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.

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)

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…

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

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 ...

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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...

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.

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

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.

The importance of protoporphyrin IX efflux for ALA-PDT dosimetry

International Nuclear Information System (INIS)

Milanetto, M C; Imasato, H; Perussi, J R

2009-01-01

One of the major advances in PDT is the use of 5-aminolevulinic acid (ALA) to induce the production of an endogenous photosensitizer inside the cells using intracellular enzymatic pathways. ALA is the first intermediate in heme biosynthesis and a precursor of the protoporphyrin IX (PpIX). When activated by light, this efficient photosensitizer accumulated in the target cells can produce cytotoxicity. The aim of this study was to find the best conditions for cell killing using ALA to temporarily increase the concentration of PpIX in two cell lines. It was shown that a considerable efflux of synthesized PpIX occurs. Since this efflux is time-dependent, it is essential to know the optimum time for irradiation after ALA administration. So, the efflux of PpIX from the cells is an important parameter to be considered for ALA-PDT dosimetry

Analysis of cell line variation in biochemical production of protoporphyrin IX

Science.gov (United States)

Gibbs, Summer L.; Chen, Bin; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2006-02-01

Protoporphyrin IX (PpIX) is produced via the heme synthesis pathway by the cell following administration of aminolevulinic acid (ALA). ALA synthase, the enzyme that produces ALA in the cell from glycine and succinyl-coenzyme A, is inhibited in a feedback mechanism by heme and thus is the rate limiting enzyme in the heme synthesis pathway. Since ALA is administered systemically, the rate limiting step that naturally exists in the cells is bypassed, however it is currently unclear why cells have different rate limiting steps in the ALA-PpIX synthesis pathway, and more specifically which types of cancer cells are most productive. It has been determined that when the same amount of ALA is administered to a wide panel of cancer cells in vitro that vastly differing amounts of PpIX are produced. The steps for the ALA-PpIX pathway occur in and around the mitochondria of the cell, but interestingly no correlation is seen between PpIX production and mitochondrial content of the cell, following ALA administration. However, total cell area shows positive correlation with PpIX production. Administration of the iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed and thus increases the detectable amount of PpIX in each cell line. The cell lines that have the lowest PpIX production following administration of ALA alone show the largest increase in production following the combined administration of ALA and L1. PpIX fluorescence is thought to be a measure of cellular activity and the goal of the current study was to determine which cell lines would be the most promising targets for fluorescence detection or monitoring response to therapy. The results indicate that the cells with larger size and larger numbers of mitochondria may be good potential targets for this therapy. While this conclusion may appear obvious, it is not universally true, and cellular specific

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.

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.

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.

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

Science.gov (United States)

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.

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.

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

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.

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.

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

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

Effect of 5-aminolevulinic acid on kinetics of protoporphyrin IX production in CHO cells.

Directory of Open Access Journals (Sweden)

W Warchoł

2004-07-01

Full Text Available 5-aminolevulinic acid (ALA is utilized in a photodynamic therapy as a compound capable of augmenting intracellular pool of protoporphyrin IX (PpIX, which exhibits properties of a photosensitizer. The studies were aimed at monitoring accumulation of endogenous protoporphyrin IX in CHO cells under effect of various concentrations of ALA in culture medium and following removal of the compound from the culture medium. Cell content of PpIX was determined following incubation of the cells for 72 h in a culture medium containing different concentration of ALA. Moreover, the cells were preincubated for 2 h in ALA at various concentrations and separated from the compound by medium change and their PpIX content was monitored following incubation. PpIX content was defined by a fluorescent technique under the confocal microscope. In the course of continuous incubation of cells with ALA, biphasic alterations were noted in cellular PpIX concentration. Removal of ALA from the incubation medium resulted at first in a decrease in PpIX content in cells, which was followed by an evidently augmented accumulation of the compound in the cells. The results suggested that in the case of CHO cells, exogenous ALA was not an exclusive source of PpIX synthesis and that alterations in enzyme activities were responsible for production of PpIX.

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.

SAH derived potent and selective EZH2 inhibitors

Energy Technology Data Exchange (ETDEWEB)

Kung, Pei-Pei; Huang, Buwen; Zehnder, Luke; Tatlock, John; Bingham, Patrick; Krivacic, Cody; Gajiwala, Ketan; Diehl, Wade; Yu, Xiu; Maegley, Karen A.

2015-04-01

A series of novel enhancer of zeste homolog 2 (EZH2) inhibitors was designed based on the chemical structure of the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50’s against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most potent SAH-derived inhibitor of the EZH2 PRC2 complex yet identified. This compound also displayed improved potency, lipophilic efficiency (LipE), and selectivity profile against other lysine methyltransferases compared with SAH.

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.…

Type IX secretion: the generation of bacterial cell surface coatings involved in virulence, gliding motility and the degradation of complex biopolymers.

Science.gov (United States)

Veith, Paul D; Glew, Michelle D; Gorasia, Dhana G; Reynolds, Eric C

2017-10-01

The Type IX secretion system (T9SS) is present in over 1000 sequenced species/strains of the Fibrobacteres-Chlorobi-Bacteroidetes superphylum. Proteins secreted by the T9SS have an N-terminal signal peptide for translocation across the inner membrane via the SEC translocon and a C-terminal signal for secretion across the outer membrane via the T9SS. Nineteen protein components of the T9SS have been identified including three, SigP, PorX and PorY that are involved in regulation. The inner membrane proteins PorL and PorM and the outer membrane proteins PorK and PorN interact and a complex comprising PorK and PorN forms a large ring structure of 50 nm in diameter. PorU, PorV, PorQ and PorZ form an attachment complex on the cell surface of the oral pathogen, Porphyromonas gingivalis. P. gingivalis T9SS substrates bind to PorV suggesting that after translocation PorV functions as a shuttle protein to deliver T9SS substrates to the attachment complex. The PorU component of the attachment complex is a novel Gram negative sortase which catalyses the cleavage of the C-terminal signal and conjugation of the protein substrates to lipopolysaccharide, anchoring them to the cell surface. This review presents an overview of the T9SS focusing on the function of T9SS substrates and machinery components. © 2017 John Wiley & Sons Ltd.

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

Solution of Schroedinger Equation for Two-Dimensional Complex Quartic Potentials

International Nuclear Information System (INIS)

Singh, Ram Mehar; Chand, Fakir; Mishra, S. C.

2009-01-01

We investigate the quasi-exact solutions of the Schroedinger wave equation for two-dimensional non-hermitian complex Hamiltonian systems within the frame work of an extended complex phase space characterized by x = x 1 + ip 3 , y = x 2 + ip 4 , p x = p 1 + ix 3 , p y = p 2 + ix 4 . Explicit expressions of the energy eigenvalues and the eigenfunctions for ground and first excited states for a complex quartic potential are obtained. Eigenvalue spectra of some variants of the complex quartic potential, including PT-symmetric one, are also worked out. (general)

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...

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

Effect of Photon Radiations in Semi-Rigid Artificial Tissue Sensitized by Protoporphyrin IX Encapsulated with Silica Nanoparticles

Science.gov (United States)

Makhadmeh, Ghaseb N.; Aziz, Azlan Abdul; Razak, Khairunisak Abdul; Al-Akhras, M.-Ali H.

2018-02-01

This study involves the synthesis of Protoporphyrin IX (PpIX) encapsulated with Silica Nanoparticles (SiNPs) as an application for Photodynamic therapy. Semi-rigid artificial tissues with optical features similar to human tissue were used as sample materials to ascertain the efficacy of PpIX encapsulated with SiNPs. The disparity in optical characteristics (transmittance, reflectance, scattering, and absorption) of tissues treated with encapsulated PpIX and naked PpIX under light exposure (Intensity at 408 nm ~1.19 mW/cm2) was explored. The optimal exposure times required for naked PpIX and SiNPs encapsulated PpIX to engulf Red Blood Cells (RBCs) in the artificial tissue were subsequently measured. Comparative analysis showed that the encapsulated PpIX has a 91.5 % higher efficacy than naked PpIX. The results prove the applicability of PpIX encapsulated with SiNP on artificial tissue and possible use on human tissue.

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.

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)

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

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.

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.

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.

Molecular and electronic structure of thin films of protoporphyrin(IX)Fe(III)Cl

Science.gov (United States)

Snyder, Shelly R.; White, Henry S.

1991-11-01

Electrochemical, scanning tunneling microscopy (STM), and tunneling spectroscopy studies of the molecular and electronic properties of thin films of protoporphyrin(IX)Fe(III)Cl (abbreviated as PP(IX)Fe(III)Cl) on highly oriented pyrolytic graphite (HOPG) electrodes are reported. PP(IX)Fe(III)Cl films are prepared by two different methods: (1) adsorption, yielding an electrochemically-active film, and (2) irreversible electrooxidative polymerization, yielding an electrochemically-inactive film. STM images, in conjunction with electro-chemical results, indicate that adsorption of PP(IX)Fe(III)Cl from aqueous solutions onto freshly cleaved HOPG results in a film comprised of molecular aggregates. In contrast, films prepared by irreversible electrooxidative polymerization of PP(IX)Fe(III)Cl have a denser, highly structured morphology, including what appear to be small pinholes (approx. 50A diameter) in an otherwise continuous film.

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

Photocytotoxic trans-diam(m)ine platinum(IV) diazido complexes more potent than their cis isomers.

Science.gov (United States)

Farrer, Nicola J; Woods, Julie A; Munk, Vivienne P; Mackay, Fiona S; Sadler, Peter J

2010-02-15

The photocytotoxicity of a series of anticancer trans-dihydroxido [Pt(N(3))(2)(OH)(2)(NH(3))(X)] (X = alkyl or aryl amine) platinum(IV) diazido complexes has been examined, and the influence of cis-trans isomerism has been investigated. A series of photoactivatable Pt(IV)-azido complexes has been synthesized: The synthesis, characterization, and photocytotoxicity of six mixed-ligand ammine/amine Pt(IV) diazido complexes, cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(X)] where X = propylamine (4c), butylamine (5c), or pentylamine (6c) and aromatic complexes where X = pyridine (7c), 2-methylpyridine (8c), or 3-methylpyridine (9c) are reported. Six all-trans isomers have also been studied where X = methylamine (2t), ethylamine (3t), 2-methylpyridine (8t), 4-methylpyridine (10t), 3-methylpyridine (9t), and 2-bromo-3-methylpyridine (11t). All of the complexes exhibit intense azide-to-Pt(IV) LMCT bands (ca. 290 nm for trans and ca. 260 nm for cis). When irradiated with UVA light (365 nm), the Pt(IV) complexes undergo photoreduction to Pt(II) species, as monitored by UV-vis spectroscopy. The trans isomers of complexes containing aliphatic or aromatic amines were more photocytotoxic than their cis isomers. One of the cis complexes (9c) was nonphotocytotoxic despite undergoing photoreduction. Substitution of NH(3) ligands by MeNH(2) or EtNH(2) results in more potent photocytotoxicity for the all-trans complexes. The complexes were all nontoxic toward human keratinocytes (HaCaT) and A2780 human ovarian cancer cells in the dark, apart from the 3-methylpyridine (9t), 2-bromo-3-methylpyridine (11t), and 4-methylpyridine (10t) derivatives.

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...

Methods of producing protoporphyrin IX and bacterial mutants therefor

Science.gov (United States)

Zhou, Jizhong; Qiu, Dongru; He, Zhili; Xie, Ming

2016-03-01

The presently disclosed inventive concepts are directed in certain embodiments to a method of producing protoporphyrin IX by (1) cultivating a strain of Shewanella bacteria in a culture medium under conditions suitable for growth thereof, and (2) recovering the protoporphyrin IX from the culture medium. The strain of Shewanella bacteria comprises at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX. In certain embodiments of the method, the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or of shew_1140. In other embodiments, the presently disclosed inventive concepts are directed to mutant strains of Shewanella bacteria having at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX during cultivation of the bacteria. In certain embodiments the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or shew_1140.

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)

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

Science.gov (United States)

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.

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

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)

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

Science.gov (United States)

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.

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…

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)

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...

Acinetobacter baumannii FolD ligand complexes --potent inhibitors of folate metabolism and a re-evaluation of the structure of LY374571.

Science.gov (United States)

Eadsforth, Thomas C; Maluf, Fernando V; Hunter, William N

2012-12-01

The bifunctional N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase (DHCH or FolD), which is widely distributed in prokaryotes and eukaryotes, is involved in the biosynthesis of folate cofactors that are essential for growth and cellular development. The enzyme activities represent a potential antimicrobial drug target. We have characterized the kinetic properties of FolD from the Gram-negative pathogen Acinetobacter baumanni and determined high-resolution crystal structures of complexes with a cofactor and two potent inhibitors. The data reveal new details with respect to the molecular basis of catalysis and potent inhibition. A unexpected finding was that our crystallographic data revealed a different structure for LY374571 (an inhibitor studied as an antifolate) than that previously published. The implications of this observation are discussed. © 2012 The Authors Journal compilation © 2012 FEBS.

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…

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

Science.gov (United States)

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

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.

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

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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.

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...

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...

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.

Pain during photodynamic therapy is associated with protoporphyrin IX fluorescence and fluence rate

DEFF Research Database (Denmark)

Wiegell, S.R.; Skiveren, J.; Philipsen, P.A.

2008-01-01

and protoporphyrin IX (PpIX) fluorescence, lesion type, lesion preparation and lesion localization. Methods Twenty-six patients with actinic keratoses (AKs) in different localizations and 34 patients with facial acne vulgaris were treated with methyl aminolaevulinate-PDT. Patients with acne were illuminated using......) patients with acne had a pain score of 6 [interquartile range (IQR) 5-7] compared with 8 (IQR 6-10) when using a fluence rate of 68 mW cm(-2) (P = 0.018). After correcting the pain score for PpIX fluorescence no differences in pain scores were found between first and second acne treatment, locations of AK...... lesions or between the two types of lesions. Conclusions Pain during PDT was correlated with the PpIX fluorescence in the treatment area prior to illumination. Pain was reduced using a lower fluence rate during PDT of acne Udgivelsesdato: 2008/4...

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…

The Bolgary IX settlement – a site of the Ananyino finale in the vicinity of Perm

Directory of Open Access Journals (Sweden)

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.

Validation of the protoporphyrin IX-triplet state lifetime technique for mitochondrial oxygen measurements in the skin

NARCIS (Netherlands)

F.A. Harms (Floor A.); S.I.A. Bodmer (Sander I. A.); N.J.H. Raat (Nicolaas); R.J. Stolker (Robert); E.G. Mik (Egbert)

2012-01-01

textabstractMitochondrial oxygen tension can be measured in vivo by means of oxygen-dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Here we demonstrate that mitochondrial PO2 (mitoPO2) can be measured in the skin of a rat after topical application of the PpIX precursor

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.

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.

Increase in protoporphyrin IX after 5-aminolevulinic acid based photodynamic therapy is due to local re-synthesis

NARCIS (Netherlands)

de Bruijn, Henriëtte S.; Kruijt, Bastiaan; van der Ploeg-van den Heuvel, Angélique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.

2007-01-01

Protoporphyrin IX (PpIX) fluorescence that is bleached during aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) increases again in time after treatment. In the present study we investigated if this increase in PpIX fluorescence after illumination is the result of local re-synthesis or of

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

Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF-200 aminolaevulinic acid declines with age

DEFF Research Database (Denmark)

Nissen, C V; Philipsen, P A; Wulf, H C

2015-01-01

BACKGROUND: Topical photodynamic therapy (PDT) is a popular treatment modality in dermatology. The effect of PDT in epidermal cells depends on formation of protoporphyrin IX (PpIX) from 5-aminolevulinic acid (ALA). A variety of physiological changes in epidermal function occur with increasing age...... assessed. Treatment efficacy in relation to age was evaluated in 100 basal cell carcinomas (BCCs) treated with MAL-PDT. RESULTS: Both photosensitizers induced significantly more PpIX formation in the younger group. Linear regression revealed a significant age-related decline in PpIX formation after...

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

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

Induction of protoporphyrin IX by aminolaevulinic acid in actinic keratosis, psoriasis and normal skin: preferential porphyrin enrichment in differentiated cells.

NARCIS (Netherlands)

Smits, T.; Laarhoven, A.I.M. van; Staassen, A.; Kerkhof, P.C.M. van de; Erp, P.E.J. van; Gerritsen, M.J.P.

2009-01-01

BACKGROUND: In photodynamic therapy the endogenous photosensitizer protoporphyrin IX (PpIX) is synthesized following topical application of aminolaevulinic acid (ALA). However, different tissues have distinct PpIX-accumulating properties, due to differences in penetration of ALA through the stratum

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…

Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis

DEFF Research Database (Denmark)

Nissen, C V; Heerfordt, I M; Wiegell, S R

2017-01-01

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is highly effective for treating actinic keratosis (AK) on the face/scalp, but less effective on the extremities. Insufficient accumulation of protoporphyrin IX (PpIX) may cause these inferior efficacy rates. However...... (P = 0·001 and P = 0·002, respectively). However, the median total clearance rates did not improve accordingly: 3hC+ (55·0%), 21hC- (55·0%) and 21hC+ (53·6%). Conversely, insufficient PpIX accumulation in the 3hC- regimen led to a significantly lower clearance rate (33·3%) than the other regimens (P...

Porphyromonas gingivalis and related bacteria: from colonial pigmentation to the type IX secretion system and gliding motility

Science.gov (United States)

Nakayama, K

2015-01-01

Porphyromonas gingivalis is a gram-negative, non-motile, anaerobic bacterium implicated as a major pathogen in periodontal disease. P. gingivalis grows as black-pigmented colonies on blood agar, and many bacteriologists have shown interest in this property. Studies of colonial pigmentation have revealed a number of important findings, including an association with the highly active extracellular and surface proteinases called gingipains that are found in P. gingivalis. The Por secretion system, a novel type IX secretion system (T9SS), has been implicated in gingipain secretion in studies using non-pigmented mutants. In addition, many potent virulence proteins, including the metallocarboxypeptidase CPG70, 35 kDa hemin-binding protein HBP35, peptidylarginine deiminase PAD and Lys-specific serine endopeptidase PepK, are secreted through the T9SS. These findings have not been limited to P. gingivalis but have been extended to other bacteria belonging to the phylum Bacteroidetes. Many Bacteroidetes species possess the T9SS, which is associated with gliding motility for some of these bacteria. PMID:25546073

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)

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.

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…

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.

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.

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.

Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

Science.gov (United States)

Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

2013-09-10

HAMLET is a complex of human α-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine α-lactalbumin (bLA) and β-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their α-helix and cross-β-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins.

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

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

Science.gov (United States)

Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

2016-03-01

To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

Systemic component of protoporphyrin IX production in nude mouse skin upon topical application of aminolevulinic acid depends on the application conditions

NARCIS (Netherlands)

van den Akker, Johanna T. H. M.; Iani, Vladimir; Star, Willem M.; Sterenborg, Henricus J. C. M.; Moan, Johan

2002-01-01

Topical application of 5-aminolevulinic acid (ALA) for protoporphyrin IX (PpIX)-based photodynamic therapy of skin cancer is generally considered not to induce systemic side effects because PpIX is supposed to be formed locally. However, earlier studies with topically applied ALA have revealed that

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.

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.

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.

Type IX secretion system PorM and gliding machinery GldM form arches spanning the periplasmic space.

Science.gov (United States)

Leone, Philippe; Roche, Jennifer; Vincent, Maxence S; Tran, Quang Hieu; Desmyter, Aline; Cascales, Eric; Kellenberger, Christine; Cambillau, Christian; Roussel, Alain

2018-01-30

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 through the outer membrane PorK-N complex. There is a complete lack of available atomic structures for any component of T9SS, including the PorKLMN complex. Here we report the crystal structure of the GldM and PorM periplasmic domains. Dimeric GldM and PorM, each contain four domains of ~180-Å length that span most of the periplasmic space. These and previously reported results allow us to propose a model of the T9SS core membrane complex as well as its functional behavior.

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

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…

Correlation between macroscopic fluorescence and protoporphyrin IX content in psoriasis and actinic keratosis following application of aminolevulinic acid.

NARCIS (Netherlands)

Smits, T.; Robles, C.A.; Erp, P.E.J. van; Kerkhof, P.C.M. van de; Gerritsen, M.J.P.

2005-01-01

In fluorescence diagnosis with 5-aminolevulinic acid (ALA)-induced porphyrins (FDAP), protoporphyrin IX (PpIX) accumulation can be macroscopically visualized. Interpretation of these data is still problematic because of the low reproducibility of the procedure and poor understanding of the

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.

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

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

Science.gov (United States)

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

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

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

"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.

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.

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

Antagonizing STAT3 dimerization with a rhodium(III) complex.

Science.gov (United States)

Ma, Dik-Lung; Liu, Li-Juan; Leung, Ka-Ho; Chen, Yen-Ting; Zhong, Hai-Jing; Chan, Daniel Shiu-Hin; Wang, Hui-Min David; Leung, Chung-Hang

2014-08-25

Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Directory of Open Access Journals (Sweden)

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

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

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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.

A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway.

Science.gov (United States)

Hajrezaie, Maryam; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Hassandarvish, Pouya; Gwaram, Nura Suleiman; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Looi, Chung Yeng; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood Ameen

2014-01-01

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.

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

Science.gov (United States)

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.

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

Full Text Available 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. oxyfluorfen + glutamato monossódico + vitaminas C e E; 2. oxyfluorfen + glutamato monossódico + vitaminas C e E + ácido levulênico; 3. oxyfluorfen; 4. carfentrazone + glutamato monossódico + vitaminas C e E; 5. carfentrazone + glutamato monossódico + vitaminas C e E + ácido levulênico; 6. carfentrazone; 7. testemunha + vitaminas C e E; 8. testemunha + vitaminas C e E + ácido levulênico; e 9. testemunha em oito genótipos de cana-de-açúcar (PO933499, RB806043, RB470355, PO830698, SP701143, PO901387, PO894414 e SP903414, dispostos em esquema fatorial 9 x 8, com quatro repetições. As repetições constituíram-se de folhas (20 cm destacadas de cada genótipo, sendo estas pulverizadas com os tratamentos mencionados, em simulador estacionário. Foram realizadas avaliações visuais de controle aos 2 DAA (dias após aplicação e, no fim do estudo, determinações analíticas via extração da biomassa fresca, verificando os teores de protoporfirina IX por cromatografia líquida de alta eficiência. Os resultados mostraram que em curto prazo foram detectados aumentos significativos nas concentrações de PROTO IX para os genótipos RB470355 e SP903414 submetidos ao tratamento 2 e para o genótipo SP701143 submetido ao tratamento 8, indicando que eles podem ser utilizados como fontes acumuladoras de protoporfirina IX.The objective of this study was to select sugarcane genotypes through PROTOX inhibitors and antioxidants to induce the accumulation

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…

Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

Science.gov (United States)

Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

2014-05-01

Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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.

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

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.

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...

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.

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 ...

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.

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

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.

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.

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

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...

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…

Organometallic complexes of thiocarbanilides and substituted thiocarbanilides using manganese (II) chloride

International Nuclear Information System (INIS)

Babiker, Musa Elaballa Mohamed

2000-01-01

Organo-metallic complexes of substituted thiocarbanilide using manganese (II) chloride were prepared, these are: (VIII) 3:3'-Dichloro thiocarbanilide. Manganese (II) chloride. (IX) 3:3'-Dimethyl thiocarbanilide. Manganese (II) chloride. (X) 2:2'-dimethyl thiocarbanilide. Manganese (II) chloride. These compounds are coloured, soluble in most organic solvents, insoluble in water, decomposed by hot solvents. The physical properties of compounds (IX) and (X) were studied by UV and IR spectra, and the physical properties of compound (VIII) were studied by UV, IR, mass spectra and NMR. The molecular weight of the compound (VIII) was determined by three different methods; Rast's camphor method, mass spectra and the nitrogen contents. The stoichiometry of the reaction was found to be 2:1, and the coordination is from sulphur atom more than nitrogen.(Author)

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.

Comparison of nitric oxide binding to different pure and mixed protoporphyrin IX monolayers

NARCIS (Netherlands)

Knoben, W.; Crego-Calama, M.; Brongersma, S.H.

2012-01-01

The nitric oxide (NO) binding properties of monolayers of four different protoporphyrins IX adsorbed on aluminum oxide surfaces have been investigated. XPS and AFM results are consistent with the presence of a monolayer of porphyrins, bound to the surface by their carboxylic acid groups and with the

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

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

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.

Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors.

Science.gov (United States)

Choi, Jun Yong; Fuerst, Rita; Knapinska, Anna M; Taylor, Alexander B; Smith, Lyndsay; Cao, Xiaohang; Hart, P John; Fields, Gregg B; Roush, William R

2017-07-13

We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn 2+ chelating unit was replaced with nonchelating polar residues that bridged over the Zn 2+ binding site and reached into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b, which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn 2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

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.

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

Science.gov (United States)

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.

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)

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

Complexation of c6-ceramide with cholesteryl phosphocholine - a potent solvent-free ceramide delivery formulation for cells in culture.

Directory of Open Access Journals (Sweden)

Pramod Sukumaran

Full Text Available Ceramides are potent bioactive molecules in cells. However, they are very hydrophobic molecules, and difficult to deliver efficiently to cells. We have made fluid bilayers from a short-chain D-erythro-ceramide (C6-Cer and cholesteryl phosphocholine (CholPC, and have used this as a formulation to deliver ceramide to cells. C6-Cer complexed with CholPC led to much larger biological effects in cultured cells (rat thyroid FRTL-5 and human HeLa cells in culture compared to C6-Cer dissolved in dimethyl sulfoxide (DMSO. Inhibition of cell proliferation and induction of apoptosis was significantly more efficient by C6-Cer/CholPC compared to C6-Cer dissolved in DMSO. C6-Cer/CholPC also permeated cell membranes and caused mitochondrial Ca(2+ influx more efficiently than C6-Cer in DMSO. Even though CholPC was taken up by cells to some extent (from C6-Cer/CholPC bilayers, and was partially hydrolyzed to free cholesterol (about 9%, none of the antiproliferative effects were due to CholPC or excess cholesterol. The ceramide effect was not limited to D-erythro-C6-Cer, since L-erythro-C6-Cer and D-erythro-C6-dihydroCer also inhibited cell priolifereation and affected Ca(2+ homeostasis. We conclude that C6-Cer complexed to CholPC increased the bioavailability of the short-chain ceramide for cells, and potentiated its effects in comparison to solvent-dissolved C6-Cer. This new ceramide formulation appears to be superior to previous solvent delivery approaches, and may even be useful with longer-chain ceramides.

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

Anti-topoisomerase drugs as potent inducers of chromosomal aberrations

Directory of Open Access Journals (Sweden)

Loredana Bassi

2000-12-01

Full Text Available DNA topoisomerases catalyze topological changes in DNA that are essential for normal cell cycle progression and therefore they are a preferential target for the development of anticancer drugs. Anti-topoisomerase drugs can be divided into two main classes: "cleavable complex" poisons and catalytic inhibitors. The "cleavable complex" poisons are very effective as anticancer drugs but are also potent inducers of chromosome aberrations so they can cause secondary malignancies. Catalytic inhibitors are cytotoxic but they do not induce chromosome aberrations. Knowledge about the mechanism of action of topoisomerase inhibitors is important to determine the best anti-topoisomerase combinations, with a reduced risk of induction of secondary malignancies.As topoisomerases de DNA catalisam alterações topológicas no DNA que são essenciais para a progressão do ciclo celular normal e, portanto, são um alvo preferencial para o desenvolvimento de drogas anticâncer. Drogas anti-topoisomerases podem ser divididas em duas classes principais: drogas anti-"complexos cliváveis" e inibidores catalíticos. As drogas anti-"complexos cliváveis" são muito eficazes como drogas anticancerígenas, mas são também potentes indutores de aberrações cromossômicas, podendo causar neoplasias malignas secundárias. Inibidores catalíticos são citotóxicos mas não induzem aberrações cromossômicas. Conhecimento a respeito do mecanismo de ação de inibidores de topoisomerases é importante para determinar as melhores combinações anti-topoisomerases, com um reduzido risco de indução de neoplasias malignas secundárias.

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.

Crystal structure of Lymnaea stagnalis AChBP complexed with the potent nAChR antagonist DHβE suggests a unique mode of antagonism.

Directory of Open Access Journals (Sweden)

Azadeh Shahsavar

Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed, activated (open, and desensitized (closed states. The acetylcholine binding protein (AChBP is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls in complex with dihydro-β-erythroidine (DHβE, which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

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%

Novel types of staphylococcal cassette chromosome mec elements identified in clonal complex 398 methicillin-resistant Staphylococcus aureus strains.

NARCIS (Netherlands)

Li, S.; Skov, R.L.; Han, X.; Larsen, A.R.; Larsen, J.; Sorum, M.; Wulf, M.; Voss, A.; Hiramatsu, K.; Ito, T.

2011-01-01

The structures of staphylococcal cassette chromosome mec (SCCmec) elements carried by 31 clonal complex 398 (CC398) methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from the participants at a conference were analyzed. The SCCmecs were classified into novel types, namely, IX, X,

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.)

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)

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.

Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

Energy Technology Data Exchange (ETDEWEB)

Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

2004-07-01

We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

International Nuclear Information System (INIS)

Yousry, Indra; Yousry, Tarek A.; Muacevic, Alexander; Olteanu-Nerbe, Vlad; Naidich, Thomas P.

2004-01-01

We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

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)

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

Science.gov (United States)

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.

Triazolophostins: a library of novel and potent agonists of IP3 receptors

OpenAIRE

Vibhute, Amol M; Konieczny, Vera; Taylor, Colin William; Sureshan, Kana M

2015-01-01

IP3 receptors are channels that mediate the release of Ca2+ from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of sy...

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°

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...

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)

A review of machines and devices to potentize homeopathic medicines.

Science.gov (United States)

Basu, Abhirup; Suresh, Akkihebbal Krishnamurthy; Kane, Shantaram Govind; Bellare, Jayesh Ramesh

2017-11-01

Potentization, consisting of serial dilution and succussion, is a key step in the manufacture of homeopathic medicines. Originally prescribed as a manual process, several attempts at mechanization have been published, patented and even commercialised in order to remove the human element and introduce reproducibility without drudgery. Various machines have been used over the years to prepare homeopathic medicines. Although these machines follow the same principles, i.e. energetically mixing the medicines and diluting them significantly, their mode of operation is different from each other. This review paper surveys the main methods of preparation of homeopathic medicines. The main machines discussed are: Boericke's potentizer, Tyler Kent's instrument, John Alphonse's machine and the fluxion potentizer, which were used in the past, as well as more recent potentizers like arm-and-weight instruments, the K-Tronic potentizer and Quinn's machine. We review the construction and operating principle of each of these machines, along with their advantages and limitations. A scheme for relative performance assessment of these machines is proposed based on the parameters mechanical efficiency, physico-chemical efficiency, turbulence generation, energy dissipation, and accuracy of dilution. Quinn's machine and the arm-and-weight potentizer perform well for generating turbulence due to high impaction forces, while John Alphonse's machine is much more accurate in diluting the homeopathic medicines at every step. Both the commercial potentizers, Quinn's machine and the K-Tronic potentizer, are completely automated and therefore reduce the manual labour and variation in succussive forces during each step, which may produce uniformity in physico-chemical changes within the resulting homeopathic medicines. Copyright © 2017. Published by Elsevier Ltd.

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...

G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses

Science.gov (United States)

2013-01-01

Background Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. Methods We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. Results We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. Conclusions Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF. PMID:24279871

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.

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

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.

Neutron contamination of Varian Clinac iX 10 MV photon beam using Monte Carlo simulation

International Nuclear Information System (INIS)

Yani, S; Haryanto, F; Arif, I; Tursinah, R; Rhani, M F; Soh, R C X

2016-01-01

High energy medical accelerators are commonly used in radiotherapy to increase the effectiveness of treatments. As we know neutrons can be emitted from a medical accelerator if there is an incident of X-ray that hits any of its materials. This issue becomes a point of view of many researchers. The neutron contamination has caused many problems such as image resolution and radiation protection for patients and radio oncologists. This study concerns the simulation of neutron contamination emitted from Varian Clinac iX 10 MV using Monte Carlo code system. As neutron production process is very complex, Monte Carlo simulation with MCNPX code system was carried out to study this contamination. The design of this medical accelerator was modelled based on the actual materials and geometry. The maximum energy of photons and neutron in the scoring plane was 10.5 and 2.239 MeV, respectively. The number and energy of the particles produced depend on the depth and distance from beam axis. From these results, it is pointed out that the neutron produced by linac 10 MV photon beam in a typical treatment is not negligible. (paper)

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

Bianchi IX dynamics in bouncing cosmologies: homoclinic chaos and the BKL conjecture

Science.gov (United States)

Maier, Rodrigo; Damião Soares, Ivano; Valentino Tonini, Eduardo

2015-12-01

We examine the dynamics of a Bianchi IX model with three scale factors on a 4-dim Lorentzian brane embedded in a 5-dim conformally flat empty bulk with a timelike extra dimension. The matter content is a pressureless perfect fluid restricted to the brane, with the embedding consistently satisfying the Gauss-Codazzi equations. The 4-dim Einstein equations on the brane reduce to a 6-dim Hamiltonian dynamical system with additional terms (due to the bulk-brane interaction) that avoid the singularity and implement nonsingular bounces in the model. We examine the complex Bianchi IX dynamics in its approach to the neighborhood of the bounce which replaces the cosmological singularity of general relativity. The phase space of the model presents (i) two critical points (a saddle-center-center and a center-center-center) in a finite region of phase space, (ii) two asymptotic de Sitter critical points at infinity, one acting as an attractor to late-time acceleration and (iii) a 2-dim invariant plane, which together organize the dynamics of the phase space. The saddle-center-center engenders in the phase space the topology of stable and unstable 4-dim cylinders R × S 3, where R is a saddle direction and S 3 is the center manifold of unstable periodic orbits, the latter being the nonlinear extension of the center-center sector. By a proper canonical transformation the degrees of freedom of the dynamics are separated into one degree connected with the expansion/contraction of the scales of the model, and two rotational degrees of freedom associated with the center manifold S 3. The typical dynamical flow is thus an oscillatory mode about the orbits of the invariant plane. The stable and unstable cylinders are spanned by oscillatory orbits about the separatrix towards the bounce, leading to the homoclinic transversal intersection of the cylinders, as shown numerically in two distinct simulations. The homoclinic intersection manifold has the topology of R × S 2 consisting of

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.

2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

Science.gov (United States)

Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

2009-09-01

This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

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...

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.

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.

Human platelet glycoprotein IX: An adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures

International Nuclear Information System (INIS)

Hickey, M.J.; Williams, S.A.; Roth, G.J.

1989-01-01

The glycoprotein (GP) Ib-IX complex on the surface of human platelets functions as the von Willebrand factor receptor and mediates von Willebrand factor-dependent platelet adhesion to blood vessels. GPIX is a relatively small (M r , 17,000) protein that may provide for membrane insertion and orientation of the larger component of the complex. GPIb (M r , 165,000). Using antibody screening, the authors cloned a cDNA encoding GPIX from a human erythroleukemia cell cDNA library constructed in phage λgt11. Lacking a 5' untranslated region and start codon, the cDNA sequence includes 604 nucleotides, beginning with 495 bases at the 5' end coding for 165 amino acids, followed by a stop codon and 106 noncoding bases at the 3' end. By Northern blot analysis, the GPIX cDNA hybridizes with a single 1.0-kilobase species of platelet poly(A) + RNA. Translation of the cDNA sequence gives a predicted protein sequence beginning with a truncated putative signal sequence of 5 amino acids followed by a sequence of 17 amino acids matching that determined directly by Edman degradation of intact GPIX. GPIX contains a leucine-rich glycoprotein (LRG) sequence of 24 amino acids similar to conserved LRG sequences in GPIb and other proteins from humans, Drosophila, and yeast. The role of the flank-LRG center-flank structure in the evolution and function of the LRG proteins remains to be defined

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

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.)

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

Science.gov (United States)

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…

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

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.

Synthesis and SAR studies of potent imidazopyridine anticoccidial agents.

Science.gov (United States)

Liang, Gui-Bai; Qian, Xiaoxia; Feng, Dennis; Fisher, Michael; Brown, Christine M; Gurnett, Anne; Leavitt, Penny Sue; Liberator, Paul A; Misura, Andrew S; Tamas, Tamas; Schmatz, Dennis M; Wyvratt, Matthew; Biftu, Tesfaye

2007-07-01

Diaryl imidazo[1,2-a]pyridine derivatives, such as 6a and 7i, have been synthesized and found to be potent inhibitors of parasite PKG activity. The most potent compounds are the 7-isopropylaminomethyl analog 6a and 2-isopropylamino analog 7i. These compounds are also fully active in in vivo assay as anticoccidial agents at 25 ppm in feed.

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.

Triazolophostins: a library of novel and potent agonists of IP3 receptors.

Science.gov (United States)

Vibhute, Amol M; Konieczny, Vera; Taylor, Colin W; Sureshan, Kana M

2015-06-28

IP3 receptors are channels that mediate the release of Ca(2+) from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of synthetic conditions for each analog. Such lengthy one-at-a-time syntheses limit access to AdA analogs. We have addressed this problem by synthesizing a library of triazole-based AdA analogs, triazolophostins, by employing click chemistry. An advanced intermediate having all the necessary phosphates and a β-azide at the anomeric position was reacted with various alkynes under Cu(i) catalysis to yield triazoles, which upon deprotection gave triazolophostins. All eleven triazolophostins synthesized are more potent than IP3 and some are equipotent with AdA in functional analyses of IP3 receptors. We show that a triazole ring can replace adenine without compromising the potency of AdA and provide facile routes to novel AdA analogs.

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)

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

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)

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.

Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of Alzheimer's Disease Therapeutics.

Science.gov (United States)

Chakraborty, Sandipan

2017-01-01

Alzheimer's Disease (AD) once considered a rare disorder emerges as a major health concern in recent times. The disease pathogenesis is very complex and yet to be understood completely. However, "Amyloid Cascade" is the central event in disease pathogenesis. Several proteins of the amyloid cascade are currently being considered as potential targets for AD therapeutics discovery. Many potential compounds are in clinical trials, but till now there is no known cure for the disease. Recent years have witnessed remarkable research interest in the search of novel concepts in drug designing for AD. Multi-targeted ligand design is a paradigm shift in conventional drug discovery. In this process rather than designing ligands targeting a single receptor, novel ligands have been designed/ synthesized that can simultaneously target many pathways involved in disease pathogenesis. Here, recent developments in computational drug designing protocols to identify multi-targeted ligand for AD have been discussed. Therapeutic potential of different multi-potent compounds also has been discussed briefly. Prime emphasis has been given to multi-potent ligand from natural resources. Polyphenols are an interesting group of compounds which show efficacy against a wide range of disease and have the property to exhibit multi-potency. Several groups attempted to identify novel multi-potent phytochemicals for AD therapy. Multi-potency of several polyphenols or compounds synthesized using the poly-phenolic scaffolds have been briefly discussed here. However, the multi-targeted drug designing for AD is still in early stages, more advancement in drug designing method/algorithm developments is urgently required to discover more efficient compounds for AD therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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.

Highly Potent Antibacterial Organometallic Peptide Conjugates

NARCIS (Netherlands)

Albada, Bauke; Metzler-Nolte, Nils

2017-01-01

ConspectusResistance of pathogenic bacteria against currently marketed antibiotics is again increasing. To meet the societal need for effective cures, scientists are faced with the challenge of developing more potent but equally bacteria-specific drugs. Currently, most efforts are directed toward

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

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.

Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration

International Nuclear Information System (INIS)

Nadanaciva, Sashi; Dykens, James A.; Bernal, Autumn; Capaldi, Roderick A.; Will, Yvonne

2007-01-01

Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II + III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II + III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others

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.

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

NARCIS (Netherlands)

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

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.

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

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'…

Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8

Energy Technology Data Exchange (ETDEWEB)

Judge, Russell A.; Zhu, Haizhong; Upadhyay, Anup K.; Bodelle, Pierre M.; Hutchins, Charles W.; Torrent, Maricel; Marin, Violeta L.; Yu, Wenyu; Vedadi, Masoud; Li, Fengling; Brown, Peter J.; Pappano, William N.; Sun, Chaohong; Petros, Andrew M.

2016-12-08

SETD8 is a histone H4–K20 methyltransferase that plays an essential role in the maintenance of genomic integrity during mitosis and in DNA damage repair, making it an intriguing target for cancer research. While some small molecule inhibitors for SETD8 have been reported, the structural binding modes for these inhibitors have not been revealed. Using the complex structure of the substrate peptide bound to SETD8 as a starting point, different natural and unnatural amino acid substitutions were tested, and a potent (Ki 50 nM, IC50 0.33 μM) and selective norleucine containing peptide inhibitor has been obtained.

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.)

Celebrity Patients, VIPs, and Potentates.

Science.gov (United States)

Groves, James E.; Dunderdale, Barbara A.; Stern, Theodore A.

2002-12-01

BACKGROUND: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of "difficult" (personality-disordered) patients. Similar problems, however, surround other types of "special" patients. METHOD: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. RESULTS: Three types of "special" patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. CONCLUSION: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are "special"-and by caregivers mending their own vulnerable self-esteem.

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.

Potent haloperidol derivatives covalently binding to the dopamine D2 receptor.

Science.gov (United States)

Schwalbe, Tobias; Kaindl, Jonas; Hübner, Harald; Gmeiner, Peter

2017-10-01

The dopamine D 2 receptor (D 2 R) is a common drug target for the treatment of a variety of neurological disorders including schizophrenia. Structure based design of subtype selective D 2 R antagonists requires high resolution crystal structures of the receptor and pharmacological tools promoting a better understanding of the protein-ligand interactions. Recently, we reported the development of a chemically activated dopamine derivative (FAUC150) designed to covalently bind the L94C mutant of the dopamine D 2 receptor. Using FAUC150 as a template, we elaborated the design and synthesis of irreversible analogs of the potent antipsychotic drug haloperidol forming covalent D 2 R-ligand complexes. The disulfide- and Michael acceptor-functionalized compounds showed significant receptor affinity and an irreversible binding profile in radioligand depletion experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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

Involvement of heme oxygenase-1 in β-cyclodextrin-hemin complex-induced cucumber adventitious rooting process.

Science.gov (United States)

Lin, Yuting; Li, Meiyue; Huang, Liqin; Shen, Wenbiao; Ren, Yong

2012-09-01

Our previous results showed that β-cyclodextrin-hemin complex (CDH) exhibited a vital protective role against cadmium-induced oxidative damage and toxicity in alfalfa seedling roots by the regulation of heme oxygenase-1 (HO-1) gene expression. In this report, we further test whether CDH exhibited the hormonal-like response. The application of CDH and an inducer of HO-1, hemin, were able to induce the up-regulation of cucumber HO-1 gene (CsHO1) expression and thereafter the promotion of adventitious rooting in cucumber explants. The effect is specific for HO-1 since the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blocked the above responses triggered by CDH, and the inhibitory effects were reversed further when 30% saturation of CO aqueous solution was added together. Further, molecular evidence showed that CDH triggered the increases of the HO-1-mediated target genes responsible for adventitious rooting, including one DnaJ-like gene (CsDNAJ-1) and two calcium-dependent protein kinase (CDPK) genes (CsCDPK1 and CsCDPK5), and were inhibited by ZnPP and reversed by CO. The calcium (Ca2+) chelator ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and the Ca2+ channel blocker lanthanum chloride (LaCl3) not only compromised the induction of adventitious rooting induced by CDH but also decreased the transcripts of above three target genes. However, the application of ascorbic acid (AsA), a well-known antioxidant in plants, failed to exhibit similar inducible effect on adventitious root formation. In short, above results illustrated that the response of CDH in the induction of cucumber adventitious rooting might be through HO-1-dependent mechanism and calcium signaling. Physiological, pharmacological and molecular evidence showed that β-cyclodextrin-hemin complex (CDH) was able to induce cucumber adventitious rooting through heme oxygenase-1 (HO-1)-dependent mechanism and calcium signaling.

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

Aminopurvalanol A, a Potent, Selective, and Cell Permeable Inhibitor of Cyclins/Cdk Complexes, Causes the Reduction of in Vitro Fertilizing Ability of Boar Spermatozoa, by Negatively Affecting the Capacitation-Dependent Actin Polymerization

Directory of Open Access Journals (Sweden)

Nicola Bernabò

2017-12-01

Full Text Available The adoption of high-througput technologies demonstrated that in mature spermatozoa are present proteins that are thought to be not present or active in sperm cells, such as those involved in control of cell cycle. Here, by using an in silico approach based on the application of networks theory, we found that Cyclins/Cdk complexes could play a central role in signal transduction active during capacitation. Then, we tested this hypothesis in the vitro model. With this approach, spermatozoa were incubated under capacitating conditions in control conditions (CTRL or in the presence of Aminopurvalanol A a potent, selective and cell permeable inhibitor of Cyclins/Cdk complexes at different concentrations (2, 10, and 20 μM. We found that this treatment caused dose-dependent inhibition of sperm fertilizing ability. We attribute this event to the loss of acrosome integrity due to the inhibition of physiological capacitation-dependent actin polymerization, rather than to a detrimental effect on membrane lipid remodeling or on other signaling pathways such as tubulin reorganization or MAPKs activation. In our opinion, these data could revamp the knowledge on biochemistry of sperm capacitation and could suggest new perspectives in studying male infertility.

Telomere dysfunction and cell survival: Roles for distinct TIN2-containing complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Sahn-ho; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis; Zou, Ying; Beausejour, Christian; Kaminker, Patrick; Yannone, Steven M.; Campisi, Judith

2007-10-02

Telomeres are maintained by three DNA binding proteins (TRF1, TRF2 and POT1), and several associated factors. One factor, TIN2, binds TRF1 and TRF2 directly and POT1 indirectly. Along with two other proteins, TPP1 and hRap1, these form a soluble complex that may be the core telomere maintenance complex. It is not clear whether sub-complexes also exist in vivo. We provide evidence for two TIN2 sub-complexes with distinct functions in human cells. We isolated these two TIN2 sub-complexes from nuclear lysates of unperturbed cells and cells expressing TIN2 mutants TIN2-13, TIN2-15C, which cannot bind TRF2 or TRF1, respectively. In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere dysfunction and cell death. Our findings suggest that distinct TIN2 complexes exist, and that TIN2-15C-sensitive subcomplexes are particularly important for cell survival in the absence of functional p53.

Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo.

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Sheila Ranganath

Full Text Available Interleukin-6 (IL-6 is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman's Disease (CD and rheumatoid arthritis (RA. Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA and C-reactive protein (CRP. This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology.

AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor

DEFF Research Database (Denmark)

Hatse, Sigrid; Princen, Katrien; De Clercq, Erik

2005-01-01

The chemokine receptors CCR5 and CXCR4 function as coreceptors for human immunodeficiency virus (HIV) and are attractive targets for the development of anti-HIV drugs. The most potent CXCR4 antagonists described until today are the bicyclams. The prototype compound, AMD3100, exhibits potent and s...

INTERACTION OF FLUORIDE COMPLEXES DERIVED FROM GLASS-IONOMER CEMENTS WITH HYDROXYAPATITE

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Lewis S. M.

2013-09-01

Full Text Available A study has been undertaken of the interaction of complexed fluoride extracted from glass-ionomer dental cements with synthetic hydroxyapatite powder. Extracts were prepared from two commercial glass-ionomers (Fuji IX and ChemFlex under both neutral and acidic conditions. They were analysed by ICP-OES and by fluoride-ion selective electrode with and without added TISAB to decomplex the fluoride. The pH of the acid extracts was 4, conditions under which fluoride complexes with protons as HF or HF2-, it also complexes with aluminium, which was found to be present in higher amounts in the acid extracts. Fluoride was found to be almost completely complexed in acid extracts, but not in neutral extracts, which contained free fluoride ions. Exposure of these extracts to synthetic hydroxyapatite powder showed that fluoride was taken up rapidly (within 5 minutes, whether or not it was complexed. SEM (EDAX study of recovered hydroxyapatite showed only minute traces of aluminium taken up under all conditions. This showed that aluminium interacts hardly at all with hydroxyapatite, and hence is probably not involved in the remineralisation process.

Identification of a methylated oligoribonucleotide as a potent inhibitor of HIV-1 reverse transcription complex.

Science.gov (United States)

Grigorov, Boyan; Bocquin, Anne; Gabus, Caroline; Avilov, Sergey; Mély, Yves; Agopian, Audrey; Divita, Gilles; Gottikh, Marina; Witvrouw, Myriam; Darlix, Jean-Luc

2011-07-01

Upon HIV-1 infection of a target cell, the viral reverse transcriptase (RT) copies the genomic RNA to synthesize the viral DNA. The genomic RNA is within the incoming HIV-1 core where it is coated by molecules of nucleocapsid (NC) protein that chaperones the reverse transcription process. Indeed, the RT chaperoning properties of NC extend from the initiation of cDNA synthesis to completion of the viral DNA. New and effective drugs against HIV-1 continue to be required, which prompted us to search for compounds aimed at inhibiting NC protein. Here, we report that the NC chaperoning activity is extensively inhibited in vitro by small methylated oligoribonucleotides (mODN). These mODNs were delivered intracellularly using a cell-penetrating-peptide and found to impede HIV-1 replication in primary human cells at nanomolar concentrations. Extensive analysis showed that viral cDNA synthesis was severely impaired by mODNs. Partially resistant viruses with mutations in NC and RT emerged after months of passaging in cell culture. A HIV-1 molecular clone (NL4.3) bearing these mutations was found to replicate at high concentrations of mODN, albeit with a reduced fitness. Small, methylated ODNs such as mODN-11 appear to be a new type of highly potent inhibitor of HIV-1.

House dust extracts contain potent immunological adjuvants

NARCIS (Netherlands)

Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

1987-01-01

A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

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

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

Science.gov (United States)

Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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...

Identification of a rhodium(iii) complex as a Wee1 inhibitor against TP53-mutated triple-negative breast cancer cells.

Science.gov (United States)

Yang, Guan-Jun; Zhong, Hai-Jing; Ko, Chung-Nga; Wong, Suk-Yu; Vellaisamy, Kasipandi; Ye, Min; Ma, Dik-Lung; Leung, Chung-Hang

2018-03-06

The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced cell damage and death in TP53-mutated triple-negative breast cancer cells. 1 represents a promising scaffold for further development of more potent metal-based Wee1 antagonists.

Studies on the ruthenium complexes. IX. Kinetic studies on the deaquation-anation reaction of aquapentaammineruthenium(III) complexes

Energy Technology Data Exchange (ETDEWEB)

Ohyoshi, A; Hiraki, S I; Odate, T; Kohata, S; Oda, J [Kumamoto Univ. (Japan). Faculty of Engineering

1975-01-01

The deaquation-anation reaction of (Ru(OH/sub 2/)(NH/sub 3/)/sub 5/)X/sub 3/-type complexes in the solid state, as shown by the (Ru(OH/sub 2/)(NH/sub 3/)/sub 5/)X/sub 3/(s)..-->..(RuX(NH/sub 3/)/sub 5/)X/sub 2/(s)+H/sub 2/O(g) equation, where X is Cl, Br, I, and NO/sub 3/ respectively, was kinetically studied by means of thermogravimetry (TG) along with differential thermal analysis (DTA). The activation energy and entropy in the reaction process (Esub(a) kcal/mol, ..delta..S c.u.) are, respectively, found by isothermal kinetic study to be (22.7, - 7.1) for the chloride, (23.4, - 5.2) for the bromide, (26.7, 5.8) for the iodide, and (19.3 - 15.9) for the nitrate. The reaction seems to proceed through the following two steps, except in the case of the iodide: (Ru(OH/sub 2/)(NH/sub 3/)/sub 5/)X/sub 3/..-->..(RuX(OH/sub 2/)(NH/sub 3/)/sub 5/)X/sub 2/..-->..(RuX(NH/sub 3/)/sub 5/)X/sub 2/+H/sub 2/O. The first step is regarded as the rate-determining one.

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands.

Science.gov (United States)

Hubin, Timothy J; Amoyaw, Prince N-A; Roewe, Kimberly D; Simpson, Natalie C; Maples, Randall D; Carder Freeman, TaRynn N; Cain, Amy N; Le, Justin G; Archibald, Stephen J; Khan, Shabana I; Tekwani, Babu L; Khan, M O Faruk

2014-07-01

Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn(2+) complex of this ligand was the most potent with IC50s of 0.127 and 0.157μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn(2+). Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development. Published by Elsevier Ltd.

Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.

Science.gov (United States)

Conroy, Trent; Guo, Jin T; Elias, Nabiha; Cergol, Katie M; Gut, Jiri; Legac, Jennifer; Khatoon, Lubna; Liu, Yang; McGowan, Sheena; Rosenthal, Philip J; Hunt, Nicholas H; Payne, Richard J

2014-12-26

Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

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Dhana G Gorasia

2016-08-01

Full Text Available The type IX secretion system (T9SS has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

Science.gov (United States)

Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

2016-08-01

The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component.

An ayurvedic formulation Sankat Mochan: A potent anthelmintic medicine

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Khomendra Kumar Sarwa

2017-01-01

Full Text Available Aim and Object: Sankat Mochan is an ayurvedic formulation used in the urban and rural area of India. This polyherbal formulation is used for general stomach problems including abdominal cramping and diarrhea. The present investigation evaluated the anthelmintic activity of an aqueous solution of an ayurvedic medicine Sankat Mochan. Materials and Method: Various concentrations (1%, 5%, and 10% of medicine were used for anthelmintic activity on Pheretima posthuma. Piperazine citrate (10 mg/ml was used as a reference standard and distilled water as a control. Result and Conclusion: The result showed that the Sankat Mochan possess anthelmintic activity more potent than that of piperazine citrate. Thus, Sankat Mochan may be used as a potent anthelmintic agent against helminthiasis.

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.

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.

Economy diversification: a potent tool for tourism development in ...

African Journals Online (AJOL)

Economy diversification: a potent tool for tourism development in Nigeria. ... AFRREV STECH: An International Journal of Science and Technology ... The diversity of cultural attractions, the friendly disposition of the people, revamped National ...

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...

Late cutaneous effects of a local potent steroid during adjuvant radiotherapy for breast cancer

DEFF Research Database (Denmark)

Ulff, Eva; Maroti, Marianne; Serup, Jörgen

2017-01-01

Purpose: The aim of this study was to evaluate whether treatment with a local potent corticosteroid during adjuvant external radiotherapy (ERT) of breast cancer is associated with late skin toxicity. Material and methods: Sixty patients (32 treated with potent corticoid cream versus 28 controls t...

Identification of a potent endothelium-derived angiogenic factor

DEFF Research Database (Denmark)

Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh

2013-01-01

The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelia...

Chloroatranol, an extremely potent allergen hidden in perfumes

DEFF Research Database (Denmark)

Johansen, Jeanne Duus; Andersen, Klaus Ejner; Svedman, Cecilia

2003-01-01

Oak moss absolute is a long-known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently...... an open test simulating the use of perfumes on the volar aspect of the forearms in a randomized and double-blinded design. A solution with 5 p.p.m. chloroatranol was used for 14 days, and, in case of no reaction, the applications were continued for another 14 days with a solution containing 25 p.p.m. All....... The dose eliciting a reaction in 50% of the test subjects at patch testing was 0.2 p.p.m. In conclusion, the hidden exposure to a potent allergen widely used in perfumes has caused a highly sensitized cohort of individuals. Judged from the elicitation profile, chloroatranol is the most potent allergen...

Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.

Science.gov (United States)

Bahl, Deepa; Athar, Fareeda; Soares, Milena Botelho Pereira; de Sá, Matheus Santos; Moreira, Diogo Rodrigo Magalhães; Srivastava, Rajendra Mohan; Leite, Ana Cristina Lima; Azam, Amir

2010-09-15

A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive ligands with transition metals. In view of this, an investigation was conducted into a new set of metal complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized furyl-thiosemicarbazones (NT1-4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure-activity relationship data revealed that the metallic complexation plays an essential role in antiprotozoal activity, rather than the simple presence of the ligand or metal alone. Important steps towards identification of novel antiplasmodium (NT1Cu, IC50 of 4.6 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) drug prototypes were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation of these parasites at concentrations that are not cytotoxic to mammalian cells. Copyright (c) 2010. Published by Elsevier Ltd.

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

Directory of Open Access Journals (Sweden)

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.

1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

Science.gov (United States)

Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

1980-10-01

The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

Scalets, wavelets and (complex) turning point quantization

Science.gov (United States)

Handy, C. R.; Brooks, H. A.

2001-05-01

Despite the many successes of wavelet analysis in image and signal processing, the incorporation of continuous wavelet transform theory within quantum mechanics has lacked a compelling, first principles, motivating analytical framework, until now. For arbitrary one-dimensional rational fraction Hamiltonians, we develop a simple, unified formalism, which clearly underscores the complementary, and mutually interdependent, role played by moment quantization theory (i.e. via scalets, as defined herein) and wavelets. This analysis involves no approximation of the Hamiltonian within the (equivalent) wavelet space, and emphasizes the importance of (complex) multiple turning point contributions in the quantization process. We apply the method to three illustrative examples. These include the (double-well) quartic anharmonic oscillator potential problem, V(x) = Z2x2 + gx4, the quartic potential, V(x) = x4, and the very interesting and significant non-Hermitian potential V(x) = -(ix)3, recently studied by Bender and Boettcher.

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...

Nanosilver: Potent antimicrobial agent and its biosynthesis | Sarsar ...

African Journals Online (AJOL)

The synthesis of silver nanoparticles has been reported using chemical and physical methods. This review describes a cost effective and ecofriendly approach for the synthesis of silver nanoparticles. Thus, in this review we focus on the role of microorganisms and plants in the synthesis of nanosilver and their potent ...

Potent antitumor activity of a urokinase-activated engineered anthrax toxin

Science.gov (United States)

Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

2003-01-01

The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

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 ...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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

Hydroxychavicol: a potent xanthine oxidase inhibitor obtained from the leaves of betel, Piper betle.

Science.gov (United States)

Murata, Kazuya; Nakao, Kikuyo; Hirata, Noriko; Namba, Kensuke; Nomi, Takao; Kitamura, Yoshihisa; Moriyama, Kenzo; Shintani, Takahiro; Iinuma, Munekazu; Matsuda, Hideaki

2009-07-01

The screening of Piperaceous plants for xanthine oxidase inhibitory activity revealed that the extract of the leaves of Piper betle possesses potent activity. Activity-guided purification led us to obtain hydroxychavicol as an active principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than allopurinol, which is clinically used for the treatment of hyperuricemia.

Modulation of solubility and dissolution of furosemide by preparation of phospholipid complex

OpenAIRE

Mona Semalty; Prateeksha Badoni; Devendra Singh; Ajay Semalty

2014-01-01

Aim: The aim of this study is to improve the solubility and dissolution of furosemide (a potent high ceiling diuretic used for the treatment of hypertension and a Class IV drug that is low solubility and low permeability drug as per the Biopharmaceutical Classification System) by preparing its phospholipid complexes or pharmacosomes. Materials and Methods: Furosemide was complexed with phosphatidylcholine in four different molar ratios (1:1, 1:2, 1:3 and 1:4) by conventional solvent-evaporati...

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.

Engineered Promoters for Potent Transient Overexpression.

Directory of Open Access Journals (Sweden)

Dan Y Even

Full Text Available The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3, which combines four core promoter elements (the TATA box, Inr, MTE and DPE into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods.

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

Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.

Science.gov (United States)

Feng, Song; Hong, Di; Wang, Baoxia; Zheng, Xiufang; Miao, Kun; Wang, Lisha; Yun, Hongying; Gao, Lu; Zhao, Shuhai; Shen, Hong C

2015-03-12

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization.

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

Science.gov (United States)

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.

Science.gov (United States)

Jung, Jaeyun; Yeom, Chanjoo; Choi, Yeon-Sook; Kim, Sinae; Lee, EunJi; Park, Min Ji; Kang, Sang Wook; Kim, Sung Bae; Chang, Suhwan

2015-08-21

The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.

Seleucid, Demotic and Mediterranean mathematics versus Chapters VIII and IX of the Nine Chapters: accidental or significant similarities?

DEFF Research Database (Denmark)

Høyrup, Jens

Similarities of geometrical diagrams and arithmetical structures of problems have often been taken as evidence of transmission of mathematical knowledge or techniques between China and “the West”. Confronting on one hand some problems from Chapter VIII of the Nine Chapters with comparable problems...... known from Ancient Greek sources, on the other a Seleucid collection of problems about rectangles with a subset of the triangle problems from Chapter IX, it is concluded, (1) that transmission of some arithmetical riddles without method – not “from Greece” but from a transnational community of traders...

Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.

Directory of Open Access Journals (Sweden)

Anna Figueiredo

2006-11-01

Full Text Available Nonnucleoside reverse transcriptase inhibitors (NNRTIs target HIV-1 reverse transcriptase (RT by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

How Title IX and Proportionality Population Concepts Have Equalized Collegiate Women's Sports Programs with Men's Sports and Allows Spillover Gains for Women in the Workplace

Science.gov (United States)

Compton, Nina H.; Compton, J. Douglas

2010-01-01

Title IX of the Education Reformation Act was passed in 1972 for the purpose of providing equality between males and females in intercollegiate sports. Since its inception the disparity between men's and women's varsity athletics programs has persisted throughout American colleges and universities. Discrimination and equal protection concerns…

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

Energy Technology Data Exchange (ETDEWEB)

Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

2015-10-15

The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC₅₀) <50 μg ml^-1. The median IC₅₀ of neutralized viruses was 0.033 μg ml^-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

FY 2000 report on the results of the development of commercialization technology of the photovoltaic power system. International cooperation project (IEA photovoltaic power generation program - Collection of the information on Task IX); 2000 nendo New sunshine keikaku seika hokokusho. Taiyoko hatsuden system jitsuyoka gijutsu kaihatsu kokusai jigyo kyoryoku (IEA taiyoko hatsuden program task IX ni kansuru joho shushu)

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

Based on 'the Implementing agreement for a research cooperation project on the photovoltaic power system' being promoted by IEA, collection of the information was made on Task IX: Promotion of the effective spread of the PV technology in developing countries, and the FY 2000 results were summarized. In Task IX, for technical/economic subjects in introducing the PV system to developing countries, a commendable/practical guide using the experiences having been gained was to be arranged. Also, workshop was to be opened in developing countries as model, and cooperation was to be promoted with international organizations such as the Bank of the World. In this fiscal year, two meetings of specialists (abroad) and four sectional meetings of operation (in Japan) were held. This fiscal year was the second year of the 5-year plan. The standard for selecting developing countries as model was studied, and a draft of the commendable/practical guide was made and discussed in the meeting of specialists. (NEDO)

FY 2000 report on the results of the development of commercialization technology of the photovoltaic power system. International cooperation project (IEA photovoltaic power generation program - Collection of the information on Task IX); 2000 nendo New sunshine keikaku seika hokokusho. Taiyoko hatsuden system jitsuyoka gijutsu kaihatsu kokusai jigyo kyoryoku (IEA taiyoko hatsuden program task IX ni kansuru joho shushu)

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

Based on 'the Implementing agreement for a research cooperation project on the photovoltaic power system' being promoted by IEA, collection of the information was made on Task IX: Promotion of the effective spread of the PV technology in developing countries, and the FY 2000 results were summarized. In Task IX, for technical/economic subjects in introducing the PV system to developing countries, a commendable/practical guide using the experiences having been gained was to be arranged. Also, workshop was to be opened in developing countries as model, and cooperation was to be promoted with international organizations such as the Bank of the World. In this fiscal year, two meetings of specialists (abroad) and four sectional meetings of operation (in Japan) were held. This fiscal year was the second year of the 5-year plan. The standard for selecting developing countries as model was studied, and a draft of the commendable/practical guide was made and discussed in the meeting of specialists. (NEDO)

Potent heme-degrading action of antimony and antimony-containing parasiticidal agents.

Science.gov (United States)

Drummond, G S; Kappas, A

1981-02-01

The ability of antimony and antimony-containing parasiticidal agents to enhance the rate of heme degradation in liver and kidney was investigated. Trivalent antimony was shown to be an extremely potent inducer of heme oxygenase, the initial and rate-limiting enzyme in heme degradation, in both organs, whereas the pentavalent form was a weak inducer of this enzyme. The ability of antimony to induce heme oxygenase was dose-dependent, independent of the salt used, and not a result of a direct activation of the enzyme in vitro. Concomitant with heme oxygenase induction by antimony, microsomal heme and cytochrome P-450 contents decreased, the cyto-chrome P-450-dependent mixed function oxidase system was impaired, and delta-ami-nolevulinate synthase (ALAS), the rate-limiting enzyme of heme synthesis, underwent the sequential changes-initial inhibition followed by rebound induction-usually associated with the administration of transition elements such as cobalt. Antimony induction of heme oxygenase however, unlike the enzyme induction elicited by cobalt, was not prevented either by cysteine administered orally or as a cysteine metal complex, or by simultaneous zinc administration. Desferoxamine also did not block heme oxygenase induction by antimony, but this chelator did prevent the rebound increase in ALAS activity associated with antimony or cobalt treatment. Antimony-containing parasiticidal drugs were also potent inducers of heme oxygenase in liver and kidney. The heme degradative action of these drugs may be related in part to the jaundice commonly associated with the prolonged therapeutic use of these agents. The heme-oxygenase-inducing action of antimony-containing parasiticidal drugs is a newly defined biological property of these compounds. The relation between the parasiticidal and the heme-oxygenase-inducing actions of such drugs is unknown. However, certain parasites contain hemoproteins or require heme compounds during their life cycle. It may therefore be

The lower cranial nerves: IX, X, XI, XII.

Science.gov (United States)

Sarrazin, J-L; Toulgoat, F; Benoudiba, F

2013-10-01

The lower cranial nerves innervate the pharynx and larynx by the glossopharyngeal (CN IX) and vagus (CN X) (mixed) nerves, and provide motor innervation of the muscles of the neck by the accessory nerve (CN XI) and the tongue by the hypoglossal nerve (CN XII). The symptomatology provoked by an anomaly is often discrete and rarely in the forefront. As with all cranial nerves, the context and clinical examinations, in case of suspicion of impairment of the lower cranial nerves, are determinant in guiding the imaging. In fact, the impairment may be located in the brain stem, in the peribulbar cisterns, in the foramens or even in the deep spaces of the face. The clinical localization of the probable seat of the lesion helps in choosing the adapted protocol in MRI and eventually completes it with a CT-scan. In the bulb, the intra-axial pathology is dominated by brain ischemia (in particular, with Wallenberg syndrome) and multiple sclerosis. Cisternal pathology is tumoral with two tumors, schwannoma and meningioma. The occurrence is much lower than in the cochleovestibular nerves as well as the leptomeningeal nerves (infectious, inflammatory or tumoral). Finally, foramen pathology is tumoral with, outside of the usual schwannomas and meningiomas, paragangliomas. For radiologists, fairly hesitant to explore these lower cranial pairs, it is necessary to be familiar with (or relearn) the anatomy, master the exploratory technique and be aware of the diagnostic possibilities. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

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.

Structural optimization and docking studies of anatoxin-a: A potent ...

African Journals Online (AJOL)

, structural properties and molecular interaction of anatoxin-a, a naturally occurring potent neurotoxin. The geometry of the anatoxin-a was fully optimized in terms of density functional theory Gaussian 09. Calculations for structural parameters ...

Potent inhibition of tau fibrillization with a multivalent ligand

International Nuclear Information System (INIS)

Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

2007-01-01

Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors

Comentarios a determinadas disposiciones establecidas en los títulos VII y IX del anteproyecto de Código Penal

OpenAIRE

José René Orúe Cruz

2000-01-01

Recientemente fue aprobado en lo general el anteproyecto de Código Penal. Al analizar algunos artículos de los Títulos VII y IX, sobre el derecho de autor, propiedad industrial, quiebra, delitos económicos y contra el patrimonio nacional y patrimonio indígena, se observan deficiencias en aspectos elementales: La división de los derechos de propiedad intelectual; el uso de expresiones que no son de uso empresarial; imprecisiones sobre la quiebra, entre otras cosas. Esto obliga a un esfue...

microRNA-101 is a potent inhibitor of autophagy

DEFF Research Database (Denmark)

Frankel, Lisa B; Wen, Jiayu; Lees, Michael

2011-01-01

performed a functional screen in search of microRNAs (miRNAs), which regulate the autophagic flux in breast cancer cells. In this study, we identified the tumour suppressive miRNA, miR-101, as a potent inhibitor of basal, etoposide- and rapamycin-induced autophagy. Through transcriptome profiling, we...

Sulfoximines as potent RORγ inverse agonists.

Science.gov (United States)

Ouvry, Gilles; Bihl, Franck; Bouix-Peter, Claire; Christin, Olivier; Defoin-Platel, Claire; Deret, Sophie; Feret, Christophe; Froude, David; Hacini-Rachinel, Feriel; Harris, Craig S; Hervouet, Catherine; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Parnet, Veronique; Pascau, Coralie; Pascau, Jonathan; Pierre, Romain; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent F

2018-05-01

Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

Science.gov (United States)

Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

2017-03-15

Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses

Bicyclams, selective antagonists of the human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication

NARCIS (Netherlands)

Horzinek, M.C.; Egberink, H.F.; Clercq, E. de; Vliet, A.L.W. van; Balzarini, J.; Bridger, G.J.; Henson, G.; Schols, D.

1999-01-01

Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we demonstrate that bicyclams are potent inhibitors of feline immunodeficiency virus (FIV) replication when

Naturin: a potent bio-immunomodifier

International Nuclear Information System (INIS)

Rong Nian Shen; Li Lu; Homayoon Shidnia; Xiao Qing Jia

1995-01-01

Mechanism of the efficacy of naturin in enhancement and rejuvenation in natural immunity including NK cells, LAK cell activity and CD4 + T-cell function against cancer and infectious diseases is still not known. However, the immunomodulating effect of naturin is similar or even better than the results of IL-1α and IL-7. It is intriguing to speculate that the potent immunomodifier effect of naturin may be mediated either entirely or partially due to a mechanism involving cytokines. Our experiments suggest that naturin plays a role in the restoration of cellular immunosuppression induced by a number of different stresses. This in turn may reflect the fact that naturin possesses a potential regulatory role in induction of some immune cytokines. 31 refs., 4 figs., 4 tabs

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

Directory of Open Access Journals (Sweden)

Dun-Xian Tan

2015-10-01

Full Text Available Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.

Marine-derived fungi: Source of biologically potent and novel compounds

Digital Repository Service at National Institute of Oceanography (India)

Majik, M.S.; Parvatkar, R.R.; Tilvi, S.; Gawas, S.G.

-83) showed potent anti-mycobacterial activity against Mycobacterium smegmatis, M. bovisand M. tuberculosis, with MIC values in the range 0.02–2.0 mg/mL, and were effective against both actively growing and dormant states. Trichodermaquinone (84...

Campus Sexual Misconduct: Restorative Justice Approaches to Enhance Compliance With Title IX Guidance.

Science.gov (United States)

Koss, Mary P; Wilgus, Jay K; Williamsen, Kaaren M

2014-07-01

Campus response to sexual violence is increasingly governed by federal law and administrative guidance such as the 1972 Title IX, the 2011 Dear Colleague Letter (DCL), and the 2013 Violence Against Women Act. Educational institutions are directed to expand disciplinary responses and establish coordinated action to eliminate sexual violence and remedy its effects. Compliance fosters a quasi-criminal justice approach not suited to all sexual misconduct and inconsistent with developing practice in student conduct management. This article envisions restorative justice (RJ) enhancements to traditional student conduct processes that maintain compliance, expand options, empower victim choice, and increase responsiveness to DCL aims. The article (1) defines sexual violence and sexual harassment within the DCL scope, (2) elaborates the DCL position on permissible alternative resolutions and differentiates mediation from RJ, (3) sequences action steps from case report to finalization, including both restorative and traditional justice pathways; and (4) discusses building support for innovation beginning with existing campus response. © The Author(s) 2014.

PROFIL PERTANYAAN SISWA TUNANETRA KELAS IX SMPLB YKAB SURAKARTA DALAM PEMBELAJARAN MATEMATIKA

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Siti Khoiriyah

2015-10-01

Full Text Available 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 reduction, data presentation and conclusion. From the data analysis was found the result that 89 questions from the students consist of 46 (51, 68 % questions that consist of C1, 2 elements (2,25 % questions that consist of C2, 25 elements (28,09 % questions that consist of C4 elements. Based on the finding of the study could be conclude that majority of visual impaired students in low categorize because of having C1, C2, and C3 elements.Keywords : visual impaired students question, mathematics learning.

Identification of 16SrIX-C phytoplasmas in Argyranthemum frutescens in Italy

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Luca FERRETTI

2015-04-01

Full Text Available Phytoplasmas are cell wall-less microorganisms associated with plant diseases worldwide. Many important food, vegetable and fruits crops as well as ornamental plants can be severely affected by these pathogens, with significant economic impacts. Phytoplasma diseases of ornamentals have been described worldwide in a wide range of plant genera, and 11 different 16Sr groups have been identified. In Italy, many ornamental plant species belonging to several botanical families have been found to be infected by phytoplasmas, classified into the ribosomal groups 16SrI, 16SrII, 16SrV and 16SrXII. During a survey carried out in commercial gardens in Rome, some marguerite daisy (Argyranthemum frutescens plants showing symptoms of phytoplasma-like disease, were collected and submitted to molecular analyses. Cloning and sequencing of the portion of the 16S rRNA gene followed by BLAST analysis, real and virtual restriction fragment length polymorphism anlaysis with AluI and RsaI, allowed assignment of the detected phytoplasma to the 16SrIX-C group (Picris echioides yellows, PEY.

Analysis of the 4d7 (4f + 6p) and 4p54d9 configurations of Sn VII, Sb VIII and Te IX

International Nuclear Information System (INIS)

Azarov, V.I.; Joshi, Y.N.; Churilov, S.S.; Ryabtsev, A.N.

1994-01-01

The spectra of tin, antimony and tellerium were photographed in the 120-200 A region on 10.7 m and 3 m grazing incidence spectrographs using a triggered spark source. The 4d 8 -4d 7 (4f + 6p) + 4p 5 4d 9 transitions of Sn VII, Sb VIII and Te IX were investigated. In the Sn VII spectrum 109 new lines were classified in the 152-192 A region and 34 new levels were established, in the Sb VIII spectrum 78 new lines were classified in the 138-158 A region and 21 new levels were established, and in the Te IX 76 new lines were classified in the 121-139 A region and 21 new levels were established. Strong configuration interaction among the 4d 7 (np + mf), and 4p 5 4d 9 (n = 5, 6; m = 4, 5) configurations was observed. Least-squares-fitting (LSF) parametric calculations involving configuration interaction were carried out to interpret the observed spectra. (orig.)

The combinatorial PP1-binding consensus Motif (R/Kx( (0,1V/IxFxx(R/Kx(R/K is a new apoptotic signature.

Directory of Open Access Journals (Sweden)

Angélique N Godet

Full Text Available BACKGROUND: Previous studies established that PP1 is a target for Bcl-2 proteins and an important regulator of apoptosis. The two distinct functional PP1 consensus docking motifs, R/Kx((0,1V/IxF and FxxR/KxR/K, involved in PP1 binding and cell death were previously characterized in the BH1 and BH3 domains of some Bcl-2 proteins. PRINCIPAL FINDINGS: In this study, we demonstrate that DPT-AIF(1, a peptide containing the AIF(562-571 sequence located in a c-terminal domain of AIF, is a new PP1 interacting and cell penetrating molecule. We also showed that DPT-AIF(1 provoked apoptosis in several human cell lines. Furthermore, DPT-APAF(1 a bi-partite cell penetrating peptide containing APAF-1(122-131, a non penetrating sequence from APAF-1 protein, linked to our previously described DPT-sh1 peptide shuttle, is also a PP1-interacting death molecule. Both AIF(562-571 and APAF-1(122-131 sequences contain a common R/Kx((0,1V/IxFxxR/KxR/K motif, shared by several proteins involved in control of cell survival pathways. This motif combines the two distinct PP1c consensus docking motifs initially identified in some Bcl-2 proteins. Interestingly DPT-AIF(2 and DPT-APAF(2 that carry a F to A mutation within this combinatorial motif, no longer exhibited any PP1c binding or apoptotic effects. Moreover the F to A mutation in DPT-AIF(2 also suppressed cell penetration. CONCLUSION: These results indicate that the combinatorial PP1c docking motif R/Kx((0,1V/IxFxxR/KxR/K, deduced from AIF(562-571 and APAF-1(122-131 sequences, is a new PP1c-dependent Apoptotic Signature. This motif is also a new tool for drug design that could be used to characterize potential anti-tumour molecules.

Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

Science.gov (United States)

Swedberg, Joakim E; Harris, Jonathan M

2011-10-04

Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

A potent cytotoxic photoactivated platinum complex

Czech Academy of Sciences Publication Activity Database

Mackay, F.S.; Woods, J.A.; Heringová, Pavla; Kašpárková, Jana; Pizarro, A.M.; Moggach, S.A.; Parsons, S.; Brabec, Viktor; Sadler, P.J.

2007-01-01

Roč. 104, č. 52 (2007), s. 20743-20748 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA305/05/2030; GA ČR(CZ) GD204/03/H016; GA MZd(CZ) NR8562; GA AV ČR(CZ) 1QS500040581 Grant - others:GA AV ČR(CZ) KAN200200651 Program:KA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cytotoxicity * DNA binding * photochemistry Subject RIV: BO - Biophysics Impact factor: 9.598, year: 2007

D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.

Science.gov (United States)

Zask, Arie; Birnberg, Gary; Cheung, Katherine; Kaplan, Joshua; Niu, Chuan; Norton, Emily; Yamashita, Ayako; Beyer, Carl; Krishnamurthy, Girija; Greenberger, Lee M; Loganzo, Frank; Ayral-Kaloustian, Semiramis

2004-08-16

Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein. Amides derived from proline had potency comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols or its conversion to acidic heterocycles also gave potent analogs. Synthetic modifications of the carboxylic acid could be carried out selectively using a wide range of synthetic reagents. Proline analog 3 was found to be effective in a human xenograft model in athymic mice.

Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

OpenAIRE

Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert; Krogstad, Paul

2012-01-01

No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and prot...

The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy

International Nuclear Information System (INIS)

De Schutter, Harlinde; Landuyt, Willy; Verbeken, Erik; Goethals, Laurence; Hermans, Robert; Nuyts, Sandra

2005-01-01

Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy ± chemotherapy. We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005). To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy

Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume IX. Reactor and fuel cycle descriptions

Energy Technology Data Exchange (ETDEWEB)

1979-12-01

The Nonproliferation Alternative Systems Assessment Program (NASAP) has characterized and assessed various reactor/fuel-cycle systems. Volume IX provides, in summary form, the technical descriptions of the reactor/fuel-cycle systems studied. This includes the status of the system technology, as well as a discussion of the safety, environmental, and licensing needs from a technical perspective. This information was then used in developing the research, development, and demonstration (RD and D) program, including its cost and time frame, to advance the existing technology to the level needed for commercial use. Wherever possible, the cost data are given as ranges to reflect the uncertainties in the estimates. Volume IX is divided into three sections: Chapter 1, Reactor Systems; Chapter 2, Fuel-Cycle Systems; and the Appendixes. Chapter 1 contains the characterizations of the following 12 reactor types: light-water reactor; heavy-water reactor; water-cooled breeder reactor; high-temperature gas-cooled reactor; gas-cooled fast reactor; liquid-metal fast breeder reactor; spectral-shift-controlled reactor; accelerator-driven reactor; molten-salt reactor; gaseous-core reactor; tokamak fusion-fisson hybrid reactor; and fast mixed-spectrum reactor. Chapter 2 contains similar information developed for fuel-cycle facilities in the following categories: mining and milling; conversion and enrichment; fuel fabrication; spent fuel reprocessing; waste handling and disposal; and transportation of nuclear materials.

Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume IX. Reactor and fuel cycle descriptions

International Nuclear Information System (INIS)

1979-12-01

The Nonproliferation Alternative Systems Assessment Program (NASAP) has characterized and assessed various reactor/fuel-cycle systems. Volume IX provides, in summary form, the technical descriptions of the reactor/fuel-cycle systems studied. This includes the status of the system technology, as well as a discussion of the safety, environmental, and licensing needs from a technical perspective. This information was then used in developing the research, development, and demonstration (RD and D) program, including its cost and time frame, to advance the existing technology to the level needed for commercial use. Wherever possible, the cost data are given as ranges to reflect the uncertainties in the estimates. Volume IX is divided into three sections: Chapter 1, Reactor Systems; Chapter 2, Fuel-Cycle Systems; and the Appendixes. Chapter 1 contains the characterizations of the following 12 reactor types: light-water reactor; heavy-water reactor; water-cooled breeder reactor; high-temperature gas-cooled reactor; gas-cooled fast reactor; liquid-metal fast breeder reactor; spectral-shift-controlled reactor; accelerator-driven reactor; molten-salt reactor; gaseous-core reactor; tokamak fusion-fisson hybrid reactor; and fast mixed-spectrum reactor. Chapter 2 contains similar information developed for fuel-cycle facilities in the following categories: mining and milling; conversion and enrichment; fuel fabrication; spent fuel reprocessing; waste handling and disposal; and transportation of nuclear materials

Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

Science.gov (United States)

Mignani, Serge; El Brahmi, Nabil; Eloy, Laure; Poupon, Joel; Nicolas, Valérie; Steinmetz, Anke; El Kazzouli, Said; Bousmina, Mosto M; Blanchard-Desce, Mireille; Caminade, Anne-Marie; Majoral, Jean-Pierre; Cresteil, Thierry

2017-05-26

A multivalent phosphorus dendrimer 1G 3 and its corresponding Cu-complex, 1G 3 -Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G 3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling.

Science.gov (United States)

Sheremet, Michael; Kapoor, Shobhna; Schröder, Peter; Kumar, Kamal; Ziegler, Slava; Waldmann, Herbert

2017-09-19

Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone-derived β-lactone as the key intermediate that was transformed into a δ-lactone appended to the D-ring of the steroidal scaffold. This natural-product-inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase-independent manner. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

Energy Technology Data Exchange (ETDEWEB)

Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S. (Harvard-Med); (Mass. Gen. Hosp.); (UIC)

2012-12-10

We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

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

Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

Science.gov (United States)

Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

2016-02-26

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

Tuning of superconductivity by Ni substitution into noncentrosymmetric ThC o1 -xN ixC2

Science.gov (United States)

Grant, T. W.; Cigarroa, O. V.; Rosa, P. F. S.; Machado, A. J. S.; Fisk, Z.

2017-07-01

The recently discovered noncentrosymmetric superconductor ThCoC2 was observed to show unusual superconducting behavior with a critical temperature of Tc=2.65 K . Here we investigate the effect of nickel substitution on the superconducting state in ThC o1 -xN ixC2 . Magnetization, resistivity, and heat capacity measurements demonstrate Ni substitution has a dramatic effect with critical temperature increased up to Tc=12.1 K for x =0.4 Ni concentration, which is a rather high transition temperature for a noncentrosymmetric superconductor. In addition, the unusual superconducting characteristics observed in pure ThCoC2 appear to be suppressed or tuned with Ni substitution towards a more conventional fully gapped superconductor.

Pseudo-Hermitian description of PT-symmetric systems defined on a complex contour

International Nuclear Information System (INIS)

Mostafazadeh, Ali

2005-01-01

We describe a method that allows for a practical application of the theory of pseudo-Hermitian operators to PT-symmetric systems defined on a complex contour. We apply this method to study the Hamiltonians H = p 2 + x 2 (ix) ν with ν ε (-2, ∞) that are defined along the corresponding anti-Stokes lines. In particular, we reveal the intrinsic non-Hermiticity of H for the cases that ν is an even integer, so that H p 2 ± x 2+ν , and give a proof of the discreteness of the spectrum of H for all ν ε (-2, ∞). Furthermore, we study the consequences of defining a square-well Hamiltonian on a wedge-shaped complex contour. This yields a PT-symmetric system with a finite number of real eigenvalues. We present a comprehensive analysis of this system within the framework of pseudo-Hermitian quantum mechanics. We also outline a direct pseudo-Hermitian treatment of PT-symmetric systems defined on a complex contour which clarifies the underlying mathematical structure of the formulation of PT-symmetric quantum mechanics based on the charge-conjugation operator. Our results provide conclusive evidence that pseudo-Hermitian quantum mechanics provides a complete description of general PT-symmetric systems regardless of whether they are defined along the real line or a complex contour

2-Arylbenzo[b]furan derivatives as potent human lipoxygenase inhibitors.

Science.gov (United States)

Lang, Li; Dong, Ningning; Wu, Deyan; Yao, Xue; Lu, Weiqiang; Zhang, Chen; Ouyang, Ping; Zhu, Jin; Tang, Yun; Wang, Wei; Li, Jian; Huang, Jin

2016-01-01

Human lipoxygenases (LOXs) have been emerging as effective therapeutic targets for inflammatory diseases. In this study, we found that four natural 2-arylbenzo[b]furan derivatives isolated from Artocarpus heterophyllus exhibited potent inhibitory activities against human LOXs, including moracin C (1), artoindonesianin B-1 (2), moracin D (3), moracin M (4). In our in vitro experiments, compound 1 was identified as the most potent LOX inhibitor and the moderate subtype selective inhibitor of 12-LOX. Compounds 1 and 2 act as competitive inhibitors of LOXs. Moreover, 1 significantly inhibits LTB4 production and chemotactic capacity of neutrophils, and is capable of protecting vascular barrier from plasma leakage in vivo. In addition, the preliminary structure-activity relationship analysis was performed based on the above four naturally occurring (1-4) and six additional synthetic 2-arylbenzo[b]furan derivatives. Taken together, these 2-arylbenzo[b]furan derivatives, as LOXs inhibitors, could represent valuable leads for the future development of therapeutic agents for inflammatory diseases.

Discovery and characterization of novel imidazopyridine derivative CHEQ-2 as a potent CDC25 inhibitor and promising anticancer drug candidate.

Science.gov (United States)

Song, Yu'ning; Lin, Xiaoqian; Kang, Dongwei; Li, Xiao; Zhan, Peng; Liu, Xinyong; Zhang, Qingzhu

2014-07-23

Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation via the interactions with CDK/Cyclin complexes. Overexpression of CDC25 proteins is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, inhibiting CDC25 activity in cancer treatment appears a good therapeutic strategy. In this article, refinement of the initial hit XDW-1 by synthesis and screening of a focused compound library led to the identification of a novel set of imidazopyridine derivatives as potent CDC25 inhibitors. Among them, the most potent molecule was CHEQ-2, which could efficiently inhibit the activities of CDC25A/B enzymes as well as the proliferation of various different types of cancer cell lines in vitro assay. Moreover, CHEQ-2 triggered S-phase cell cycle arrest in MCF-7, HepG2 and HT-29 cell lines, accompanied by generation of ROS, mitochondrial dysfunction and apoptosis. Besides, oral administration of CHEQ-2 (10 mg/kg) significantly inhibited xenografted human liver tumor growth in nude mice, while demonstrated extremely low toxicity (LD50 > 2000 mg/kg). These findings make CHEQ-2 a good starting point for further investigation and structure modification. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Editorial - Special Issue on the Ninth International Conference on Aeolian Research - ICAR IX (Coastal Dune Processes and Aeolian Transport)

Science.gov (United States)

da Silva, Graziela Miot

2018-04-01

This special issue combines some of the papers related to coastal dune processes and aeolian sediment transport that were presented at the Ninth International Conference on Aeolian Research - ICAR IX. The conference was held between 4 and 8 of July 2016 in Mildura, Australia, organized by the International Society for Aeolian Research (ISAR) and convened by Adrian Chappell (Cardiff University), Craig Strong (Australian National University), Stephen Cattle (University of Sydney), Patrick Hesp (Flinders University), John Leys (New South Wales Office of Environment and Heritage), Lynda Petherick (University of Wellington) and Nick Webb (USDA-ARS Jornada Experimental Range).

Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

Science.gov (United States)

Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

2017-01-24

Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

Science.gov (United States)

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Proceedings of IX International Conference for Renewable Energy, Energy Saving and Energy Education (CIER 2017)

International Nuclear Information System (INIS)

2017-01-01

The Study Centre for Renewable Energy Technologies (CETER) located at the Technological University of Havana Jose Antonio Echeverria (CUJAE) Cuba hosted the IX International Renewable Energy Conference, Energy Saving and Energy Education (CIER 2017). The current focus on Cuba's renewable energy sector is ambitious with the Government proposing to boost investment by USD 3.5 billion in order to reach its goal of generating 24 per cent of its power from renewable energy by 2030. CIER 2017 brought together hundreds of scientist, engineers, manufactures, investors, policy makers, energy users and other specialists from across the entire international renewable energy spectrum to exchange knowledge, debate and analyze the global efforts currently being carried out in the field. This is all with the objective of intensifying the introduction of renewable energy technologies and promoting the sustainable energetic development in Cuba and the Caribe.

Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.

Science.gov (United States)

Lin, Wenwei; Yang, Lei; Chai, Sergio C; Lu, Yan; Chen, Taosheng

2016-01-27

Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug-resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure-activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A Concise Total Synthesis of (R)-Fluoxetine, a Potent and Selective Serotonin Reuptake Inhibitor

OpenAIRE

de Fátima, Ângelo; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

2005-01-01

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (R)-Fluoxetina, um inibidor potente e seletivo da recaptação da serotonina, foi sintetizada em seis etapas, 50% de rendimento total e 99% de excesso enantiomérico a partir do benzaldeído via alilação catalítica assimétrica empregando-se o sistema catalítico desenvolvido por Maruoka e...

Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK) inhibitors.

Science.gov (United States)

Sato, Yoshiyuki; Onozaki, Yu; Sugimoto, Tetsuya; Kurihara, Hideki; Kamijo, Kaori; Kadowaki, Chie; Tsujino, Toshiaki; Watanabe, Akiko; Otsuki, Sachie; Mitsuya, Morihiro; Iida, Masato; Haze, Kyosuke; Machida, Takumitsu; Nakatsuru, Yoko; Komatani, Hideya; Kotani, Hidehito; Iwasawa, Yoshikazu

2009-08-15

A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model.

Alkylsulfanyl analogs as potent α2δ ligands.

Science.gov (United States)

Shimada, Kousei; Ohata, Yasuo; Kobayashi, Jun; Onishi, Yoshiyuki; Kawamura, Asuka; Domon, Yuki; Arakawa, Naohisa; Inoue, Tatsuya; Kitano, Yutaka; Matsuda, Fumihiko; Abe, Yuki; Deguchi, Tsuneo

2018-06-15

We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

Directory of Open Access Journals (Sweden)

Ana Paula Martins

Full Text Available Aquaporins (AQPs are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III complexes screened on human red blood cells (hRBC and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50 = 0.8±0.08 µM in hRBC. Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

Ares I-X Launch Abort System, Crew Module, and Upper Stage Simulator Vibroacoustic Flight Data Evaluation, Comparison to Predictions, and Recommendations for Adjustments to Prediction Methodology and Assumptions

Science.gov (United States)

Smith, Andrew; Harrison, Phil

2010-01-01

The National Aeronautics and Space Administration (NASA) Constellation Program (CxP) has identified a series of tests to provide insight into the design and development of the Crew Launch Vehicle (CLV) and Crew Exploration Vehicle (CEV). Ares I-X was selected as the first suborbital development flight test to help meet CxP objectives. The Ares I-X flight test vehicle (FTV) is an early operational model of CLV, with specific emphasis on CLV and ground operation characteristics necessary to meet Ares I-X flight test objectives. The in-flight part of the test includes a trajectory to simulate maximum dynamic pressure during flight and perform a stage separation of the Upper Stage Simulator (USS) from the First Stage (FS). The in-flight test also includes recovery of the FS. The random vibration response from the ARES 1-X flight will be reconstructed for a few specific locations that were instrumented with accelerometers. This recorded data will be helpful in validating and refining vibration prediction tools and methodology. Measured vibroacoustic environments associated with lift off and ascent phases of the Ares I-X mission will be compared with pre-flight vibration predictions. The measured flight data was given as time histories which will be converted into power spectral density plots for comparison with the maximum predicted environments. The maximum predicted environments are documented in the Vibroacoustics and Shock Environment Data Book, AI1-SYS-ACOv4.10 Vibration predictions made using statistical energy analysis (SEA) VAOne computer program will also be incorporated in the comparisons. Ascent and lift off measured acoustics will also be compared to predictions to assess whether any discrepancies between the predicted vibration levels and measured vibration levels are attributable to inaccurate acoustic predictions. These comparisons will also be helpful in assessing whether adjustments to prediction methodologies are needed to improve agreement between the

Organoruthenium Complexes with CN Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action

Czech Academy of Sciences Publication Activity Database

Novohradský, Vojtěch; Yellol, J.; Stuchlíková, O.; Santana, M.D.; Kostrhunová, Hana; Yellol, G.; Kašpárková, Jana; Bautista, D.; Ruiz, J.; Brabec, Viktor

2017-01-01

Roč. 23, č. 61 (2017), s. 15294-15299 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GA17-05302S Institutional support: RVO:68081707 Keywords : chemotherapeutic-agents * ruthenium(ii) complexes * iridium(iii) complexes Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 5.317, year: 2016

Identification of a potent endothelium-derived angiogenic factor.

Directory of Open Access Journals (Sweden)

Vera Jankowski

Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

Directory of Open Access Journals (Sweden)

Matthias G. J. Baud

2013-01-01

Full Text Available There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric (thiol form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and enzymatic inhibitory activity against recombinant HDAC1. The latter effect is surprising since previous SAR suggested that modification of the thiol functionality should detrimentally affect HDAC potency. We therefore also report our preliminary studies on the mechanism of action of this observed effect.

Using Leather Puppets as Local Wisdom Based Learning Mediafor Teaching the Material of Heredity of the Natural Sciencessubject for Grade IX Students

OpenAIRE

Rakhmawati, Yesi; Apriliani, Putri; Wulansari, Merya

2013-01-01

The objectives of this study were (1) to reveal the improvement of students'understanding about heredity by using the media of leather puppets, and (2) to findout the use of leather puppets as learning media for teaching heredity to the grade IXstudents.The method used in this study was quasi experiment post test only. The subjectand object of this study were leather puppets as learning media of heredity at gradeIX and the improvement of the students' understanding about the heredity. About 2...

Identification of the chlE gene encoding oxygen-independent Mg-protoporphyrin IX monomethyl ester cyclase in cyanobacteria.

Science.gov (United States)

Yamanashi, Kaori; Minamizaki, Kei; Fujita, Yuichi

2015-08-07

The fifth ring (E-ring) of chlorophyll (Chl) a is produced by Mg-protoporphyrin IX monomethyl ester (MPE) cyclase. There are two evolutionarily unrelated MPE cyclases: oxygen-independent (BchE) and oxygen-dependent (ChlA/AcsF) MPE cyclases. Although ChlA is the sole MPE cyclase in Synechocystis PCC 6803, it is yet unclear whether BchE exists in cyanobacteria. A BLAST search suggests that only few cyanobacteria possess bchE. Here, we report that two bchE candidate genes from Cyanothece strains PCC 7425 and PCC 7822 restore the photosynthetic growth and bacteriochlorophyll production in a bchE-lacking mutant of Rhodobacter capsulatus. We termed these cyanobacterial bchE orthologs "chlE." Copyright © 2015 Elsevier Inc. All rights reserved.

Whole body application of a potent topical corticosteroid for bullous pemphigoid

NARCIS (Netherlands)

Terra, J. B.; Potze, W. J. B.; Jonkman, M. F.

BackgroundCurrent standard of treatment of bullous pemphigoid (BP) is systemic oral corticosteroids (CS). However, significant iatrogenic morbidity and mortality is reported. Studies have shown that topical potent CS is safer than oral prednisolone in BP. ObjectivesTo examine the local and systemic

Proceedings of XV Workshop on Nuclear Physics. IX International Symposium on Nuclear and Related Techniques. WONP-NURT 2015

International Nuclear Information System (INIS)

2015-02-01

This year 2015, the XV Workshop on Nuclear Physics and IX International Symposium on Nuclear and Related Techniques, WONP-NURT 2015 organized by the Center of Technological Applications and Nuclear Development from 9 to 13 February at the National Museum of Fine Arts. NURT is one of the key Cuban scientific meetings since 1997 dealing with the peaceful applications of nuclear techniques in several domains of the society. WONP and NURT provide an unique opportunity for the national and international scientific community to meet outstanding researchers and discuss current trends in several areas of theoretical, experimental and applied nuclear physics and related topics. The papers submitted to this event are presented in this CD-ROM.

Potent inhibition of HIV-1 replication by a Tat mutant.

Directory of Open Access Journals (Sweden)

Luke W Meredith

Full Text Available Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.

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.

The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex

Energy Technology Data Exchange (ETDEWEB)

He, Yupeng; Selvaraju, Sujatha; Curtin, Michael L.; Jakob, Clarissa G.; Zhu, Haizhong; Comess, Kenneth M.; Shaw, Bailin; The, Juliana; Lima-Fernandes, Evelyne; Szewczyk, Magdalena M.; Cheng, Dong; Klinge, Kelly L.; Li, Huan-Qiu; Pliushchev, Marina; Algire, Mikkel A.; Maag, David; Guo, Jun; Dietrich, Justin; Panchal, Sanjay C.; Petros, Andrew M.; Sweis, Ramzi F.; Torrent, Maricel; Bigelow, Lance J.; Senisterra, Guillermo; Li, Fengling; Kennedy, Steven; Wu, Qin; Osterling, Donald J.; Lindley, David J.; Gao, Wenqing; Galasinski, Scott; Barsyte-Lovejoy, Dalia; Vedadi, Masoud; Buchanan, Fritz G.; Arrowsmith, Cheryl H.; Chiang, Gary G.; Sun, Chaohong; Pappano , William N. (AbbVie); (Toronto)

2017-01-30

Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. Phenotypic effects observed in vitro and in vivo are similar to those of known PRC2 enzymatic inhibitors; however, A-395 retains potent activity against cell lines resistant to the catalytic inhibitors. A-395 represents a first-in-class antagonist of PRC2 protein–protein interactions (PPI) for use as a chemical probe to investigate the roles of EED-containing protein complexes.

External morphology of the immature stages of Neotropical heliconians: IX. Dione glycera (C. Felder & R. Felder (Lepidoptera, Nymphalidae, Heliconiinae

Directory of Open Access Journals (Sweden)

Héctor A. Vargas

2014-06-01

Full Text Available External morphology of the immature stages of Neotropical heliconians: IX. Dione glycera (C. Felder & R. Felder (Lepidoptera, Nymphalidae, Heliconiinae. The biology of the Andean silverspot butterfly Dione glycera (C. Felder & R. Felder, 1861 is still poorly known. This species is restricted to high elevations in the Andes, where the immature stages are found in close association with species of Passiflora belonging to the section Tacsonia (Juss. Harms, especially P. tripartida var. mollissima (Kunth, which is grown for subsistence by villagers. Herein we describe and illustrate the external features of the egg, larva and pupa of D. glycera, based on light and scanning electron microscopy.

Hořava-Lifshitz bouncing Bianchi IX universes: A dynamical system analysis

Science.gov (United States)

Maier, Rodrigo; Soares, Ivano Damião

2017-11-01

We examine the Hamiltonian dynamics of bouncing Bianchi IX cosmologies with three scale factors in Hořava-Lifshitz (HL) gravity. We assume a positive cosmological constant plus noninteracting dust and radiation as the matter content of the models. In this framework the modified field equations contain additional terms which turn the dynamics nonsingular. The six-dimensional phase space presents (i) two critical points in a finite region of the phase space, (ii) one asymptotic de Sitter attractor at infinity and (iii) a two-dimensional invariant plane containing the critical points; together they organize the dynamics of the phase space. We identify four distinct parameter domains A , B , C and D for which the pair of critical points engenders distinct features in the dynamics, connected to the presence of centers of multiplicity 2 and saddles of multiplicity 2. In the domain A the dynamics consists basically of periodic bouncing orbits, or oscillatory orbits with a finite number of bounces before escaping to the de Sitter attractor. The center with multiplicity 2 engenders in its neighborhood the topology of stable and unstable cylinders R ×S3 of orbits, where R is a saddle direction and S3 is the center manifold of unstable periodic orbits. We show that the stable and unstable cylinders coalesce, realizing a smooth homoclinic connection to the center manifold, a rare event of regular/nonchaotic dynamics in bouncing Bianchi IX cosmologies. The presence of a saddle of multiplicity 2 in the domain B engenders a high instability in the dynamics so that the cylinders emerging from the center manifold about P2 towards the bounce have four distinct attractors: the center manifold itself, the de Sitter attractor at infinity and two further momentum-dominated attractors with infinite anisotropy. In the domain C we examine the features of invariant manifolds of orbits about a saddle of multiplicity 2 P2. The presence of the saddle of multiplicity 2 engenders bifurcations

Bioconjugated nano-bactericidal complex for potent activity against human and phytopathogens with concern of global drug resistant crisis.

Science.gov (United States)

Syed, Baker; Nagendra Prasad, M N; Mohan Kumar, K; Satish, S

2018-05-09

The present study emphasizes the need for novel antimicrobial agents to combat the global drug resistant crisis. The development of novel nanomaterials is reported to be of the alternative tool to combat drug resistant pathogens. In present investigation, bioconjugated nano-complex was developed from secondary metabolite secreted from endosymbiont. The endosymbiont capable of secreting antimicrobial metabolite was subjected to fermentation and the culture supernatant was assessed for purification of antimicrobial metabolite via bio-assay guided fraction techniques such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and column chromatography. The metabolite was characterized as 2,4-Diacetylphloroglucinol (2,4 DAPG) which was used to develop bioconjugated nano-complex by treating with 1 mM silver nitrate under optimized conditions. The purified metabolite 2,4 DAPG reduced silver nitrate to form bioconjugated nano-complex to form association with silver nanoparticles. The oxidized form of DAPG consists of four hard ligands that can conjugate on to the surface of silver nanoparticles cluster. The bioconjugation was confirmed with UV-visible spectroscopy which displayed the shift and shoulder peak in the absorbance spectra. This biomolecular interaction was further determined by the Fourier-transform spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses which displayed different signals ascertaining the molecular binding of 2,4,DAPG with silver nanoparticles. The transmission electron microscopy (TEM) analysis revealed the cluster formation due to bioconjugation. The XRD analysis revealed the crystalline nature of nano-complex with the characteristic peaks indexed to Bragg's reflection occurring at 2θ angle which indicated the (111), (200), (220) and (311) planes. The activity of bioconjugated nano-complex was tested against 12 significant human and phytopathogens. Among all the test pathogens, Shigella flexneri (MTCC

Unraveling the electronic structures of low-valent naphthalene and anthracene iron complexes: X-ray, spectroscopic, and density functional theory studies

NARCIS (Netherlands)

Schnoeckelborg, E.M.; Khusniyarov, M.M.; de Bruin, B.; Hartl, F.; Langer, T.; Eul, M.; Schulz, S.; Poettgen, R.; Wolf, R.

2012-01-01

Naphthalene and anthracene transition metalates are potent reagents, but their electronic structures have remained poorly explored. A study of four Cp*-substituted iron complexes (Cp* = pentamethylcyclopentadienyl) now gives rare insight into the bonding features of such species. The highly oxygen-

Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics

NARCIS (Netherlands)

Leene, W.; de Waal Malefijt, R.; Roholl, P. J.; Hoeben, K. A.

1988-01-01

In situ pre-existing complexes of epithelial cells and thymocytes having thymic nurse cell characteristics were visualized in the murine thymus cortex using dexamethasone as a potent killer of cortisone-sensitive thymocytes. The degradation and subsequent depletion of cortisone-sensitive thymocytes

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.

CLINICAL EXPERIENCE OF CANCER IMMUNOTHERAPY INTEGRATED WITH OLEIC ACID COMPLEXED WITH DE-GLYCOSYLATED VITAMIN D BINDING PROTEIN

OpenAIRE

Emma Ward; Rodney Smith; Jacopo J.V. Branca; David Noakes; Gabriele Morucci; Lynda Thyer

2014-01-01

Proteins highly represented in milk such as α-lactalbumin and lactoferrin bind Oleic Acid (OA) to form complexes with selective anti-tumor activity. A protein present in milk, colostrum and blood, vitamin D binding protein is the precursor of a potent Macrophage Activating Factor (GcMAF) and in analogy with other OA-protein complexes, we proposed that OA-GcMAF could demonstrate a greater immunotherapeutic activity than that of GcMAF alone. We describe a preliminary experience treating p...

Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

Directory of Open Access Journals (Sweden)

Mehul M. Patel

2014-01-01

Full Text Available Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl-2-(substituted-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT by Schrodinger’s Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections.

Carrageenan is a potent inhibitor of papillomavirus infection.

Directory of Open Access Journals (Sweden)

Christopher B Buck

2006-07-01

Full Text Available Certain sexually transmitted human papillomavirus (HPV types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate-independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs.

Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

Science.gov (United States)

Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

2015-04-09

Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. © 2015 by The American Society of Hematology.

Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

Science.gov (United States)

Chen, D Z; Patel, D V; Hackbarth, C J; Wang, W; Dreyer, G; Young, D C; Margolis, P S; Wu, C; Ni, Z J; Trias, J; White, R J; Yuan, Z

2000-02-15

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

NEW Fe IX LINE IDENTIFICATIONS USING SOLAR AND HELIOSPHERIC OBSERVATORY/SOLAR ULTRAVIOLET MEASUREMENT OF EMITTED RADIATION AND HINODE/EIS JOINT OBSERVATIONS OF THE QUIET SUN

International Nuclear Information System (INIS)

Landi, E.; Young, P. R.

2009-01-01

In this work, we study joint observations of Hinode/EUV Imaging Spectrometer (EIS) and Solar and Heliospheric Observatory/Solar Ultraviolet Measurement of Emitted Radiation of Fe IX lines emitted by the same level of the high energy configuration 3s 2 3p 5 4p. The intensity ratios of these lines are dependent on atomic physics parameters only and not on the physical parameters of the emitting plasma, so that they are excellent tools to verify the relative intensity calibration of high-resolution spectrometers that work in the 170-200 A and 700-850 A wavelength ranges. We carry out extensive atomic physics calculations to improve the accuracy of the predicted intensity ratio, and compare the results with simultaneous EIS-SUMER observations of an off-disk quiet Sun region. We were able to identify two ultraviolet lines in the SUMER spectrum that are emitted by the same level that emits one bright line in the EIS wavelength range. Comparison between predicted and measured intensity ratios, wavelengths and energy separation of Fe IX levels confirms the identifications we make. Blending and calibration uncertainties are discussed. The results of this work are important for cross-calibrating EIS and SUMER, as well as future instrumentation.

Asymmetric mesoporous silica nanoparticles as potent and safe immunoadjuvants provoke high immune responses.

Science.gov (United States)

Abbaraju, Prasanna Lakshmi; Jambhrunkar, Manasi; Yang, Yannan; Liu, Yang; Lu, Yao; Yu, Chengzhong

2018-02-20

Asymmetric mesoporous silica nanoparticles with a head-tail structure are potent immunoadjuvants for delivering a peptide antigen, generating a higher antibody immune response in mice compared to their symmetric counterparts.

Interpretation of the possibility of extensive clause IX article 103 of the Federal Constitution by collective protection of procedure

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Letícia de Oliveira Catani Ferreira

2018-03-01

Full Text Available The aim of this study is to analyze the broad interpretation of the rule present in article 103 of the Brazilian Federal Constitution (CF, specifically in section IX, which in its entirety provides an exhaustive list that gives legitimacy to the use of the Direct Action of Unconstitutionality. In this context, which raises doubts to the practicality of having access to courts – specifically for those who have substantial interest in the matter – the claim of the IBDFAM (Brazilian Institute of Family Law, a fair provocation of the Supreme Court, raises the question whether the taxation of child support is income tax and if its practice is unconstitutional. Moreover, seeking the core of the tribute in question, the fact of which is that the increase of equity, or acquisition of the economic or legal availability of income and earnings of any nature, does not prove correct in violating the dignity of those who provide and receive child support. Therefore, this discussion has general repercussions that can affect significantly the Brazilian populace. As can be seen, the inspiration for this work comes from the recent ADI IBDFAM filing, dated November 25, 2015, an opportunity, which set in motion this discussion, as it covered the procedural aspect of the parts’ legitimacy, since it is discussed whether the IBDFAM is considered a class entity of national scope, thusly fulfilling the requirement of art. 2, IX, of Law 9,868 of 1999, and consequently article 103 of the CF. In this chain, IBDFAM was inspired by the IDECON (Consumer Law Institute, which filed the ADI n. 5291 that seeks consumer claims and argues for active legitimacy, with a view to its representativeness at the national level.

Synthesis, spectral, thermal and antimicrobial studies on cobalt(II), nickel(II), copper(II), zinc(II) and palladium(II) complexes containing thiosemicarbazone ligand

Science.gov (United States)

El-Sawaf, Ayman K.; El-Essawy, Farag; Nassar, Amal A.; El-Samanody, El-Sayed A.

2018-04-01

The coordination characteristic of new N4-morpholinyl isatin-3-thiosemicarbazone (HL) towards Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) has been studies. The structures of the complexes were described by elemental analyses, molar conductivity, magnetic, thermal and spectral (IR, UV-Vis, 1H and 13C NMR and ESR) studies. On the basis of analytical and spectral studies the ligand behaves as monobasic tridentate ONS donor forming two five membered rings towards cobalt, copper and palladium and afforded complexes of the kind [M(L)X], (Mdbnd Co, Cu or Pd; Xdbnd Cl, Br or OAc). Whereas the ligand bound to NiCl2 as neutral tridentate ONS donor and with ZnCl2 as neutral bidentate NS donor. The newly synthesized thiosemicarbazone ligand and some of its complexes were examined for antimicrobial activity against 2 gram negative bacterial strains (Escherichia coli Pseudomonas and aeruginosa), 2 gram positive bacterial strains (Streptococcus pneumoniae and Staphylococcus aureus)} and two Pathogenic fungi (Aspergillus fumigatus and Candida albicans). All metal complexes possess higher antimicrobial activity comparing with the free thiosemicarbazone ligand. The high potent activities of the complexes may arise from the coordination and chelation, which tends to make metal complexes act as more controlling and potent antimicrobial agents, thus hindering the growing of the microorganisms. The antimicrobial results also show that copper bromide complex is better antimicrobial agent as compared to the Schiff base and its metal complexes.

Comentarios a determinadas disposiciones establecidas en los títulos VII y IX del anteproyecto de Código Penal

Directory of Open Access Journals (Sweden)

José René Orúe Cruz

2000-08-01

Full Text Available Recientemente fue aprobado en lo general el anteproyecto de Código Penal. Al analizar algunos artículos de los Títulos VII y IX, sobre el derecho de autor, propiedad industrial, quiebra, delitos económicos y contra el patrimonio nacional y patrimonio indígena, se observan deficiencias en aspectos elementales: La división de los derechos de propiedad intelectual; el uso de expresiones que no son de uso empresarial; imprecisiones sobre la quiebra, entre otras cosas. Esto obliga a un esfuerzo conjunto para contribuir a que se corrijan aquellos aspectos necesarios para que dispongamos de un nuevo Código Penal que responda a las necesidades de Nicaragua.

SCCmec Type IX Element in Methicillin Resistant Staphylococcusaureusspa Type t337 (CC9) Isolated from Pigs and Pork in Thailand

DEFF Research Database (Denmark)

Vestergaard, Martin; Cavaco, Lina M; Sirichote, Pantip

2012-01-01

blaZ, aac-aphD, vga(A), tetM, and a tet efflux marker, in all strains and additionally ermB and aadD, cat and fex(A) in the pork isolates. None of the isolates were found PVL-positive, but enterotoxins were identified in all isolates. To our knowledge, only a few descriptions of MRSA in livestock...... and food products in Thailand have been observed but this is the first observation of MRSA CC9 associated with SCCmec IX in pork. This study indicates a likely widespread distribution of MRSA in pig and pork in Thailand and further investigation on the prevalence and importance of livestock associated MRSA...

A concise synthesis of the potent inflammatory mediator 5-oxo-ETE

DEFF Research Database (Denmark)

Tyagi, Rahul; Shimpukade, Bharat; Blättermann, Stefanie

2012-01-01

A concise and practical method for synthesis of the potent inflammatory mediator 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE, 1) from arachidonic acid in four steps and 70% overall yield is reported. Stability studies indicate that 1 can be safely handled without rigorous precautions...

Genetic immunization in the lung induces potent local and systemic immune responses

NARCIS (Netherlands)

Song, Kaimei; Bolton, Diane L.; Wilson, Robert L.; Camp, Jeremy V.; Bao, Saran; Mattapallil, Joseph J.; Herzenberg, Leonore A.; Herzenberg, Leonard A.; Andrews, Charla A.; Sadoff, Jerald C.; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A.; Kozlowski, Pamela A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.

2010-01-01

Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver

Analogues of the Potent Antitumor Compound Leiodermatolide from a Deep-Water Sponge of the Genus Leiodermatium.

Science.gov (United States)

Wright, Amy E; Roberts, Jill C; Guzmán, Esther A; Pitts, Tara P; Pomponi, Shirley A; Reed, John K

2017-03-24

Two new analogues of the potent antitumor compound leiodermatolide, which we call leiodermatolides B and C, have been isolated from specimens of a deep-water sponge of the genus Leiodermatium collected off Florida. The compounds were purified using standard chromatographic methods, and the structures defined through interpretation of the HRMS and 1D and 2D NMR data. Leiodermatolide B (2) lacks the C-21 hydroxy group found in leiodermatolide and has equal potency as the parent compound, providing a simpler analogue for possible clinical development. It inhibits the proliferation of the AsPC-1 human pancreatic adenocarcinoma cell line with an IC 50 of 43 nM. Leiodermatolide C (3) has a modified macrolide ring and is over 85-fold less potent with an IC 50 of 3.7 μM against the same cell line. These compounds add to the knowledge of the pharmacophore of this class of potent antitumor agents.

Near-infrared-emitting heteroleptic cationic iridium complexes derived from 2,3-diphenylbenzo[g]quinoxaline as in vitro theranostic photodynamic therapy agents

Energy Technology Data Exchange (ETDEWEB)

Wang, Li; Yin, Huimin; Cui, Peng; Hetu, Marc; Wang, Chengzhe; Monro, Susan; Schaller, Richard D.; Cameron, Colin G.; Liu, Bingqing; Kilina, Svetlana; McFarland, Sherri A.; Sun, Wenfang

2017-05-19

Five heteroleptic cationic iridium complexes with a π-expansive cyclometalating 2,3-diphenylbenzo[g] quinoxaline (dpbq) ligand (C^N ligand) and different diimine ligands (N^N ligands) (i.e. 2,2’-bipyridine (bpy, 1), phenanthroline (phen, 2), 2-(2-pyridinyl)quinoline (pqu, 3), 2,2’-bisquinoline (bqu, 4), and 2-(quinolin-2-yl)quinoxaline (quqo, 5)) were synthesized and characterized. The lowest-energy singlet electronic transitions (S1 states) were mainly dpbq ligand-centred 1ILCT (intraligand charge transfer)/1MLCT (metal to ligand charge transfer) transitions mixed with some 1π,π* transitions for complexes 1–4 with increased contributions from 1LLCT (ligand to ligand charge transfer) in 3 and 4. For complex 5, the S1 state was switched to the 1LLCT/1MLCT transitions. All five complexes displayed weak near-infrared (NIR) phosphorescence, with maximal emission output spanning 700–1400 nm and quantum yields being on the order of 10-3. The triplet state absorptions of 1–4 all resembled that of the [Ir(dpbq)2Cl]2 dimer with lifetimes of ca. 400 ns, while the TA spectrum of 5 possessed the characteristics of both the quqo ligand and the [Ir(dpbq)2Cl]2 dimer with a bi-exponential decay of ca. 5 μs and 400 ns. While the photophysics of these complexes differ slightly, their theranostic photodynamic therapy (PDT) effects varied drastically. All of the complexes were biologically active toward melanoma cells. Complexes 2 and 3 were the most cytotoxic, with 230–340 nM activity and selectivity factors for melanoma cells over normal skin fibroblasts of 34 to 40 fold. Complexes 2, 3, and 5 became very potent cytotoxins with light activation, with EC50 values as low as 12–18 nM. This potent nanomolar light-triggered activity combined with a lower dark toxicity resulted in 5 having a phototherapeutic index (PI) margin of almost 275. The bpy coligand led to the least amount of dark toxicity of 1, while phen and pqu produced cytotoxic but selective complexes 2 and

Isolation and identification of a new homoisoflavan with potent antioxidant activity from Commelina Elegans

International Nuclear Information System (INIS)

Kabbash, A.; Yagi, A.; Ishizu, T.; Haraguchi, H.; Fujioka, T.; Moustafa, S.M.; El-Bassouny, Ashraf A.

2008-01-01

Potent antioxidative compounds have been isolated from the ethyl acetate extract of Commelina Elegans, Commelinaceae, using a repeated column chromatography. On the basis of spectral analysis, the compounds were identified as brazilin, brazilein and the new homoisoflavan-3, 7, 9, 3, 4-ol (4-4) dimer with X- and Y-conformers. The compounds inhibited both enzymatic lipid peroxidation using a rat liver microsomes and mitochondria and non-enzymatic reactions. The compounds completely protected the activities of the mitochondrial enzymes NADH- and succinate-cytochrome c reductase. Furthermore, radical scavenging activity on enzymatically and non-enzymatically generated superoxide anion was investigated. Electron spin resonance using spin trapping method suggested that the compounds have potent superoxide anion scavenging activities. (author)

Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity

Science.gov (United States)

Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

2015-10-01

Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.

Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma.

Science.gov (United States)

Pomel, Vincent; Klicic, Jasna; Covini, David; Church, Dennis D; Shaw, Jeffrey P; Roulin, Karen; Burgat-Charvillon, Fabienne; Valognes, Delphine; Camps, Montserrat; Chabert, Christian; Gillieron, Corinne; Françon, Bernard; Perrin, Dominique; Leroy, Didier; Gretener, Denise; Nichols, Anthony; Vitte, Pierre Alain; Carboni, Susanna; Rommel, Christian; Schwarz, Matthias K; Rückle, Thomas

2006-06-29

Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kgamma, have become attractive drug targets for inflammatory and autoimmune diseases. Here, we disclose a novel series of furan-2-ylmethylene thiazolidinediones as selective, ATP-competitive PI3Kgamma inhibitors. Structure-based design and X-ray crystallography of complexes formed by inhibitors bound to PI3Kgamma identified key pharmacophore features for potency and selectivity. An acidic NH group on the thiazolidinedione moiety and a hydroxy group on the furan-2-yl-phenyl part of the molecule play crucial roles in binding to PI3K and contribute to class IB PI3K selectivity. Compound 26 (AS-252424), a potent and selective small-molecule PI3Kgamma inhibitor emerging from these efforts, was further profiled in three different cellular PI3K assays and shown to be selective for class IB PI3K-mediated cellular effects. Oral administration of 26 in a mouse model of acute peritonitis led to a significant reduction of leukocyte recruitment.

Evolutionary pattern of mutation in the factor IX genes of great apes: How does it compare to the pattern of recent germline mutation in patients with hemophilia B?

Energy Technology Data Exchange (ETDEWEB)

Grouse, L.H.; Ketterling, R.P.; Sommer, S.S. [Mayo Clinic/Foundation, Rochester, MN (United States)

1994-09-01

Most mutations causing hemophilia B have arisen within the past 150 years. By correcting for multiple biases, the underlying rates of spontaneous germline mutation have been estimated in the factor IX gene. From these rates, an underlying pattern of mutation has emerged. To determine if this pattern compares to a underlying pattern found in the great apes, sequence changes were determined in intronic regions of the factor IX gene. The following species were studied: Gorilla gorilla, Pan troglodytes (chimpanzee), Pongo pygmacus (orangutan) and Homo sapiens. Intronic sequences at least 200 bp from a splice junction were randomly chosen, amplified by cross-species PCR, and sequenced. These regions are expected to be subject to little if any selective pressure. Early diverged species of Old World monkeys were also studied to help determine the direction of mutational changes. A total of 62 sequence changes were observed. Initial data suggest that the average pattern since evolution of the great apes has a paucity of transitions at CpG dinucleotides and an excess of microinsertions to microdeletions when compared to the pattern observed in humans during the past 150 years (p<.05). A larger study is in progress to confirm these results.

Origen y formación de una villa de repoblación. Benavente durante los reinados de Fernando II y Alfonso IX

Directory of Open Access Journals (Sweden)

Rafael GONZÁLEZ RODRÍGUEZ

2009-12-01

Full Text Available RESUMEN: Durante los reinados de Fernando II y Alfonso IX asistimos a un ambicioso proyecto de repoblación urbana, coincidiendo con el período de separación política entre los reinos de León y Castilla. Este proceso tuvo como resultado el establecimiento de nuevas villas, en buena parte de los casos herederas de los antiguos "castros" y "castellos" altomedievales. La repoblación de Benavente, inscrita dentro de este contexto histórico, se realizó a partir de un núcleo preurbano anterior: el "castrum" de Malgrad, organizando un vasto territorio que se extendía por buena parte del norte de la actual provincia de Zamora, configurándose así como uno de los concejos más extensos al norte del río Duero.ABSTRACT: During the reigns of King Fernando II and King Alfonso IX we witness an ambitious initiative of urban repopulation, coinciding with the period of political separation between the Kingdoms of Castile and León. This process resulted in the establishment of new villages, in many cases originating from ancient "castros" and "castellos" from the high Middle Ages. The repopulation of Benavente, integrated in this historical context, was formed from a previous pre—urban nucleus: the "castrum" of Malgrad, organizing a vast territory that extended mainly in the northern part of fhc present province of Zamora, establishing itself as one of the most extensive councils to the north of the Duero River.

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells.

Science.gov (United States)

D'Sousa Costa, Cinara O; Araujo Neto, João H; Baliza, Ingrid R S; Dias, Rosane B; Valverde, Ludmila de F; Vidal, Manuela T A; Sales, Caroline B S; Rocha, Clarissa A G; Moreira, Diogo R M; Soares, Milena B P; Batista, Alzir A; Bezerra, Daniel P

2017-11-28

Piplartine (piperlongumine) is a plant-derived molecule that has been receiving intense interest due to its anticancer characteristics that target the oxidative stress. In the present paper, two novel piplartine-containing ruthenium complexes [Ru(piplartine)(dppf)(bipy)](PF 6 ) 2 (1) and [Ru(piplartine)(dppb)(bipy)](PF 6 ) 2 (2) were synthesized and investigated for their cellular and molecular responses on cancer cell lines. We found that both complexes are more potent than metal-free piplartine in a panel of cancer cell lines on monolayer cultures, as well in 3D model of cancer multicellular spheroids formed from human colon carcinoma HCT116 cells. Mechanistic studies uncovered that the complexes reduced the cell growth and caused phosphatidylserine externalization, internucleosomal DNA fragmentation, caspase-3 activation and loss of the mitochondrial transmembrane potential on HCT116 cells. Moreover, the pre-treatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced the complexes-induced apoptosis, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. Treatment with the complexes also caused a marked increase in the production of reactive oxygen species (ROS), including hydrogen peroxide, superoxide anion and nitric oxide, and decreased reduced glutathione levels. Application of N-acetyl-cysteine, an antioxidant, reduced the ROS levels and apoptosis induced by the complexes, indicating activation of ROS-mediated apoptosis pathway. RNA transcripts of several genes, including gene related to the cell cycle, apoptosis and oxidative stress, were regulated under treatment. However, the complexes failed to induce DNA intercalation. In conclusion, the complexes are more potent than piplartine against different cancer cell lines and are able to induce caspase-dependent and mitochondrial intrinsic apoptosis on HCT116 cells by ROS-mediated pathway.

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

Energy Technology Data Exchange (ETDEWEB)

Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

2017-06-06

We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

The 4p-5d, 6d and 4p-6s, 7s transitions of Mo IX

International Nuclear Information System (INIS)

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

1979-01-01

The transitions 4p-5d, 6d and 4p-6s, 7s have been studied for the first time in Mo IX. The authors have identified 42 4p-5d, 36 4p-6d, 22 4p-6s and 22 4p-7s transitions, establishing 16 4p 3 5d, 14 4p 3 6d and all the ten 4p 3 6s, 7s levels of the spectrum concerned. The ionization energy is estimated to be (1 323 700 +- 700)cm -1 or (164.11 +- 0.09)eV. The spectrum was recorded in sliding and open spark discharges with a 5 m grazing incidence spectrograph of Lund University (Sweden) from about 40 A to 440 A. (Auth.)

"Appearance potent"? A content analysis of UK gay and straight men's magazines.

Science.gov (United States)

Jankowski, Glen S; Fawkner, Helen; Slater, Amy; Tiggemann, Marika

2014-09-01

With little actual appraisal, a more 'appearance potent' (i.e., a reverence for appearance ideals) subculture has been used to explain gay men's greater body dissatisfaction in comparison to straight men's. This study sought to assess the respective appearance potency of each subculture by a content analysis of 32 issues of the most read gay (Attitude, Gay Times) and straight men's magazines (Men's Health, FHM) in the UK. Images of men and women were coded for their physical characteristics, objectification and nudity, as were the number of appearance adverts and articles. The gay men's magazines featured more images of men that were appearance ideal, nude and sexualized than the straight men's magazines. The converse was true for the images of women and appearance adverts. Although more research is needed to understand the effect of this content on the viewer, the findings are consistent with a more appearance potent gay male subculture. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Synthesis of Cr(III-Morin Complex: Characterization and Antioxidant Study

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Qadeer K. Panhwar

2014-01-01

Full Text Available The complex formation between Cr(III and morin was carried out in methanol and confirmed by analytical characterization using UV-Vis, IR, 1H NMR, and TG-DTA. UV-Vis shows significant bathochromic shift in benzoyl upon coordination as well as IR well illustrates the peak shift of C=O group and formation of a O–Cr(III bond. Likewise, 1H NMR studies clarify that Cr(III metal ion replaces the 5OH proton hence; 5-hydroxy-4-keto site is employed by morin in chelation to form six-membered stable ring system out of three available chelating sites. In addition, TG-DTA denotes the presence of coordinated and crystalline water molecules. The melting point of the complex was found to be 389°C by DSC. In addition, Cr(III-morin complex was found to be a more potent antioxidant than morin as evaluated by DPPH• and FRAP methods.

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

Science.gov (United States)

Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

2013-12-01

Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

Science.gov (United States)

Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

2011-08-01

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

A Rhodium(III) Complex as an Inhibitor of Neural Precursor Cell Expressed, Developmentally Down-Regulated 8-Activating Enzyme with in Vivo Activity against Inflammatory Bowel Disease.

Science.gov (United States)

Zhong, Hai-Jing; Wang, Wanhe; Kang, Tian-Shu; Yan, Hui; Yang, Yali; Xu, Lipeng; Wang, Yuqiang; Ma, Dik-Lung; Leung, Chung-Hang

2017-01-12

We report herein the identification of the rhodium(III) complex [Rh(phq) 2 (MOPIP)] + (1) as a potent and selective ATP-competitive neural precursor cell expressed, developmentally down-regulated 8 (NEDD8)-activating enzyme (NAE) inhibitor. Structure-activity relationship analysis indicated that the overall organometallic design of complex 1 was important for anti-inflammatory activity. Complex 1 showed promising anti-inflammatory activity in vivo for the potential treatment of inflammatory bowel disease.

Nuclear proliferation and civilian nuclear power. Report of the Nonproliferation Alternative Systems Assessment Program. Volume IX. Reactor and fuel cycle description

Energy Technology Data Exchange (ETDEWEB)

1980-06-01

The Nonproliferation Alterntive Systems Assessment Program (NASAP) has characterized and assessed various reactor/fuel-cycle systems. Volume IX provides, in summary form, the technical descriptions of the reactor/fuel-cycle systems studied. This includes the status of the system technology, as well as a discussion of the safety, environmental, and licensing needs from a technical perspective. This information was then used in developing the research, development, and demonstration (RD and D) program, including its cost and time frame, to advance the existing technology to the level needed for commercial use. Wherever possible, the cost data are given as ranges to reflect the uncertainties in the estimates.

Nuclear proliferation and civilian nuclear power. Report of the Nonproliferation Alternative Systems Assessment Program. Volume IX. Reactor and fuel cycle description

International Nuclear Information System (INIS)

1980-06-01

The Nonproliferation Alterntive Systems Assessment Program (NASAP) has characterized and assessed various reactor/fuel-cycle systems. Volume IX provides, in summary form, the technical descriptions of the reactor/fuel-cycle systems studied. This includes the status of the system technology, as well as a discussion of the safety, environmental, and licensing needs from a technical perspective. This information was then used in developing the research, development, and demonstration (RD and D) program, including its cost and time frame, to advance the existing technology to the level needed for commercial use. Wherever possible, the cost data are given as ranges to reflect the uncertainties in the estimates

Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

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Anna Lundin

2014-05-01

Full Text Available Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs, a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6, a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV, and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

Carbon anhydrase IX specific immune responses in patients with metastatic renal cell carcinoma potentially cured by interleukin-2 based immunotherapy

DEFF Research Database (Denmark)

Rasmussen, Susanne; Donskov, Frede; Pedersen, Johannes W

2013-01-01

Abstract The majority of clear-cell renal cell carcinomas (ccRCC) show high and homogeneous expression levels of the tumor associated antigen (TAA) carbonic anhydrase IX (CAIX), and treatment with interleukin-2 (IL-2) based immunotherapy can lead to cure in patients with metastatic renal cell...... of disease (NED) following treatment with IL-2 based immunotherapy, and thus potentially cured. Immune reactivity in these patients was compared with samples from patients with dramatic tumor response obtained immediately at the cessation of therapy, samples from patients that experienced progressive disease...... interest in future cancer vaccines, but more studies are needed to elucidate the immunological mechanisms of action in potentially cured patients treated with an immunotherapeutic agent....

Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists

DEFF Research Database (Denmark)

Mohsen, Amal M Y; Mandour, Yasmine M; Sarukhanyan, Edita

2016-01-01

of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment...

Geothermal direct heat use: market potential/penetration analysis for Federal Region IX (Arizona, California, Hawaii, Nevada)

Energy Technology Data Exchange (ETDEWEB)

Powell, W.; Tang, K. (eds.)

1980-05-01

A preliminary study was made of the potential for geothermal direct heat use in Arizona, California, Hawaii, and Nevada (Federal Region IX). The analysis for each state was performed by a different team, located in that state. For each state, the study team was asked to: (1) define the resource, based on the latest available data; (2) assess the potential market growth for geothermal energy; and (3) estimate the market penetration, projected to 2020. Each of the four states of interest in this study is unique in its own way. Rather than impose the same assumptions as to growth rates, capture rates, etc. on all of the study teams, each team was asked to use the most appropriate set of assumptions for its state. The results, therefore, should reflect the currently accepted views within each state. The four state reports comprise the main portion of this document. A brief regional overview section was prepared by the Jet Propulsion Laboratory, following completion of the state reports.

A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

International Nuclear Information System (INIS)

Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

2005-01-01

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)

Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

Science.gov (United States)

Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

Parallela, a.c. di/Hrsg. Roland Bauer e Hans Goebl, Testo - Variazione - Informatica / Text ž Variation - Informatik, Atti del IX incontro italo-austriaco dei linguisti (Salisburgo, 1-4 novembre 2000 / Akten des IX. österreichisch-italienischen Linguiste

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Pavao Tekavčić

2003-12-01

Full Text Available I sottotitolo stesso del presente volume dice che i contributi appartengono ai domini piu attuali della linguistica. I 26 contributi sono raggruppati nelle seguenti tre sezioni (entro ciascuna i nomi degli autori in ordine alfabetico: 1. Linguistica variazionale/Variationslinguistik. (13 contributi, 2. Linguistica testuale/Textlinguistik (10 contributi, 3. Linguistica computazionale/Computerlinguistik (3 contributi. La miscellanea si apre con la Prefazione dei curatori/Vorwort der Herausgeber (V-V11I, seguita dall'Indice tematico/Thematisches Inhaltverzeichnis (IX-XI e dagli lndirizzi elet­ tronici (E-Mail Adressen degli autori e dei curatori. Dei 26 testi 21 sono in italiano e 5 in tedesco. In seguito presentiamo, in forma quanto piu succinta, i contributi, citando gli autori con le relative sedi (tra parentesi e le pagine (anche queste tra par­entesi, ma omettendo per brevita i titoli (alcuni abbastanza  lunghi.  La numer­ azione  dei contributi (13 + 10+3 e nostra.

Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication

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Mélanie Bourjot

2014-03-01

Full Text Available Trigocherrierin A (1 and trigocherriolide E (2, two new daphnane diterpenoid orthoesters (DDOs, and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7.

Discovery of a potent and selective GPR120 agonist

DEFF Research Database (Denmark)

Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel

2012-01-01

GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation...... is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist....

Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies.

Science.gov (United States)

Collins, Juliet; Cilibrizzi, Agostino; Fedorova, Marina; Whyte, Gillian; Mak, Lok Hang; Guterman, Inna; Leatherbarrow, Robin; Woscholski, Rudiger; Vilar, Ramon

2016-04-28

Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.

Influenza type A virus: an outstandingly protean pathogen and a potent modular weapon.

Science.gov (United States)

Shoham, Dany

2013-05-01

A remarkable debate recently arose on a global scale, about bioethics, biohazard, bioweaponry and bioterrorism issues related to scientific research concerning the induced transition of the highly lethal H5N1 avian flu virus from a non-pandemic to a tentatively pandemic strain, which might fall into malevolent hands. Appreciable ecogenetic complexity marks the main attributes of influenza type A viruses, namely infectivity, virulence, antigenicity, transmissibility, host range, endemicity, and epidemicity. They all shape, conjunctively, the outstanding protean nature of this pathogen, hence the modularity of the latter as a potent weapon. The present analysis inquires into those attributes, so as to profile and gauge threat, usability, impact and coping, particularly that the dimension of genetic engineering of this virus largely amplifies its potential. Within that context, various human interventions and misuses, including human experimental infections, undesirable vaccinations, as well as unauthorized and unskillful operations, led to bad corollaries and are also discussed in the present study. Altogether, a variety of interrelated properties underlying the complicatedness of and menaces posed by influenza A virus as a grave medical challenge, a dually explorable pathogen, and a modular biological warfare agent, are thereby illuminated, alongside with their scientific, strategic and practical implications.

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.

Description of the Earth in the Works of Arabic Geographers from IX to XII Century

Science.gov (United States)

Cvijanovic, I.

2012-12-01

The works of Arabic writers provide data about shape, position and size of the Earth, planets and zodiac signs. They include preserved maps of Ibn Haukal, Al-Masudi and Al-Idrisi. Al-Masudi (871-956/7) made a map of the world and wrote that the Earth is round, before the Christians in Europe were ready to accept that idea. The famous geographer and cartographer Al-Idrisi (IX/X., died in 903/913.) has lived on the court of Norman king Roger II of Sicily, and after his death on the court of his son William I on Sicily, where he obtained the data from European and Arabic geographers. On the basis of this data he wrote a work known entitled Roger's book. Besides this important work he made a celestial globe and a map of the world in the shape of a silver disk. The lines that marked the borders of seven regions of the inhabited world were engraved on this disk. The Arabs had excellent knowledge of Greek astronomy and accepted their division of the world in seven climatic zones.

Effectiveness and competing capacity of native Rhizobium strains evaluated in IX Region soils

International Nuclear Information System (INIS)

Barrientos D, Leticia; Mendez A, Edith; Pino N, Ines

1995-01-01

Symbiotic nitrogen fixation in legumes reaches its optimum when the host plants are nodulated by highly competitive and effective Rhizobium strains. With the purpose of assessing competition and nitrogen fixing capacity of native Rhizobium leguminosarum bio-var trifolii strains, a greenhouse test was carried out using white clover (Trifolium re-pens) and four kinds of soils, which represent the main agroecological areas of the IX Region. Eleven strains were evaluated, they were both native and collected and were streptomycin sulphate antibiotic resistant. A nitrogen and a nitrogen-less without inoculation testers were used as controls. All pots received a solution of ammonium sulphate marked with 10% 15 N a.e, equivalent to 10 kg ha -1 of N. Rye-grass was used as reference crop, cv. Nu-i. In general, the evaluated strains were very efficient. After three or four cuts they became the only source of nitrogen for the plants. They were also very competitive, getting to over 70% of root infection with regard to those present in soils. In Curacautin and Tolten soils, biological nitrogen fixation begins later than other soils evaluated, which is coincident with soils having a higher nitrogen content. Symbiosis occurs when the soil nitrogen content exhausts or diminishes. (author)

A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

Energy Technology Data Exchange (ETDEWEB)

Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: pilli@iqm.unicamp.br

2005-05-15

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)

The PorX response regulator of the Porphyromonas gingivalis PorXY two-component system does not directly regulate the Type IX secretion genes but binds the PorL subunit.

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Maxence S Vincent

2016-08-01

Full Text Available The Type IX secretion system (T9SS is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion of surface attachment of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY and PorX encode typical two-component system (TCS sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of the porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we showed that PorX does not bind and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

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.

Crystallization and preliminary X-ray analysis of the C-terminal fragment of PorM, a subunit of the Porphyromonas gingivalis type IX secretion system.

Science.gov (United States)

Stathopulos, Julien; Cambillau, Christian; Cascales, Eric; Roussel, Alain; Leone, Philippe

2015-01-01

PorM is a membrane protein involved in the assembly of the type IX secretion system (T9SS) from Porphyromonas gingivalis, a major bacterial pathogen responsible for periodontal disease in humans. The periplasmic domain of PorM was overexpressed in Escherichia coli and purified. A fragment of the purified protein was obtained by limited proteolysis. Crystals of this fragment belonged to the tetragonal space group P4(3)2(1)2. Native and MAD data sets were recorded to 2.85 and 3.1 Å resolution, respectively, using synchrotron radiation.

Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.

Science.gov (United States)

Kwiatkowski, Jacek; Liu, Boping; Tee, Doris Hui Ying; Chen, Guoying; Ahmad, Nur Huda Binte; Wong, Yun Xuan; Poh, Zhi Ying; Ang, Shi Hua; Tan, Eldwin Sum Wai; Ong, Esther Hq; Nurul Dinie; Poulsen, Anders; Pendharkar, Vishal; Sangthongpitag, Kanda; Lee, May Ann; Sepramaniam, Sugunavathi; Ho, Soo Yei; Cherian, Joseph; Hill, Jeffrey; Keller, Thomas H; Hung, Alvin W

2018-05-24

Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

Synthesis, Spectral, and In Vitro Antibacterial Studies of Organosilicon(IV) Complexes with Schiff Bases Derived from Amino Acids.

Science.gov (United States)

Singh, Har Lal; Singh, Jangbhadur; Mukherjee, A

2013-01-01

The present work stems from our interest in the synthesis, characterization, and antibacterial evaluation of organosilicon(IV) complexes of a class of amino-acid-based Schiff base which have been prepared by the interaction of ethoxytrimethylsilane with the Schiff bases (N OH) in 1 : 1 molar ratio. These complexes have been characterized by elemental analysis, molar conductance, and spectroscopic studies including electronic IR and NMR ((1)H, (13)C, and (29)Si) spectroscopy. The analytical and spectral data suggest trigonal bipyramidal geometry around the silicon atom in the resulting complexes. The ligands and their organosilicon complexes have also been evaluated for in vitro antimicrobial activity against bacteria (Bacillus cereus, Nocardia spp., E. aerogenes, Escherichia coli, Klebsiella spp., and Staphylococcus spp.). The complexes were found to be more potent as compared to the ligands.

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

Science.gov (United States)

Wiesenberg-Boettcher, I; Schweizer, A; Green, J R; Mueller, K; Maerki, F; Pfeilschifter, J

1989-01-01

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.) and pronounced analgesic and antipyretic activity in acute models in mice and rats (ED50 2-5 mg/kg, p.o.), but has clear advantages over reference NSAIDs with respect to gastro-intestinal tolerability. Threshold doses for gastro-intestinal ulcerogenicity in rats after single and repeated (10x) doses were found to be 30 mg/kg, p.o., and prostaglandin (PGE2) production in rat gastric and ileal mucosa was only marginally inhibited (ED50 greater than 30 mg/kg, p.o.). On the other hand, PGE2 production in rat inflammatory exudate and thromboxane synthesis in rat blood were inhibited with ED50 values of less than or equal to 2 mg/kg, p.o. Although CGP28238 does not inhibit cyclooxygenase in bovine seminal vesicle microsomal preparations (IC50 greater than 10(-3) mol/l), potent inhibition of prostaglandin synthesis was shown in various in vitro systems using human and animal cells with IC50 values of less than 10(-6) mol/l. IL-1-stimulated bone resorption and PGE2 production in murine calvarial cultures were inhibited with IC50 values of 3 x 10(-7) and 2 x 10(-8) mol/l, respectively. 5-Lipoxygenase (murine macrophages), phospholipase A2 (human PMN) and phospholipase C (human platelets) were not inhibited. CGP 28238 may represent a novel highly potent anti-inflammatory compound with improved gastro-intestinal safety.

SCCmec type IX element in Methicillin resistant Staphylococcus aureus spa-type t337 (CC9 isolated from pigs and pork in Thailand

Directory of Open Access Journals (Sweden)

Martin eVestergaard

2012-03-01

Full Text Available Methicillin resistant Staphylococcus aureus (MRSA have emerged among livestock in several countries. In this study, we describe the results of a screening performed in pigs and raw pork samples in Thailand. Ten pork samples and 15 nasal swabs from pigs were collected from two markets and one pig farm in the Samuth Songkhram province in Thailand. MRSA were isolated using selective isolation procedures and confirmed by mecA PCR. The MRSA were characterized by antimicrobial susceptibility testing, PFGE, spa typing, SCCmec typing, and MLST. Resistance and virulence markers were screened using a microarray. Five of the pork samples and six pig nasal swabs were positive for MRSA. All 11 isolates belonged to spa type t337 and CC9 but showed diversity in antimicrobial resistance patterns and PFGE profiles. All isolates harbored SCCmec IX and were resistant to seven out of 14 tested antimicrobials; additional resistances were found in the pork isolates. Microarray analysis identified blaZ, aac-aphD, vga(A, tetM, and a tet efflux marker, in all strains and additionally ermB and aadD, cat and fex(A in the pork isolates. None of the isolates were found PVL-positive, but enterotoxins were identified in all isolates. This is, to our knowledge, the first description of MRSA in livestock and food products in Thailand and also the first observation of MRSA CC9 associated with SCCmec IX. This study indicates a likely widespread distribution of MRSA in pig and pork in Thailand and further investigation on the prevalence and importance of livestock associated MRSA in Thailand is needed.

Faktor-faktor yang berhubungan dengan Pengolahan Sampah Organik Rumah Tangga menjadi Kompos di Jorong IX Pancahan Kecamatan Rao Kebupaten Pasaman Tahun 2013

Directory of Open Access Journals (Sweden)

Nurdin ,

2015-07-01

Full Text Available Dari 10 responden yang di wawancarai oleh peneliti 6 responden mengaku mengetahui cara pembuatan kompos dan 4 di antaranya tidak mengetahui bagaimana cala pembuatan kompos. Dari hasil observasi yang peneliti lakukan responden membuang sampah rumah tangganya ke belakang rumah. Penelitian ini berlujuan untuk mengetahui Faktor-Faktor yang berhubungan dengan Pengolahan Sampah Organik Rumah Tangga Menjadi Kompos Di Jorong trX Pancahan Kecamatan Rao Kabupaten Pasaman Tahun 2013.Penelitian ini bersifat Deskriptif Analitik dengan pendekatan Cross secsional. Dan analisis data dilakukan dengan analisis univariat dan analisis bivariat dengan uji Chi Square. Populasi dalam penelitian ini adalah 330 kepala keluarga dengan jurnlah sampel 75 kepala keluarga yang ada di Jorong IX Pancahan Kecamatan Rao Kabupaten Pasatnan. Data diperoleh dengan cara wawancara dengan menggunakan kuesioner. Dimana variabel dependen adalah Pengolahan sampah organik rumah tangga menjadi kompos. sedangkan paria variabel independennya adalah pengetahuan, kebutuhan, dan kemampuan.Berdasarkan hasil penelitian terdapat 47 (6 I,8% responden mempunyai pengetahuan rendah dengan p=0,03 dan OR=0,308. Responden yang tidak membutuhkan kompos yaitu 44 (57,9% responden dengan p=0,05 dan OR=2,826. Responden yang mampu mengolah sarnpah organik rumah tangga 52 (68,4% responden dengan p=0,10 dan OR=2,623.Dapat disimpulkan bahwa sebagian besar masyarakat di Jorong IX Pancahan memiliki pengetahuan yang rendah" Pengetahuan dan kebutuhan berhubungan dengan pengolahan sampah organik rumah tangga menjadi kompos, sedangkan kemampuan tidak memiliki hubungan yang signifikan. Diperlukan upaya meningkatkan pengetahuan pengolahan sampah organik rumah tangga menjadi kompos dan memberikan pemahaman kepada mayarakat tentang kebutuhan dan manfaat kompos.Kata Kunci: Pengetahuan, kebutuhan, kemampuan, Sampah rumah tangga

Evaluación de un procedimiento de soldadura para el AISI 4130 sin PWHT bajo normas API 6A y ASME Sección IX

OpenAIRE

Naranjo, Carlos; Sánchez, Xavier; Morales, Juan

2014-01-01

Resumen— Debido a la complejidad de realizar postcalentamiento en campo necesario para garantizar las propiedades mecánicas de una junta soldada de acero AISI 4130 de acuerdo con las normas API 6A [1] y ASME Sección IX[2], y evitar la presencia de martensita en la estructura metalográfica de la junta, siendo esta última perjudicial en los aceros y provocada por enfriamientos rápidos. Se ve la necesidad de desarrollar un procedimiento de soldadura capaz de satisfacer mencionadas condiciones si...

Modulation of solubility and dissolution of furosemide by preparation of phospholipid complex

Directory of Open Access Journals (Sweden)

Mona Semalty

2014-01-01

Full Text Available Aim: The aim of this study is to improve the solubility and dissolution of furosemide (a potent high ceiling diuretic used for the treatment of hypertension and a Class IV drug that is low solubility and low permeability drug as per the Biopharmaceutical Classification System by preparing its phospholipid complexes or pharmacosomes. Materials and Methods: Furosemide was complexed with phosphatidylcholine in four different molar ratios (1:1, 1:2, 1:3 and 1:4 by conventional solvent-evaporation technique. The pharmacosomes prepared were evaluated for drug content, solubility, X-ray powder diffraction (XRPD and in-vitro dissolution study. Results: Pharmacosomes of furosemide showed high drug content ranging from 88.30% to 100%. XRPD studies confirmed the formation of phospholipid complex and the amorphization of drug in the complex. The water solubility was found to be increased up to six-fold in the complexes. The octanol solubility also increased in the complexes indicating the probable increase in permeability. The in-vitro dissolution profile of the prepared complexes was found to be much better than furosemide. Conclusion: It was concluded that the phospholipid complexes can be effectively used for improving the solubility, dissolution, permeability and hence the bioavailability of furosemide like Class IV drugs.

Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.

Science.gov (United States)

Wang, Qi-Qin; Cheng, Ning; Zheng, Xiao-Wei; Peng, Sheng-Ming; Zou, Xiao-Qing

2013-07-15

Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) μM to (2.833±0.102) μM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fragment-based discovery of a potent NAMPT inhibitor.

Science.gov (United States)

Korepanova, Alla; Longenecker, Kenton L; Pratt, Steve D; Panchal, Sanjay C; Clark, Richard F; Lake, Marc; Gopalakrishnan, Sujatha M; Raich, Diana; Sun, Chaohong; Petros, Andrew M

2017-12-12

NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypothermia and Platelet Dysfunction

National Research Council Canada - National Science Library

Michelson, A

1994-01-01

... (the GPIIb-IIIa complex). Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPIb-IX and GPIIb-IIIa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

Science.gov (United States)

Anderson, C D; Moisyadi, S; Avelar, A; Walton, C B; Shohet, R V

2016-06-01

Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

Relative excitation functions for singly-excited and core-excited levels of S V--S IX populated by the beam-foil interaction

International Nuclear Information System (INIS)

Moenke, D.; Bengtsson, P.; Engstroem, L.; Hutton, R.; Jupen, C.; Kirm, M.; Westerlind, M.

1994-01-01

We have investigated the relative excitation functions for low-lying singly excited and low-lying core-excited levels in S V (S 4+ ) to S IX (S 8+ ) after beam-foil excitation using ions in the energy range 2--10 MeV. The spectral line intensities have been normalized to the same number of particles at each ion energy and corrections for the level lifetimes have been made. The overall accuracy of the measured relative excitation function at each energy and charge state is estimated to be better than 2%. A comparison of the relative excitation functions for singly excited and core-excited lines shows a difference in S VII, but not in S VI

When Complexity becomes Interesting: An Inquiry into the Information eXperience

NARCIS (Netherlands)

van der Sluis, Frans

2013-01-01

Understanding the experience of a user during information interaction is recognized as a grand challenge for the development of information systems. Yet, in parallel, it is this challenge that is mostly left ignored. Through three studies, this thesis makes the IX -- the experience while interacting

Potent peptidic fusion inhibitors of influenza virus

Energy Technology Data Exchange (ETDEWEB)

Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

2017-09-28

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

Discovery of potent and selective CDK8 inhibitors through FBDD approach.

Science.gov (United States)

Han, Xingchun; Jiang, Min; Zhou, Chengang; Zhou, Zheng; Xu, Zhiheng; Wang, Lisha; Mayweg, Alexander V; Niu, Rui; Jin, Tai-Guang; Yang, Song

2017-09-15

A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.

Science.gov (United States)

Petros, Andrew M; Swann, Steven L; Song, Danying; Swinger, Kerren; Park, Chang; Zhang, Haichao; Wendt, Michael D; Kunzer, Aaron R; Souers, Andrew J; Sun, Chaohong

2014-03-15

Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.

Science.gov (United States)

Reader, John C; Matthews, Thomas P; Klair, Suki; Cheung, Kwai-Ming J; Scanlon, Jane; Proisy, Nicolas; Addison, Glynn; Ellard, John; Piton, Nelly; Taylor, Suzanne; Cherry, Michael; Fisher, Martin; Boxall, Kathy; Burns, Samantha; Walton, Michael I; Westwood, Isaac M; Hayes, Angela; Eve, Paul; Valenti, Melanie; de Haven Brandon, Alexis; Box, Gary; van Montfort, Rob L M; Williams, David H; Aherne, G Wynne; Raynaud, Florence I; Eccles, Suzanne A; Garrett, Michelle D; Collins, Ian

2011-12-22

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.

Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

Science.gov (United States)

Nicolaou, K C; Chen, Pengxi; Zhu, Shugao; Cai, Quan; Erande, Rohan D; Li, Ruofan; Sun, Hongbao; Pulukuri, Kiran Kumar; Rigol, Stephan; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

2017-11-01

A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

Directory of Open Access Journals (Sweden)

Rui Feng

2018-03-01

Full Text Available Nattokinase (NK, which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.0 had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NK-TUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK. Keywords: Nattokinase, Tauroursodeoxycholate, Complex, Toxicity test, In vitro thrombolytic test

Hypothermia and Platelet Dysfunction

National Research Council Canada - National Science Library

Michelson, Alan

1993-01-01

... (the OPlib-Illa complex).3 Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPTh-IX and OPlib-Illa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

Discovery, synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists.

Science.gov (United States)

Stasi, Luigi Piero; Artusi, Roberto; Bovino, Clara; Buzzi, Benedetta; Canciani, Luca; Caselli, Gianfranco; Colace, Fabrizio; Garofalo, Paolo; Giambuzzi, Silvia; Larger, Patrice; Letari, Ornella; Mandelli, Stefano; Perugini, Lorenzo; Pucci, Sabrina; Salvi, Matteo; Toro, PierLuigi

2013-05-01

Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tea Contains Potent Inhibitors of Tyrosine Phosphatase PTP1B

OpenAIRE

Ma, Junfeng; Li, Zhe; Xing, Shu; Ho, Wanting Tina; Fu, Xueqi; Zhao, Zhizhuang Joe

2011-01-01

Tea is widely consumed all over the world. Studies have demonstrated the role of tea in prevention and treatment of various chronic diseases including diabetes and obesity, but the underlying mechanism is unclear. PTP1B is a widely expressed tyrosine phosphatase which has been defined as a target for therapeutic drug development to treat diabetes and obesity. In screening for inhibitors of PTP1B, we found that aqueous extracts of teas exhibited potent PTP1B inhibitory effects with an IC50 val...

Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents.

Science.gov (United States)

Biftu, Tesfaye; Feng, Dennis; Fisher, Michael; Liang, Gui-Bai; Qian, Xiaoxia; Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Liberator, Paul A; Brown, Chris; Gurnett, Anne; Leavitt, Penny S; Thompson, Donald; Mathew, John; Misura, Andrew; Samaras, Samantha; Tamas, Tamas; Sina, Joseph F; McNulty, Kathleen A; McKnight, Crystal G; Schmatz, Dennis M; Wyvratt, Matthew

2006-05-01

Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.

Copper-based metal coordination complexes with Voriconazole ligand: Syntheses, structures and antimicrobial properties

Science.gov (United States)

Zhao, Yan-Ming; Tang, Gui-Mei; Wang, Yong-Tao; Cui, Yue-Zhi; Ng, Seik Weng

2018-03-01

Three new chiral metal coordination complexes, namely, [Cu(FZ)2(CH3COO)2(H2O)]·2H2O (1), [Cu(FZ)2(NO3)2] (2), and [Cu2(FZ)2 (H2O)8](SO4)2·4H2O (3) [FZ = (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidiny)-1-(1H-1,2,4-triazol-1-yl)-2-butanol) (Voriconazole)] have been obtained by the reaction of Cu(II) salts and the free ligand FZ at room temperature. Complexes 1-3 were structurally characterized by X-ray single-crystal diffraction, IR, UV-vis, powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). Complex 1 crystallizes in the chiral space group C2, which exhibits a mono-nuclear structure. Both complexes 2 and 3 display a one-dimensional (1D) tape structure, which crystallize in chiral space group P21212 and P212121, respectively. Among these complexes, there exist a variety of hydrogen bonds and stacking interactions, through which a three-dimensional supramolecular architecture will be generated. Compared with the standard (Voriconazole), these Cu-based complexes show the more potent inhibiting efficiency against the species of Candida and Aspergillus. Moreover, among these complexes, complex 1 shows the most excellent efficiency.

Semi-synthesis of a HGF/SF kringle one (K1) domain scaffold generates a potent in vivo MET receptor agonist.

Science.gov (United States)

Simonneau, Claire; Bérénice Leclercq; Mougel, Alexandra; Adriaenssens, Eric; Paquet, Charlotte; Raibaut, Laurent; Ollivier, Nathalie; Drobecq, Hervé; Marcoux, Julien; Cianférani, Sarah; Tulasne, David; de Jonge, Hugo; Melnyk, Oleg; Vicogne, Jérôme

2015-03-01

The development of MET receptor agonists is an important goal in regenerative medicine, but is limited by the complexity and incomplete understanding of its interaction with HGF/SF (Hepatocyte Growth Factor/Scatter Factor). NK1 is a natural occurring agonist comprising the N-terminal (N) and the first kringle (K1) domains of HGF/SF. In the presence of heparin, NK1 can self-associate into a "head to tail" dimer which is considered as the minimal structural module able to trigger MET dimerization and activation whereas isolated K1 and N domains showed a weak or a complete lack of agonistic activity respectively. Starting from these structural and biological observations, we investigated whether it was possible to recapitulate the biological properties of NK1 using a new molecular architecture of isolated N or K1 domains. Therefore, we engineered multivalent N or K1 scaffolds by combining synthetic and homogeneous site-specifically biotinylated N and K1 domains (NB and K1B) and streptavidin (S). NB alone or in complex failed to activate MET signaling and to trigger cellular phenotypes. Importantly and to the contrary of K1B alone, the semi-synthetic K1B/S complex mimicked NK1 MET agonist activity in cell scattering, morphogenesis and survival phenotypic assays. Impressively, K1B/S complex stimulated in vivo angiogenesis and, when injected in mice, protected the liver against fulminant hepatitis in a MET dependent manner whereas NK1 and HGF were substantially less potent. These data reveal that without N domain, proper multimerization of K1 domain is a promising strategy for the rational design of powerful MET agonists.

Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

Energy Technology Data Exchange (ETDEWEB)

Yedidi, Ravikiran S. [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Muhuhi, Joseck M. [Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); Liu, Zhigang [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Bencze, Krisztina Z. [Department of Chemistry, Fort Hays State University, Hays, KS 67601 (United States); Koupparis, Kyriacos [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); O’Connor, Carrie E.; Kovari, Iulia A. [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Spaller, Mark R. [Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); Kovari, Ladislau C., E-mail: kovari@med.wayne.edu [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States)

2013-09-06

Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.

Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

International Nuclear Information System (INIS)

Yedidi, Ravikiran S.; Muhuhi, Joseck M.; Liu, Zhigang; Bencze, Krisztina Z.; Koupparis, Kyriacos; O’Connor, Carrie E.; Kovari, Iulia A.; Spaller, Mark R.; Kovari, Ladislau C.

2013-01-01

Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC 50 : 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the 15 N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC 50 : 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of 15 N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250.

Science.gov (United States)

Muselaers, Constantijn H J; Rijpkema, Mark; Bos, Desirée L; Langenhuijsen, Johan F; Oyen, Wim J G; Mulders, Peter F A; Oosterwijk, Egbert; Boerman, Otto C

2015-08-01

Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation (111)In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma. BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq (111)In or 10 μg of the dual labeled irrelevant control antibody NUH-82 (20 mice each). To evaluate when tumors could be detected, 4 mice per group were imaged weekly during 5 weeks with single photon emission computerized tomography/computerized tomography and the fluorescence imaging followed by ex vivo biodistribution studies. As early as 1 week after tumor cell inoculation single photon emission computerized tomography and fluorescence images showed clear delineation of intraperitoneal clear cell renal cell carcinoma with good concordance between single photon emission computerized tomography/computerized tomography and fluorescence images. The high and specific accumulation of the dual labeled antibody conjugate in tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed 1 week after inoculation (mean ± SD 58.5% ± 18.7% vs 5.6% ± 2.3% injected dose per gm for DTPA-G250-IRDye800CW vs NUH-82, respectively). High tumor uptake was also observed at other time points. This study demonstrates the feasibility of dual modality imaging with dual labeled antibody (111)In-DTPA-G250-IRDye800CW in a clear cell renal cell carcinoma model. Results indicate that preoperative and intraoperative detection of carbonic anhydrase IX expressing tumors, positive resection margins and metastasis might be feasible with this approach. Copyright © 2015 American Urological Association Education and Research

Iconoclasmo e iconodulia entre oriente y occidente (siglos VIII-IX Iconoclasm and iconoduly between east and west (8th-9th centuries

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Alfonso Hernández Rodríguez

2011-10-01

Full Text Available El siguiente artículo trata acerca de la recepción en el occidente carolingio de la crisis iconoclasta. Reflexiona sobre la forma en que ambas cristiandades trataron el problema que las imágenes representan para las prácticas religiosas y las consecuencias políticas del culto de los iconos. El escrito afirma también que durante los siglos VIII y IX la crisis iconoclasta permitió la aparición de una tradición cristiana latina consciente de sí misma. Por lo tanto, se trató del momento que puso en evidencia el nacimiento de dos formas divergentes de piedad cristiana y la alienación de una respecto de la otra. La cristiandad occidental centrada en el edificio eclesiástico y que privilegiaba la ubicación de lo sagrado en el rito eucarístico, y la oriental cuyo centro era la adoración de las imágenes, con la consecuente multiplicación de los espacios sagrados.The following paper deals with the reception in the Carolingian west of the Byzantine Iconoclast Crisis. It considers the way both Christianities dealed with the problem that images presented to religious practices and the political consequences of iconic worship. The paper also states that during the VIII and IX centuries the iconoclast crisis allowed the emergence of a self conscious Latin Christian tradition. Consequently it was the moment that showed the beginning of two differing ways of Christian piety and the alienation of one towards the other. Western Christianity focused its religion practice in church building and the idea of Sacrality in the Eucharistic Rite. The oriental church, moreovers, centered its practices and theology on icon worship.

IX - MR Control Chart as a Tool in Assessment of the Cast Iron Properties Stability

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F. Binczyk

2007-07-01

Full Text Available The study offers a statistical assessment of the stability of a technological process of melting and pouring low-carbon grey iron assigned for casting of brake discs. Some specific characteristics were presented that should be taken into consideration when statistical methods are used for technology improvement. The stability of the cast iron melting process was evaluated using data read out from the thermal analysis curve and true data, i.e. the results of spectrometric analysis of the chemical composition and measured values of the mechanical properties. The method for assessment of process stability was discussed on the example of carbon content and Brinell hardness. The examined parameters of the technological process of grey iron melting and casting are independent of each other (the results of carbon content determination in successive melts, the results of hardness measurements, etc.. Therefore, for analysis, the IX - MR type charts were chosen, where single measurements of the selected property (n = 1 serve as a measure of location, while a measure of variability are the, so called, Moving Ranges (MR, which are an absolute value of the difference between the two successive measurements.

Highly potent fibrinolytic serine protease from Streptomyces.

Science.gov (United States)

Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

2011-01-05

We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. Copyright © 2010 Elsevier Inc. All rights reserved.

The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

Science.gov (United States)

Vincent, Maxence S.; Durand, Eric; Cascales, Eric

2016-01-01

The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS. PMID:27630829

Direct Regulation of Androgen Receptor Activity by Potent CYP17 Inhibitors in Prostate Cancer Cells*

Science.gov (United States)

Soifer, Harris S.; Souleimanian, Naira; Wu, Sijian; Voskresenskiy, Anatoliy M.; Kisaayak Collak, Filiz; Cinar, Bekir; Stein, Cy A.

2012-01-01

TOK-001 and abiraterone are potent 17-heteroarylsteroid (17-HAS) inhibitors of Cyp17, one of the rate-limiting enzymes in the biosynthesis of testosterone from cholesterol in prostate cancer cells. Nevertheless, the molecular mechanism underlying the prevention of prostate cell growth by 17-HASs still remains elusive. Here, we assess the effects of 17-HASs on androgen receptor (AR) activity in LNCaP and LAPC-4 cells. We demonstrate that both TOK-001 and abiraterone reduced AR protein and mRNA expression, and antagonized AR-dependent promoter activation induced by androgen. TOK-001, but not abiraterone, is an effective apparent competitor of the radioligand [3H]R1881 for binding to the wild type and various mutant AR (W741C, W741L) proteins. In agreement with these data, TOK-001 is a consistently superior inhibitor than abiraterone of R1881-induced transcriptional activity of both wild type and mutant AR. However, neither agent was able to trans-activate the AR in the absence of R1881. Our data demonstrate that phospho-4EBP1 levels are significantly reduced by TOK-001 and to a lesser extent by abiraterone alcohol, and suggest a mechanism by which cap-dependent translation is suppressed by blocking assembly of the eIF4F and eIF4G complex to the mRNA 5′ cap. Thus, the effects of these 17-HASs on AR signaling are complex, ranging from a decrease in testosterone production through the inhibition of Cyp17 as previously described, to directly reducing both AR protein expression and R1881-induced AR trans-activation. PMID:22174412

Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.

Science.gov (United States)

Apfel, C; Banner, D W; Bur, D; Dietz, M; Hirata, T; Hubschwerlen, C; Locher, H; Page, M G; Pirson, W; Rossé, G; Specklin, J L

2000-06-15

Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives have been synthesized and found to be potent inhibitors of Escherichia coli peptide deformylase (PDF). Most of the compounds synthesized and tested displayed antibacterial activities that cover several pathogens found in respiratory tract infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The potential of these compounds as antibacterial agents is discussed with respect to selectivity, intracellular concentrations in bacteria, and potential for resistance development.

Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium ophioglossum.

Science.gov (United States)

Firdous, Sadiqa; Ansari, Nida Hassan; Fatima, Itrat; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Lateef, Mehreen

2012-07-01

Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n-hexane subfraction of the MeOH extract of the whole plant of Heliotropium ophioglossum along with glycerol monopalmitate (3) and β-sitosterol 3-O-β-D: -glucoside (4) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme urease.

Effect of size heterogeneity on community identification in complex networks

Energy Technology Data Exchange (ETDEWEB)

Danon, L.; Diaz-Guilera, A.; Arenas, A.

2008-01-01

Identifying community structure can be a potent tool in the analysis and understanding of the structure of complex networks. Up to now, methods for evaluating the performance of identification algorithms use ad-hoc networks with communities of equal size. We show that inhomogeneities in community sizes can and do affect the performance of algorithms considerably, and propose an alternative method which takes these factors into account. Furthermore, we propose a simple modification of the algorithm proposed by Newman for community detection (Phys. Rev. E 69 066133) which treats communities of different sizes on an equal footing, and show that it outperforms the original algorithm while retaining its speed.

El Espíritu, memoria y testimonio de Cristo. A propósito de la «Tertio Millennio Adveniente», Actas del IX Simposio de Teología histórica (Reseña)

OpenAIRE

Luque-Alcaide, E. (Elisa)

1998-01-01

Reseña del libro de Alfonso ESPONERA CERDÁN (ed.), El Espíritu, memoria y testimonio de Cristo. A propósito de la «Tertio Millennio Adveniente», Actas del IX Simposio de Teología histórica, Facultad de Teología San Vicente Ferrer («Series Valentina» 40), Valencia 1997,528 pp.

Aurintricarboxylic acid is a potent inhibitor of phosphofructokinase.

Science.gov (United States)

McCune, S A; Foe, L G; Kemp, R G; Jurin, R R

1989-01-01

Aurintricarboxylic acid (ATA) was found to be a very potent inhibitor of purified rabbit liver phosphofructokinase (PFK), giving 50% inhibition at 0.2 microM. The inhibition was in a manner consistent with interaction at the citrate-inhibitory site of the enzyme. The data suggest that inhibition of PFK by ATA was not due to denaturation of the enzyme or the irreversible binding of inhibitor, since the inhibition could be reversed by addition of allosteric activators of PFK, i.e. fructose 2,6-bisphosphate or AMP. Two other tricarboxylic acids, agaric acid and (-)-hydroxycitrate, were found to inhibit PFK. ATA at much higher concentrations (500 microM) was shown to inhibit fatty acid synthesis from endogenous glycogen in rat hepatocytes; however, protein synthesis was not altered. PMID:2525029

Red wine contains a potent inhibitor of phenolsulphotransferase.

Science.gov (United States)

Littlewood, J T; Glover, V; Sandler, M

1985-01-01

Many ethanolic drinks, especially red wine, contain potent inhibitors of phenolsulphotransferase. At a dilution of 1/75 from the original beverage, extracts from six types of red wine inhibited human platelet phenolsulphotransferase P by a mean of 99% and human platelet phenolsulphotransferase M by 12%. Such extracts had no significant effect on rat liver monoamine oxidase A or human platelet monoamine oxidase B. The inhibitors, which have not yet been identified, can be extracted into ethyl acetate at acid or neutral pH. Thus, they are not monoamines. Flavonoid phenols are plausible candidates. As phenolsulphotransferase M and P are involved in the metabolism of many phenols, including drugs, the inhibition of these enzymes could result in the enhancement of pharmacological potency and have important clinical consequences. PMID:3857069

Establishing Approaches to Modeling the Ares I-X and Ares I Roll Control System with Free-stream Interaction

Science.gov (United States)

Pao, S. Paul; Deere, Karen A.; Abdol-Hamid, Khales S.

2011-01-01

Approaches were established for modeling the roll control system and analyzing the jet interactions of the activated roll control system on Ares-type configurations using the USM3D Navier-Stokes solver. Components of the modeling approach for the roll control system include a choice of turbulence models, basis for computing a dynamic equivalence of the real gas rocket exhaust flow in terms of an ideal gas, and techniques to evaluate roll control system performance for wind tunnel and flight conditions. A simplified Ares I-X configuration was used during the development phase of the roll control system modeling approach. A limited set of Navier-Stokes solutions was obtained for the purposes of this investigation and highlights of the results are included in this paper. The USM3D solutions were compared to equivalent solutions at select flow conditions from a real gas Navier- Stokes solver (Loci-CHEM) and a structured overset grid Navier-Stokes solver (OVERFLOW).

Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics

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Virapong Prachayasittikul

2008-12-01

Full Text Available Nicotinic acid (also known as vitamin B3 is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids. The tested copper complexes exhibited superoxide dismutase (SOD mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph was the most potent with a SOD mimetic activity of IC50 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.

Synthesis, spectral characterisation, morphology, biological activity and DNA cleavage studies of metal complexes with chromone Schiff base

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P. Kavitha

2016-07-01

Full Text Available Cu(II, Co(II, Ni(II and Zn(II complexes have been synthesized using 3-((pyridine-2-yliminomethyl-4H-chromen-4-one as a ligand derived from 3-formyl chromone and 2-amino pyridine. All the complexes were characterised by analytical, conductivity, IR, electronic, magnetic, ESR, thermal, powder XRD and SEM studies. The analytical data revealed that the metal to ligand molar ratio is 1:2 in all the complexes. Molar conductivity data indicates that all the complexes are neutral in nature. On the basis of magnetic and electronic spectral data, octahedral geometry is proposed for all the complexes. Thermal behaviour of the synthesized complexes indicates the coordinated and lattice water molecules are present in the complexes. The X-ray diffraction data suggest a triclinic system for all compounds. Different surface morphologies were identified from SEM micrographs. All metal complexes exhibit fluorescence. The antimicrobial and nematicidal activity data show that metal complexes are more potent than the parent ligand. The DNA cleavage activity of the ligand and its metal complexes were observed in the presence of H2O2.

Fatty Acid Biosynthesis IX

DEFF Research Database (Denmark)

Carey, E. M.; Hansen, Heinz Johs. Max; Dils, R.

1972-01-01

# 1. I. [I-14C]Acetate was covalently bound to rabbit mammary gland fatty acid synthetase by enzymic transacylation from [I-14C]acetyl-CoA. Per mole of enzyme 2 moles of acetate were bound to thiol groups and up to I mole of acetate was bound to non-thiol groups. # 2. 2. The acetyl-fatty acid...... synthetase complex was isolated free from acetyl-CoA. It was rapidly hydrolysed at 30°C, but hydrolysis was greatly diminished at o°C and triacetic lactone synthesis occurred. In the presence of malonyl-CoA and NADPH, all the acetate bound to fatty acid synthetase was incorporated into long-chain fatty acids....... Hydrolysis of bound acetate and incorporation of bound acetate into fatty acids were inhibited to the same extent by guanidine hydrochloride. # 3. 3. Acetate was also covalently bound to fatty acid synthetase by chemical acetylation with [I-14C]acetic anhydride in the absence of CoASH. A total of 60 moles...

Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

OpenAIRE

Rao, L V; Rapaport, S I

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

Inelastic x-ray scattering from polycrystalline materials

International Nuclear Information System (INIS)

Fischer, I.

2008-09-01

Inelastic X-ray scattering (IXS) is a tool to determine the phonon dispersion along high symmetry directions in single crystals. However, novel materials and crystals under extreme conditions are often only available in form of polycrystalline samples. Thus the investigation is limited to orientation-averaged properties. To overcome these limitations, a methodology to extract the single crystal phonon dispersion from polycrystalline materials was developed. The approach consists of recording IXS spectra over a large momentum transfer region and confront them with a Born - von Karman model calculation. A least-square refinement of the model IXS spectra then provides the single crystal dispersion scheme. In this work the method is developed on the test case Be. Further studies were performed on more and more complex systems, in order to explore the limitations. This novel application of IXS promises to be a valuable tool in cases where single crystalline materials are not available. (author)

Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino[2,3-d]pyrimidine core.

Science.gov (United States)

Dow, Robert L; Andrews, Melissa; Aspnes, Gary E; Balan, Gayatri; Michael Gibbs, E; Guzman-Perez, Angel; Karki, Kapil; Laperle, Jennifer L; Li, Jian-Cheng; Litchfield, John; Munchhof, Michael J; Perreault, Christian; Patel, Leena

2011-10-15

A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synthesis of these targets facilitated confirmation of predictions regarding the stereochemical-dependence of DGAT-1 inhibition for this series. Compound 10 was shown to be a potent inhibitor of human DGAT-1 (10 nM) and to suppress triglyceride synthesis at oral doses of <3mg/kg. Copyright © 2011 Elsevier Ltd. All rights reserved.

Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.

Science.gov (United States)

Prati, Federica; Zuccotto, Fabio; Fletcher, Daniel; Convery, Maire A; Fernandez-Menendez, Raquel; Bates, Robert; Encinas, Lourdes; Zeng, Jingkun; Chung, Chun-Wa; De Dios Anton, Paco; Mendoza-Losana, Alfonso; Mackenzie, Claire; Green, Simon R; Huggett, Margaret; Barros, David; Wyatt, Paul G; Ray, Peter C

2018-04-06

Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

Science.gov (United States)

Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

2010-04-22

Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

eCD4-Ig variants that more potently neutralize HIV-1.

Science.gov (United States)

Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

Potent inhibition of mammalian ribonucleases by 3', 5'-pyrophosphate-linked nucleotides.

Science.gov (United States)

Russo, N; Shapiro, R

1999-05-21

Molecular modeling based on the crystal structure of the complex of bovine pancreatic RNase A with the inhibitor 5'-diphosphoadenosine 3'-phosphate (ppAp) (Leonidas, D. D., Shapiro, R., Irons, L. I., Russo, N., and Acharya, K. R. (1997) Biochemistry 36, 5578-5588) was used to design new inhibitors that extend into unoccupied regions of the enzyme active site. These compounds are dinucleotides that contain an unusual 3',5'-pyrophosphate linkage and were synthesized in solution by a combined chemical and enzymatic procedure. The most potent of them, 5'-phospho-2'-deoxyuridine 3'-pyrophosphate, P' --> 5'-ester with adenosine 3'-phosphate (pdUppAp), binds to RNase A with Ki values of 27 and 220 nM at pH 5.9 and 7, respectively. These values are 6-9-fold lower than those for ppAp and 50-fold lower than that for the transition state analogue, uridine vanadate. pdUppAp has broad specificity; it is an effective inhibitor of at least two other members of the pancreatic RNase superfamily, human RNase-2 (eosinophil-derived neurotoxin) and RNase-4, which share only 36-44% sequence identity with the pancreatic enzyme. The potency of pdUppAp and the other inhibitors described here depends critically on the extended internucleotide linkage; the pyrophosphate group enhances dinucleotide binding to the three RNases by 2.1-2.9 orders of magnitude, as compared with a monophosphate. These data give further insight into the organization of the catalytic centers of the various RNases. Moreover, the new class of inhibitors provides a useful means by which to probe the biological actions of these and other related enzymes.

Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening.

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Chiara Ruggeri

Full Text Available The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach.