL of 24 hr material extract was mixed with human peripheral blood lymphocyte tested for comet assay by single cell DNA comet assay and apoptosis by DNA diffusion assay. Hemolytic activity of non irradiated Glass ionomer cement type IX after 24 hrs, 7 days and 14 days was 78.18±10.13, 32.57±12.28, 38.56±4.68 respectively whereas hemolytic activity of irradiated Glass ionomer cement type IX after 24 hrs, 7 days and 14 days was 58.90±2.28, 35.04±1.09 and 34.26±7.71 respectively. The irradiation of Glass ionomer cement type IX with 10 KGy dose of electron beam irradiation did not show significant increase in the frequency of DNA damage when compared to that of the nonirradiated group. Apoptotic index did not show much difference between non-irradiated and irradiated groups. Taken together, we conclude that some components of glass ionomer cements show both genotoxic and cytotoxic effects. (author)

Metal-free Phtalocyanine and 5-Aminolevulenic Acid in Photodynamic Treatment of Human Vascular Cells

Science.gov (United States)

Udartseva, Olga O.; Andreeva, Elena R.; Buravkova, Ludmila B.; Tararak, Eduard M.

2010-05-01

Originally developed as a tumor therapy, now photodynamic therapy (PDT) may become a useful tool for treatment of cardiovascular diseases. Different cell types are involved in this vascular pathology, and these cells possess different susceptibility to PDT. In this study we screened the effects of two new photosensitizers (PtS and ALA) on human vascular cells. Human macrophages (Mph), aorta endothelial (HAEC) and smooth muscle (SMC) cells were obtained and cultured as described elsewhere. 2-10 ug/ml PtS was added to culture medium 24 h before PDT. ALA was added in 2-10 mM concentration in serum-free culture medium. Then cells were washed carefully and illuminated with 692-nm (PtS) or 633-nm (ALA) light. Cellular viability was measured with MTT-test. Except the case of use 5-10 mM ALA, either photosensitizer accumulation alone or laser illumination alone did not affect cells. Illumination of PtS or ALA-loaded cells (1-20 J/cm2) impaired cellular viability in dose-dependent manner. LD90 for different vascular cells with PtS were as follows: HAEC -1 J/cm2, SMC -2 J/cm2, Mph -5 J/cm2. HAEC and some Mph were unsusceptible to ALA-PDT. SMC LD90 with ALA was 20 J/cm2. Effects of ALA-PDT depended on protoporphyrin IX (PpIX) formation in cells. HAEC didn't accumulate PpIX and were non-sensitive to ALA-PDT. PpIX formation in Mph changed individually according to donor. Illumination of ALA-loaded Mph with low PpIX formation did not affect cells. However LD90 for Mph with high PpIX formation comprised 20 J/cm2. All cell types were more susceptible to PtS-PDT compared to ALA-PDT. Among tested photosensitizers PtS was the most effective one. HAEC were the most susceptible to PtS-PDT.

Effect of production system and flock age on eggshell and egg internal quality measurements.

Science.gov (United States)

Samiullah, Sami; Omar, Amal Saleh; Roberts, Juliet; Chousalkar, Kapil

2017-01-01

Egg quality was measured in eggs from different flocks that were reared together and then allocated to different production systems. Eggs were processed for measurements of eggshell and egg internal quality variables, scoring of ultrastructural mammillary layer features, completeness of cuticle cover, and protoporphyrin IX (PP IX) quantification. There was a significant main effect (P egg weight, and egg internal quality and significant effects of flock age on most measurements. The mammillary layer ultrastructural variables showed no clear relationship with production system and flock age. However, there was a significant interaction between production system and flock age for mammillary cap, early and late fusions. Cuticle cover ([Formula: see text]), was significantly higher in barn eggs (19.20), followed by free range (17.57), and cage eggs (15.99). Completeness of cuticle cover was significantly higher in eggs from the 44 week old flock than for 64 week and 73 week old flocks. For eggshells with cuticle intact, there was a significant main effect of both production system and flock age, and significant interaction between the two, for shell reflectivity, L*a*b* values and amount of PP IX. For PP IX, when this difference was calculated for the cuticle alone, there were no statistically significant differences. In 1 g of shell with and without cuticle, there was more PP IX in cage eggs (9.49 × 10 -8 , 7.90 × 10 -8  mM) followed by free range (8.24 × 10 -8 , 6.90 × 10 -8  mM), and barn eggs (8.64 × 10 -8 , 7.28 × 10 -8  mM). Similar trends were recorded for the amount of PP IX in 1 g of cuticle, but the difference was not statistically significant. The amount of PP IX decreased significantly with increasing flock age. Comparing the cage and barn production systems at 68 week of flock age, there was no difference for the amount of PP IX in shell with or without cuticle, or in the cuticle alone. Eggs from the cage production system were darker in color

Histamine release from rodent and human mast cells induced by protoporphyrin and ultraviolet light: studies of the mechanism of mast-cell activation in erythropoietic protoporphyria

International Nuclear Information System (INIS)

Glover, R.A.; Bailey, C.S.; Barrett, K.E.; Wasserman, S.I.; Gigli, I.

1990-01-01

We report that protoporphyrin (PP) and ultraviolet light (UVA) induces histamine release from rat peritoneal mast cells, mouse bone marrow mast cells and human cutaneous mast cells in a dose- and temperature-dependent manner. The mast-cell activation was associated with loss of membrane integrity and inhibited by the hydrogen peroxide scavenger, catalase. Histamine release was independent of extracellular calcium in the rodent mast cells, but was markedly reduced in the absence of calcium in human cells. These findings indicate that PP and UVA induce mast-cell-mediator release by a process that may involve hydrogen peroxide formation. There appear to be differences in response to PP and UVA between rodent and human mast cells. (author)

Histamine release from rodent and human mast cells induced by protoporphyrin and ultraviolet light: studies of the mechanism of mast-cell activation in erythropoietic protoporphyria

Energy Technology Data Exchange (ETDEWEB)

Glover, R.A.; Bailey, C.S.; Barrett, K.E.; Wasserman, S.I.; Gigli, I. (California Univ., San Diego, CA (USA). Dept. of Medicine)

1990-04-01

We report that protoporphyrin (PP) and ultraviolet light (UVA) induces histamine release from rat peritoneal mast cells, mouse bone marrow mast cells and human cutaneous mast cells in a dose- and temperature-dependent manner. The mast-cell activation was associated with loss of membrane integrity and inhibited by the hydrogen peroxide scavenger, catalase. Histamine release was independent of extracellular calcium in the rodent mast cells, but was markedly reduced in the absence of calcium in human cells. These findings indicate that PP and UVA induce mast-cell-mediator release by a process that may involve hydrogen peroxide formation. There appear to be differences in response to PP and UVA between rodent and human mast cells. (author).

Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies

NARCIS (Netherlands)

Burgess, Janette K.; Lopez, Jose A.; Gaudry, Leonie E.; Chong, Beng H.

2000-01-01

The drug-dependent antibody of a patient with rifampicin-induced thrombocytopenia was characterized using the antigen-capture enzyme-linked immunosorbent assay (MAIPA assay), flow cytometry, and immunoprecipitation. The antibody was found to bind glycoprotein (GP) Ib-IX but not GPIIb-IIIa because

Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6

International Nuclear Information System (INIS)

Suzuki, Nobuhiro; Shikamoto, Yasuo; Fujimoto, Zui; Morita, Takashi; Mizuno, Hiroshi

2004-01-01

Crystals of habu coagulation factor IX-binding protein have been obtained at pH 6.5 and 4.6 and characterized by X-ray diffraction. Coagulation factor IX-binding protein isolated from Trimeresurus flavoviridis (IX-bp) is a C-type lectin-like protein. It is an anticoagulant protein consisting of homologous subunits A and B. The subunits both contain a Ca 2+ -binding site with differing affinity (K d values of 14 and 130 µM at pH 7.5). These binding characteristics are pH-dependent; under acidic conditions, the affinity of the low-affinity site was reduced considerably. In order to identify which site has high affinity and also to investigate the Ca 2+ -releasing mechanism, IX-bp was crystallized at pH 6.5 and 4.6. The crystals at pH 6.5 and 4.6 diffracted to 1.72 and 2.29 Å resolution, respectively; the former crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 60.7, b = 63.5, c = 66.9 Å, β = 117.0°, while the latter belong to the monoclinic space group C2, with a = 134.1, b = 37.8, c = 55.8 Å, β = 110.4°

Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.

Science.gov (United States)

Bolliger, Daniel; Sreeram, Gautam; Duncan, Alexander; Molinaro, Ross J; Szlam, Fania; Chen, Edward P; Tanaka, Kenichi A

2009-11-01

In Jehovah's Witness patients, the use of red blood cells, platelets, and fresh frozen plasma is not optional. Various blood conservation techniques are available, but complex cardiac surgery remains a major challenge. The feasibility of fractions of "primary components" has not been fully considered in published case reports. For Jehovah's Witness patients who preoperatively give consent, factor IX concentrates may be acceptable for hemostatic therapy. We hereby describe a combination of "secondary components" to prevent excessive bleeding in a Jehovah's Witness patient undergoing complex replacement of the aortic arch.

Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B

DEFF Research Database (Denmark)

Miesbach, Wolfgang; Meijer, Karina; Coppens, Michiel

2018-01-01

Hemophilia B gene therapy aims to ameliorate bleeding risk and provide endogenous factor IX (FIX) activity/synthesis through a single treatment, eliminating the requirement for FIX concentrate. AMT-060 combines an adeno-associated virus-5 (AAV5) vector with a liver-specific promoter driving expre...

Toxicology of dimethyl and monomethyl derivatives of acetamide and formamide: a second update.

Science.gov (United States)

Kennedy, Gerald L

2012-11-01

formamide and their monomethyl derivatives as well as the commercially important DMAC and DMF. Since a large portion of the newer information deals with effects in humans and biomonitoring, these sections are presented at the start of this review.

Japanese contributions to IAEA INTOR workshop, phase two A, part 2, chapter IX: engineering

International Nuclear Information System (INIS)

Iida, Hiromasa; Seki, Masahiro; Sawada, Yoshio

1985-07-01

This report corresponds to Chapter IX of Japanese contribution report to IAEA INTOR Workshop, Phase Two A, Part 2. Data base assessment are made for systems engineering, magnet systems, torus systems, and NBI heating systems. R and D programme and impact on INTOR design are also specified. In addition to the data base assessment, studies have been made for several new tasks. (author)

Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

Directory of Open Access Journals (Sweden)

Li-Wen Zhang

2011-03-01

Full Text Available Photodynamic therapy (PDT is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA, is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.

PROFIL PERTANYAAN SISWA TUNANETRA KELAS IX SMPLB YKAB SURAKARTA DALAM PEMBELAJARAN MATEMATIKA

OpenAIRE

Siti Khoiriyah

2015-01-01

Abstract Thinking can be drilled to the student by developing question skill during teaching process. Personal life quality is determined from question quality; the more qualified a question the more success a person in life. Therefore, this study analyzed the students question to find out the students question quality. The subject of this study is IX class of SMPLB YKAB students Surakarta. The data was found by observation with handy cam. The data analysis was conducted through data reductio...

Novel drug delivery strategies for porphyrins and porphyrin precursors

Science.gov (United States)

Morrow, D. I. J.; Donnelly, R. F.

2009-06-01

superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

Caught between a Rock and a Hard Place: The Title IX Generation, Mathematics, and the State of Feminist Quantitative Social Science Research

Directory of Open Access Journals (Sweden)

Jill R. Williams

2012-12-01

Full Text Available In this essay I reflect on the fortieth anniversary of the Mink Equal Opportunity in Education Act of 1972 (Title IX, which prohibited discrimination based on sex in federally funded education programs in the United States and inspired educational programs that encourage girls to pursue math and science careers. I argue that despite the feminist underpinnings of Title IX, in recent years feminism has discouraged the advancement of women in math and science by excluding quantitative research from its publications, quantitative researchers from women's and gender studies programs, and quantitative training from its curriculum. I examine my own experience of growing up with Title IX programs, the long-term ramifications of those programs, and my recent struggles to do feminist demography to show how the relationship of feminism to the promotion of quantitative sciences has changed over time. I argue that there is an unfinished revolution in feminism and a stall in the development of feminist quantitative social science research that can only be resolved by creating intellectual space for feminist quantitative work in the academy.

Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication.

Science.gov (United States)

Grinblat, Borislava; Pour, Nir; Malik, Zvi

2006-01-01

Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid (ALA) and light irradiation. The influence of two environmental heavy metal poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu-ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead poisoning significantly decreased the PBGD cellular level and inhibited its enzymatic activity, whereas the effects of gallium were less prominent. Although, the protein levels were reduced, the mRNA levels of PBGD remained unchanged during metal intoxication. These findings show additional inhibitory activity of lead on top of its classical effect on ALAD. Proteasome activity was enhanced during lead treatment, as measured by the AMC fluorigenic proteasome assay. The reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis, which remained unchanged as shown by RT-PCR analysis. As a result of the lead poisoning, marked alterations in the cell cycle were observed, including a decreased G1 phase and an increased number of S phase cells. The efficacy of ALA-PDT was reduced in correlation with decreased activities of the enzymes during lead intoxication. We may conclude that lead poisoning adversely affects the outcome of ALA photodynamic therapy of cancer.

Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

Science.gov (United States)

Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

2009-06-01

Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

The Effect of Using Origami Paper to Teach the Perimeter of Plane Figures on Cognitive Achievement of Students Grade IX

Directory of Open Access Journals (Sweden)

Yael Narwastu Jati

2017-03-01

BAHASA INDONESIA ABSTRAK: Desain penelitian eksperimen ini dilakukan untuk melihat apakah terdapat pengaruh penggunaan kertas origami untuk mengajar keliling dari suatu bidang datar terhadap hasil belajar kognitif siswa kelas IX dan bagaimana penggunaan tersebut mempengaruhi hsil belajar. Sampel penelitian adalah 16 siswa kelas IX-A sebagai kelompok ekperimen yang akan menggunakan kertas origami. Data diperolehh dari hasil pre-tests dan post-tests. Hasil penelitian menunjukkan ada perbedaan rata-rata skor yang signifikan antara hasil pre-tests dan post-tests yang di duga, yaitu 4.0 (normalized gain, bahkan mencapai 0.8 yang termasuk golongan tinggi. Sehingga, dapat disimpulkan bahwa terdapat pengaruh pada hasil belajar kognitif pada pengajaran keliling suatu bidang datar dengan menggunakan kertas origami

Broadband X-ray spectra of the ultraluminous X-ray source Holmberg IX X-1 observed with NuSTAR, XMM-Newton, and Suzaku

Energy Technology Data Exchange (ETDEWEB)

Walton, D. J.; Harrison, F. A.; Grefenstette, B. W.; Fuerst, F.; Madsen, K. K.; Rana, V.; Stern, D. [Space Radiation Laboratory, California Institute of Technology, Pasadena, CA 91125 (United States); Miller, J. M. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109-1042 (United States); Bachetti, M.; Barret, D.; Webb, N. [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Boggs, S. E.; Craig, W. W. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Christensen, F. E. [DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Fabian, A. C.; Parker, M. L. [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Hailey, C. J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Ptak, A.; Zhang, W. W., E-mail: dwalton@srl.caltech.edu [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

2014-09-20

We present results from the coordinated broadband X-ray observations of the extreme ultraluminous X-ray source Holmberg IX X-1 performed by NuSTAR, XMM-Newton, and Suzaku in late 2012. These observations provide the first high-quality spectra of Holmberg IX X-1 above 10 keV to date, extending the X-ray coverage of this remarkable source up to ∼30 keV. Broadband observations were undertaken at two epochs, between which Holmberg IX X-1 exhibited both flux and strong spectral variability, increasing in luminosity from L {sub X} = (1.90 ± 0.03) × 10{sup 40} erg s{sup –1} to L {sub X} = (3.35 ± 0.03) × 10{sup 40} erg s{sup –1}. Neither epoch exhibits a spectrum consistent with emission from the standard low/hard accretion state seen in Galactic black hole binaries, which would have been expected if Holmberg IX X-1 harbors a truly massive black hole accreting at substantially sub-Eddington accretion rates. The NuSTAR data confirm that the curvature observed previously in the 3-10 keV bandpass does represent a true spectral cutoff. During each epoch, the spectrum appears to be dominated by two optically thick thermal components, likely associated with an accretion disk. The spectrum also shows some evidence for a nonthermal tail at the highest energies, which may further support this scenario. The available data allow for either of the two thermal components to dominate the spectral evolution, although both scenarios require highly nonstandard behavior for thermal accretion disk emission.

Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

Science.gov (United States)

Herzog, R W; Yang, E Y; Couto, L B; Hagstrom, J N; Elwell, D; Fields, P A; Burton, M; Bellinger, D A; Read, M S; Brinkhous, K M; Podsakoff, G M; Nichols, T C; Kurtzman, G J; High, K A

1999-01-01

Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.

Microsatellite alterations in head and neck squamous cell carcinoma and relation to expression of pimonidazole, CA IX and GLUT-1

International Nuclear Information System (INIS)

Schutter, Harlinde de; Barbe, Barbara; Spaepen, Marijke

2006-01-01

Background and Purpose: Because the locoregional control for HNSCC is still disappointing, research efforts focus on the exploration of new molecular markers located in both tumour and microenvironment, which could help stratify patients. The aim of the present work was therefore first to assess microsatellite alterations and hypoxia in HNSCC as possible molecular markers. Second, a relation between both was investigated, as hypoxia is known to select for genetic alterations. Material and methods: Forty-eight patients with advanced HNSCC treated by surgery ± radiotherapy were included. MSI and LOH were investigated with microsatellite markers using automatic fragment analysis. The presence of hypoxia was assessed by immunohistochemistry for pimonidazole, CA IX and GLUT-1. The mutual relationship between MSI/LOH and hypoxia was evaluated. Results: No MSI was detected in this patient group. LOH occurred mostly on chromosomal arms 3p, 5q, 9p, 17p and 17q. Patients with LOH at D17S799, located in the near environment of p53, showed a higher CA IX expression (p = 0.01). Conclusions: LOH is a possible molecular marker in HNSCC. The positive correlation between LOH at D17S799 and CA IX is in full concordance with previous publications linking hypoxia to selective pressure on the p53 gene

Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

International Nuclear Information System (INIS)

Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

1990-01-01

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

The order of chaos on a Bianch IX cosmological model

Energy Technology Data Exchange (ETDEWEB)

Bugalho, H; da Silva, A R; Ramos, J S

1986-12-01

The purpose of this paper is to analyze the chaotic behavior that can arise on a type-IX cosmological model using methods from dynamic systems theory and symbolic dynamics. Specifically, instead of the Belinski-Khalatnikov-Lifschitz model, we use the iterates of a monotonously increasing map of the circle with a discontinuity, and for the Hamiltonian dynamics of Misner's Mixmaster model we introduce the iterates of a noninvertible map. An equivalence between these two models can easily be brought upon by translating them in symbolic dynamical terms. The resulting symbolic orbits can be inserted in an ordered tree structure set, and so we can present an effective counting and referentation of all period orbits.

PEMBERDAYAAN EKONOMI MASYARAKAT RT 05 RW IX KELURAHAN KROBOKAN KECAMATAN SEMARANG BARAT MELALUI PENGOLAHAN BAHAN PANGAN LOKAL DAN PEMASARANNYA

Directory of Open Access Journals (Sweden)

Mei Sulistyoningsih

2015-09-01

Full Text Available Abstract ?é?á The purpose of this activity is to increase of people?óÔé¼Ôäós income through local food processing and its marketing by empowerment of communities. Participants of these activities include member of RT 05 RW IX, Kelurahan Krobokan, sub-district of West Semarang, Semarang City. The method are discussion, practice, and simulation. Implementation of activities is to encourage community to be entrepreneurs in increasing family incomes not only just relying on the income from the work as laborers or workers. Training activities of local food into a healthy diet has a positive response from family group in RT 05 RW IX, Kelurahan Krobokan, sub-district of West Semarang, Semarang City. ?é?á Keywords : family income, local food, entrepreneur, marketing

Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell carcinoma of the head and neck with known modifiable hypoxia: An evaluation of the DAHANCA 5 study

DEFF Research Database (Denmark)

Eriksen, Jesper Grau; Overgaard, Jens

2007-01-01

BACKGROUND AND PURPOSE: CA IX is suggested to be an endogenous marker of hypoxia in tumours like squamous cell carcinomas of the head and neck (HNSCC). The aim of the present study was to investigate whether CA IX served as a prognostic factor for outcome in a large population of HNSCC and if CA IX...... was able to discriminate the tumours that did benefit from hypoxic modification with nimorazole. MATERIALS AND METHODS: Paraffin-embedded formalin-fixed pre-treatment tumour tissue was available from 320 of the 414 patients treated in the randomized DAHANCA 5 protocol with primary radiotherapy...

The analysis of the 3d8, 3d74p and 3p53d9 configurations of Se IX

International Nuclear Information System (INIS)

Kleef, T.A.M. van; Uylings, P.; Joshi, Y.N.; Podobedova, L.I.; Ryabtsev, A.N.

1984-01-01

The ninth spectrum of selenium (Se IX) was photographed in the region 100-140 A on a variety of grazing incidence spectrographs using a triggered spark or an open spark as sources. On the basis of these measurements all levels of the 3d 8 configuration, 11 out of 12 levels of the 3p 5 3d 9 configuration and 95 out of 110 levels of the 3d 7 4p configuration have been established. A strong configuration interaction exists between the two odd configurations. Least-squares-fit and Hartree-Fock parameter calculations support the analysis. Two hundred and twenty-five (225) lines have been classified in Se IX. (orig.)

Further analysis of the FRONT model in ASTEC by simulating the hydrogen deflagration experiment BMC Ix9

International Nuclear Information System (INIS)

Braehler, Thimo; Koch, Marco K.

2011-01-01

Effects of possible hydrogen deflagration like pressure built up and temperature increase can become important for the evaluation of late phases in loss of coolant accidents. In this compact the simulation of the hydrogen deflagration test BMC Ix9 with the FRONT model of the integral lumped-parameter-code ASTEC is treated. This model is available since mid of 2009, released with ASTEC V2.0. To check the validity of the model related to the applicability on different phenomena, a large number of simulations are necessary. The model was used by RUB in the frame of the 'International Standard Problem on Hydrogen Combustion (ISP-49)' and within the EC NoE SARNET2. It has been concluded that the model is able to simulate a broad range of hydrogen deflagration phenomena under different experimental conditions. Experiments analysed in the mentioned benchmarks are characterised by flame propagation in vertical direction. Moreover there were no considerations of flame propagation in multi compartment geometries. In the BMC Ix9 test horizontal hydrogen deflagration with flame propagation in 3 rooms was investigated. The FRONT model was already validated on the BMC Hx23 experiment with sufficient results. In comparison to this test the number of compartments and the initial gas composition, like hydrogen and steam concentration differs from the BMC Ix9 experiment. Previous investigations of RUB showed that the modelling of turbulence related to the transport between different compartment and the determination of this quantity has a strong influence on the simulation results. In the following the FRONT model is described briefly, the simulation results are discussed and a first recommendation for the nodalisation is given. (orig.)

Recent development of fluorescent imaging for specific detection of tumors

International Nuclear Information System (INIS)

Nakata, Eiji; Morii, Takashi; Uto, Yoshihiro; Hori, Hitoshi

2011-01-01

Increasing recent studies on fluorescent imaging for specific detection of tumors are described here on strategies of molecular targeting, metabolic specificity and hypoxic circumstance. There is described an instance of a conjugate of antibody and pH-activable fluorescent ligand, which specifically binds to the tumor cells, is internalized in the cellular lysozomes where their pH is low, and then is activated to become fluorescent only in viable tumor cells. For the case of metabolic specificity, excessive loading of the precursor (5-aminolevulinic acid) of protoporphyrin IX (ppIX), due to their low activity to convert ppIX to heme B, results in making tumors observable in red as ppIX emits fluorescence (red, 585 nm) when excited by blue ray of 410 nm. Similarly, imaging with indocyanine green which is accumulated in hepatoma cells is reported in success in detection of small lesion and metastasis when the dye is administered during operation. Reductive reactions exceed in tumor hypoxic conditions, of which feature is usable for imaging. Conjugates of nitroimidazole and fluorescent dye are reported to successfully image tumors by nitro reduction. Authors' UTX-12 is a non-fluorescent nitroaromatic derivative of pH-sensitive fluorescent dye seminaphtharhodafluor (SNARF), and is designed for the nitro group, the hypoxia-responding sensor, to be reduced in tumor hypoxic conditions and then for the aromatic moiety to be cleaved to release free SNARF. Use of hypoxia-inducible factor-1 (HIF-1) for imaging has been also reported in many. As above, studies on fluorescent imaging for specific detection of tumors are mostly at fundamental step but its future is conceivably promising along with advances in other technology like fluorescent endoscopy and multimodal imaging. (author)

Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

Science.gov (United States)

Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

2014-09-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

The prototypical ranitidine analog JWS-USC-75-IX improves information processing and cognitive function in animal models.

Science.gov (United States)

Terry, Alvin V; Buccafusco, Jerry J; Herman, Elizabeth J; Callahan, Patrick M; Beck, Wayne D; Warner, Samantha; Vandenhuerk, Leah; Bouchard, Kristy; Schwarz, Gary M; Gao, Jie; Chapman, James M

2011-03-01

This study was designed to evaluate further a prototypical ranitidine analog, JWS-USC-75-IX, [(3-[[[2-[[(5-dimethylaminomethyl)-2-furanyl]methyl]thio]ethyl]amino]-4-nitropyridazine, JWS], for neuropharmacologic properties that would theoretically be useful for treating cognitive and noncognitive behavioral symptoms of neuropsychiatric disorders. JWS was previously found to inhibit acetylcholinesterase (AChE) activity, serve as a potent ligand at muscarinic M₂ acetylcholine receptors, and elicit positive effects on spatial learning, passive avoidance, and working memory in rodents. In the current study, JWS was evaluated for binding activity at more than 60 neurotransmitter receptors, transporters, and ion channels, as well as for inhibitory activity at AChE and butyrylcholinesterase (BChE). The results indicate that JWS inhibits AChE and BChE at low (micromolar) concentrations and that it is a functional antagonist at M₂ receptors (K(B) = 320 nM). JWS was subsequently evaluated orally across additional behavioral assays in rodents (dose range, 0.03-10.0 mg/kg) as well as nonhuman primates (dose range, 0.05-2.0 mg/kg). In rats, JWS improved prepulse inhibition (PPI) of the acoustic startle response in nonimpaired rats and attenuated PPI deficits in three pharmacologic impairment models. JWS also attenuated scopolamine and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801)-related impairments in a spontaneous novel object recognition task and a five-choice serial reaction time task, respectively. In monkeys, JWS elicited dose-dependent improvements of a delayed match-to-sample task as well as an attention-related version of the task where randomly presented (task-relevant) distractors were presented. Thus, JWS (potentially via effects at several drug targets) improves information processing, attention, and memory in animal models and could potentially treat the cognitive and behavioral symptoms of some neuropsychiatric illnesses.

Porphyrin Interactions with Wild Type and Mutant Mouse Ferrochelatase

Energy Technology Data Exchange (ETDEWEB)

Ferreira, Gloria C.; Franco, Ricardo; Lu, Yi; Ma, Jian-Guo; Shelnutt, John A.

1999-05-19

Ferrochelatase (EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, catalyzes Fe²⁺ chelation into protoporphyrin IX. Resonance Raman and W-visible absorbance spectroscopes of wild type and engineered variants of murine ferrochelatase were used to examine the proposed structural mechanism for iron insertion into protoporphyrin by ferrochelatase. The recombinant variants (i.e., H207N and E287Q) are enzymes in which the conserved amino acids histidine-207 and glutamate-287 of murine ferrochelatase were substituted with asparagine and glutamine, respectively. Both of these residues are at the active site of the enzyme as deduced from the Bacillus subtilis ferrochelatase three-dimensional structure. Addition of free base or metalated porphyrins to wild type ferrochelatase and H207N variant yields a quasi 1:1 complex, possibly a monomeric protein-bound species. In contrast, the addition of porphyrin (either free base or metalated) to E287Q is sub-stoichiometric, as this variant retains bound porphyrin in the active site during isolation and purification. The specificity of porphyrin binding is confirmed by the narrowing of the structure-sensitive resonance Raman lines and the vinyl vibrational mode. Resonance Raman spectra of free base and metalated porphyrins bound to the wild type ferrochelatase indicate a nonplanar distortion of the porphyrin macrocycle, although the magnitude of the distortion cannot be determined without first defining the specific type of deformation. Significantly, the extent of the nonplanar distortion varies in the case of H207N- and E287Q-bound porphyrins. In fact, resonance Raman spectral decomposition indicates a homogeneous ruffled distortion for the nickel protoporphyrin bound to the wild type ferrochelatase, whereas both a planar and ruffled conformations are present for the H207N-bound porphyrin. Perhaps more revealing is the unusual resonance , 3 Raman spectrum of the endogenous E287Q-bound porphyrin, which has

Identification of genes encoding the type IX secretion system and secreted proteins in Flavobacterium columnare IA-S-4

Science.gov (United States)

Flavobacterium columnare, a member of the phylum Bacteroidetes, causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. Many members of the phylum Bacteroidetes use type IX secretion systems (T9SSs) to secrete enzymes...

In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients

NARCIS (Netherlands)

Preijers, T.; Hazendonk, H. C. A. M.; Fijnvandraat, K.; Leebeek, F. W. G.; Cnossen, M. H.; Mathôt, R. A. A.

2017-01-01

Background Patients with severe hemophilia B regularly administer prophylactic intravenous doses of clotting factor IX concentrate to maintain a trough level of at least 0.01 IU mL(-1) in order to prevent joint bleeds. Assessment of individual pharmacokinetic (PK) parameters allows individualization

Comparative proteomic analysis of Typha angustifolia leaf under chromium, cadmium and lead stress

Energy Technology Data Exchange (ETDEWEB)

Bah, Alieu Mohamed; Sun Hongyan; Chen Fei; Zhou Jing; Dai Huaxin; Zhang Guoping [Department of Agronomy, College of Agriculture and Biotechnology, Huajiachi Campus, Zhejiang University, Hangzhou 310029 (China); Wu Feibo, E-mail: wufeibo@zju.edu.cn [Department of Agronomy, College of Agriculture and Biotechnology, Huajiachi Campus, Zhejiang University, Hangzhou 310029 (China)

2010-12-15

The present study investigated Typha angustifolia leaf proteome in response to Cr, Cd and Pb stress. T. angustifolia of 90 (D90) and 130 d (D130) old plants were subjected to 1 mM Cr, Cd and Pb and samples were collected 30 d after treatment. 2-DE coupled with MS (mass spectrometry) was used to analyze and identify Cr, Cd and Pb-responsive proteins. More than 1600 protein spots were reproducibly detected on each gel, wherein 44, 46, 66 and 33, 26, 62 spots in D90 and D130 samples were differentially expressed by Cr, Cd, Pb over the control, respectively. Of these differentially expressed proteins, 3, 1, 8 overlapped in D90 and D130; while 5, 8, 5 with regulation factors above 3 in one of D90 or D130 samples. Total of 22 and 4 up- and down-regulated proteins were identified using MS and data bank analysis. Cr-induced expression of ATP synthase, RuBisCO small subunit and coproporphyrinogen III oxidase; Cd-induced RuBisCO large subunit; Pb up-regulated carbohydrate metabolic pathway enzymes of fructokinase, and improved RuBisCO activase and large subunit, Mg-protoporphyrin IX chelatase. Contrarily, elF4F was inhibited by Cr/Pb, chloroplast FtsZ-like protein and GF14omega impeded by Cd and Pb, respectively.

Comparative proteomic analysis of Typha angustifolia leaf under chromium, cadmium and lead stress

International Nuclear Information System (INIS)

Bah, Alieu Mohamed; Sun Hongyan; Chen Fei; Zhou Jing; Dai Huaxin; Zhang Guoping; Wu Feibo

2010-01-01

The present study investigated Typha angustifolia leaf proteome in response to Cr, Cd and Pb stress. T. angustifolia of 90 (D90) and 130 d (D130) old plants were subjected to 1 mM Cr, Cd and Pb and samples were collected 30 d after treatment. 2-DE coupled with MS (mass spectrometry) was used to analyze and identify Cr, Cd and Pb-responsive proteins. More than 1600 protein spots were reproducibly detected on each gel, wherein 44, 46, 66 and 33, 26, 62 spots in D90 and D130 samples were differentially expressed by Cr, Cd, Pb over the control, respectively. Of these differentially expressed proteins, 3, 1, 8 overlapped in D90 and D130; while 5, 8, 5 with regulation factors above 3 in one of D90 or D130 samples. Total of 22 and 4 up- and down-regulated proteins were identified using MS and data bank analysis. Cr-induced expression of ATP synthase, RuBisCO small subunit and coproporphyrinogen III oxidase; Cd-induced RuBisCO large subunit; Pb up-regulated carbohydrate metabolic pathway enzymes of fructokinase, and improved RuBisCO activase and large subunit, Mg-protoporphyrin IX chelatase. Contrarily, elF4F was inhibited by Cr/Pb, chloroplast FtsZ-like protein and GF14omega impeded by Cd and Pb, respectively.

The chlorophyll-deficient golden leaf mutation in cucumber is due to a single nucleotide substitution in CsChlI for magnesium chelatase I subunit.

Science.gov (United States)

Gao, Meiling; Hu, Liangliang; Li, Yuhong; Weng, Yiqun

2016-10-01

The cucumber chlorophyll-deficient golden leaf mutation is due to a single nucleotide substitution in the CsChlI gene for magnesium chelatase I subunit which plays important roles in the chlorophyll biosynthesis pathway. The Mg-chelatase catalyzes the insertion of Mg(2+) into the protoporphyrin IX in the chlorophyll biosynthesis pathway, which is a protein complex encompassing three subunits CHLI, CHLD, and CHLH. Chlorophyll-deficient mutations in genes encoding the three subunits have played important roles in understanding the structure, function and regulation of this important enzyme. In an EMS mutagenesis population, we identified a chlorophyll-deficient mutant C528 with golden leaf color throughout its development which was viable and able to set fruits and seeds. Segregation analysis in multiple populations indicated that this leaf color mutation was recessively inherited and the green color showed complete dominance over golden color. Map-based cloning identified CsChlI as the candidate gene for this mutation which encoded the CHLI subunit of cucumber Mg-chelatase. The 1757-bp CsChlI gene had three exons and a single nucleotide change (G to A) in its third exon resulted in an amino acid substitution (G269R) and the golden leaf color in C528. This mutation occurred in the highly conserved nucleotide-binding domain of the CHLI protein in which chlorophyll-deficient mutations have been frequently identified. The mutant phenotype, CsChlI expression pattern and the mutated residue in the CHLI protein suggested the mutant allele in C528 is unique among mutations identified so far in different species. This golden leaf mutant not only has its potential in cucumber breeding, but also provides a useful tool in understanding the CHLI function and its regulation in the chlorophyll biosynthesis pathway as well as chloroplast development.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro

Directory of Open Access Journals (Sweden)

Xiang GH

2013-12-01

Full Text Available Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Department of Radiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China*These two authors contributed equally to this workObjective: To evaluate the cytotoxicity of poly(ethylene glycol-block-poly(D,L-lactic acid (PEG-PDLLA nanovesicles loaded with doxorubicin (DOX and the photosensitizer hematoporphyrin monomethyl ether (HMME on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms.Methods: PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME, and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX, HMME (PEG-PDLLA-HMME, or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined.Results: Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with

Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

Science.gov (United States)

Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

2016-01-01

Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

Unity in John 17 and in IQS I-IX: A comparative study

Directory of Open Access Journals (Sweden)

B. W. de Wet

1997-08-01

Full Text Available The unity theme as it is found in John 17 and in IQS I-IX provides sufficient comparative material to give an indication of the extent to which John�s theology flourished within the contemporary Jewish context. It is argued that the events surrounding Christ constituted for John the central point of orientation according to which the typical Jewish ideas could be interpreted and reformulated. It is finally concluded that, according to this radical and exclusive Christian dynamic approach, certain elements within Judaism, also found among members of the Qumran community, were reinterpreted, while others were either continued or discontinued.

[Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

Science.gov (United States)

Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

2018-04-25

The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

One of Gibbs's ideas that has gone unnoticed (comment on chapter IX of his classic book)

International Nuclear Information System (INIS)

Sukhanov, Alexander D; Rudoi, Yurii G

2006-01-01

We show that contrary to the commonly accepted view, Chapter IX of Gibbs's book [1] contains the prolegomena to a macroscopic statistical theory that is qualitatively different from his own microscopic statistical mechanics. The formulas obtained by Gibbs were the first results in the history of physics related to the theory of fluctuations in any macroparameters, including temperature. (from the history of physics)

Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

International Nuclear Information System (INIS)

Yang, Hanna; Kwon, Chang Seob; Choi, Yoonjung; Lee, Daeyoup

2016-01-01

Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Yang, Hanna [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kwon, Chang Seob [Department of Chemistry and Biology, Korea Science Academy of KAIST, Busan, 614-822 (Korea, Republic of); Choi, Yoonjung, E-mail: jjungii@kaist.ac.kr [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Daeyoup, E-mail: daeyoup@kaist.ac.kr [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

2016-08-05

Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

Weighted oscillator strengths and lifetimes for the S IX and S X spectra

International Nuclear Information System (INIS)

Borges, F.O.; Cavalcanti, G.H.; Trigueiros, A.G.

2003-01-01

The weighted oscillator strengths (gf) and the lifetimes presented in this work were carried out in a multi configuration Hartree-Fock relativistic (HFR) approach. In this calculation, the electrostatic parameters were optimized by a least-squares procedure, in order to improve the adjustment to experimental energy levels. This method produces gf-values that are in better agreement with intensity observations and lifetime values that are closer to the experimental ones. In this work, we presented all the experimentally known electric dipole S IX and S X spectral lines

IX Simposio Ibérico sobre Nutrición Mineral de las Plantas

OpenAIRE

Abadía Bayona, Javier

2003-01-01

Del 10 al 13 de Septiembre de 2002 se celebró el IX Simposio Ibérico sobre Nutrición Mineral de las Plantas en el Campus de Aula Dei de Zaragoza. El Simposio se realizó bajo los auspicios de la Sociedad Española de Fisiología Vegetal, el Consejo Superior de Investigaciones Científicas (CSIC), el Instituto Agronómico Mediterráneo de Zaragoza-Centro Internacional de Altos Estudios Agronómicos Mediterráneos (CIHEAM-IAMZ), la Asociación Internacional para la Optimización de...

Simulation of an IXS imaging analyzer with an extended scattering source

Energy Technology Data Exchange (ETDEWEB)

Suvorov, Alexey [Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II; Cai, Yong Q. [Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II

2016-09-15

A concept of an inelastic x-ray scattering (IXS) spectrograph with an imaging analyzer was proposed recently and discussed in a number of publications (see e.g. Ref.1). The imaging analyzer as proposed combines x-ray lenses with highly dispersive crystal optics. It allows conversion of the x-ray energy spectrum into a spatial image with very high energy resolution. However, the presented theoretical analysis of the spectrograph did not take into account details of the scattered radiation source, i.e. sample, and its impact on the spectrograph performance. Using numerical simulations we investigated the influence of the finite sample thickness, the scattering angle and the incident energy detuning on the analyzer image and the ultimate resolution.

AGuIX, a theranostic nano-particle to improve image-guided radiation therapy: a proof of concept in pancreatic cancer

International Nuclear Information System (INIS)

Detappe, Alexandre

2017-01-01

Previous studies demonstrated AGuIX ability to act as an efficient radiosensitizer under the presence of preclinical radiations or monoenergetic radiation beams for multiple cancer models. The preclinical irradiation (220 kV) has been shown effective in activating high atomic number (Z) nanoparticles. The energy peak is close to the k-edge of the different high-Z elements used (50.2 keV for the gadolinium), leading to a strong photoelectric effect. Auger electrons generation and biological effects occur afterwards creating a local dose enhancement. However, clinical treatments use a higher energy beam (≥6 MV). At these energy ranges, the photoelectric probability is less important, decreasing the direct interaction of the nanoparticles with the incoming photons. We performed a proof of concept on a pancreatic tumor model, known for its low survival rates, with preclinical and clinical radiation beams to evaluate the efficacy of the AGuIX. To increase the efficacy of the clinical radiation beam without modifying the nanoparticle structure in order to obtain a dose enhancement close to the one observed with the preclinical beam, we evaluated key clinical beam parameters to understand and increase the mechanisms of interaction between the incident photons and the high-Z nanoparticles. Hence, we evaluated analytically the impact of the radiation beam under different conditions of irradiation, confirming the potential of the AGuIX with a preclinical beam, and finally shown their significant efficacy under a clinical setup. This study is the first to evaluate the potential of a high-Z nanoparticle to act as radiosensitizer following low dose intravenous injections. (author)

THE IX EUROPEAN FORUM ON ANTIPHOSPHOLIPID ANTIBODIES. A BRIEF REVIEW

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Nataliya V Seredavkina

2014-01-01

Full Text Available The article presents a brief review of the proceedings of the IX European Forum on antiphospholipid antibodies held in May 2013 in Krakow (Poland. The aim of the Forum is to coordinate multicenter projects focused on antiphospholipid antibodies (aPL, both clinical and fundamental research, based on cooperation between the European countries. The main purpose is to stimulate research into all aspects of aPL, to facilitate the exchange of information between institutions, and to involve many centers in different countries into scientific research on this issue. The issues of standardization of the diagnostic criteria for antiphospholipid syndrome (APS, primarily serological markers (their specificity, sensitivity and correlation with clinical manifestations, as well as non-criterial manifestations of APS, were considered at the meeting. In addition, the therapy problems were discussed.

In vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints

Science.gov (United States)

Mallidi, Srivalleesha; Mai, Zhiming; Rizvi, Imran; Hempstead, Joshua; Arnason, Stephen; Celli, Jonathan; Hasan, Tayyaba

2015-04-01

In view of the increase in cancer-related mortality rates in low- to middle-income countries (LMIC), there is an urgent need to develop economical therapies that can be utilized at minimal infrastructure institutions. Photodynamic therapy (PDT), a photochemistry-based treatment modality, offers such a possibility provided that low-cost light sources and photosensitizers are available. In this proof-of-principle study, we focus on adapting the PDT light source to a low-resource setting and compare an inexpensive, portable, battery-powered light-emitting diode (LED) light source with a standard, high-cost laser source. The comparison studies were performed in vivo in a xenograft murine model of human squamous cell carcinoma subjected to 5-aminolevulinic acid-induced protoporphyrin IX PDT. We observed virtually identical control of the tumor burden by both the LED source and the standard laser source. Further insights into the biological response were evaluated by biomarker analysis of necrosis, microvessel density, and hypoxia [carbonic anhydrase IX (CAIX) expression] among groups of control, LED-PDT, and laser-PDT treated mice. There is no significant difference in the percent necrotic volume and CAIX expression in tumors that were treated with the two different light sources. These encouraging preliminary results merit further investigations in orthotopic animal models of cancers prevalent in LMICs.

Photodynamic Therapy and Non-Melanoma Skin Cancer

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Liezel L. Griffin

2016-10-01

Full Text Available Non-melanoma skin cancer (NMSC is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT is gaining popularity for the treatment of basal cell carcinoma (BCC, Bowen’s disease (BD and actinic keratosis (AK. A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate PDT for AKs has the advantage of decreased pain and better patient tolerance. PDT is an effective treatment for superficial BCC, BD and both individual and field treatment of AKs. Excellent cosmesis can be achieved with high patient satisfaction. Variable results have been reported for nodular BCC, with improved outcomes following pretreatment and repeated PDT cycles. The more aggressive basisquamous, morphoeic infiltrating subtypes of BCC and invasive squamous cell carcinoma (SCC are not suitable for PDT. Prevention of “field cancerization” in organ transplant recipients on long-term immunosuppression and patients with Gorlin syndrome (naevoid basal cell carcinoma syndrome is a promising development. The optimisation of PDT techniques with improved photosensitiser delivery to target tissues, new generation photosensitisers and novel light sources may expand the future role of PDT in NMSC management.

Clinical application of photodynamic medicine technology using light-emitting fluorescence imaging based on a specialized luminous source.

Science.gov (United States)

Namikawa, Tsutomu; Fujisawa, Kazune; Munekage, Eri; Iwabu, Jun; Uemura, Sunao; Tsujii, Shigehiro; Maeda, Hiromichi; Kitagawa, Hiroyuki; Fukuhara, Hideo; Inoue, Keiji; Sato, Takayuki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2018-04-04

The natural amino acid 5-aminolevulinic acid (ALA) is a protoporphyrin IX (PpIX) precursor and a new-generation photosensitive substance that accumulates specifically in cancer cells. When indocyanine green (ICG) is irradiated with near-infrared (NIR) light, it shifts to a higher energy state and emits infrared light with a longer wavelength than the irradiated NIR light. Photodynamic diagnosis (PDD) using ALA and ICG-based NIR fluorescence imaging has emerged as a new diagnostic technique. Specifically, in laparoscopic examinations for serosa-invading advanced gastric cancer, peritoneal metastases could be detected by ALA-PDD, but not by conventional visible-light imaging. The HyperEye Medical System (HEMS) can visualize ICG fluorescence as color images simultaneously projected with visible light in real time. This ICG fluorescence method is widely applicable, including for intraoperative identification of sentinel lymph nodes, visualization of blood vessels in organ resection, and blood flow evaluation during surgery. Fluorescence navigation by ALA-PDD and NIR using ICG imaging provides good visualization and detection of the target lesions that is not possible with the naked eye. We propose that this technique should be used in fundamental research on the relationship among cellular dynamics, metabolic enzymes, and tumor tissues, and to evaluate clinical efficacy and safety in multicenter cooperative clinical trials.

Dye Sensitizers for Photodynamic Therapy

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Harold S. Freeman

2013-03-01

Full Text Available Photofrin® was first approved in the 1990s as a sensitizer for use in treating cancer via photodynamic therapy (PDT. Since then a wide variety of dye sensitizers have been developed and a few have been approved for PDT treatment of skin and organ cancers and skin diseases such as acne vulgaris. Porphyrinoid derivatives and precursors have been the most successful in producing requisite singlet oxygen, with Photofrin® still remaining the most efficient sensitizer (quantum yield = 0.89 and having broad food and drug administration (FDA approval for treatment of multiple cancer types. Other porphyrinoid compounds that have received approval from US FDA and regulatory authorities in other countries include benzoporphyrin derivative monoacid ring A (BPD-MA, meta-tetra(hydroxyphenylchlorin (m-THPC, N-aspartyl chlorin e6 (NPe6, and precursors to endogenous protoporphyrin IX (PpIX: 1,5-aminolevulinic acid (ALA, methyl aminolevulinate (MAL, hexaminolevulinate (HAL. Although no non-porphyrin sensitizer has been approved for PDT applications, a small number of anthraquinone, phenothiazine, xanthene, cyanine, and curcuminoid sensitizers are under consideration and some are being evaluated in clinical trials. This review focuses on the nature of PDT, dye sensitizers that have been approved for use in PDT, and compounds that have entered or completed clinical trials as PDT sensitizers.

Seth Nicholson's First Satellite Discovery: Jupiter IX and His Orbit for It

Science.gov (United States)

Osterbrock, Donald E.

2006-12-01

Seth B. Nicholson was a graduate astronomy student at the University of California in Berkeley when he discovered his first satellite in 1914. He was later to discover three more, after he had joined the Mount Wilson Observatory staff following his PhD in 1915. Nicholson had begun his thesis on the problem of computing an improved orbit for J VIII, which had been discovered by Melotte in England in 1908, a distant irregular satellite like J VI and J VII. Nicholson was taking photographic plates to measure the position of J VIII in the summer of 1914 with the Crossley 36-inch reflector of Lick Observatory. He was a teaching assistant at Berkeley that summer, but would go up to Mount Hamilton to observe on weekends in the dark of the moon, traveling by rail, stage (an automobile on a regular schedule between San Jose and the observatory) and interurban trolley car, and sleeping in a shed near the Crossley dome. He first saw J IX as a much fainter object with the same motion as J VIII on a plate he took in late July 1914, and realized it must be another satellite of the giant planet. Nicholson obtained his first orbit of J IX, which had by then become his new thesis topic, in September, and published a paper on it in early 1915. Its orbit, like that of J VIII, was retrograde and irregular, but it was considerably fainter. Nicholson, a loyal student of Armin O. Leuschner, the head of the Berkeley Astronomy Division, used his teacher's "short method" (or analytic method) to calculate the orbit.

Pengembangan Soal Penalaran Model TIMSS Konteks Sumatera Selatan di Kelas IX SMP

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Hazlita Hazlita

2015-10-01

Full Text Available AbstrakPenelitian ini bertujuan untuk menghasilkan soal-soal penalaran model TIMSS konteks Sumatera Selatan yang valid dan praktis dan untuk melihat efek potensial soal matematika tipe TIMSS konteks Sumatera Selatan terhadap kemampuan penalaran matematis siswa. Subjek penelitian adalah siswa kelas IX SMPN 9 Palembang yang berjumlah 29 orang. Metode penelitian adalah penelitian pengembangan. Hasil penelitian menunjukkan bahwa sebanyak 37,93% siswa menunjukkan tingkat kemampuan penalaran matematis yang baik. Sebanyak 55,17% siswa menunjukkan tingkat kemampuan penalaran matematis yang cukup dan sebanyak 6,90% siswa menunjukkan tingkat kemampuan penalaran matematis yang kurang. Berdasarkan hasil tes tersebut, jika nilai rata-rata siswa siswa sebesar 39,24 dijadikan sebagai batas acuan, maka bisa disimpulkan bahwa 31,03% siswa memiliki kemampuan penalaran matematis yang kurang, sementara 68,97% siswa sudah memiliki kemampuan pelanaran matematis yang cukup baik. Kata Kunci: Soal Penalaran; TIMSS; Konteks Sumatera Selatan  AbstractThe aim of this research was developing valid and practical TIMSS reasoning problem on mathematics context of South Sumatra. The subjects of this research were 29 students of class IX SMPN 9 Palembang. The method of research is the development of research. The results showed that 37.93% of students showed levels of good mathematical reasoning abilities, 55.17% of students showed levels sufficient mathematical reasoning ability and 6.90% of students showed levels of mathematical reasoning abilities are lacking. Based on the test results, if the 39.24 was determined as minimum limit of success, it means that 31.03% of students have less mathematical reasoning ability, while 68.97% of students already have sufficient mathematical reasoning ability. Keywords: Problem Reasoning; TIMSS; Context South Sumatra

Performance and life cycle environmental benefits of recycling spent ion exchange brines by catalytic treatment of nitrate.

Science.gov (United States)

Choe, Jong Kwon; Bergquist, Allison M; Jeong, Sangjo; Guest, Jeremy S; Werth, Charles J; Strathmann, Timothy J

2015-09-01

Salt used to make brines for regeneration of ion exchange (IX) resins is the dominant economic and environmental liability of IX treatment systems for nitrate-contaminated drinking water sources. To reduce salt usage, the applicability and environmental benefits of using a catalytic reduction technology to treat nitrate in spent IX brines and enable their reuse for IX resin regeneration were evaluated. Hybrid IX/catalyst systems were designed and life cycle assessment of process consumables are used to set performance targets for the catalyst reactor. Nitrate reduction was measured in a typical spent brine (i.e., 5000 mg/L NO3(-) and 70,000 mg/L NaCl) using bimetallic Pd-In hydrogenation catalysts with variable Pd (0.2-2.5 wt%) and In (0.0125-0.25 wt%) loadings on pelletized activated carbon support (Pd-In/C). The highest activity of 50 mgNO3(-)/(min - g(Pd)) was obtained with a 0.5 wt%Pd-0.1 wt%In/C catalyst. Catalyst longevity was demonstrated by observing no decrease in catalyst activity over more than 60 days in a packed-bed reactor. Based on catalyst activity measured in batch and packed-bed reactors, environmental impacts of hybrid IX/catalyst systems were evaluated for both sequencing-batch and continuous-flow packed-bed reactor designs and environmental impacts of the sequencing-batch hybrid system were found to be 38-81% of those of conventional IX. Major environmental impact contributors other than salt consumption include Pd metal, hydrogen (electron donor), and carbon dioxide (pH buffer). Sensitivity of environmental impacts of the sequencing-batch hybrid reactor system to sulfate and bicarbonate anions indicate the hybrid system is more sustainable than conventional IX when influent water contains reuse cycles. The study showed that hybrid IX/catalyst reactor systems have potential to reduce resource consumption and improve environmental impacts associated with treating nitrate-contaminated water sources. Copyright © 2015 Elsevier Ltd. All rights

5. IX avati Pärnus paralleelselt Eesti Litograafiakeskuse korraldatud litograafiasümpoosioniga...

Index Scriptorium Estoniae

2003-01-01

Litograafiakeskuses litograafia ajalugu tutvustav näitus. Pärnu kontserdimajas noorte - Jaak Visnap, Inga Heamägi, Kadri Alesmaa, Marko Mäetamm, Viljar Kõiv, Lembe Ruben - litograafianäitus "New generation". Endla teatri näitusesaalides näitus "Old Stars" - esinevad Evi Tihemets, Marje Üksine, Raul Meel, Leonhard Lapin, Tiia Külv, Urmas Vaino, Herald Eelma. Teatri Küüni ja kohviku seintel noorte soome ja rootsi litograafide tööd. Pärnu mudaravilas ülevaade litokeskuse kursustel valminud töödest. Endises Linnagaleriis Rüütli t. näitus 6.-12. IX sümpoosioni raames toimunud workshop'ide töödest

"Prompt and Equitable" Explained: How to Craft a Title IX Compliant Sexual Harassment Policy and Why It Matters

Science.gov (United States)

Block, Jason A.

2012-01-01

An April 2011 "Dear Colleague" letter issued by the U.S. Department of Education's Office for Civil Rights provided new guidance related to Title IX and the civil rights violation inherent in sexual harassment cases. Using the "Dear Colleague" letter as a guide, this article will provide best practice suggestions to remedy…

Su Santidad el Papa Pío IX, y la semana santa romana de 1866, visto por un ilustre valenciano

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Del Río Hijas Ximenez, María Elena

2007-12-01

Full Text Available Francisco de Paula Ximénez and Marco made a trip to Italy in 1866. He left a chronicle unpublished. The story of his stay in Rome is published, during the Easter of this year. The chronicle of the celebrations reveals the fascination that exerted Pío IX on the travelling ones and it informs to us on the organization into which it was left of the Pontifical States.Francisco de Paula Ximénez y Marco hizo un viaje a Italia en 1866. Dejó una crónica inédita. Se publica el relato de su estancia en Roma, durante la semana santa de este año. La crónica de las celebraciones revela la fascinación que ejercía Pío IX sobre los peregrinos y nos informa sobre la organización de lo que quedaba de loa Estados Pontificios.

Seleção de genótipos de cana-de-açúcar para acúmulo de protoporfirina ix com uso de herbicidas inibidores da protox

OpenAIRE

Barberis,L.R.M.; Trindade,M.L.B.; Velini,E.D.

2009-01-01

O objetivo do presente trabalho foi selecionar genótipos de cana-de-açúcar por meio de inibidores da PROTOX e antioxidantes para indução do acúmulo de protoporfirina IX (PROTO IX) e/ou de seus precursores em plantas. Esses compostos podem ser utilizados como agentes sensibilizantes em terapia fotodinâmica (TFD), os quais possibilitam uma fonte de baixo custo para o tratamento de neoplasias e carcinomas. O experimento foi montado em câmara climatizada, com aplicação de nove tratamentos (1. oxy...

Lotófagos (Odisseia IX, 82-104: comida floral fácil e risco de desistência

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Teodoro Rennó Assunção

2016-03-01

Full Text Available Este artigo propõe uma tradução e um comentário do episódio dos Lotófagos na Odisseia (IX, 82-104, atentando tanto para sua organização interna enquanto episódio de viagem com uma cena típica de hospitalidade (resumida apenas à oferta de comida, quanto para sua posição e especificidade no conjunto das viagens maravilhosas de Odisseu (cantos IX a XII e no conjunto da Odisseia. Ele tenta definir os significados possíveis de lōtós (“lótus”, tais como apresentados por Heródoto e Teofrasto, em confronto com os poucos dados presentes na Odisseia (convergindo em ser ele uma planta não cultivada e colhida, e – o que é mais importante – tenta definir também os efeitos do consumo do lótus, que são como os de uma droga perigosa (como o haxixe, o ópio ou a mescalina que suprime a vontade de agir, ameaçando retrospectivamente o retorno de Odisseu e a própria narrativa da Odisseia.

Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression.

Science.gov (United States)

Cheng, Baohua; Guo, Yunliang; Li, Chuangang; Ji, Bingyuan; Pan, Yanyou; Chen, Jing; Bai, Bo

2014-08-15

Oxidative stress is involved in the pathogenesis of Parkinson's disease (PD). Edaravone has been shown to have a neuroprotective effect. In the present work, we investigated the effect of edaravone on 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells. Edaravone inhibited the decrease of cell viability and apoptosis induced by MPP(+) in PC12 cells. In addition, edaravone alleviated intracellular reactive oxygen species (ROS) production. MPP(+) induced heme oxygenase-1 (HO-1) expression, which was further enhanced by edaravone. The inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of edaravone. So edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating HO-1 expression. The data showed that edaravone was neuroprotective and could be potentially therapeutics for PD in future. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins

International Nuclear Information System (INIS)

Mack, John; Vermeiren, Christie; Heinrichs, David E.; Stillman, Martin J.

2004-01-01

We report the first characterization of the in vivo porphyrin scavenging abilities of two components of a newly discovered heme scavenging system involving iron-regulated surface determinant (Isd) proteins. These proteins are present within the cell envelope of the Gram-positive human pathogen Staphylococcus aureus. IsdC and IsdE, when expressed heterologously in Escherichia coli, efficiently scavenged intracellular heme and resulted in de novo heme synthesis in excess of 100-fold above background. Magnetic circular dichroism analyses showed that the heme-binding properties of the two proteins differ significantly from one another. IsdC bound almost exclusively free-base protoporphyrin IX, whereas the IsdE protein was associated with low spin Fe(III) and Fe(II) heme. These properties provide important insight into the possible mechanisms of iron scavenging from bound heme by Isd proteins

The Bolgary IX settlement – a site of the Ananyino finale in the vicinity of Perm

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Vasilyeva Anastasia V.

2015-06-01

Full Text Available The article presents materials recovered from the Bolgary IX settlement, attributed to the late Ananyino group of sites, discovered in the vicinity of the city of Perm on the left bank of the Kama River. The structures thus found were interpreted by the authors as, presumably, a dwelling (? and a cult building. The pre-Ananyino cult buildings are well known by two hillforts – Zuevy Klychi-1 on the Lower Kama and Argyzh on the Vyatka River. Small clay figurines, arrow heads, spindle whorls, small oblational cups and household ceramics were found within the cult buildings. Household ceramics are represented by some typical late Ananyino vessel forms: mainly bowls with a closed throat, sometimes with profiled pronounced neck. Some vessels have a collar on the rim. Ornamentation of the vessels includes versatile corded, combed and recessed compositions. The Bolgary IX material culture is considered in complex with simultaneous Protasy burial ground, which is located on a nearby promontory and has similar ceramics among the grave goods. This complex of sites (the settlement and the burial ground is dated back to 3rd-2nd centuries BC and is related by the authors to the period of transition from the Ananyino to the Glyadenovo cultures in the Kama River region.

Synthesis of chlorophyll-binding proteins in a fully-segregated ∆ycf54 strain of the cyanobacterium Synechocystis PCC 6803

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Sarah eHollingshead

2016-03-01

Full Text Available In the chlorophyll (Chl biosynthesis pathway the formation of protochlorophyllide is catalyzed by Mg-protoporphyrin IX methyl ester (MgPME cyclase. The Ycf54 protein was recently shown to form a complex with another component of the oxidative cyclase, Sll1214 (CycI, and partial inactivation of the ycf54 gene leads to Chl deficiency in cyanobacteria and plants. The exact function of the Ycf54 is not known, however, and further progress depends on construction and characterisation of a mutant cyanobacterial strain with a fully inactivated ycf54 gene. Here, we report the complete deletion of the ycf54 gene in the cyanobacterium Synechocystis 6803; the resulting ycf54 strain accumulates huge concentrations of the cyclase substrate MgPME together with another pigment, which we identified using nuclear magnetic resonance as 3-formyl MgPME. The detection of a small amount (~13% of Chl in the ycf54 mutant provides clear evidence that the Ycf54 protein is important, but not essential, for activity of the oxidative cyclase. The greatly reduced formation of protochlorophyllide in the ycf54 strain provided an opportunity to use 35S protein labelling combined with 2D electrophoresis to examine the synthesis of all known Chl-binding protein complexes under drastically restricted de novo Chl biosynthesis. We show that although the ycf54 strain synthesizes very limited amounts of photosystem I and the CP47 and CP43 subunits of photosystem II (PSII, the synthesis of PSII D1 and D2 subunits and their assembly into the reaction centre (RCII assembly intermediate were not affected. Furthermore, the levels of other Chl complexes such as cytochrome b6f and the HliD– Chl synthase remained comparable to wild-type. These data demonstrate that the requirement for de novo Chl molecules differs completely for each Chl-binding protein. Chl traffic and recycling in the cyanobacterial cell as well as the function of Ycf54 are discussed.

Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

Science.gov (United States)

Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

2016-02-05

Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Type IX Collagen Gene Mutations Can Result in Multiple Epiphyseal Dysplasia That Is Associated With Osteochondritis Dissecans and a Mild Myopathy

NARCIS (Netherlands)

Jackson, Gail C.; Marcus-Soekarman, Dominique; Stolte-Dijkstra, Irene; Verrips, Aad; Taylor, Jacqueline A.; Briggs, Michael D.

Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.

NARCIS (Netherlands)

Jackson, G.C.; Marcus-Soekarman, D.; Stolte-Dijkstra, I.; Verrips, A.; Taylor, J.A.; Briggs, M.D.

2010-01-01

Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

Enhancing Title Ix Due Process Standards in Campus Sexual Assault Adjudication: Considering the Roles of Distributive, Procedural, and Restorative Justice

Science.gov (United States)

Harper, Shannon; Maskaly, Jon; Kirkner, Anne; Lorenz, Katherine

2017-01-01

Title IX prohibits sex discrimination--including sexual assault--in higher education. The Department of Education Office for Civil Rights' 2011 "Dear Colleague Letter" outlines recommendations for campus sexual assault adjudication allowing a variety of procedures that fail to protect accused students' due process rights and victims'…

Optimalisasi Prestasi Belajar Materi Elektromagnet dengan Menggunakan Pendekatan Eksperimen dalam Pembelajaran IPA pada Peserta Didik Kelas IX A SMP Negeri 3 Teras Semester Gasal Kabupaten Boyolali Tahun Pelajaran 2011/2012

OpenAIRE

Budiharjo Budiharjo

2015-01-01

This research purpose is to describe about effort to increase learning achievement giving task autonomous structure in learning electromagnet material of the student’s class IX A SMP Negeri 3 Teras Boyolali regency semester 2011/2012. Subject and data source of the research the students class IX A sum 40 students. Collecting data method uses observation, documentation and test. Analysis data uses critic and comparative. Reaching indicator uses KKM 63 and complete target 100%. Research procedu...

Infrared photometry of the nova-like system IX Velorum (= CPD -4801577)

International Nuclear Information System (INIS)

Haug, Karlheinz

1988-01-01

Continuous IR photometry of the UX UMa-type nova-like system IX Velorum reveals phase-correlated light variations in JHK filter bands with an amplitude of about O m .06. From a periodogram analysis an orbital period of P = 0.1939 ± 0.0001 day is determined. Physical reasons for the observed IR light variability are discussed. Model light curve calculations demonstrate that the observed light curves can be interpreted by a superposition of ellipsoidal light variations and asymmetric light distribution on the surface of the secondary component owing to illumination from the disc. The observation of different heights of the two light maxima might be an indication for an additional orbital light variation due to the changing aspect of the disc and/or bright spot region. (author)

Oscillating Bianchi IX universe in Horava-Lifshitz gravity

International Nuclear Information System (INIS)

Misonoh, Yosuke; Maeda, Kei-ichi; Kobayashi, Tsutomu

2011-01-01

We study a vacuum Bianchi IX universe in the context of Horava-Lifshitz gravity. In particular, we focus on the classical dynamics of the universe and analyze how anisotropy changes the history of the universe. For small anisotropy, we find an oscillating universe as well as a bounce universe just as the case of the Friedmann-Lemaitre-Robertson-Walker spacetime. However, if the initial anisotropy is large, we find the universe which ends up with a big crunch after oscillations if a cosmological constant Λ is zero or negative. For Λ>0, we find a variety of histories of the universe, that is a de Sitter expanding universe after oscillations in addition to the oscillating solution and the previous big crunch solution. This fate of the universe shows sensitive dependence of initial conditions, which is one of the typical properties of a chaotic system. If the initial anisotropy is near the upper bound, we find the universe starting from a big bang and ending up with a big crunch for Λ≤0, and a de Sitter expanding universe starting from a big bang for Λ>0.

The 3d84s-3d84p transitions in Br IX

International Nuclear Information System (INIS)

Zeng, X.T.; Jupen, C.; Livingston, A.E.; Westerlind, M.; Engstroem, L.; Martinson, I.

1990-01-01

The spectrum of bromine was studied in the region 450-1100 A, using the beam-foil method with 6 MeV ions from a tandem accelerator. On the basis of isoelectronic extrapolations and theoretical calculations, 32 lines were classified as transitions between the 3p 6 3d 8 4s and 3p 6 3d 8 4p configurations of Co-like BrIX. Fo the 16 possible 4s levels 13 have been located, and 11 new 4p levels have been added to the previously known ones. Only 4 of all the 4p levels (45 in total) remain to be found. (orig.)

Significant Microsynteny with New Evolutionary Highlights Is Detected through Comparative Genomic Sequence Analysis of Maize CCCH IX Gene Subfamily

Directory of Open Access Journals (Sweden)

Wei-Jun Chen

2015-01-01

Full Text Available CCCH zinc finger proteins, which are characterized by the presence of three cysteine residues and one histidine residue, play important roles in RNA processing in plants. Subfamily IX CCCH proteins were recently shown to function in stress tolerances. In this study, we analyzed CCCH IX genes in Zea mays, Oryza sativa, and Sorghum bicolor. These genes, which are almost intronless, were divided into four groups based on phylogenetic analysis. Microsynteny analysis revealed microsynteny in regions of some gene pairs, indicating that segmental duplication has played an important role in the expansion of this gene family. In addition, we calculated the dates of duplication by Ks analysis, finding that all microsynteny blocks were formed after the monocot-eudicot divergence. We found that deletions, multiplications, and inversions were shown to have occurred over the course of evolution. Moreover, the Ka/Ks ratios indicated that the genes in these three grass species are under strong purifying selection. Finally, we investigated the evolutionary patterns of some gene pairs conferring tolerance to abiotic stress, laying the foundation for future functional studies of these transcription factors.

The Ripple Effect of Title IX on Women's Health Issues: Treating an Increasingly Active Population.

Science.gov (United States)

Mees, Patricia D

2003-04-01

Perhaps no area in sports medicine has changed as dramatically in the last 30 years as women's health. Title IX of the Education Amendments of 1972 prohibited discrimination on the basis of sex in all curricular and extracurricular activities at educational institutions that receive federal funding. Before 1972, many assumed that women were not interested in sports and that there was no need to provide programs for girls and women, and most primary care physicians had little experience in treating female athletes and other active women.

Puzzle of the particles and the universe. The inner life of the elementary particles IX d

International Nuclear Information System (INIS)

Geitner, Uwe W.

2013-01-01

The series The Inner Life of the Elementary Particles attempts to develop the elementary particles along of a genealogical tree, which begins before the ''big bang''. The simple presentation without mathematics opens also for the interested layman a plastic understanding. Volume IX discusses the known puzzles of particle physics and cosmology and offers for many of them explanation models. Explanation approaches are among others the ''DNA'' of the elementary particles and the interpretation of the quanta and the spin.

Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

Science.gov (United States)

Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

2013-03-01

Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray.

Science.gov (United States)

Pan, Chien-Lin; Chen, Ming-Hong; Tung, Fu-I; Liu, Tse-Ying

2017-01-01

Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently

[Rheumatoid arthritis among mapuche aborigines. A 16 years experience in the IX Region of the Chile].

Science.gov (United States)

Kaliski, S; Bustos, L; Artigas, C; Alarcón, C; Vega, M A; Cárdenas, C

2001-03-01

Mapuche, Chilean natives, represent approximately 9.8% of Chilean population and in the IX region of the country, they account for 18.4% of population over 15 years old. They preserve some socio-cultural characteristics that make them different to the rest of the population. To describe the epidemiological characteristics rheumatoid arthritis among Mapuche natives. Retrospective review of patients of Mapuche origin with rheumatoid arthritis, seen at Temuco Hospital between 1980 and 1996. Among 308 cases gathered, only 106 (93 women, aged 55 +/- 10 years old) complied with 1987 American College of Rheumatology (ACR) criteria for rheumatoid arthritis. The disease began between 29 and 52 years old in 73% of patients and the mean delay in diagnosis was 4.4 years. At diagnosis, 99% had symmetric poliarthritis, 28.3% had either fatigue, fever or weight loss, and 46.9% were in class III or in class IV of ACR-1991. Fifty three percent of patients developed Sicca syndrome, 36% developed nodules, 23% developed Raynaud phenomenon, 11% developed pulmonary involvement, 7% developed vasculitis, 5% developed neurological manifestations and 19% developed ophthalmologic involvement. Rheumatoid factor was positive in 78% and 73% had erosions. HLA DR4 was (+) in 60% of 30 patients. Thirty percent required 3 or more disease modifying drugs and prednisone over 10 mg/day. There was no correlation between functional capacity and several other features of the disease. Mapuche rheumatoid arthritis patients are detected late and have a poor functional capacity at the time of diagnosis. They also have a higher proportion of extraarticular manifestations, more erosions and require more aggressive treatments.

Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B

Science.gov (United States)

Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H.; Streatfield, Stephen J.; Herzog, Roland W.; Daniell, Henry

2015-01-01

Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. PMID:26302233

Data Summary Report for the Annual Fourmile Branch and F- and H-Area Seeplines, Appendix IX Metals and Radionuclides, 1998

International Nuclear Information System (INIS)

Koch, J.

1999-01-01

This report presents a summary of the definitive data validation and verification for the 1998 RFI/RI annual Appendix IX metals and radionuclides survey for Fourmile Branch and the F- and H-Area Seeplines. The validation process began with project mobilization and continued through the delivery of EDDs and this report

X-ray spectral line coincidences between fluorine VIII (and IX) and transition metal lines

International Nuclear Information System (INIS)

Charatis, G.; Rockett, P.D.; Burkhalter, P.G.

1983-01-01

X-ray spectroscopy was performed in the 12 to 15 A region, recording L-shell lines from selected laser-irradiated transition metals. Line coincidences and near coincidences were identified between Fe, Cr, Mn, and Ni L-spectra, and F VIII and F IX K-shell lines. Wavelengths were determined to accuracies of 1 to 3 mA and will be utilized in selecting potential pumping candidates in future x-ray lasing schemes. High-resolution x-ray spectra were collected under controlled illumination and target conditions using 1.05 μm and 0.527 μm laser excitation with the KMS CHROMA laser

Photodetection with 5-Aminolevulinic acid-induced protoporphyrin IX in the rat abdominal cavity: drug-dose-dependent fluorescence kinetics

NARCIS (Netherlands)

Aalders, M. C.; Sterenborg, H. J.; Stewart, F. A.; van der Vange, N.

2000-01-01

In 75% of cases, ovarian carcinoma has already metastasized in the abdominal cavity at the time of diagnosis. For determination of the necessity for a supplementary therapy, in addition to surgical resection, it is important to localize and stage microscopical intraperitoneal metastases of the

The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide

Energy Technology Data Exchange (ETDEWEB)

Lee, Wen-Ying [Department of Pathology, Chi-Mei Hospital, Tainan, Taiwan (China); Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Chen, Yen-Chou [Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Shih, Chwen-Ming; Lin, Chun-Mao; Cheng, Chia-Hsiung; Chen, Ku-Chung [Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Cheng-Wei, E-mail: cwlin@tmu.edu.tw [Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2014-01-01

Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitumor activity; the inhibitory mechanism, however, is still unclear. In the present study, we found that treatment with [Ru(CO){sub 3}Cl{sub 2}]{sub 2} (RuCO), a CO-releasing compound, reduced the growth of human MCF7 and MDA-MB-231 breast cancer cells. Analysis of growth-related proteins showed that treatment with RuCO down-regulated cyclinD1, CDK4, and hTERT protein expressions. Interestingly, RuCO treatment resulted in opposite effects on wild-type and mutant p53 proteins. These results were similar to those of cells treated with geldanamycin (a heat shock protein (HSP)90 inhibitor), suggesting that RuCO might affect HSP90 activity. Moreover, RuCO induced mutant p53 protein destabilization accompanied by promotion of ubiquitination and proteasome degradation. The induction of HO-1 by cobalt protoporphyrin IX (CoPP) showed consistent results, while the addition of tin protoporphyrin IX (SnPP), an HO-1 enzymatic inhibitor, diminished the RuCO-mediated effect. RuCO induction of HO-1 expression was reduced by a p38 mitogen-activated protein kinase inhibitor (SB203580). Additionally, treatment with a chemopreventive compound, curcumin, induced HO-1 expression accompanied with reduction of HSP90 client protein expression. The induction of HO-1 by curcumin inhibited 12-O-tetradecanoyl-13-acetate (TPA)-elicited matrix metalloproteinase-9 expression and tumor invasion. In conclusion, we provide novel evidence underlying HO-1's antitumor mechanism. CO, a byproduct of HO-1, suppresses HSP90 protein activity, and the induction of HO-1 may possess potential as a cancer therapeutic. - Highlights: • CO and HO-1 inhibited the growth of human breast cancer cells. • CO and HO-1 attenuated HSP90 and its client proteins expression. • CO induced mutant p53 protein

HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.

Science.gov (United States)

Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

2016-08-18

This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

Nucleoli in large (giant bi- and multinucleate cells after apoptosis-inducing photodynamic treatment

Directory of Open Access Journals (Sweden)

K Smetana

2009-06-01

Full Text Available The present experimental study was undertaken to provide information on nucleolar changes accompanying the apoptotic process in large or giant binucleate and multinucleate cells (LBMNCs. Such cells were present in a small but constant percentage in cultures of HL-60 cells. The apoptotic process was induced by photodynamic treatment (PDT by means of 5-aminolaevulinic acid (ALA as the precursor of the photosensitizer protoporphyrin IX and irradiation with broad spectrum blue light (BL. Nucleolar changes in LBMNCs were characterized by marked reduction or disappearance of silver stained particles representing AgNORs in nucleoli including the large ones. In addition, PDT also significantly reduced the number of nucleoli regardless of their size. These changes apparently reflected the decrease or cessation of nucleolar biosynthetic activities and resembled those which were previously observed in naturally maturing bone marrow megakaryocytes (Janoutová et al., 2001.

Interaction of porphyrins with CdTe quantum dots

International Nuclear Information System (INIS)

Zhang Xing; Liu Zhongxin; Ma Lun; Hossu, Marius; Chen Wei

2011-01-01

Porphyrins may be used as photosensitizers for photodynamic therapy, photocatalysts for organic pollutant dissociation, agents for medical imaging and diagnostics, applications in luminescence and electronics. The detection of porphyrins is significantly important and here the interaction of protoporphyrin-IX (PPIX) with CdTe quantum dots was studied. It was observed that the luminescence of CdTe quantum dots was quenched dramatically in the presence of PPIX. When CdTe quantum dots were embedded into silica layers, almost no quenching by PPIX was observed. This indicates that PPIX may interact and alter CdTe quantum dots and thus quench their luminescence. The oxidation of the stabilizers such as thioglycolic acid (TGA) as well as the nanoparticles by the singlet oxygen generated from PPIX is most likely responsible for the luminescence quenching. The quenching of quantum dot luminescence by porphyrins may provide a new method for photosensitizer detection.

Design of PDT protocols using delta-aminolevulinic acid (5ALA)

Science.gov (United States)

Jacques, Steven L.; He, Xiao-Yan; Gofstein, Gary

1993-06-01

The kinetics of protoporphyrin IX (PPIX) synthesis, bioconversion to other metabolic products, and photobleaching were measured in cell cultures after incubation in media containing the metabolic precursor for heme synthesis, (delta) -aminolevulinic acid (5 ALA). A compartmental model described the kinetics in terms of rate constants for the three processes. The maximum amount of PPIX that can be attained in the cells and the concentration of 5 ALA in the medium that obtains this maximum were determined. Using this information, two dosimetry protocols are outlined which both involve complete photobleaching of the PPIX: (1) the classical acute protocol using maximum 5 ALA to produce maximum PPIX and a light treatment of about 0.5 - 1 hr, and (2) a novel prolonged protocol using continuous low-level 5 ALA delivery to produce only slightly elevated PPIX and an extended light exposure time of over 24 hrs.

Homoclinic chaos in axisymmetric Bianchi IX cosmologies reexamined

International Nuclear Information System (INIS)

Soares, I. Damiao; Stuchi, T.J.

2005-01-01

The dynamics of Bianchi IX models with two scale factors A(t) and B(t) is reexamined. The matter content of the model is assumed to be comoving dust plus a positive cosmological constant. We make a complete numerical construction of topological structures present in the phase space of the model, as the center manifold of periodic orbits and the stable and unstable cylinders of orbits that emerge from the center manifold, associated to a saddle-center critical point. We exhibit the homoclinic intersections of the unstable and stable cylinders that produce homoclinic chaos in the models. A=0 is not a singularity of the Hamiltonian dynamics and any truncation of the dynamics at A=0 is bound to a loss of information. We make an explicit construction of a set with a horseshoe structure in the A>0 region, of initial conditions corresponding to initially expanding universes. We show that the dynamics of this set is chaotic even if restricted to the region A>0 and has the Einstein universe configuration as a chaotic scatterer. The result however demands the information of the Hamiltonian dynamics in whole phase space, including the region A<0. This refutes recent claims that no homoclinic chaos is present in the dynamics of the model

Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats.

Science.gov (United States)

Yokoo, T; Kamimura, K; Suda, T; Kanefuji, T; Oda, M; Zhang, G; Liu, D; Aoyagi, Y

2013-08-01

The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml(-1)) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone.

Retsensioon : Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare. Peatoimetaja Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. 326 lk. / Mart Nutt

Index Scriptorium Estoniae

Nutt, Mart, 1962-

2004-01-01

Arvustus: Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare / peatoim. Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. - Lisatud: Ott Heinapuu tutvustav sõnum retsenseeritud väljaande kohta lk. 193. - Vt. ka: http://www.riigikogu.ee/rito/index.php?id=11357

Breeding of transgenic cattle for human coagulation factor IX by a combination of lentiviral system and cloning.

Science.gov (United States)

Monzani, P S; Sangalli, J R; De Bem, T H C; Bressan, F F; Fantinato-Neto, P; Pimentel, J R V; Birgel-Junior, E H; Fontes, A M; Covas, D T; Meirelles, F V

2013-02-28

Recombinant coagulation factor IX must be produced in mammalian cells because FIX synthesis involves translational modifications. Human cell culture-based expression of human coagulation factor IX (hFIX) is expensive, and large-scale production capacity is limited. Transgenic animals may greatly increase the yield of therapeutic proteins and reduce costs. In this study, we used a lentiviral system to obtain transgenic cells and somatic cell nuclear transfer (SCNT) to produce transgenic animals. Lentiviral vectors carrying hFIX driven by 3 bovine β-casein promoters were constructed. Bovine epithelial mammary cells were transduced by lentivirus, selected with blasticidin, plated on extracellular matrix, and induced by lactogenic hormones; promoter activity was evaluated by quantitative PCR. Transcriptional activity of the 5.335-kb promoter was 6-fold higher than the 3.392- and 4.279-kb promoters, which did not significantly differ. Transgenic bovine fibroblasts were transduced with lentivirus carrying the 5.335-kb promoter and used as donor cells for SCNT. Cloned transgenic embryo production yielded development rates of 28.4%, similar to previous reports on cloned non-transgenic embryos. The embryos were transferred to recipient cows (N = 21) and 2 births of cloned transgenic cattle were obtained. These results suggest combination of the lentiviral system and cloning may be a good strategy for production of transgenic cattle.

Discharge behaviour of Mg-Al-Pb and Mg-Al-Pb-In alloys as anodes for Mg-air battery

International Nuclear Information System (INIS)

Wang, Naiguang; Wang, Richu; Peng, Chaoqun; Peng, Bing; Feng, Yan; Hu, Chengwang

2014-01-01

Highlights: • We investigate the effect of indium on the discharge behaviour of Mg-Al-Pb alloy. • We evaluate the performance of Mg-air batteries with Mg-Al-Pb and Mg-Al-Pb-In anodes. • We analyze the activation mechanism of Mg-Al-Pb-In alloy in the discharge process. - Abstract: The discharge behaviour of Mg-Al-Pb and Mg-Al-Pb-In alloys in 3.5 wt.% NaCl solution is investigated by electrochemical techniques, and compared with that of pure magnesium. The results show that Mg-Al-Pb-In alloy provides a more negative potential and exhibits a higher utilization efficiency in contrast with Mg-Al-Pb alloy and pure magnesium during the half-cell test at a large current density, and gives desirable discharge performance when used as anode for Mg- air battery. The peak power density of the Mg-air battery with Mg-Al-Pb-In anode is 94.5 mW cm −2 , which is comparable with those of Mg-H 2 O 2 semi-fuel batteries. Moreover, the activation mechanism of Mg-Al-Pb-In alloy during the discharge process is also analyzed

ADVANCES AND CHALLENGES IN SUGARCANE BIOTECHNOLOY AND PLANT PATHOLOGY: A REVIEW OF THE IX PLANT PATHOLOGY WORKSHOP AND VI MOLECULAR BIOLOGY WORKSHOP

Science.gov (United States)

The IX Pathology Workshop and VI Molecular Biology Workshop of the International Society of Sugar Cane Technologists (ISSCT) were organised jointly and hosted by the Colombian Sugarcane Research Centre (CENICAÑA) from 23-27 June 2008 at the Radisson Royal Hotel in Cali, Colombia. The Workshop was we...

The effect of the MgO buffer layer thickness on magnetic anisotropy in MgO/Fe/Cr/MgO buffer/MgO(001)

Energy Technology Data Exchange (ETDEWEB)

Kozioł-Rachwał, Anna, E-mail: a.koziolrachwal@aist.go.jp [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, al. Mickiewicza 30, 30-059 Kraków (Poland); Nozaki, Takayuki; Zayets, Vadym; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Suzuki, Yoshishige [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)

2016-08-28

The relationship between the magnetic properties and MgO buffer layer thickness d was studied in epitaxial MgO/Fe(t)/Cr/MgO(d) layers grown on MgO(001) substrate in which the Fe thickness t ranged from 0.4 nm to 1.1 nm. For 0.4 nm ≤ t ≤ 0.7 nm, a non-monotonic coercivity dependence on the MgO buffer thickness was shown by perpendicular magneto-optic Kerr effect magnetometry. For thicker Fe films, an increase in the buffer layer thickness resulted in a spin reorientation transition from perpendicular to the in-plane magnetization direction. Possible origins of these unusual behaviors were discussed in terms of the suppression of carbon contamination at the Fe surface and changes in the magnetoelastic anisotropy in the system. These results illustrate a method to control magnetic anisotropy in MgO/Fe/Cr/MgO(d) via an appropriate choice of MgO buffer layer thickness d.

Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B.

Science.gov (United States)

Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H; Streatfield, Stephen J; Herzog, Roland W; Daniell, Henry

2015-11-01

Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (∼1 mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ∼2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP(+) regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ∼870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft(2) per annum yielding 24,000-36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Microstructural evolution in Mg-rich Mg-Zn-Y alloys

International Nuclear Information System (INIS)

Biswas, T.; Ranganathan, S.; Nair, S.; Bajargan, G.

2005-01-01

Mg-rich Mg-Zn-Y alloys with nominal compositions Mg 97 Zn 1 Y 2 , Mg 97 Zn 2 Y 1 , Mg 92 Zn 6.5 Y 1.5 and Mg 97-x Zn 1 Y 2 Zr x have been chosen for the present study. These alloys are prepared by using sand casting mold. The sand cast alloys are remelted and subjected to copper mold casting and melt spinning techniques. The effect of cooling rate on microstructures was studied. It is observed that the size of the precipitates decreases with an increase of cooling rate. The formation of nano precipitates results in higher strength of the alloy as compared to the conventional alloys. The microstructures of melt spun ribbons are compared with RS/PM (rapidly solidified power metallurgy) Mg 97 Zn 1 Y 2 alloy, obtained from a different source. (author)

Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

International Nuclear Information System (INIS)

Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K.; Lord, Peter

2006-01-01

Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 μmol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 μmol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed with

Effects of occupational lead exposure.

Science.gov (United States)

Wang, Y L; Lu, P K; Chen, Z Q; Liang, Y X; Lu, Q M; Pan, Z Q; Shao, M

1985-01-01

Fifty-three workers in a battery factory, 52 solderers in a television factory, and 50 embroidery workers (a reference group) were studied. The average air lead levels of the three workplaces were 0.578 mg/m3, 0.002 mg/m3, and 0.001 mg/m3, respectively. Adverse effects in terms of clinical manifestations and biochemical criteria were evident among the battery factory workers. A significant dose-response relationship existed between the toxic effects and the air lead levels. The solderers showed no apparent abnormalities in comparison with the embroidery workers. The early clinical manifestations were dysfunction of the central nervous system, indigestion, arthralgia, and myalgia in the extremities. A positive association was observed between the prevalence of fatigue, mild abdominal pain, and arthralgia and the blood lead (PbB), urinary lead (PbU), and zinc protoporphyrin (ZPP) levels. The symptomatic threshold values of PbB, PbU, and ZPP were 30 micrograms/dl (1.5 mumol/l), 0.045 mg/l (0.2 mumol/l), and 40 micrograms/dl (0.7 mumol/l), respectively. The PbB, PbU, free erythrocyte protoporphyrin, and ZPP levels and the blood aminolevulinic dehydratase ratio could be used as indicators of lead exposure, although ZPP is preferred for a preventive monitoring program. The motor and sensory conduction velocities of the median nerve were slower in the exposed groups than in the reference group. No effects on behavioral function were observed among the solderers.

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

Science.gov (United States)

Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S; Liang, Kaiwei; Takahashi, Yoh-Hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C Peter; Shilatifard, Ali

2012-12-01

Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.

Photodynamic management of bladder cancer

Science.gov (United States)

Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

2009-06-01

Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

Heme oxygenase-1 prevents non-alcoholic steatohepatitis through suppressing hepatocyte apoptosis in mice

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Fu Na

2010-10-01

Full Text Available Abstract Objective Heme oxygenase-1 (HO-1, the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant properties. However, the role of HO-1 on hepatocyte apoptosis remains unclear. We aim to elucidate the effects of HO-1 on oxidative stress related hepatocellular apoptosis in nutritional steatohepatitis in mice. Methods C57BL/6J mice were fed with methionine-choline deficient (MCD diet for four weeks to induce hepatic steatohepatitis. HO-1 chemical inducer (hemin, HO-1 chemical inhibitor zinc protoporphyrin IX (ZnPP-IX and/or adenovirus carrying HO-1 gene (Ad-HO-1 were administered to mice, respectively. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay, the mRNA and protein expression of apoptosis related genes were assayed by quantitative real-time PCR and Western blot. Results Hepatocyte signs of oxidative related apoptotic injury were presented in mice fed with MCD diet for 4 weeks. Induction of HO-1 by hemin or Ad-HO-1 significantly attenuated the severity of liver histology, which was associated with decreased hepatic lipid peroxidation content, reduced number of apoptotic cells by TUNEL staining, down-regulated expression of pro-apoptosis related genes including Fas/FasL, Bax, caspase-3 and caspase-9, reduced expression of cytochrome p4502E1 (CYP2E1, inhibited cytochrome c (Cyt-c release, and up-regulated expression of anti-apoptosis gene Bcl-2. Whereas, inhibition of HO-1 by ZnPP-IX caused oxidative stress related hepatic injury, which concomitant with increased number of TUNEL positive cells and up-regulated expression of pro-apoptosis related genes. Conclusions The present study provided evidences for the protective role of HO-1 in preventing nutritional steatohepatitis through suppressing hepatocyte apoptosis in mice.

Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors.

Science.gov (United States)

Klaeger, Susan; Gohlke, Bjoern; Perrin, Jessica; Gupta, Vipul; Heinzlmeir, Stephanie; Helm, Dominic; Qiao, Huichao; Bergamini, Giovanna; Handa, Hiroshi; Savitski, Mikhail M; Bantscheff, Marcus; Médard, Guillaume; Preissner, Robert; Kuster, Bernhard

2016-05-20

Many protein kinases are valid drug targets in oncology because they are key components of signal transduction pathways. The number of clinical kinase inhibitors is on the rise, but these molecules often exhibit polypharmacology, potentially eliciting desired and toxic effects. Therefore, a comprehensive assessment of a compound's target space is desirable for a better understanding of its biological effects. The enzyme ferrochelatase (FECH) catalyzes the conversion of protoporphyrin IX into heme and was recently found to be an off-target of the BRAF inhibitor Vemurafenib, likely explaining the phototoxicity associated with this drug in melanoma patients. This raises the question of whether FECH binding is a more general feature of kinase inhibitors. To address this, we applied a chemical proteomics approach using kinobeads to evaluate 226 clinical kinase inhibitors for their ability to bind FECH. Surprisingly, low or submicromolar FECH binding was detected for 29 of all compounds tested and isothermal dose response measurements confirmed target engagement in cells. We also show that Vemurafenib, Linsitinib, Neratinib, and MK-2461 reduce heme levels in K562 cells, verifying that drug binding leads to a loss of FECH activity. Further biochemical and docking experiments identified the protoporphyrin pocket in FECH as one major drug binding site. Since the genetic loss of FECH activity leads to photosensitivity in humans, our data strongly suggest that FECH inhibition by kinase inhibitors is the molecular mechanism triggering photosensitivity in patients. We therefore suggest that a FECH assay should generally be part of the preclinical molecular toxicology package for the development of kinase inhibitors.

Fundamental study of photoradiation therapy for cancer

Energy Technology Data Exchange (ETDEWEB)

Kashimura, Hiromasa; Kawakita, Isao; Nakahara, Akira; Sai, Shoki; Mitamura, Keiji; Fukutomi, Hisayuki; Sakita, Takao

1984-12-01

In an attempt to obtain basic data for endoscopical photoactivation therapy for cancer, photoactivation effect of various porphyrins have been studied using a human hepatoceller carcinoma cell line (PLC/PRF/5) and its transplanted tumors. Porphyrins tested were hematoporphyrin derivative (HpD), protoporphyrin disodium (PPNa), hematoporphyrin (Hp), coproporphyrin, and cobalt-protoporphyrin (COPP). To investigate cytocidal effects by laser irradiation with these drugs, the /sup 51/Cr release assay was used. The results indicate that laser irradiation only has no cytocidal effect, while PPNa has more intense cytocidal effect than that of HpD. To investigate anti-tumor effect by PRT further, 2mg of HpD, 2mg of PPNa or 0.9% NaCl were injected into human hepatocellar cartinomas transplanted to the flanks of BALB/c nu nu mice 48 hours before laser irradiation (514.5nm, 0.1 W, 30 min). The results were analized with respect to effects on tumor regression curve and their histology. The results suggest that laser irradiation alone has no antitumor effect, while PRT with PPNa has stronger anti-tumor effect than PRT with HpD. Therefore, PPNa may be used as a new photosensitizer for photoradiation therapy for cancer. (author).

U.S. Navy Marine Climatic Atlas of the World. Volume IX. World-Wide Means and Standard Deviations

Science.gov (United States)

1981-10-01

TITLE (..d SobtII,) S. TYPE OF REPORT & PERIOD COVERED U. S. Navy Marine Climatic Atlas of the World Volume IX World-wide Means and Standard Reference...Ives the best estimate of the population standard deviations. The means, , are com~nuted from: EX IIN I 90 80 70 60" 50’ 40, 30 20 10 0 1070 T- VErr ...or 10%, whichever is greater Since the mean ice limit approximates the minus two de l temperature isopleth, this analyzed lower limit was Wave Heights

Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

International Nuclear Information System (INIS)

Huang, L.H.; Cheng, H.; Sweeney, W.V.; Pardi, A.; Tam, J.P.

1991-01-01

Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp 28 , with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

Science.gov (United States)

Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

2017-01-01

Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: 250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Role of dopants in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P detectors

International Nuclear Information System (INIS)

Mohammadi, Kh.; Moussavi Zarandi, A.; Afarideh, H.; Shahmaleki, S.

2013-01-01

In this study, electronic structure of LiF crystal doped with Mg,Cu,P impurities was studied with WIEN2k code on the basis of FPLAPW+lo method. Results show that in Mg-doped LiF composition, an electronic trap was created with impurity concentration of 1.56% and 3.125%. In this condition, the electronic trap with increasing the percentage of the impurities up to 4.687% is annihilated. It was found, that by doping of Mg and Cu or P simultaneously, a hole-trap is created in valence band. It was realized that in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P, Cu impurity and Li atom, have a key role in creation of levels which lead to create electronic and hole traps. Mg impurity and F atom, only have a role in creation of electronic traps. In addition, P impurity has a main role in creation of the electronic and hole traps in LiF:Mg,Cu,P. The activation energy of electronic and hole trap in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P crystalline lattice were obtained as 0.3 and 5.5 eV, 0.92 and 3.4 eV and 0.75 and 3.1 eV, respectively. - Graphical abstract: Figure (a) and (b) shows changes in electronic structure and band gap energy of LiF crystal due to presence of Mg and Cu, Mg and P ions respectively. - Highlights: • Electronic structure of LiF, LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P materials were studied with WIEN2K code. • In LiF:Mg,Cu and LiF:Mg,Cu,P, Li atom and Cu impurity have a key role in creation of levels. • F atom and Mg impurity only have a role in creation of electronic traps. • In LiF:Mg,Cu,P, P impurity has a main role in creation of electronic and hole traps

Carbonic anhydrase IX and response to postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of the DBCG82 b and c trials

DEFF Research Database (Denmark)

Kyndi, M.; Sorensen, F.B.; Alsner, J.

2008-01-01

-points were loco-regional recurrence, distant metastases, disease-specific survival and overall survival. Statistical analyses included kappa statistics, chi(2) or exact tests, Kaplan-Meier probability plots, Log-rank test and Cox regression analyses. Results CA IX was assessable in 945 cores. The percentage...

Use of fluorescence spectroscopy to measure molecular autofluorescence in diabetic subjects

International Nuclear Information System (INIS)

Gomes, Cinthia Zanini

2011-01-01

Diabetes Mellitus (DM) comprises a complex metabolic syndrome, caused by reduced or absent secretion of insulin by pancreatic beta cells, leading to hyperglycemia. Hyperglycemia promotes glycation of proteins and, consequently, the appearance of advanced glycation end products (AGEs). Currently, diabetic patients are monitored by determining levels of glucose and glycated hemoglobin (HbA1c). The complications caused by hyperglycemia may be divided into micro and macrovascular complications, represented by retinopathy, nephropathy, neuropathy and cardiovascular disease. Albumin (HSA) is the most abundant serum protein in the human body and is subject to glycation. The Protoporphyrin IX (PpIX) is the precursor molecule of heme synthesis, structural component of hemoglobin. The in vitro and animals studies have indicated that hyperglycemia promotes a decrease in its concentration in erythrocytes. The fluorescence spectroscopy is a technique widely used in biomedical field. The autofluorescence corresponds to the intrinsic fluorescence present in some molecules, this being associated with the same structure. The aim of this study was to use fluorescence spectroscopy to measure levels of erythrocyte PpIX autofluorescence and AGE-HSA in diabetic and healthy subjects and compare them with levels of blood glucose and HbA1c. This study was conducted with 151 subjects (58 controls and 93 diabetics). Epidemiological data of patients and controls were obtained from medical records. For control subjects, blood glucose levels were obtained from medical records and levels of Hb1Ac obtained by using commercial kits. The determination of the PpIX autofluorescence was performed with excitation at 405 nm and emission at 632 nm. Determination of AGE-HSA was performed with excitation at 370 nm and emission at 455 nm. Approximately 50% of diabetic had micro and macrovascular lesions resulting from hyperglycemia. There were no significant differences in the PpIX emission intensity values

Use of fluorescence spectroscopy to measure molecular autofluorescence in diabetic subjects; Utilizacao da espectroscopia de fluorescencia para mensuramento de moleculas autofluorescentes em individuos diabeticos

Energy Technology Data Exchange (ETDEWEB)

Gomes, Cinthia Zanini

2011-07-01

Diabetes Mellitus (DM) comprises a complex metabolic syndrome, caused by reduced or absent secretion of insulin by pancreatic beta cells, leading to hyperglycemia. Hyperglycemia promotes glycation of proteins and, consequently, the appearance of advanced glycation end products (AGEs). Currently, diabetic patients are monitored by determining levels of glucose and glycated hemoglobin (HbA1c). The complications caused by hyperglycemia may be divided into micro and macrovascular complications, represented by retinopathy, nephropathy, neuropathy and cardiovascular disease. Albumin (HSA) is the most abundant serum protein in the human body and is subject to glycation. The Protoporphyrin IX (PpIX) is the precursor molecule of heme synthesis, structural component of hemoglobin. The in vitro and animals studies have indicated that hyperglycemia promotes a decrease in its concentration in erythrocytes. The fluorescence spectroscopy is a technique widely used in biomedical field. The autofluorescence corresponds to the intrinsic fluorescence present in some molecules, this being associated with the same structure. The aim of this study was to use fluorescence spectroscopy to measure levels of erythrocyte PpIX autofluorescence and AGE-HSA in diabetic and healthy subjects and compare them with levels of blood glucose and HbA1c. This study was conducted with 151 subjects (58 controls and 93 diabetics). Epidemiological data of patients and controls were obtained from medical records. For control subjects, blood glucose levels were obtained from medical records and levels of Hb1Ac obtained by using commercial kits. The determination of the PpIX autofluorescence was performed with excitation at 405 nm and emission at 632 nm. Determination of AGE-HSA was performed with excitation at 370 nm and emission at 455 nm. Approximately 50% of diabetic had micro and macrovascular lesions resulting from hyperglycemia. There were no significant differences in the PpIX emission intensity values

Light-activated nanotube–porphyrin conjugates as effective antiviral agents

International Nuclear Information System (INIS)

Banerjee, Indrani; Douaisi, Marc P; Mondal, Dhananjoy; Kane, Ravi S

2012-01-01

Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents. (paper)

Tyrosine oxidation in heme oxygenase: examination of long-range proton-coupled electron transfer.

Science.gov (United States)

Smirnov, Valeriy V; Roth, Justine P

2014-10-01

Heme oxygenase is responsible for the degradation of a histidine-ligated ferric protoporphyrin IX (Por) to biliverdin, CO, and the free ferrous ion. Described here are studies of tyrosyl radical formation reactions that occur after oxidizing Fe(III)(Por) to Fe(IV)=O(Por(·+)) in human heme oxygenase isoform-1 (hHO-1) and the structurally homologous protein from Corynebacterium diphtheriae (cdHO). Site-directed mutagenesis on hHO-1 probes the reduction of Fe(IV)=O(Por(·+)) by tyrosine residues within 11 Å of the prosthetic group. In hHO-1, Y58· is implicated as the most likely site of oxidation, based on the pH and pD dependent kinetics. The absence of solvent deuterium isotope effects in basic solutions of hHO-1 and cdHO contrasts with the behavior of these proteins in the acidic solution, suggesting that long-range proton-coupled electron transfer predominates over electron transfer.

Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

Science.gov (United States)

Takahashi, Junko; Murakami, Mami; Mori, Takashi; Iwahashi, Hitoshi

2018-02-09

Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

Preparation and Hydrogen Storage Properties of Mg-Rich Mg-Ni Ultrafine Particles

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Jianxin Zou

2012-01-01

Full Text Available In the present work, Mg-rich Mg-Ni ultrafine powders were prepared through an arc plasma method. The phase components, microstructure, and hydrogen storage properties of the powders were carefully investigated. It is found that Mg2Ni and MgNi2 could be obtained directly from the vapor state reactions between Mg and Ni, depending on the local vapor content in the reaction chamber. A nanostructured MgH2 + Mg2NiH4 hydrogen storage composite could be generated after hydrogenation of the Mg-Ni ultrafine powders. After dehydrogenation, MgH2 and Mg2NiH4 decomposed into nanograined Mg and Mg2Ni, respectively. Thermogravimetry/differential scanning calorimetry (TG/DSC analyses showed that Mg2NiH4 phase may play a catalytic role in the dehydriding process of the hydrogenated Mg ultrafine particles.

Type IX secretion system PorM and gliding machinery GldM form arches spanning the periplasmic space

OpenAIRE

Leone, Philippe; Roche, Jennifer; Vincent, Maxence S.; Tran, Quang Hieu; Desmyter, Aline; Cascales, Eric; Kellenberger, Christine; Cambillau, Christian; Roussel, Alain

2018-01-01

Type IX secretion system (T9SS), exclusively present in the Bacteroidetes phylum, has been studied mainly in Flavobacterium johnsoniae and Porphyromonas gingivalis. Among the 18 genes, essential for T9SS function, a group of four, porK-N (P. gingivalis) or gldK-N (F. johnsoniae) belongs to a co-transcribed operon that expresses the T9SS core membrane complex. The central component of this complex, PorM (or GldM), is anchored in the inner membrane by a trans-membrane helix and interacts throug...

Síndrome pulmonar por hantavirus en población infantil. Chile: Regiones IX y X. 1998-2000

OpenAIRE

SOZA C., GUILLERMO; LORCA O., PEDRO; PUEBLA M., SERGIO; WENZEL M., MARISOL; NAVARRETE C., MARITZA; VILLAGRA C., ELIECER; MORA R., JUDITH; LEVIS C., SILVANA; AVILES A., GABRIELA

2000-01-01

El síndrome pulmonar por hantavirus (SPH) ha estado presente en Chile desde 1993 y ha sido detectado desde 1997 en la IX Región. Es una grave zoonosis con alta mortalidad, que afecta a gente joven incluyendo niños. Se ha estimado oportuno dar a conocer nuestra experiencia en la atención de 6 pacientes pediátricos, atendidos en las unidades de Cuidados Intensivos y Aislamiento en el Hospital Regional de Temuco, entre enero de 1998 y enero de 2000 mediante un estudio descriptivo de la experienc...

Pengaruh Pola Asuh Orang Tua Terhadap Agresivitas pada Persepsi Siswa Kelas IX

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wening suko utami

2017-10-01

Full Text Available The purpose of this study was to determine how much the influence of the authoritarian, democratic, and permissive parenting to the aggressiveness of the students.In this study used a sample of students class IX in Kesatrian 2 Junior High School Semarang as many as 66 students of 228 students. The variables studied in this research were variable of parenting and aggressiveness. The data collection is done by using a questionnaire. Data were analyzed using descriptive analysis and multiple regression technique. The results of this multiple regression analysis is Y = 21.836 + 1.073 X1 + 0.393 X2 + 0.963 X3. There is a simultaneous contribution of 62.7%. There was effect of positive correlation parenting authoritarian, democratic and permissive to partially aggressiveness. The conclusion of this study, there was positive corelation foster parents towards aggressiveness simultaneously or partially.

Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

International Nuclear Information System (INIS)

Dubois, Ludwig; Peeters, Sarah G.J.A.; Kuijk, Simon J.A. van; Yaromina, Ala; Lieuwes, Natasja G.; Saraya, Ruchi; Biemans, Rianne; Rami, Marouan; Parvathaneni, Nanda Kumar; Vullo, Daniela; Vooijs, Marc; Supuran, Claudiu T.; Winum, Jean-Yves

2013-01-01

Background and purpose: Carbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth and metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce tumor growth and sensitize tumors to irradiation in a CAIX dependent manner. Material and methods: The effect of the dual targeting anti-CAIX (DH348) and its single targeting control drugs on extracellular acidification and radiosensitivity was examined in HT-29 colorectal carcinoma cells. Tumor growth and time to reach 4× start volume (T4×SV) was monitored for animals receiving DH348 (10 mg/kg) combined with tumor single dose irradiation (10 Gy). Results: In vitro, DH348 reduced hypoxia-induced extracellular acidosis, but did not change hypoxic radiosensitivity. In vivo, DH348 monotherapy decreased tumor growth rate and sensitized tumors to radiation (enhancement ratio 1.50) without systemic toxicity only for CAIX expressing tumors. Conclusions: A newly designed nitroimidazole and sulfamide dual targeting drug reduces hypoxic extracellular acidification, slows down tumor growth at nontoxic doses and sensitizes tumors to irradiation all in a CAIX dependent manner, suggesting no “off-target” effects. Our data therefore indicate the potential utility of a dual drug approach as a new strategy for tumor-specific targeting

Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

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Xiuxiu Li

2017-04-01

Full Text Available Chlorin e6-C15-monomethyl ester (CMME is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS. CMME and the IS were separated on a Diamonsil C18 (2 column (100 mm × 4.6 mm, 5 μm with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v. The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ of 0.05 μg/mL and had a good linearity (r2 > 0.999 over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.

Wheat nitrogen fertilizer residues on an ultisol from the IX Region

International Nuclear Information System (INIS)

Rouanet M, Juan Luis; Pino N, Ines; Nario M, Adriana; Jobet, Claudio; Parada V, Ana Maria; Videla L, Ximena

2005-01-01

The soil nitrogen fertilizer residue is a relevant issue on a wheat production system at the IX Region of Chile, due to the high level of yield and use of resources, having an environmental impact from the use of fertilizer economy. The N-soil residue, not absorb by the plant, can be leach and contaminate the groundwater with nitrates or be redistributed by erosion. The application of isotopic techniques, using fertilizer labeled with 15 N, providing the quantitative information of the fate of this nutrient in the plant-soil system, important in the rate formulation based on the nitrogen use efficiency and in the benefit/cost relation. An assay was carried out in an Ultisol Metrenco Soil (Family fine, mixed, mesic, Typic Paleudults) at Pumalal locality. A Kumpa wheat variety was used, with a control treatment and five N rates applied as Urea labeled with 10% 15 N a.e., split in four times during the crop growth cycle. Total N (Kjeldhal) and 15 N optical emission spectrometer were determined in grain and straw samples harvested in February. Before to the next sow on may, soil sample were taken with an 3 cm diameter hugger (0-20; 20-40 and 40-60 cm depth). The samples were air dried, sieved and analyzed for total N and 15 N. The parameters determined for each depth were: N total (%), 15 N a.e. to obtain the plant-soil system N fertilizer recovery and its N residues in the soil profile. The wheat yield obtained was related with a cubic model using the N fertilizer rate applied (R 2 =0.75). The highest yield for the grain, 9.8 Mg ha -1 , was obtained applying 197 k ha -1 of N, with 45% of 15 N recovered by the grain. Nevertheless, the soil-crop system obtained a high 15 N recovery (>88%), in the soil remained 32-60% as N residue, being not used by the plant during the growth period. Between 27-54% of the 15 N total residue was found at the 0-20 cm soil depth, portion that is susceptible of distribution by erosion, implied in the use of fertilizer economy. Around 4

Re-examining the 26Mg(α ,α')26Mg reaction: Probing astrophysically important states in 26Mg

Science.gov (United States)

Adsley, P.; Brümmer, J. W.; Li, K. C. W.; Marín-Lámbarri, D. J.; Kheswa, N. Y.; Donaldson, L. M.; Neveling, R.; Papka, P.; Pellegri, L.; Pesudo, V.; Pool, L. C.; Smit, F. D.; van Zyl, J. J.

2017-11-01

Background: The 22Ne(α ,n )25Mg reaction is one of the neutron sources for the s process in massive stars. The properties of levels in 26Mg above the α -particle threshold control the strengths of the 22Ne(α ,n )25Mg and 22Ne(α ,γ )26Mg reactions. The strengths of these reactions as functions of temperature are one of the major uncertainties in the s process. Purpose: Information on the existence, spin, and parity of levels in 26Mg can assist in constraining the strengths of the 22Ne(α ,γ )26Mg and 22Ne(α ,n )25Mg reactions, and therefore in constraining s -process abundances. Methods: Inelastically scattered α particles from a 26Mg target were momentum-analyzed in the K600 magnetic spectrometer at iThemba LABS, South Africa. The differential cross sections of states were deduced from the focal-plane trajectory of the scattered α particles. Based on the differential cross sections, spin and parity assignments to states are made. Results: A newly assigned 0+ state was observed in addition to a number of other states, some of which can be associated with states observed in other experiments. Some of the deduced Jπ values of the states observed in the present study show discrepancies with those assigned in a similar experiment performed at RCNP Osaka. The reassignments and additions of the various states can strongly affect the reaction rate at low temperatures. Conclusion: The number, location, and assignment of levels in 26Mg that may contribute to the 22Ne+α reactions are not clear. Future experimental investigations of 26Mg must have an extremely good energy resolution to separate the contributions from different levels. Coincidence experiments of 26Mg provide a possible route for future investigations.

77 FR 29633 - Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC...

Science.gov (United States)

2012-05-18

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-68-000] Alta Wind VII, LLC, Alta Wind IX, LLC, Alta Wind X, LLC, Alta Wind XI, LLC, Alta Wind XII, LLC, Alta Wind XIII, LLC, Alta Wind XIV, LLC, Alta Wind XV, LLC, Alta Windpower Development, LLC, TGP Development Company, LLC...

The magnesium chelation step in chlorophyll biosynthesis

Energy Technology Data Exchange (ETDEWEB)

Weinstein, J.

1990-11-01

In photosynthetic organisms, the biogenesis of energy transducing membranes requires the coordinate synthesis of prosthetic groups, proteins, and various lipids. Two of the major prosthetic groups, chlorophyll and heme, share a common biosynthetic pathway that diverges at the point of metal insertion into protoporphyrin IX (Proto). Insertion of iron leads to the formation of hemes, while insertion of magnesium is the first step unique to chlorophyll formation. This project is directed toward identifying the enzyme(s) responsible for magnesium chelation and elucidating the mechanism which regulates the flux of precursors through the branch point enzymes in isolated chloroplasts. Using intact chloroplasts from greening cucumber cotyledons, we have confirmed the ATP requirement for Mg-Proto formation. Use of non-hydrolyzable ATP analogs, uncouplers and ionophores has led to the conclusions that ATP hydrolysis is necessary, but that this hydrolysis is not linked to the requirement for membrane intactness by transmembrane ion gradients or electrical potentials. The enzyme(s) are flexible with respect to the porphyrin substrate specificity, accepting porphyrins with -vinyl, -ethyl, or -H substituents at the 2 and 4 positions. The activity increases approximately four-fold during greening. Possible physiological feedback inhibitors such as heme, protochlorophyllide, and chlorophyllide had no specific effect on the activity. The activity has now been assayed in barely, corn and peas, with the system from peas almost ten-fold more active than the cucumber system. Work is continuing in pea chloroplasts with the development of a continuous assay and investigation of the feasibility of characterizing an active, organelle-free preparation. 6 figs.

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer

OpenAIRE

Buchlis, George; Podsakoff, Gregory M.; Radu, Antonetta; Hawk, Sarah M.; Flake, Alan W.; Mingozzi, Federico; High, Katherine A.

2012-01-01

In previous work we transferred a human factor IX–encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier ...

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product.

Science.gov (United States)

Dailey, Harry A; Dailey, Tamara A; Gerdes, Svetlana; Jahn, Dieter; Jahn, Martina; O'Brian, Mark R; Warren, Martin J

2017-03-01

The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized. Copyright © 2017 American Society for Microbiology.

Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

International Nuclear Information System (INIS)

Zhou, Zhao-Hua; Kumari, Namita; Nekhai, Sergei; Clouse, Kathleen A.; Wahl, Larry M.; Yamada, Kenneth M.; Dhawan, Subhash

2013-01-01

Highlights: •Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages. •The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1α and MIP1β. •This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. -- Abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1α and MIP1β) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1α, MIP1β, and LD78β chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM

Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

Directory of Open Access Journals (Sweden)

Katarzyna Magierowska

Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

Optical absorption and thermoluminescence in Mg O, Mg O:Ni and Mg O:Li irradiated at room temperature; Absorcion optica y termoluminiscencia en MgO, MgO:Ni y MgO:Li irradiados a temperatura ambiente

Energy Technology Data Exchange (ETDEWEB)

Delgado, L

1984-07-01

Optical absorption and thermoluminescence (TL) studies in Mg O, Mg O:Ni and Mg O:Li irradiated at room temperature are presented. In pure Mg O the thermal annihilation of Fe3+ by recombination with thermally released electrons at {approx} 90 and 175 degree centigree and the V center annealing by hole release up to 100 degree centigree cause the observed glow peaks at these temperatures. The TL excitation spectrum shows two maxima at 245 nm (electron center) and 288 nm (Fe3+). In Mg O:Ni X irradiation induces Fe{sup 2}+ {yields}- Fe{sup 3}+ and Ni{sup 2}+ {yields} Ni{sup 3}+ oxidations. Two TL emission bands centered at 110 degree centigree (red) and 80 o{sup C} (green) are assigned to electron release and their recombination at Fe{sup 3}+ and Ni{sup 3}+ respectively. In Mg O:Li two TL emission bands, one blue (430 nm) and the other red (730 nm) with excitation maxima at 245 nm (electron center) and 200 nm (hole center) respectively are observed. No V-center formation was detected in both Ni and Li doped samples. (Author) 42 refs.

Spectral analysis of the 4d96s configuration in eight times ionized xenon, Xe IX

International Nuclear Information System (INIS)

Raineri, M.; Gallardo, M.; Reyna Almandos, J.G.

2006-01-01

A capillary light source was used to observe the spectrum of eight times ionized xenon, Xe IX, in the vacuum ultraviolet range, 270-2000 A. Sixteen transitions have been identified as combinations between energy levels of the 4d 9 6s with 4d 9 5p configuration, and all 4d 9 6s levels have been determined. The present analysis is based on an accurate extrapolation of energy parameters and experimental energy level values in the Pd I isoelectronic sequence. The energy parameters were obtained with Hartree-Fock relativistic calculations. Least-squares parametric calculation has been carried out to study the fit between experimental and theoretical values