Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

Application of 6D Building Information Model (6D BIM) for Business-storage Building in Slovenia

NASA Astrophysics Data System (ADS)

Pučko, Zoran; Vincek, Dražen; Štrukelj, Andrej; Šuman, Nataša

2017-10-01

The aim of this paper is to present an application of 6D building information modelling (6D BIM) on a real business-storage building in Slovenia. First, features of building maintenance in general are described according to the current Slovenian legislation, and also a general principle of BIM is given. After that, step-by-step activities for modelling 6D BIM are exposed, namely from Element list for maintenance, determination of their lifetime and service measures, cost analysing and time analysing to 6D BIM modelling. The presented 6D BIM model is designed in a unique way in which cost analysis is performed as 5D BIM model with linked data to use BIM Construction Project Management Software (Vico Office), integrated with 3D BIM model, whereas time analysis as 4D BIM model is carried out as non-linked data with the help of Excel (without connection to 3D BIM model). The paper is intended to serve as a guide to the building owners to prepare 6D BIM and to provide an insight into the relevant dynamic information about intervals and costs for execution of maintenance works in the whole building lifecycle.

C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis.

PubMed

Vaisman, Carolina E; Del Moral-Hernandez, Oscar; Moreno-Campuzano, Samadhi; Aréchaga-Ocampo, Elena; Bonilla-Moreno, Raul; Garcia-Aguiar, Israel; Cedillo-Barron, Leticia; Berumen, Jaime; Nava, Porfirio; Villegas-Sepúlveda, Nicolas

2018-03-02

The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells. Transfection with the E6^E7-GFP or E7-GFP construct had no effect on the number of the apoptotic cells, compared with control cells. Conversely, transfection with the E6*II construct resulted in higher cell death than the control cells. Taken together, these results suggested that E6*I or E6*II, the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis, when transfected in C-33A cells. Copyright © 2018 Elsevier B.V. All rights reserved.

6d, Coulomb branch anomaly matching

NASA Astrophysics Data System (ADS)

Intriligator, Kenneth

2014-10-01

6d QFTs are constrained by the analog of 't Hooft anomaly matching: all anomalies for global symmetries and metric backgrounds are constants of RG flows, and for all vacua in moduli spaces. We discuss an anomaly matching mechanism for 6d theories on their Coulomb branch. It is a global symmetry analog of Green-Schwarz-West-Sagnotti anomaly cancellation, and requires the apparent anomaly mismatch to be a perfect square, . Then Δ I 8 is cancelled by making X 4 an electric/magnetic source for the tensor multiplet, so background gauge field instantons yield charged strings. This requires the coefficients in X 4 to be integrally quantized. We illustrate this for theories. We also consider the SCFTs from N small E8 instantons, verifying that the recent result for its anomaly polynomial fits with the anomaly matching mechanism.

CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol-induced extrapyramidal symptoms.

PubMed

Šimić, Iveta; Potočnjak, Ines; Kraljičković, Iva; Stanić Benić, Mirjana; Čegec, Ivana; Juričić Nahal, Danica; Ganoci, Lana; Božina, Nada

2016-08-01

A 66-year-old male Caucasian, received 1 mg of haloperidol orally and rapidly developed severe iatrogenic extrapyramidal symptoms. Treatment was immediately discontinued, and the side effects resolved. Haloperidol is mainly metabolized by Phase I CYP2D6 and to the lesser extent by CYP3A4 and by Phase II UGT2B7 enzymes. Genotyping was performed revealing CYP2D6*6/*6, CYP3A4*1/*1, and UGT2B7 -161 C/T genotypes, implicating poor, extensive and intermediate metabolism, respectively. Of the CYPs, haloperidol is metabolized by CYP2D6 and CYP3A4 primarily. It was the introduction of ciprofloxacin which was a trigger for the development of adverse drug reaction due to inhibition of CYP3A4, which was in presented patient main metabolic pathway for haloperidol since he was CYP2D6 poor metabolizer. Presented case report highlights the importance of genotyping. Pharmacogenetics testing should be considered when drug toxicity is suspected, polymorphic metabolic pathways used and drugs concomitantly applied.

Synthesis, spectral, thermal, optical and theoretical studies of (2E,6E)-2-benzylidene-6-(4-methoxybenzylidene)cyclohexanone.

PubMed

Meenatchi, V; Muthu, K; Rajasekar, M; Meenakshisundaram, Sp

2014-01-01

Single crystals of (2E,6E)-2-benzylidine-6-(4-methoxybenzylidine)cyclohexanone are grown by slow evaporation of ethanolic solution at room temperature. The characteristic functional groups present in the molecule are confirmed by Fourier transform infrared and Fourier transform Raman analyses. The scanning electron microscopy study reveals the surface morphology of the material. Thermogravimetric/differential thermal analysis study reveals the purity of the material and the crystal is transparent in the visible region having a lower optical cut-off at ∼487nm. The second harmonic generation efficiency of as-grown material is estimated by Kurtz and Perry technique. Optimized geometry has been derived using Hartree-Fock calculations performed at the level 6-31G (d,p) and the first-order molecular hyperpolarizability (β) is estimated. The specimen is further characterized by nuclear magnetic resonance spectroscopy. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Anomaly of strings of 6d {N}=(1,0) theories

NASA Astrophysics Data System (ADS)

Shimizu, Hiroyuki; Tachikawa, Yuji

2016-11-01

We obtain the anomaly polynomial of strings of general 6d {N}=(1,0) theories in terms of anomaly inflow. Our computation sheds some light on the reason why the simplest 6d {N}=(1,0) theory has E 8 flavor symmetry, and also partially explains a curious numerology in F-theory.

E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

PubMed Central

Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

2010-01-01

High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

40 CFR 721.10268 - [5,6]Fullerene-C70-D5h(6).

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10268 [5,6]Fullerene-C70-D5h(6). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C70-D5h(6) (PMN P-09-55; CAS No. 115383...

40 CFR 721.10268 - [5,6]Fullerene-C70-D5h(6).

Code of Federal Regulations, 2014 CFR

2014-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10268 [5,6]Fullerene-C70-D5h(6). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C70-D5h(6) (PMN P-09-55; CAS No. 115383...

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

PubMed Central

Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

2015-01-01

Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

E6-associated protein is required for human papillomavirus type 16 E6 to cause cervical cancer in mice.

PubMed

Shai, Anny; Pitot, Henry C; Lambert, Paul F

2010-06-15

High-risk human papillomaviruses (HPV) cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins, including Bak, E6BP1, and E6TP1, and proteins that contain PDZ domains, such as hScrib and hDlg. Many of these activities are thought to contribute to the role of E6 in carcinogenesis. The interaction of E6 with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through the ability of E6 to recruit the ubiquitin ligase E6-associated protein (E6AP) into complexes with these cellular proteins, resulting in their ubiquitin-mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating acute and oncogenic phenotypes of E6, including induction of epithelial hyperplasia, abrogation of DNA damage response, and induction of cervical cancer. Loss of E6AP had no discernible effect on the ability of E6 to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of the oncogenic potential of E6 in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer.

The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells.

PubMed Central

Halbert, C L; Demers, G W; Galloway, D A

1992-01-01

Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation. Images PMID:1312623

[Profiles of cell proliferation and apoptosis in the mouse epithelial regeneration model K6b-E6/E7].

PubMed

Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Cortés-Malagón, Enoc Mariano; Sierra Martínez, Mónica; Acosta-Altamirano, Gustavo; Gariglio-Vidal, Patricio

2012-01-01

Mammals have limited epithelial regeneration capacity. The K6b-E6/E7 mice model has been described as useful for the study of epithelial regeneration. The objective of this study is to compare the expression of E6/E7 oncogenes with those of cell proliferation and apoptosis during epithelization. The hypothesis of this study is that alterations in cell proliferation and apoptosis in K6b-E6/E7 mice will only occur during epithelization. Deep 2 mm punches were performed in the middle of transgenic and control mice's ears. A biopsy was collected from the epithelization zone 72 hours and 2 weeks post-injury. Assays for cell proliferation and apoptosis were carried out by immunohistochemistry and TUNEL techniques, respectively. RT-PCR in situ was performed to compare E6/E7 expressions in the areas studied. Transgenic strain K6b-E6/E7 presented more proliferative cells and less apoptotic cells in epithelizated zones. This effect was limited to suprabasal stratum only, and correlates with E6/E7 oncogenes expression. Two weeks post-injury, cell proliferation and apoptosis were similar in both samples as the E6/E7 expression went down. K6b-E6/E7 mouse model is useful for epithelial regeneration. Its mechanisms should be considered for the treatment of deep wounds.

The 6D superswirl

NASA Astrophysics Data System (ADS)

Parameswaran, S. L.; Tasinato, G.; Zavala, I.

2006-03-01

We present a novel supersymmetric solution to a nonlinear sigma model coupled to supergravity. The solution represents a static, supersymmetric, codimension-two object, which is different to the familiar cosmic strings. In particular, we consider 6D chiral gauged supergravity, whose spectrum contains a number of hypermultiplets. The scalar components of the hypermultiplet are charged under a gauge field, and supersymmetry implies that they experience a simple paraboloid-like (or 2D infinite well) potential, which is minimised when they vanish. Unlike conventional vortices, the energy density of our configuration is not localized to a string-like core. The solutions have two timelike singularities in the internal manifold, which provide the necessary boundary conditions to ensure that the scalars do not lie at the minimum of their potential. The 4D spacetime is flat, and the solution is a continuous deformation of the so-called "rugby ball" solution, which has been studied in the context of the cosmological constant problem. It represents an unexpected class of supersymmetric solutions to the 6D theory, which have gravity, gauge fluxes and hyperscalars all active in the background.

Bridge-in-a-Backpack(TM) task 6 : guidelines for long term inspection and maintenance.

DOT National Transportation Integrated Search

2016-01-01

This report includes fulfillment of Task 6 of a multi-task contract to further enhance concrete filled FRP tubes, or the Bridge in a Backpack. Task 6 provides guidelines for long term inspection and maintenance.This bridge consists of a buried arch s...

Bridge-in-a-Backpack(TM) task 6 : guidelines for long term inspection and maintenance.

DOT National Transportation Integrated Search

2016-01-01

This report includes fulfillment of Task 6 of a multi-task contract to further enhance concrete filled FRP tubes, or : the Bridge in a Backpack. Task 6 provides guidelines for long term inspection and maintenance. : This bridge consists of a buried a...

On generalized Melvin solution for the Lie algebra E_6

NASA Astrophysics Data System (ADS)

Bolokhov, S. V.; Ivashchuk, V. D.

2017-10-01

A multidimensional generalization of Melvin's solution for an arbitrary simple Lie algebra G is considered. The gravitational model in D dimensions, D ≥ 4, contains n 2-forms and l ≥ n scalar fields, where n is the rank of G. The solution is governed by a set of n functions H_s(z) obeying n ordinary differential equations with certain boundary conditions imposed. It was conjectured earlier that these functions should be polynomials (the so-called fluxbrane polynomials). The polynomials H_s(z), s = 1,\\ldots ,6, for the Lie algebra E_6 are obtained and a corresponding solution for l = n = 6 is presented. The polynomials depend upon integration constants Q_s, s = 1,\\ldots ,6. They obey symmetry and duality identities. The latter ones are used in deriving asymptotic relations for solutions at large distances. The power-law asymptotic relations for E_6-polynomials at large z are governed by the integer-valued matrix ν = A^{-1} (I + P), where A^{-1} is the inverse Cartan matrix, I is the identity matrix and P is a permutation matrix, corresponding to a generator of the Z_2-group of symmetry of the Dynkin diagram. The 2-form fluxes Φ ^s, s = 1,\\ldots ,6, are calculated.

E6^E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78

PubMed Central

Ajiro, Masahiko

2015-01-01

ABSTRACT Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role of E6^E7, a novel isoform containing the 41 N-terminal amino acid (aa) residues of E6 and the 38 C-terminal aa residues of E7, in the regulation of E6 and E7 stability. Through mass spectrometric analysis, we identified that HSP90 and GRP78, which are frequently upregulated in cervical cancer tissues, are two E6^E7-interacting proteins responsible for the stability and function of E6^E7, E6, and E7. Although GRP78 and HSP90 do not bind each other, GRP78, but not HSP90, interacts with E6 and E7. E6^E7 protein, in addition to self-binding, interacts with E6 and E7 in the presence of GRP78 and HSP90, leading to the stabilization of E6 and E7 by prolonging the half-life of each protein. Knocking down E6^E7 expression in HPV16-positive CaSki cells by a splice junction-specific small interfering RNA (siRNA) destabilizes E6 and E7 and prevents cell growth. The same is true for the cells with a GRP78 knockdown or in the presence of an HSP90 inhibitor. Moreover, mapping and alignment analyses for splicing elements in 36 alpha-HPVs (α-HPVs) suggest the possible expression of E6^E7 mostly by other oncogenic or possibly oncogenic α-HPVs (HPV18, -30, -31, -39, -42, -45, -56, -59, -70, and -73). HPV18 E6^E7 is detectable in HPV18-positive HeLa cells and HPV18-infected raft tissues. All together, our data indicate that viral E6^E7 and cellular GRP78 or HSP90 might be novel targets for cervical cancer therapy. PMID:25691589

D 6ℛ4 amplitudes in various dimensions

NASA Astrophysics Data System (ADS)

Pioline, Boris

2015-04-01

Four-graviton couplings in the low energy effective action of type II string vacua compactified on tori are strongly constrained by supersymmetry and U-duality. While the ℛ4 and D 4ℛ4 couplings are known exactly in terms of Langlands-Eisenstein series of the U-duality group, the D 6ℛ4 couplings are not nearly as well understood. Exploiting the coincidence of the U-duality group in D = 6 with the T-duality group in D = 5, we propose an exact formula for the D 6ℛ4 couplings in type II string theory compactified on T 4, in terms of a genus-two modular integral plus a suitable Eisenstein series. The same modular integral computes the two-loop correction to D 6ℛ4 in 5 dimensions, but here provides the non-perturbative completion of the known perturbative terms in D = 6. This proposal hinges on a systematic re-analysis of the weak coupling and large radius of the D 6ℛ4 in all dimensions D ≥ 3, which fills in some gaps and resolves some inconsistencies in earlier studies.

Planar dicyclic B{sub 6}S{sub 6}, B{sub 6}S{sub 6}{sup −}, and B{sub 6}S{sub 6}{sup 2−} clusters: Boron sulfide analogues of naphthalene

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

Li, Da-Zhi; Bai, Hui; Ou, Ting

2015-01-07

Inorganic analogues of hydrocarbons or polycyclic aromatic hydrocarbons (PAHs) are of current interest in chemistry. Based upon global structural searches and B3LYP and CCSD(T) calculations, we present herein the perfectly planar dicyclic boron sulfide clusters: D{sub 2h} B{sub 6}S{sub 6} (1, {sup 1}A{sub g}), D{sub 2h} B{sub 6}S{sub 6}{sup −} (2, {sup 2}B{sub 3u}), and D{sub 2h} B{sub 6}S{sub 6}{sup 2−} (3, {sup 1}A{sub g}). These are the global minima of the systems, being at least 0.73, 0.81, and 0.53 eV lower in energy, respectively, than their alternative isomers at the CCSD(T) level. The D{sub 2h} structures feature twin B{submore » 3}S{sub 2} five-membered rings, which are fused together via a B{sub 2} unit and terminated by two BS groups. Bonding analyses show that the closed-shell B{sub 6}S{sub 6}{sup 2−} (3) cluster possesses 10 delocalized π electrons, closely analogous to the bonding pattern of the aromatic naphthalene C{sub 10}H{sub 8}. The B{sub 6}S{sub 6}{sup −} (2) and B{sub 6}S{sub 6} (1) species are readily obtained upon removal of one or two π electrons from B{sub 6}S{sub 6}{sup 2−} (3). The results build a new analogous relationship between boron sulfide clusters and their PAH counterparts. The B{sub 6}S{sub 6}{sup −} (2) monoanion and B{sub 6}S{sub 6}{sup 2−} (3) dianion can be effectively stabilized in neutral LiB{sub 6}S{sub 6} and Li{sub 2}B{sub 6}S{sub 6} salts, respectively.« less

Molecular structure, quantum mechanical calculation and radical scavenging activities of (E)-4,6-dibromo-2-[(3,5-dimethylphenylimino)methyl]-3-methoxyphenol and (E)-4,6-dibromo-2-[(2,6-dimethylphenylimino)methyl]-3-methoxyphenol compounds.

PubMed

Alaşalvar, Can; Soylu, Mustafa Serkan; Güder, Aytaç; Albayrak, Çiğdem; Apaydın, Gökhan; Dilek, Nefise

2014-09-15

In this study, (E)-4,6-dibromo-2-[(3,5-dimethylphenylimino)methyl]-3-methoxyphenol and (E)-4,6-dibromo-2-[(2,6-dimethylphenylimino)methyl]-3-methoxyphenol compounds have been synthesized and characterized by using X-ray crystallographic method, FT-IR and Density functional method. The molecular geometry, vibrational frequencies of the title compounds in the ground state have been calculated by using B3LYP with the 6-31G(d,p) basis set. The tautomeric form of the compounds has been demonstrated by using single crystal X-ray method, FT-IR spectrometer and DFT method. In addition, HOMO-LUMO energy gap, molecular electrostatic potential map and NBO analysis of the compounds are performed at B3LYP/6-31G(d,p) level. It may be remarked that the free radical scavenging activities of the title compounds were assessed using DPPH, DMPD+, and ABTS+ assays. The obtained results show that especially compound 2 has effective DPPH (SC50 1.52±0.14 μg/mL), DMPD+ (SC50 1.22±0.21 μg/mL), and ABTS+ (SC50 3.32±0.17 μg/mL) scavenging activities compared with standards (BHA, rutin, and trolox). Copyright © 2014 Elsevier B.V. All rights reserved.

6D fractional quantum Hall effect

NASA Astrophysics Data System (ADS)

Heckman, Jonathan J.; Tizzano, Luigi

2018-05-01

We present a 6D generalization of the fractional quantum Hall effect involving membranes coupled to a three-form potential in the presence of a large background four-form flux. The low energy physics is governed by a bulk 7D topological field theory of abelian three-form potentials with a single derivative Chern-Simons-like action coupled to a 6D anti-chiral theory of Euclidean effective strings. We derive the fractional conductivity, and explain how continued fractions which figure prominently in the classification of 6D superconformal field theories correspond to a hierarchy of excited states. Using methods from conformal field theory we also compute the analog of the Laughlin wavefunction. Compactification of the 7D theory provides a uniform perspective on various lower-dimensional gapped systems coupled to boundary degrees of freedom. We also show that a supersymmetric version of the 7D theory embeds in M-theory, and can be decoupled from gravity. Encouraged by this, we present a conjecture in which IIB string theory is an edge mode of a 10 + 2-dimensional bulk topological theory, thus placing all twelve dimensions of F-theory on a physical footing.

6D SCFTs and phases of 5D theories

NASA Astrophysics Data System (ADS)

Del Zotto, Michele; Heckman, Jonathan J.; Morrison, David R.

2017-09-01

Starting from 6D superconformal field theories (SCFTs) realized via F-theory, we show how reduction on a circle leads to a uniform perspective on the phase structure of the resulting 5D theories, and their possible conformal fixed points. Using the correspon-dence between F-theory reduced on a circle and M-theory on the corresponding elliptically fibered Calabi-Yau threefold, we show that each 6D SCFT with minimal supersymmetry directly reduces to a collection of between one and four 5D SCFTs. Additionally, we find that in most cases, reduction of the tensor branch of a 6D SCFT yields a 5D generalization of a quiver gauge theory. These two reductions of the theory often correspond to different phases in the 5D theory which are in general connected by a sequence of flop transitions in the extended Kähler cone of the Calabi-Yau threefold. We also elaborate on the structure of the resulting conformal fixed points, and emergent flavor symmetries, as realized by M-theory on a canonical singularity.

Non-BPS attractors in 5 d and 6 d extended supergravity

NASA Astrophysics Data System (ADS)

Andrianopoli, L.; Ferrara, S.; Marrani, A.; Trigiante, M.

2008-05-01

We connect the attractor equations of a certain class of N=2, d=5 supergravities with their (1,0), d=6 counterparts, by relating the moduli space of non-BPS d=5 black hole/black string attractors to the moduli space of extremal dyonic black string d=6 non-BPS attractors. For d=5 real special symmetric spaces and for N=4,6,8 theories, we explicitly compute the flat directions of the black object potential corresponding to vanishing eigenvalues of its Hessian matrix. In the case N=4, we study the relation to the (2,0), d=6 theory. We finally describe the embedding of the N=2, d=5 magic models in N=8, d=5 supergravity as well as the interconnection among the corresponding charge orbits.

The 6dFGS Fundamental Plane

NASA Astrophysics Data System (ADS)

Springob, Chris M.; Colless, M.; Jones, D. H.; Magoulas, C.; Mould, J. R.; Campbell, L.; Lah, P.; Lucey, J.; Merson, A.; Proctor, R.

2010-01-01

The 6dF Galaxy Survey (6dFGS) is an all southern sky galaxy survey, including 125,000 redshifts and more than 10,000 peculiar velocities, making it the largest peculiar velocity sample to date. In combination with 2MASS surface brightnesses and effective radii, 6dFGS yields the near-infrared Fundamental Plane (FP) for a large and uniform sample. We have fit the FP relation for the galaxies in the peculiar velocity sample using a maximum likelihood method which allows us to precisely account for selection effects and observational errors. We investigate the effects of varying stellar populations and environments on the FP. Finally, we discuss the implications of these results both for our understanding of the origin of the FP for early-type galaxies and bulges and for deriving unbiased distances and peculiar velocities in the local universe.

Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it compromise tamoxifen metabolism?

PubMed

Borba, Maria Acsm; Melo-Neto, Renato P; Leitão, Glauber M; Castelletti, Carlos Hm; Lima-Filho, José L; Martins, Danyelly Bg

2016-04-01

CYP2D6 is a high polymorphic enzyme from P450, responsible for metabolizing almost 25% of drugs. The distribution of different mutations among CYP2D6 alleles has been associated with poor, intermediate, extensive and ultra-metabolizers. To evaluate how missenses mutations in CYP2D6*7 and CYP2D6*14A poor metabolizer alleles affect CYP2D6 stability and function. CYPalleles database was used to collect polymorphisms data present in 105 alleles. We selected only poor metabolizers alleles that presented exclusively missenses mutations. They were analyzed through seven algorithms to predict the impact on CYP2D6 structure and function. H324P, the unique mutation in CYP2D6*7, has high impact in enzyme function due to its occurrence between two alpha-helixes involved in active site dynamics. G169R, a mutation that occurs only in CYP2D6*14A, leads to the gain of solvent accessibility and severe protein destabilization. Our in silico analysis showed that missenses mutations in CYP2D6*7 and CYP2D6*14A cause CYP2D6 dysfunction.

Alternative Z ' bosons in E 6

NASA Astrophysics Data System (ADS)

Rojas, Eduardo; Erler, Jens

2015-10-01

We classify the quantum numbers of the extra U(1)' symmetries contained in E 6. In particular, we categorize the cases with rational charges and present the full list of models which arise from the chains of the maximal subgroups of E 6. As an application, the classification allows us to determine all embeddings of the Standard Model fermions in all possible decompositions of the fundamental representation of E 6 under its maximal subgroups. From this we find alternative chains of subgroups for Grand Unified Theories. We show how many of the known models including some new ones appear in alternative breaking patterns. We also use low energy constraints coming from parity-violating asymmetry measurements and atomic parity non-conservation to set limits on the E 6 motivated parameter space for a Z ' boson mass of 1.2 TeV. We include projected limits for the present and upcoming QWEAK, MOLLER and SOLID experiments.

Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity

PubMed Central

Wang, Danxin; Poi, Ming J.; Sun, Xiaochun; Gaedigk, Andrea; Leeder, J. Steven; Sadee, Wolfgang

2014-01-01

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically used drugs. Genetic polymorphisms cause substantial variation in CYP2D6 activity and serve as biomarkers guiding drug therapy. However, genotype–phenotype relationships remain ambiguous except for poor metabolizers carrying null alleles, suggesting the presence of yet unknown genetic variants. Searching for regulatory CYP2D6 polymorphisms, we find that a SNP defining the CYP2D6*2 allele, rs16947 [R296C, 17–60% minor allele frequency (MAF)], previously thought to convey normal activity, alters exon 6 splicing, thereby reducing CYP2D6 expression at least 2-fold. In addition, two completely linked SNPs (rs5758550/rs133333, MAF 13–42%) increase CYP2D6 transcription more than 2-fold, located in a distant downstream enhancer region (>100 kb) that interacts with the CYP2D6 promoter. In high linkage disequilibrium (LD) with each other, rs16947 and the enhancer SNPs form haplotypes that affect CYP2D6 enzyme activity in vivo. In a pediatric cohort of 164 individuals, rs16947 alone (minor haplotype frequency 28%) was associated with reduced CYP2D6 metabolic activity (measured as dextromethorphan/metabolite ratios), whereas rs5758550/rs133333 alone (frequency 3%) resulted in increased CYP2D6 activity, while haplotypes containing both rs16947 and rs5758550/rs133333 were similar to the wild-type. Other alleles used in biomarker panels carrying these variants such as CYP2D6*41 require re-evaluation of independent effects on CYP2D6 activity. The occurrence of two regulatory variants of high frequency and in high LD, residing on a long haplotype, highlights the importance of gene architecture, likely shaped by evolutionary selection pressures, in determining activity of encoded proteins. PMID:23985325

Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6*1 and CYP2D6*10 using cell-based models in vitro

PubMed Central

Qu, Qiang; Qu, Jian; Han, Lu; Zhan, Min; Wu, Lan-xiang; Zhang, Yi-wen; Zhang, Wei; Zhou, Hong-hao

2014-01-01

Aim: Herbal products have been widely used, and the safety of herb-drug interactions has aroused intensive concerns. This study aimed to investigate the effects of phytochemicals on the catalytic activities of human CYP2D6*1 and CYP2D6*10 in vitro. Methods: HepG2 cells were stably transfected with CYP2D6*1 and CYP2D6*10 expression vectors. The metabolic kinetics of the enzymes was studied using HPLC and fluorimetry. Results: HepG2-CYP2D6*1 and HepG2-CYP2D6*10 cell lines were successfully constructed. Among the 63 phytochemicals screened, 6 compounds, including coptisine sulfate, bilobalide, schizandrin B, luteolin, schizandrin A and puerarin, at 100 μmol/L inhibited CYP2D6*1- and CYP2D6*10-mediated O-demethylation of a coumarin compound AMMC by more than 50%. Furthermore, the inhibition by these compounds was dose-dependent. Eadie-Hofstee plots demonstrated that these compounds competitively inhibited CYP2D6*1 and CYP2D6*10. However, their Ki values for CYP2D6*1 and CYP2D6*10 were very close, suggesting that genotype-dependent herb-drug inhibition was similar between the two variants. Conclusion: Six phytochemicals inhibit CYP2D6*1 and CYP2D6*10-mediated catalytic activities in a dose-dependent manner in vitro. Thus herbal products containing these phytochemicals may inhibit the in vivo metabolism of co-administered drugs whose primary route of elimination is CYP2D6. PMID:24786236

A convenient synthesis of 6-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one and related 4,6-disubstituted pyrazolopyrimidine nucleosides.

PubMed Central

Cottam, H B; Revankar, G R; Robins, R K

1983-01-01

The glycosylation of 4,6-dichloropyrazolo[3,4-d]pyrimidine and 4-chloro-6-methylthiopyrazolo[3,4-d]pyrimidine via the corresponding trimethylsilyl intermediate and tetra-O-acetyl-beta-D-ribofuranose in the presence of trimethylsilyl triflate as a catalyst, gave selective glycosylation at N1 as the only nucleoside product. The intermediates 4,6-dichloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 7 and 4-chloro-6-methylthio-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 13 gave new and convenient synthetic routes to the inosine analog 1, the guanosine analog 2, the adenosine analog 3, and the isoguanosine analog 16. Glycosylation of the trimethylsilyl derivative of 6-chloropyrazolo[3,4-d]pyrimidine-4-one unexpectedly gave the N2-glycosyl isomer 20 as the major product. A number of new 4,6-disubstituted pyrazolo[3,4-d]pyrimidine nucleosides were prepared from these glycosyl intermediates. PMID:6835838

Search for rare and forbidden decays D+ --> h+/- e+/- e+.

PubMed

He, Q; Muramatsu, H; Park, C S; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Crede, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weaver, K M; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Williams, J; Wiss, J; Asner, D M; Edwards, K W; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Severini, H; Dytman, S A; Love, W; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Cravey, M; Cummings, J P; Danko, I; Napolitano, J

2005-11-25

Using 0.8 x 10(6) D+ D- pairs collected with the CLEO-c detector at the psi(3770) resonance, we have searched for flavor-changing neutral current and lepton-number-violating decays of D+ mesons to final states with dielectrons. We find no indication of either, obtaining 90% confidence level upper limits of B(D+ --> pi+ e+ e-) < 7.4 x 10(-6), B(D+ --> pi- e+ d+) < 3.6 x 10(-6), B(D+ --> K+ e+ e-) < 6.2 x 10(-6), and B(D+ --> K- e+ e+) < 4.5 x 10(-6).

Aha! The Power of Using 6 E's.

ERIC Educational Resources Information Center

Tall, Lyssa; Luttrell-Montes, Sally

1999-01-01

Describes the 6 E's approach which enhances student learning and encourages stronger conceptual connections. Provides step-by-step details of how the 6E Teaching/Learning Model was incorporated during the Make It R.E.A.L. Institute. (CCM)

Orbital Transfer Rocket Engine Technology. Advanced Engine Study, Task D.6 Final Report

DTIC Science & Technology

1992-06-01

PROPERTIES _- -,mr m" , MANUAL a PAQ *E,- 7.3.2.1.2. IA .A.2 ,C -- 70-t’ i Rl I _ N -’.±v-j-. .......-441I 0.2% YS Design Allowable • -’Moo 0 2W0" 6W...Storage External Radiation Environment ( Buried Engine) The engine thrust chamber would be cold to the touch even at full thrust operation from the

Cytochrome P450 2D6 polymorphism and character traits.

PubMed

Suzuki, Eiji; Kitao, Yoshie; Ono, Yutaka; Iijima, Yoshimi; Inada, Toshiya

2003-06-01

It has been suggested that cytochrome P450 2D6 (CYP2D6) is involved in dopamine metabolism within the brain. The dopamine system is suggested to play a role in determining normal character. The purpose of this study was to examine whether character traits are dependent on cytochrome P450 2D6 activity. We investigated the association between temperament and CYP2D6 gene polymorphism. The subjects were all Japanese and the polymorphism genotyped in the present study was CYP2D6*10. Character traits were assessed using the Temperament and Character Inventory. There was no overall or specific association between personality traits and the CYP2D6*10 allele and genotype frequencies. The present results do not support the hypothesis that CYP2D6 activity affects temperament and character.

Analysis of the spectrum of the (5d6+5d56s) -(5d56p+5d46s6p) transitions of two times ionized osmium (Os III)

NASA Astrophysics Data System (ADS)

Azarov, Vladimir I.; Tchang-Brillet, W.-Ü. Lydia; Gayasov, Robert R.

2018-05-01

The spectrum of osmium was observed in the (225-2100) Å wavelength region. The (5d6 + 5d56s) - (5d56p + 5d46s6p) transition array of two times ionized osmium, Os III, has been investigated and 1039 spectral lines have been classified in the region. The analysis has led to the determination of the 5d6, 5d56s, 5d56p and 5d46s6p configurations. Fifty-eight levels of the 5d6 and 5d56s configurations in the even system and 142 levels of the 5d56p and 5d46s6p configurations in the odd system have been established. The orthogonal operators technique was used to calculate the level structure and transition probabilities. The energy parameters have been determined by the least squares fit to the observed levels. Calculated transition probability and energy values, as well as LS-compositions obtained from the fitted parameters are presented.

Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53

PubMed Central

Zanier, Katia; Sidi, Abdellahi ould M’hamed ould; Boulade-Ladame, Charlotte; Rybin, Vladimir; Chappelle, Anne; Atkinson, Andrew; Kieffer, Bruno; Travé, Gilles

2012-01-01

The viral oncoprotein E6 is an essential factor for cervical cancers induced by “high-risk” mucosal HPV. Among other oncogenic activities, E6 recruits the ubiquitin ligase E6AP to promote the ubiquitination and subsequent proteasomal degradation of p53. E6 is prone to self-association, which long precluded its structural analysis. Here we found that E6 specifically dimerizes through its N-terminal domain and that disruption of the dimer interface strongly increases E6 solubility. This allowed us to raise the first structural data covering the entire HPV16 E6 protein, including the high-resolution NMR structures of the two zinc-binding domains of E6 and a robust data-driven model structure of the N-terminal domain homodimer. Interestingly, homodimer interface mutations that disrupt E6 self-association also inactivate E6-mediated p53 degradation. These data suggest that E6 needs to self-associate via its N-terminal domain to promote the poly-ubiquitination of p53 by E6AP. PMID:22483108

21 CFR 74.2306 - D&C Red No. 6.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2306 D&C Red No. 6. (a) Identity and specifications.The color additive D&C Red No. 6 shall conform in identity and specifications to the requirements of § 74.1306 (a)(1) and (b). (b) Uses and restrictions. The color additive D&C Red No. 6 may be safely used for...

21 CFR 74.2306 - D&C Red No. 6.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2306 D&C Red No. 6. (a) Identity and specifications.The color additive D&C Red No. 6 shall conform in identity and specifications to the requirements of § 74.1306 (a)(1) and (b). (b) Uses and restrictions. The color additive D&C Red No. 6 may be safely used for...

21 CFR 74.2306 - D&C Red No. 6.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2306 D&C Red No. 6. (a) Identity and specifications.The color additive D&C Red No. 6 shall conform in identity and specifications to the requirements of § 74.1306 (a)(1) and (b). (b) Uses and restrictions. The color additive D&C Red No. 6 may be safely used for...

21 CFR 74.2306 - D&C Red No. 6.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2306 D&C Red No. 6. (a) Identity and specifications.The color additive D&C Red No. 6 shall conform in identity and specifications to the requirements of § 74.1306 (a)(1) and (b). (b) Uses and restrictions. The color additive D&C Red No. 6 may be safely used for...

Test Plans. Lightweight Durable TPS: Tasks 1,2,4,5, and 6

NASA Technical Reports Server (NTRS)

Greenberg, H. S.; Tu, Tina

1994-01-01

The objective of this task is to develop the fluted core flexible blankets, also referred to as the Tailorable Advanced Blanket Insulation (TABI), to a technology readiness level (TRL) of 6. This task is one of the six tasks under TA 3, Lightweight Durable TPS study, of the Single Stage to Orbit (SSTO) program. The purpose of this task is to develop a durable and low maintenance flexible TPS blanket material to be implemented on the SSTO vehicle.

The structure of the TsaB/TsaD/TsaE complex reveals an unexpected mechanism for the bacterial t6A tRNA-modification.

PubMed

Missoury, Sophia; Plancqueel, Stéphane; Li de la Sierra-Gallay, Ines; Zhang, Wenhua; Liger, Dominique; Durand, Dominique; Dammak, Raoudha; Collinet, Bruno; van Tilbeurgh, Herman

2018-05-08

The universal N6-threonylcarbamoyladenosine (t6A) modification at position A37 of ANN-decoding tRNAs is essential for translational fidelity. In bacteria the TsaC enzyme first synthesizes an l-threonylcarbamoyladenylate (TC-AMP) intermediate. In cooperation with TsaB and TsaE, TsaD then transfers the l-threonylcarbamoyl-moiety from TC-AMP onto tRNA. We determined the crystal structure of the TsaB-TsaE-TsaD (TsaBDE) complex of Thermotoga maritima in presence of a non-hydrolysable AMPCPP. TsaE is positioned at the entrance of the active site pocket of TsaD, contacting both the TsaB and TsaD subunits and prohibiting simultaneous tRNA binding. AMPCPP occupies the ATP binding site of TsaE and is sandwiched between TsaE and TsaD. Unexpectedly, the binding of TsaE partially denatures the active site of TsaD causing loss of its essential metal binding sites. TsaE interferes in a pre- or post-catalytic step and its binding to TsaBD is regulated by ATP hydrolysis. This novel binding mode and activation mechanism of TsaE offers good opportunities for antimicrobial drug development.

The 6dFGS Peculiar Velocity Field

NASA Astrophysics Data System (ADS)

Springob, Chris M.; Magoulas, C.; Colless, M.; Mould, J.; Erdogdu, P.; Jones, D. H.; Lucey, J.; Campbell, L.; Merson, A.; Jarrett, T.

2012-01-01

The 6dF Galaxy Survey (6dFGS) is an all southern sky galaxy survey, including 125,000 redshifts and a Fundamental Plane (FP) subsample of 10,000 peculiar velocities, making it the largest peculiar velocity sample to date. We have fit the FP using a maximum likelihood fit to a tri-variate Gaussian. We subsequently compute a Bayesian probability distribution for every possible peculiar velocity for each of the 10,000 galaxies, derived from the tri-variate Gaussian probability density distribution, accounting for our selection effects and measurement errors. We construct a predicted peculiar velocity field from the 2MASS redshift survey, and compare our observed 6dFGS velocity field to the predicted field. We discuss the resulting agreement between the observed and predicted fields, and the implications for measurements of the bias parameter and bulk flow.

Dark matter in E 6 Grand unification

NASA Astrophysics Data System (ADS)

Schwichtenberg, Jakob

2018-02-01

We discuss fermionic dark matter in non-supersymmetric E 6 Grand Unification. The fundamental representation of E 6 contains, in addition to the standard model fermions, exotic fermions and we argue that one of them is a viable, interesting dark matter candidate. Its stability is guaranteed by a discrete remnant symmetry, which is an unbroken subgroup of the E 6 gauge symmetry. We compute the symmetry breaking scales and the effect of possible threshold corrections by solving the renormalization group equations numerically after imposing gauge coupling unification. Since the Yukawa couplings of the exotic and the standard model fermions have a common origin, the mass of the dark matter particles is constrained. We find a mass range of 3 · 109 GeV ≲ m DM ≲ 1 · 1013 GeV for our E 6 dark matter candidate, which is within the reach of next-generation direct detection experiments.

Placental expression of D6 decoy receptor in preeclampsia

PubMed Central

Cho, Geum Joon; Lee, Eun Sung; Jin, Hye Mi; Lee, Ji Hye; Kim, Yeun Sun; Seol, Hyun-Joo; Hong, Soon-Cheol; Kim, Hai-Joong

2015-01-01

Objective The purpose of this study was to investigate the expression of the D6 decoy receptor that can bind chemokines and target them for degradation, resulting in inhibition of inflammation in placentas from preeclamptic and normal pregnancies. Methods The current study was carried out in 35 pregnant women (23 patients with preeclampsia and 12 healthy, normotensive pregnant women) during the third trimester of pregnancy. The expressions of D6 decoy receptor in the placenta were determined with real time reverse transcriptase polymerase chain reaction and western blotting. Results The mRNA and protein of D6 decoy receptor were detected in all of placentas from preeclamptic and normal pregnancies. Placental D6 decoy receptor mRNA expression was significantly lower in patients with preeclampsia than in patients with normal pregnancies. Western blot analyses revealed decreased protein expression in cases of preeclampsia. Conclusion The expression of the D6 decoy receptor in preeclamptic placentas was significantly lower than in normal placentas. Further studies are needed to clarify the underlying mechanisms that link decreased expression of placental D6 decoy receptor and preeclampsia. PMID:26430656

Synthesis of N-peptide-6-amino-D-luciferin Conjugates.

PubMed

Kovács, Anita K; Hegyes, Péter; Szebeni, Gábor J; Nagy, Lajos I; Puskás, László G; Tóth, Gábor K

2018-01-01

A general strategy for the synthesis of N -peptide-6-amino-D-luciferin conjugates has been developed. The applicability of the strategy was demonstrated with the preparation of a known substrate, N -Z-Asp-Glu-Val-Asp-6-amino-D-luciferin ( N -Z-DEVD-aLuc). N -Z-DEVD-aLuc was obtained via a hybrid liquid/solid phase synthesis method, in which the appropriately protected C-terminal amino acid was coupled to 6-amino-2-cyanobenzothiazole and the resulting conjugate was reacted with D-cysteine in order to get the protected amino acid-6-amino-D-luciferin conjugate, which was then attached to resin. The resulting loaded resin was used for the solid-phase synthesis of the desired N -peptide-6-amino-D-luciferin conjugate without difficulties, which was then attested with NMR spectroscopy and LC-MS, and successfully tested in a bioluminescent system.

Synthesis of N-peptide-6-amino-D-luciferin Conjugates

PubMed Central

Kovács, Anita K.; Hegyes, Péter; Szebeni, Gábor J.; Nagy, Lajos I.; Puskás, László G.; Tóth, Gábor K.

2018-01-01

A general strategy for the synthesis of N-peptide-6-amino-D-luciferin conjugates has been developed. The applicability of the strategy was demonstrated with the preparation of a known substrate, N-Z-Asp-Glu-Val-Asp-6-amino-D-luciferin (N-Z-DEVD-aLuc). N-Z-DEVD-aLuc was obtained via a hybrid liquid/solid phase synthesis method, in which the appropriately protected C-terminal amino acid was coupled to 6-amino-2-cyanobenzothiazole and the resulting conjugate was reacted with D-cysteine in order to get the protected amino acid-6-amino-D-luciferin conjugate, which was then attached to resin. The resulting loaded resin was used for the solid-phase synthesis of the desired N-peptide-6-amino-D-luciferin conjugate without difficulties, which was then attested with NMR spectroscopy and LC-MS, and successfully tested in a bioluminescent system. PMID:29725588

The 6dF Galaxy Survey: First Data Release

NASA Astrophysics Data System (ADS)

Jones, H.; Saunders, W.; Colless, M.; Read, M.; Parker, Q.; Watson, F.; Campbell, L.

2005-06-01

The 6dF Galaxy Survey (6dFGS) is currently measuring the redshifts of around 170 000 galaxies and the peculiar velocities of a 15 000-member sub-sample. It will be the largest redshift survey of the local universe and more than an order of magnitude larger than any peculiar velocity survey to date. When complete, it will cover essentially the entire southern sky around a mean redshift of z = 0.05. Central to the survey is the Six-Degree Field (6dF) multi-fibre spectrograph, an instrument able to record 150 simultaneous spectra over the 5.7°-field of the UK Schmidt Telescope. Targets have been drawn from the 2MASS Extended Source Catalog (XSC) to include all galaxies brighter than Ktot = 12.75, supplemented by 2MASS and SuperCOSMOS galaxies that complete the sample to limits of (H, J, rF, bJ) = (13.05, 13.75, 15.6, 16.75). Here we describe the implementation of the survey and the procedures used to select sources and determine redshifts. We also describe early results utilising the First Data Release of ˜ 45 000 redshifts. There is an online database of 6dFGS data accessible from the 6dFGS web site (http://www.mso.anu.edu.au/6dFGS).

A Highly Capable Year 6 Student's Response to a Challenging Mathematical Task

ERIC Educational Resources Information Center

Livy, Sharyn; Holmes, Marilyn; Ingram, Naomi; Linsell, Chris; Sullivan, Peter

2016-01-01

Highly capable mathematics students are not usually considered strugglers. This paper reports on a case study of a Year 6 student, Debbie, her response to a lesson, and her learning involving a challenging mathematical task. Debbie, usually a highly capable student, struggled to complete a challenging mathematical task by herself, but as the…

NASA CF6 jet engine diagnostics program: Long-term CF6-6D low-pressure turbine deterioration

NASA Technical Reports Server (NTRS)

Smith, J. J.

1979-01-01

Back-to-back performance tests were run on seven airline low pressure turbine (LPT) modules and four new CF6-6D modules. Back-to-back test cell runs, in which an airline LPT module was directly compared to a new production module, were included. The resulting change, measured in fuel burn, equaled the level of LPT module deterioration. Three of the LPT modules were analytically inspected followed by a back-to-back test cell run to evaluate current refurbishment techniques.

High-pressure dielectric studies on 1,6-anhydro-β -D-mannopyranose (plastic crystal) and 2,3,4-tri-O-acetyl-1,6-anhydro-β -D-glucopyranose (canonical glass)

NASA Astrophysics Data System (ADS)

Heczko, Dawid; Kamińska, Ewa; Minecka, Aldona; Dzienia, Andrzej; Jurkiewicz, Karolina; Tarnacka, Magdalena; Talik, Agnieszka; Kamiński, Kamil; Paluch, Marian

2018-05-01

Broadband Dielectric Spectroscopy was applied to investigate molecular dynamics of two anhydrosaccharides, i.e., 1,6-anhydro-β-D-mannopyranose, anhMAN (hydrogen-bonded system) and 2,3,4-tri-O-acetyl-1,6-anhydro-β-D-glucopyranose, ac-anhGLU (van der Waals material), at different thermodynamic conditions. Moreover, the reported data were compared with those recently published for two other H-bonded systems, i.e., 1,6-anhydro-β-D-glucopyranose (anhGLU) and D-glucose (D-GLU). A direct comparison of the dynamical behavior of the materials with a similar chemical structure but significantly differing by the degrees of freedom, complexity, and intermolecular interactions made it possible to probe the impact of compression on the fragility, Temperature-Pressure Superpositioning and pressure coefficient of the glassy crystal/glass transition temperatures (d Tg c/d p ; d Tg/d p ). Moreover, the correlation between d Tg c/d p determined experimentally from the high-pressure dielectric data and the Ehrenfest equation has been tested for the plastic crystals (anhGLU and anhMAN) for the first time. Interestingly, a satisfactory agreement was found between both approaches. It is a quite intriguing finding which can be rationalized by the fact that the studied materials are characterized by the low complexity (lower degrees of freedom with respect to the molecular mobility) as well as ordered internal structure. Therefore, one can speculate that in contrast to the ordinary glasses the dynamics of the plastic crystals might be described with the use of a single order parameter. However, to confirm this thesis further, pressure-volume-temperature (PVT) experiments enabling calculations of the Prigogine Defay ratio are required.

Inert Reassessment Document for D & C Green No. 6

EPA Pesticide Factsheets

Based upon the reasonable certainty of no harm safety findings, D&C Green No. 6, D&C Red No. 17, D&C Red No. 33, D&C Violet No. 2, and FD&C Yellow No. 6 Aluminum Lake can each be classified as L ist 4B inert ingredients.

Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes

PubMed Central

Kubota, T; Yamaura, Y; Ohkawa, N; Hara, H; Chiba, K

2000-01-01

Aims To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2,*3,*4,*5,*8,*10,*11,*12,*14,*17 and *18), and their relation to the metabolic capacity of CYP2D6 in Japanese subjects. Methods One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 subjects were phenotyped with dextromethorphan. Results The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly greater than that of heterozygotes for functional and defective alleles. Conclusions CYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6. PMID:10886115

40 CFR 721.10270 - [5,6]Fullerene-C84-D2d.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10270 [5,6]Fullerene-C84-D2d. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C84-D2d (PMN P-09-57; CAS No. 145809-20-7...

40 CFR 721.10270 - [5,6]Fullerene-C84-D2d.

Code of Federal Regulations, 2014 CFR

2014-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10270 [5,6]Fullerene-C84-D2d. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C84-D2d (PMN P-09-57; CAS No. 145809-20-7...

16 CFR 240.6 - Interstate commerce.

Code of Federal Regulations, 2013 CFR

2013-01-01

...(d) and 2(e) of the Act. (The commerce standard for sections 2 (d) and (e) is at least as inclusive... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Interstate commerce. 240.6 Section 240.6... ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.6 Interstate commerce. The term interstate...

16 CFR 240.6 - Interstate commerce.

Code of Federal Regulations, 2012 CFR

2012-01-01

...(d) and 2(e) of the Act. (The commerce standard for sections 2 (d) and (e) is at least as inclusive... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Interstate commerce. 240.6 Section 240.6... ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.6 Interstate commerce. The term interstate...

16 CFR 240.6 - Interstate commerce.

Code of Federal Regulations, 2011 CFR

2011-01-01

...(d) and 2(e) of the Act. (The commerce standard for sections 2 (d) and (e) is at least as inclusive... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Interstate commerce. 240.6 Section 240.6... ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.6 Interstate commerce. The term interstate...

16 CFR 240.6 - Interstate commerce.

Code of Federal Regulations, 2010 CFR

2010-01-01

...(d) and 2(e) of the Act. (The commerce standard for sections 2 (d) and (e) is at least as inclusive... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Interstate commerce. 240.6 Section 240.6... ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.6 Interstate commerce. The term interstate...

16 CFR 240.6 - Interstate commerce.

Code of Federal Regulations, 2014 CFR

2014-01-01

...(d) and 2(e) of the Act. (The commerce standard for sections 2 (d) and (e) is at least as inclusive... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Interstate commerce. 240.6 Section 240.6... ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.6 Interstate commerce. The term interstate...

Sharing Data between Mobile Devices, Connected Vehicles and Infrastructure Task 6: Prototype Acceptance Test Summary Report

DOT National Transportation Integrated Search

2017-10-30

The Task 6 Prototype Acceptance Test Summary Report summarizes the results of Acceptance Testing carried out at Battelle facilities in accordance with the Task 6 Acceptance Test Plan. The Acceptance Tests were designed to verify that the prototype sy...

The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo

PubMed Central

Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.

2003-01-01

Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014

CYP2D6 variability in populations from Venezuela.

PubMed

Moreno, Nancy; Flores-Angulo, Carlos; Villegas, Cecilia; Mora, Yuselin

2016-12-01

CYP2D6 is an important cytochrome P450 enzyme that plays an important role in the metabolism of about 25% of currently prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatments. The most prevalent diseases in the admixed population from Venezuela are cardiovascular and cancer, whereas viral, bacterial and parasitic diseases, particularly malaria, are prevalent in Amerindian populations; in the treatment of these diseases, several drugs that are metabolized by CYP2D6 are used. In this work, we reviewed the data on CYP2D6 variability and predicted metabolizer phenotypes, in healthy volunteers of two admixed and five Amerindian populations from Venezuela. The Venezuelan population is very heterogeneous as a result of the genetic admixture of three major ethnical components: Europeans, Africans and Amerindians. There are noticeable inter-regional and inter-population differences in the process of mixing of this population. Hitherto, there are few published studies in Venezuela on CYP2D6; therefore, it is necessary to increase research in this regard, in particular to develop studies with a larger sample size. There is a considerable amount of work remaining before CYP2D6 is integrated into clinical practice in Venezuela.

Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces anti-fibrotic effect via inhibition of Wnt and TGF-β signaling.

PubMed

Lee, Won Jai; Lee, Jung-Sun; Ahn, Hyo Min; Na, Youjin; Yang, Chae Eun; Lee, Ju Hee; Hong, JinWoo; Yun, Chae-Ok

2017-11-08

Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants. Higher Wnt3a and β-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of β-catenin and mRNA expression of type-I and -III collagen were significantly decreased following treatment with dE1-k35/sLRP6E1E2 in HDFs and KFs. The expression of LRP6, β-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-β1 were decreased in Wnt3a- or TGF-β1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both β-catenin and Smad 2/3 complex. The expression levels of type-I and -III collagen, fibronectin, and elastin were also significantly reduced in keloid tissue explants after treatment with dE1-k35/sLRP6E1E2. These results indicate that Wnt decoy receptor-expressing Ad can degrade extracellular matrix in HDFs, KFs, and primary keloid tissue explants, and thus it may be beneficial for treatment of keloids.

The Efficiency of Delone Coverings of the Canonical Tilings T^*(A4) and D_6)) -> T^*(D6)

NASA Astrophysics Data System (ADS)

Papadopolos, Zorka; Kasner, Gerald

This chapter is devoted to the coverings of the two quasiperiodic canonical tilings T^*(A4) and D_6)) equiv {cal T}(*(2F)) -> T^*(D6) T^*(2F), obtained by projection from the root lattices A4 and D6, respectively. In the first major part of this chapter, in Sect. 5.2, we shall introduce a Delone covering C^sT^*(A4) of the 2-dimensional decagonal tiling T^*(A4). In the second major part of this chapter, Sect. 5.3, we summarize the results related to the Delone covering of the icosahedral tiling D_6)) -> T^*(D6), D_6)}) -> CT^*(D6) and determine the zero-, single-, and double- deckings and the resulting thickness of the covering. In the conclusions section, we give some suggestions as to how the definition of the Delone covering might be changed in order to reach some real (full) covering of the icosahedral tiling D_6)) -> T^*(D6). In Section 5.2 the definition of the Delone covering is also changed in order to avoid an unnecessary large thickness of the covering.

Lessons from Cuba for Global Precision Medicine: CYP2D6 Genotype Is Not a Robust Predictor of CYP2D6 Ultrarapid Metabolism.

PubMed

Dorado, Pedro; González, Idilio; Naranjo, María Eugenia G; de Andrés, Fernando; Peñas-Lledó, Eva María; Calzadilla, Luis Ramón; LLerena, Adrián

2017-01-01

A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping. Thus, the present study evaluated, using dextromethorphan as a phenotyping probe, the relationship between CYP2D6 phenotype and CYP2D6 genotype, especially for the ultrarapid metabolizer (UM) phenotype. We report in this study, to the best of our knowledge, the first comparative clinical pharmacogenomics study in a Cuban population sample (N = 174 healthy volunteers) and show that the CYP2D6 genotype is not a robust predictor of the CYP2D6 ultrarapid metabolizer (mUM) status in Cubans. Importantly, the ultrarapid CYP2D6 phenotype can result in a host of health outcomes, such as drug resistance associated with subtherapeutic drug concentrations, overexposure to active drug metabolites, and altered sensitivity to certain human diseases by virtue of altered metabolism of endogenous substrates of CYP2D6. Hence, phenotyping tests for CYP2D6 UMs appear to be a particular necessity for precision medicine in the Cuban population. Finally, in consideration of ethical and inclusive representation in global science, we recommend further precision medicine biomarker research and funding in support of neglected or understudied populations worldwide.

Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

PubMed Central

Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

2010-01-01

Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

Enhanced degradation of p53 protein in HPV-6 and BPV-1 E6-immortalized human mammary epithelial cells.

PubMed Central

Band, V; Dalal, S; Delmolino, L; Androphy, E J

1993-01-01

Normal mammary epithelial cells are efficiently immortalized by the E6 gene of human papillomavirus (HPV)-16, a virus commonly associated with cervical cancers. Surprisingly, introduction of the E6 gene from HPV-6, which is rarely found in cervical cancer, or bovine papillomavirus (BPV)-1, into normal mammary cells resulted in the generation of immortal cell lines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. While the half-life of p53 protein in normal mammary epithelial cells was approximately 3 h, it was reduced to approximately 15 min in all the E6-immortalized cells. These results demonstrate that the E6 genes of both high-risk and low-risk papilloma viruses immortalize human mammary epithelial cells and induce a marked degradation of p53 protein in vivo. Images PMID:8387914

3D organic Na4C6O6/graphene architecture for fast sodium storage with ultralong cycle life.

PubMed

Gu, Jianan; Gu, Yue; Yang, Shubin

2017-11-23

Sodium-ion batteries (SIBs) have aroused increasing interest as one of the most promising replacements for lithium-ion batteries (LIBs). Here, a novel organic-inorganic 3D Na 4 C 6 O 6 -graphene architecture was successfully fabricated from commercial Na 2 C 6 O 6 and for the first time applied for sodium storage. Hence, the 3D Na 4 C 6 O 6 -graphene architecture exhibits a high reversible capacity, good cyclic performance and high-rate capability for sodium storage.

SU-E-J-34: Setup Accuracy in Spine SBRT Using CBCT 6D Image Guidance in Comparison with 6D ExacTrac

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

Han, Z; Yip, S; Lewis, J

2015-06-15

Purpose Volumetric information of the spine captured on CBCT can potentially improve the accuracy in spine SBRT setup that has been commonly performed through 2D radiographs. This work evaluates the setup accuracy in spine SBRT using 6D CBCT image guidance that recently became available on Varian systems. Methods ExacTrac radiographs have been commonly used for Spine SBRT setup. The setup process involves first positioning patients with lasers followed by localization imaging, registration, and repositioning. Verification images are then taken providing the residual errors (ExacTracRE) before beam on. CBCT verification is also acquired in our institute. The availability of both ExacTracmore » and CBCT verifications allows a comparison study. 41 verification CBCT of 16 patients were retrospectively registered with the planning CT enabling 6D corrections, giving CBCT residual errors (CBCTRE) which were compared with ExacTracRE. Results The RMS discrepancies between CBCTRE and ExacTracRE are 1.70mm, 1.66mm, 1.56mm in vertical, longitudinal and lateral directions and 0.27°, 0.49°, 0.35° in yaw, roll and pitch respectively. The corresponding mean discrepancies (and standard deviation) are 0.62mm (1.60mm), 0.00mm (1.68mm), −0.80mm (1.36mm) and 0.05° (0.58°), 0.11° (0.48°), −0.16° (0.32°). Of the 41 CBCT, 17 had high-Z surgical implants. No significant difference in ExacTrac-to-CBCT discrepancy was observed between patients with and without the implants. Conclusion Multiple factors can contribute to the discrepancies between CBCT and ExacTrac: 1) the imaging iso-centers of the two systems, while calibrated to coincide, can be different; 2) the ROI used for registration can be different especially if ribs were included in ExacTrac images; 3) small patient motion can occur between the two verification image acquisitions; 4) the algorithms can be different between CBCT (volumetric) and ExacTrac (radiographic) registrations.« less

Modular properties of 6d (DELL) systems

NASA Astrophysics Data System (ADS)

Aminov, G.; Mironov, A.; Morozov, A.

2017-11-01

If super-Yang-Mills theory possesses the exact conformal invariance, there is an additional modular invariance under the change of the complex bare charge [InlineMediaObject not available: see fulltext.]. The low-energy Seiberg-Witten prepotential ℱ( a), however, is not explicitly invariant, because the flat moduli also change a - → a D = ∂ℱ/∂ a. In result, the prepotential is not a modular form and depends also on the anomalous Eisenstein series E 2. This dependence is usually described by the universal MNW modular anomaly equation. We demonstrate that, in the 6 d SU( N) theory with two independent modular parameters τ and \\widehat{τ} , the modular anomaly equation changes, because the modular transform of τ is accompanied by an ( N -dependent!) shift of \\widehat{τ} and vice versa. This is a new peculiarity of double-elliptic systems, which deserves further investigation.

DoD Needs to Reinitiate Migration to Internet Protocol Version 6 (REDACTED)

DTIC Science & Technology

2014-12-01

whether DoD was effectively migrating to Internet Protocol Version 6 ( IPv6 ). Finding Although DoD satisfied the requirement to demonstrate IPv6 on the...enterprise network to IPv6 . This occurred because: • DoD Chief Information Officer (CIO) and U.S. Cyber Command (USCYBERCOM) did not make IPv6 a...resources to further DoD-wide transition toward IPv6 ; and • DoD CIO did not have a current plan of action and milestones to advance DoD IPv6 migration

21 CFR 74.1206 - D&C Green No. 6.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Green No. 6. 74.1206 Section 74.1206 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1206 D&C Green No. 6. (a) Identity. The color additive D&C...

Oak Ridge Health Studies Phase 1 report, Volume 2: Part D, Dose Reconstruction Feasibility Study. Tasks 6, Hazard summaries for important materials at the Oak Ridge Reservation

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

Bruce, G.M.; Walker, L.B.; Widner, T.E.

1993-09-01

The purpose of Task 6 of Oak Ridge Phase I Health Studies is to provide summaries of current knowledge of toxic and hazardous properties of materials that are important for the Oak Ridge Reservation. The information gathered in the course of Task 6 investigations will support the task of focussing any future health studies efforts on those operations and emissions which have likely been most significant in terms of off-site health risk. The information gathered in Task 6 efforts will likely also be of value to individuals evaluating the feasibility of additional health,study efforts (such as epidemiological investigations) in themore » Oak Ridge area and as a resource for citizens seeking information on historical emissions.« less

The polymorphisms of LCR, E6, and E7 of HPV-58 isolates in Yunnan, Southwest China.

PubMed

Xi, Juemin; Chen, Junying; Xu, Miaoling; Yang, Hongying; Wen, Songjiao; Pan, Yue; Wang, Xiaodan; Ye, Chao; Qiu, Lijuan; Sun, Qiangming

2018-04-25

Variations in HPV LCR/E6/E7 have been shown to be associated with the viral persistence and cervical cancer development. So far, there are few reports about the polymorphisms of the HPV-58 LCR/E6/E7 sequences in Southwest China. This study aims to characterize the gene polymorphisms of the HPV-58 LCR/E6/E7 sequences in women of Southwest China, and assess the effects of variations on the immune recognition of viral E6 and E7 antigens. Twelve LCR/E6/E7 of the HPV-58 isolates were amplified and sequenced. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED v3.3. The selection pressure acting on the HPV-58 E6 and E7 coding regions was estimated by Bayes empirical Bayes analysis of PAML 4.8. Meanwhile, the MHC class-I and II binding peptides were predicted by the ProPred-I server and ProPred server. The transcription factor binding sites in the HPV-58 LCR were analyzed using the JASPAR database. Twenty nine SNPs (20 in the LCR, 3 in the E6, 6 in the E7) were identified at 27 nucleotide sites across the HPV-58 LCR/E6/E7. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. The combinations of all the SNPs resulted in 11 unique sequences, which were clustered into the A lineage (7 belong to A1, 2 belong to A2, and 2 belong to A3). An insertion (TGTCAGTTTCCT) was found between the nucleotide sites 7280 and 7281 in 2 variants, and a deletion (TTTAT) was found between 7429 and 7433 in 1 variant. The most common non-synonymous substitution V77A in the E7 was observed in the sequences encoding the α-helix. 63G in the E7 was determined to be the only one positively selected site in the HPV-58 E6/E7 sequences. Six non-synonymous amino acid substitutions (including S71F and K93 N in the E6, and T20I, G41R, G63S/D, and V77A in the E7) were affecting multiple putative epitopes for both CD4 + and CD8 + T-cells. In the LCR, C7265G and C

21 CFR 74.2206 - D&C Green No. 6.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2206 D&C Green No. 6. (a) Identity and specifications. The color additive D&C Green No. 6 shall conform in identity and specifications to the requirements of § 74... applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling requirements. The...

21 CFR 74.2206 - D&C Green No. 6.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2206 D&C Green No. 6. (a) Identity and specifications. The color additive D&C Green No. 6 shall conform in identity and specifications to the requirements of § 74... applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling requirements. The...

21 CFR 74.2206 - D&C Green No. 6.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2206 D&C Green No. 6. (a) Identity and specifications. The color additive D&C Green No. 6 shall conform in identity and specifications to the requirements of § 74... applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling requirements. The...

21 CFR 74.2206 - D&C Green No. 6.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2206 D&C Green No. 6. (a) Identity and specifications. The color additive D&C Green No. 6 shall conform in identity and specifications to the requirements of § 74... applied cosmetics in amounts consistent with good manufacturing practice. (c) Labeling requirements. The...

Study of the decays D0-->pi{-}e{+}nu{e}, D{0}-->K{-}e{+}nu{e}, D{+}-->pi{0}e{+}nu{e}, and D{+}-->K0e{+}nu{e}.

PubMed

Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Severini, H; Dytman, S A; Love, W; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Patel, R; Potlia, V; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R; Besson, D; Pedlar, T K

2008-06-27

By using 1.8x10{6} DDpairs, we have measured B(D{0}-->pi{-}e{+}nu{e})=0.299(11)(9)%, B(D{+}-->pi{0}e{+}nu{e})=0.373(22)(13)%, B(D{0}-->K{-}e{+}nu{e})=3.56(3)(9)%, and B(D{+}-->K{0}e{+}nu{e})=8.53(13)(23)% and have studied the q;{2} dependence of the form factors. By combining our results with recent lattice calculations, we obtain |V{cd}|=0.217(9)(4)(23) and |V{cs}|=1.015(10)(11)(106).

Li3Ge3Se6: the first ternary lithium germanium selenide with interesting ∞[Ge6Se12]n chains constructed by ethane-like [Ge2Se6]6- clusters.

PubMed

Li, Guangmao; Zhen, Ni; Chu, Yu; Zhou, Zhongxiang

2017-12-21

Li 3 Ge 3 Se 6 , the first compound of the ternary Li/Ge/Se system, has been synthesized. Note that interesting 1D ∞ [Ge 6 Se 12 ] n chains constructed by ethane-like [Ge 2 Se 6 ] 6- clusters were discovered in its structure. Investigations on the structures of all the [Ge 2 Se 6 ] 6- cluster-containing compounds have shown that only in Li 3 Ge 3 Se 6 are there 1D chains composed of [Ge 2 Se 6 ] 6- clusters, which result from the space limitation within the tunnels surrounded by LiSe 6 octahedra. Raman spectrum was obtained to demonstrate the existence of Ge-Ge bonds. UV-visible-NIR diffuse reflection spectrum showed an optical bandgap of 2.08 eV. Theoretical calculations based on first principles have also been performed for its band structure and density of states to analyze its structure-property relationship.

Manifestation of intra-atomic 5d6s-4f exchange coupling in photoexcited gadolinium

NASA Astrophysics Data System (ADS)

Zhang, G. P.; Jenkins, T.; Bennett, M.; Bai, Y. H.

2017-12-01

Intra-atomic exchange couplings (IECs) between 5d6s and 4f electrons are ubiquitous in rare-earth metals and play a critical role in spin dynamics. However, detecting them in real time domain has been difficult. Here we show the direct evidence of IEC between 5d6s and 4f electrons in gadolinium. Upon femtosecond laser excitation, 5d6s electrons are directly excited; their majority bands shift toward the Fermi level while their minority bands do the opposite. For the first time, our first-principles minority shift now agrees with the experiment quantitatively. Excited 5d6s electrons lower the exchange potential barrier for 4f electrons, so the 4f states are also shifted in energy, a prediction that can be tested experimentally. Although a significant number of 5d6s electrons, some several eV below the Fermi level, are excited out of the Fermi sea, there is no change in the 4f states, a clear manifestation of intra-atomic exchange coupling.

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)-Octa-2,4,6-trienoic Esters.

PubMed

Gandolfi, Raffaella; Contini, Alessandro; Pinto, Daniela; Marzani, Barbara; Pandini, Stefano; Nava, Donatella; Pini, Elena

2017-12-01

In the present study the esterification of the OH groups of resveratrol, caffeic acid, ferulic acid, and β-sitosterol with an antioxidant polyconjugated fatty acid, (2E,4E,6E)-octa-2,4,6-trienoic acid, was achieved. As the selective esterification of OH groups of natural compounds can affect their biological activity, a selective esterification of resveratrol and caffeic acid was performed by an enzymatic approach. The new resulting compounds were characterized spectroscopically (FT-IR, NMR mono, and bidimensional techniques); when necessary the experimental data were integrated by quantum chemical calculations. The antioxidant, anti-inflammatory and proliferative activity was evaluated. The good results encourage the use of these molecules as antioxidant and/or anti-inflammatory agents in dermocosmetic application. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

IIB supergravity and the E 6(6) covariant vector-tensor hierarchy

DOE PAGES

Ciceri, Franz; de Wit, Bernard; Varela, Oscar

2015-04-20

IIB supergravity is reformulated with a manifest local USp(8) invariance that makes the embedding of five-dimensional maximal supergravities transparent. In this formulation the ten-dimensional theory exhibits all the 27 one-form fields and 22 of the 27 two-form fields that are required by the vector-tensor hierarchy of the five-dimensional theory. The missing 5 two-form fields must transform in the same representation as a descendant of the ten-dimensional ‘dual graviton’. The invariant E 6(6) symmetric tensor that appears in the vector-tensor hierarchy is reproduced. Generalized vielbeine are derived from the supersymmetry transformations of the vector fields, as well as consistent expressions formore » the USp(8) covariant fermion fields. Implications are further discussed for the consistency of the truncation of IIB supergravity compactified on the five-sphere to maximal gauged supergravity in five space-time dimensions with an SO(6) gauge group.« less

SESAME 7363: A new Li(6)D equation of state

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

Sheppard, Daniel Glen; Kress, Joel David; Crockett, Scott

2015-09-21

A new Equation of State (EOS) for Lithium 6 Deuteride ( 6LiD) was created, sesame 7363. This EOS was released to the user community under “eos-developmental” as sesame 97363. The construction of this new EOS is a modification of a previously released EOS, sesame 7360 1. Sesame 7360 is too stiff (5-10% excess pressure) at high compressions and high temperatures (ρ = 4-110g/cm 3, T = 30-10,000 eV) compared to orbital-free density-functional theory. Sesame 7363 is softer and gives a better representation of the physics over this range without compromising the agreement with the experimental and simulation data that sesamemore » 7360 was based on.« less

SF-6D population norms for the Hong Kong Chinese general population.

PubMed

Wong, Carlos K H; Mulhern, Brendan; Cheng, Garvin H L; Lam, Cindy L K

2018-05-24

To estimate population norms for the SF-6D health preference (utility) scores derived from the MOS SF-36 version 1 (SF-36v1), SF-36 version 2 (SF-36v2), and (SF-12v2) health surveys collected from a representative adult sample in Hong Kong, and to assess differences in SF-6D scores across sociodemographic subgroups. A random telephone survey of 2410 Chinese adults was conducted. All respondents completed questionnaires on sociodemographics and presence of chronic diseases (hypertension, diabetes, chronic rheumatism, chronic lung diseases, stroke, and mental illness), and the short-form 36-item health survey (SF-36) version 1, and selected items of the SF-36v2 that were different from those of SF-36v1. Responses of short-form 12-item health survey (SF-12) were extracted from responses of the SF-36 items. SF-6D health utility scores were derived from SF-36 version 1 (SF-6D SF-36v1 ), SF-36 version 2 (SF-6D SF-36v2 ), and SF-12 version 2 (SF-6D SF-12v2 ) using Hong Kong SF-6D value set. Population norms of SF-6D SF-36v1 , SF-6D SF-36v2 , and SF-6D SF-12v2 for the Hong Kong Chinese were 0.7947 (± 0.0048), 0.7862 (± 0.0049), and 0.8147 (± 0.0050), respectively. Three SF-6D scores were highly correlated (0.861-0.954), and had a high degree of reliability and absolute agreement. Males had higher health utility scores (SF-6D SF-36v1 : 0.0025; SF-6D SF-36v2 : 0.025; SF-6D SF-12v2 : 0.018) but reported less problems in all the dimensions than women. Respondents with a higher number of chronic diseases had lower SF-6D scores. Among all respondents with one or more chronic diseases, those with hypertension scored the highest whereby those with mental illness scored the least. The SF-6D utility scores derived from different SF-36 or SF-12 health surveys were different. The population norms based on these three health surveys enable the normative comparisons of health utility scores from specific population or patient groups, and provide estimates of age-gender adjusted

Synthesis of 6-Substituted-2,4-Diamino-5,6,7,8-Tetrahydropyrimido(4-5-d)Pyrimidines.

DTIC Science & Technology

1979-10-01

triaminopyrihidifle with substituted Andines 2, 1. Anilines 2 2. 0-Arylhydroxylami nes 3 3. Benzylamines 4 4. O-Benzyl hydroxylamines 4 5. PhenylethylamineS 5 6...by hydrazinolysis of the phthaliinide intermediate. 5. Phenylethylamines The reaction of 2,4,6-triaminopyrimidine with phenylethyl- amines and...5,6,7,8-tetrahydropyrimido L!,5-d_1 pyrimidines were excellent. These products were summarized in Table 1. The phenylethylamines were usually prepared

21 CFR 74.2206 - D&C Green No. 6.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Green No. 6. 74.2206 Section 74.2206 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR....1206 (a) and (b). (b) Uses and restrictions. D&C Green No. 6 may be safely used for coloring externally...

Big 6 Tips: Teaching Information Problem Solving. #1 Task Definition: What Needs To Be Done.

ERIC Educational Resources Information Center

Eisenberg, Michael

1997-01-01

Explains task definition which is the first stage in the Big 6, an approach to information and technology skills instruction. Highlights include defining the problem; identifying the information requirements of the problem; transferability from curriculum-based problems to everyday tasks; and task definition logs kept by students. (LRW)

FUN3D Manual: 12.6

NASA Technical Reports Server (NTRS)

Biedron, Robert T.; Derlaga, Joseph M.; Gnoffo, Peter A.; Hammond, Dana P.; Jones, William T.; Kleb, William L.; Lee-Rausch, Elizabeth M.; Nielsen, Eric J.; Park, Michael A.; Rumsey, Christopher L.;

Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.

PubMed

Pence, Matthew G; Choi, Jeong-Yun; Egli, Martin; Guengerich, F Peter

2010-12-24

O(6)-methylguanine (O(6)-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase ι core enzyme was determined for nucleoside triphosphate incorporation opposite O(6)-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol ι, which showed that dTTP incorporation occurs with high efficiency opposite O(6)-methylG. Misincorporation of dTTP opposite O(6)-methylG occurred with ∼6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol ι with O(6)-methylG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated into the syn conformation in the pol ι active site and that dTTP misincorporation by pol ι is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O(6)-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O(6)-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O(6) atoms of O(6)-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol ι, in contrast to the mispairing modes observed previously for O(6)-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.

Mechanistic studies of the biosynthesis of 3,6-dideoxyhexoses in Yersinia pseudotuberculosis: purification and characterization of CDP-4-keto-6-deoxy-D-glucose-3-dehydrase.

PubMed

Weigel, T M; Liu, L D; Liu, H W

1992-02-25

CDP-4-keto-6-deoxy-D-glucose-3-dehydrase (E1) is a PMP-dependent enzyme which plays an essential role in C-O bond cleavage leading to the formation of 3,6-dideoxyhexoses. Although E1 catalysis has long been recognized as a unique biological deoxygenation reaction, the catalytic mechanism of this unusual enzyme has never been fully elucidated. The lack of methods that would allow this enzyme's activity to be monitored directly has been an impediment to E1 purification and has consequently hampered the mechanistic studies. In order to circumvent this problem, we have developed a few convenient and sensitive methods to facilitate the E1 assay. The first method relies on the fact that E1-catalyzed dehydration is initiated by a proton abstraction from C-4' of the PMP-substrate adduct. By using a tritium-labeled cofactor in the incubation that was later quenched with charcoal, the amount of E1 present could be determined from the amount of released tritium in the supernatant. The second method was designed on the basis of the expectation that E1 will bind and rupture the C-F bond of a substrate analogue, CDP-4-keto-3,6-dideoxy-3-fluoro-D-glucose, which was derived from CDP-3-deoxy-3-fluoro-D-glucose. Since the bond length and electronegativity of the C-F group are similar to those of a C-OH group, we anticipated that the proposed compound would be processed by E1, an assumption which was later substantiated. Another assay useful for measuring E1 activity couples the E1 transformation with the subsequent reduction step catalyzed by CDP-6-deoxy-delta 3,4-D-glucoseen reductase (E3) to a thiobarbituric acid (TBA) reaction. Since the condensation product of TBA and malonaldehyde derived from oxidative degradation of the E1/E3 product gave a pink chromophore at 532 nm with a known absorption coefficient, the yield of deoxysugar formation could be directly deduced on the basis of the observed absorbance. The most conclusive evidence confirming the role of E1 was attained by a

Novel drug form of chlorin e6

NASA Astrophysics Data System (ADS)

Abakumova, O. Y.; Baum, Rudolf P.; Ermakova, Natalia Y.; Gradyushko, A. T.; Guseva-Donskaya, T. N.; Karmenyan, Artashes V.; Koraboyev, U. M.; Laptev, V. P.; Mechkov, V. M.; Mikhailova, L. M.; Panferova, N. G.; Rebeko, Aleksei G.; Reshetnickov, Andrei V.; Ryabov, M. V.; Stranadko, Eugeny P.; Tsvetkova, Tatyana A.; Zhukova, O. S.

1999-12-01

A novel stable water-soluble form of well known photosensitizer chlorin e6 named `Photodithazine' has been obtained from Spirulina Platensis cyanobacteria as a noncovalent complex with N-methyl-D-glucosamine, and its biological characteristics evaluate, which proved to be as follows: in vitro photocytotoxicity was 1 (mu) M (EC50) as determined by the extent of DNA synthesis inhibition in CaOv cells after irradiation with 650 - 900 nm light, and 5 (mu) M (EC65) as determined using MTT test on PC12 cells after irradiation with 670 nm laser light at the doses of 15 and 20 J/cm2, respectively, with Al-sulfophthalocyanine `Photosense' (Russia; oligomerized hematoporphyrin-IX mixture `Photogen', Russia) being used as permitted reference drugs.

21 CFR 82.1306 - D&C Red No. 6.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Red No. 6. 82.1306 Section 82.1306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF CERTIFIED...) and (b) of this chapter. (b) The color additive D&C Red No. 6 may be safely used for coloring drugs...

21 CFR 82.1306 - D&C Red No. 6.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Red No. 6. 82.1306 Section 82.1306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF CERTIFIED...) and (b) of this chapter. (b) The color additive D&C Red No. 6 may be safely used for coloring drugs...

Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice.

PubMed

Nguyen, Linda; Scandinaro, Anna L; Matsumoto, Rae R

2017-10-01

The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy. To utilize DM clinically, however, a major challenge that must be addressed is its rapid first-pass metabolism. Two strategies to inhibit metabolism of DM and maintain stable therapeutic blood levels are 1) chemically modifying DM and 2) adding quinidine, an inhibitor of the primary metabolizer of DM, the cytochrome P450 (CYP) 2D6 enzyme. The purpose of this study was to determine if modified DM (deuterated (d6)-DM) elicits antidepressant-like effects and if AMPA and sigma-1 receptors are involved. Furthermore, d6-DM was tested in conjunction with quinidine to determine if further slowing the metabolism of d6-DM affects its antidepressant-like actions. In the FST and TST, d6-DM produced antidepressant-like effects. Upon further investigation in the FST, the most validated animal model for predicting antidepressant efficacy, d6-DM produced antidepressant-like effects both in the absence and presence of quinidine. However, pretreatment with neither an AMPA receptor antagonist (NBQX) nor sigma-1 receptor antagonists (BD1063, BD1047) significantly attenuated the antidepressant-like effects. The data suggest d6-DM has antidepressant-like effects, though it may be recruiting different molecular targets and/or acting through a different mix or ratio of metabolites from regular DM. Copyright © 2017 Elsevier Inc. All rights reserved.

32 CFR 147.6 - Guidance D-Sexual behavior.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Guidance D-Sexual behavior. 147.6 Section 147.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prosecuted; (2) Compulsive or addictive sexual behavior when the person is unable to stop a pattern or self...

32 CFR 147.6 - Guidance D-Sexual behavior.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Guidance D-Sexual behavior. 147.6 Section 147.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prosecuted; (2) Compulsive or addictive sexual behavior when the person is unable to stop a pattern or self...

32 CFR 147.6 - Guidance D-Sexual behavior.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Guidance D-Sexual behavior. 147.6 Section 147.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prosecuted; (2) Compulsive or addictive sexual behavior when the person is unable to stop a pattern or self...

32 CFR 147.6 - Guidance D-Sexual behavior.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Guidance D-Sexual behavior. 147.6 Section 147.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prosecuted; (2) Compulsive or addictive sexual behavior when the person is unable to stop a pattern or self...

PBP5, PBP6 and DacD play different roles in intrinsic β-lactam resistance of Escherichia coli.

PubMed

Sarkar, Sujoy Kumar; Dutta, Mouparna; Chowdhury, Chiranjit; Kumar, Akash; Ghosh, Anindya S

2011-09-01

Escherichia coli PBP5, PBP6 and DacD, encoded by dacA, dacC and dacD, respectively, share substantial amino acid identity and together constitute ~50 % of the total penicillin-binding proteins of E. coli. PBP5 helps maintain intrinsic β-lactam resistance within the cell. To test if PBP6 and DacD play simlar roles, we deleted dacC and dacD individually, and dacC in combination with dacA, from E. coli 2443 and compared β-lactam sensitivity of the mutants and the parent strain. β-Lactam resistance was complemented by wild-type, but not dd-carboxypeptidase-deficient PBP5, confirming that enzymic activity of PBP5 is essential for β-lactam resistance. Deletion of dacC and expression of PBP6 during exponential or stationary phase did not alter β-lactam resistance of a dacA mutant. Expression of DacD during mid-exponential phase partially restored β-lactam resistance of the dacA mutant. Therefore, PBP5 dd-carboxypeptidase activity is essential for intrinsic β-lactam resistance of E. coli and DacD can partially compensate for PBP5 in this capacity, whereas PBP6 cannot.

48 CFR 3452.239-70 - Internet protocol version 6 (IPv6).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 6 (IPv6). 3452.239-70 Section 3452.239-70 Federal Acquisition Regulations System DEPARTMENT OF... Provisions and Clauses 3452.239-70 Internet protocol version 6 (IPv6). As prescribed in 3439.701, insert the...) version 6 (IPv6) as set forth in Internet Engineering Task Force (IETF) Request for Comments (RFC) 2460...

48 CFR 3452.239-70 - Internet protocol version 6 (IPv6).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 6 (IPv6). 3452.239-70 Section 3452.239-70 Federal Acquisition Regulations System DEPARTMENT OF... Provisions and Clauses 3452.239-70 Internet protocol version 6 (IPv6). As prescribed in 3439.701, insert the...) version 6 (IPv6) as set forth in Internet Engineering Task Force (IETF) Request for Comments (RFC) 2460...

In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4 phenotypes

PubMed Central

Gardner, Stephanie F.; Hubbard, Martha A.; Williams, D. Keith; Gentry, W. Brooks; Khan, Ikhlas A.; Shah., Amit

2007-01-01

Objectives Phytochemical-mediated modulation of cytochrome P-450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal (Hydrastis canadensis), black cohosh (Cimicifuga racemosa), kava kava (Piper methysticum), or valerian (Valeriana officinalis) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. Methods Twelve healthy volunteers (6 females) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquine were administered before (baseline) and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquine urinary recovery ratios (8-hour collection), respectively. The content of purported “active” phytochemicals was determined for each supplement. Results Comparisons of pre- and post-supplementation phenotypic ratio means revealed significant inhibition (~40%) of CYP2D6 (difference = −0.228; 95% CI = −0.268 to −0.188) and CYP3A4/5 (difference = −1.501; 95% CI = −1.840 to −1.163) activity for goldenseal. Kava produced significant reductions (~40%) in CYP2E1 only (difference = −0.192; 95% CI = −0.325 to −0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference = −0.046; 95% CI = −0.085 to −0.007), but the magnitude of the effect (~7%) did not appear clinically relevant. No significant changes in phenotypic ratios were observed for valerian. Conclusions Botanical

32 CFR 147.6 - Guidance D-Sexual behavior.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., exploitation, or duress, or reflects lack of judgment or discretion. 1 Sexual orientation or preference may not... 32 National Defense 1 2010-07-01 2010-07-01 false Guidance D-Sexual behavior. 147.6 Section 147.6... Guidance D—Sexual behavior. (a) The concern. Sexual behavior is a security concern if it involves a...

Photodynamic inactivation of bacteria using polyethylenimine-chlorin(e6) conjugates: Effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH.

PubMed

Huang, Liyi; Zhiyentayev, Timur; Xuan, Yi; Azhibek, Dulat; Kharkwal, Gitika B; Hamblin, Michael R

2011-04-01

Antimicrobial photodynamic therapy (APDT) is a novel technique to treat local infections. Previously we reported that the attachment of chlorin(e6) to polyethylenimine (PEI) polymers to form PEI-ce6 conjugates is an effective way to improve ce6 PDT activity against bacteria. The aim of this work was to explore how the polymer molecular weight, substitution ratio (SR) of ce6 and pH value affect the PDT efficacy. We have synthesized PEI-ce6(10) (MW = 60,000, SR = 1) and PEI-ce6(11) (MW = 60,000, SR = 5) and compared these with the previous PEI-ce6(9) (MW = 10,000, SR = 1). We tested the PDT efficacy of these three conjugates against Gram-negative E. coli and Gram-positive bacteria (S. aureus and E. fecalis) at three different pH values (5.0, 7.4, 10.0) that may affect the charge on both the bacterial cells and on the conjugate (that has both basic and acidic groups). PEI-ce6(9) and PEI-ce6(10) were the most effective against these tested bacteria. The PDT effect of all three conjugates depended on pH values. The effective order was pH = 10.0 > pH = 7.4 > pH = 5.0 on E. coli. For S. aureus and E. fecalis the order was pH = 5.0 > pH = 10.0 > pH = 7.4. PEI-ce6(11) PDT activity was worse than PEI-ce6(10) activity which is probably connected to the fact that ce6 molecules are self-quenched within the PEI-ce6(11) molecule. Ce6 quenching within the PEI-ce6 molecules was proved by analyzing fluorescence spectra of PEI-ce6 conjugates at different pH values. There were no differences in bacterial uptake between different pH values in three PEI-ce6 conjugates. We assume high pH (rather than low pH as was hypothesized) disaggregates the conjugates, so the higher pH was more effective than the lower pH against E. coli. But for Gram-positive bacteria, low pH was more effective possibly due to more overall positive charge on the conjugate. Copyright © 2011 Wiley-Liss, Inc.

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

PubMed

Zhang, Rong; He, Yi-feng; Chen, Mo; Chen, Chun-mei; Zhu, Qiu-jing; Lu, Huan; Wei, Zhen-hong; Li, Fang; Zhang, Xiao-xin; Xu, Cong-jian; Yu, Long

2014-10-02

Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75

Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: A case control study in Guizhou Province, China.

PubMed

Yang, Yingjie; Ren, Jie; Zhang, Qizhu

2016-02-01

HPV-16 varies geographically and is correlated with cervical cancer genesis and progression. This study aimed to determine the distribution of HPV-16 E6/E7 genetic variation in patients with invasive cervical cancer or precancer in Guizhou Province, China. A case-control study was designed, and the distribution of HPV-16 E6/E7 genetic variation was compared among women with cervical cancer, precancer, and sexually active without cervical lesion. HPV infection was detected through flow-through hybridization and gene chip techniques to determine the prevalence of HPV 16 E6/E7 genetic variation. Among 90 specimens (30 cervical cancer, 30 precancer, 30 controls), 81 were subjected to HPV-16 E6/E7 gene sequencing. The rates of DNA sequence mutation and amino acid mutation were 76.5% (62/81) and 66.7% (54/81), respectively. Both E6 and E7 genes showed higher mutation rate than their prototypes. The prevalence of E6/E7 mutation significantly differed between the cervical cancer and the controls (P < 0.05) and between the cervical precancer and the controls (P < 0.05). Mutations were simultaneously detected at the E6-D32E (T96A) and E7-M28V (A82G)/L94P (T281C) sites of the amino acid sequence. The most common genetic variation was D32E/M28V/L94P, which accounted for 35.8% of the cases (29/81). D32E/M28V/L94P mutation was higher in the cervical cancer and precancer compared with the prototype. HPV-16 E6/E7 genetic variations, such as D32E/M28V/L94P, are more prevalent in cervical cancer or precancer than those in the controls. The possible correlation between genetic variation and cancerigenesis may be used to design an HPV vaccine for cervical carcinoma. © 2015 Wiley Periodicals, Inc.

Device 2E6 (ACMS) Air Combat Maneuvering Simulator Instructor Console Review.

DTIC Science & Technology

1983-12-01

While the device provides some new features which support training such as a debrief facility and a computer based instructor training module, the...Equipment Center, Orlando, FL (in printing). - 11 - -~.-. -- ~ --- NAVTRAEQUI PCEN 82-M-0767- 1 PROJECTORS DOE COMPUTER SYSTEMS Figure 1. General...arrangement (2E6) - 12 7 NAVTRAEQUIPCEN 82-M--0767-1 d. instructor stations, e. computer systems, ftarget model subsystem, g. debrief subsystem, h

The Coast Artillery Journal. Volume 61, Number 6, December 1924

DTIC Science & Technology

1924-12-01

NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) Coast Artillery... ES ) 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release...obtainable locally. I ques - tion the advisability of a continuance of this policy, involving as it does the placing of dependence upon Filipino troops

Identification of rare 6-deoxy-D-altrose from an edible mushroom (Lactarius lividatus).

PubMed

Tako, Masakuni; Dobashi, Yahiko; Tamaki, Yukihiro; Konishi, Teruko; Yamada, Masashi; Ishida, Hideharu; Kiso, Makoto

2012-03-01

6-Deoxy-L-altrose is well known as a constituent sugar moiety of lipopolysaccharides in Gram-negative bacteria. However, its isomer, 6-deoxy-D-altrose, is little known. Identification of 6-deoxy-D-altrose isolated from a polysaccharide extracted from an edible mushroom (Lactarius lividatus), its comparison with chemically synthesized 6-deoxy-D-altrose using (1)H and (13)C NMR including COSY, HMQC spectroscopy, and investigation of its specific optical rotation were all conducted in this study. The 6-deoxy-hexose isolated from acid hydrolysate of the polysaccharide extracted from L. lividatus was involved in four anomeric isomers (α-pyranose and β-pyranose, and α-furanose and β-furanose), as was chemically synthesized 6-deoxy-d-altrose in an aqueous solution because of mutarotation. Almost all signals of 1D ((1)H NMR and (13)C NMR) and 2D (COSY and HMQC)-NMR spectra agreed with those of the authentic 6-deoxy-D-altrose. The specific optical rotation [α](589) of 6-deoxy-sugar showed a value of +18.2°, which was in agreement with that of authentic 6-deoxy-D-altrose. Consequently, 6-deoxy-hexose was identified as the 6-deoxy-D-altrose. This work is the first complete identification of 6-deoxy-D-altrose in a natural environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK

PubMed Central

Beltrán, Leopoldo R.; Dawid, Corinna; Beltrán, Madeline; Gisselmann, Guenter; Degenhardt, Katharina; Mathie, Klaus; Hofmann, Thomas; Hatt, Hanns

2013-01-01

For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine. PMID:24302912

Cytochrome P450-2D6 Screening Among Elderly Using Antidepressants (CYSCE)

ClinicalTrials.gov

2017-08-15

Depression; Depressive Disorder; Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Intermediate Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant

48 CFR 3452.239-70 - Internet protocol version 6 (IPv6).

Code of Federal Regulations, 2013 CFR

2013-10-01

... (IPv6). 3452.239-70 Section 3452.239-70 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION... Clauses 3452.239-70 Internet protocol version 6 (IPv6). As prescribed in 3439.701, insert the following...) version 6 (IPv6) as set forth in Internet Engineering Task Force (IETF) Request for Comments (RFC) 2460...

15 CFR 6.1 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Definitions. 6.1 Section 6.1 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION ADJUSTMENTS § 6.... (d) Section Five means section 5 of the Inflation Adjustment Act. (e) Department means the Department...

15 CFR 6.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Definitions. 6.1 Section 6.1 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION ADJUSTMENTS § 6.... (d) Section Five means section 5 of the Inflation Adjustment Act. (e) Department means the Department...

15 CFR 6.1 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Definitions. 6.1 Section 6.1 Commerce and Foreign Trade Office of the Secretary of Commerce CIVIL MONETARY PENALTY INFLATION ADJUSTMENTS § 6.... (d) Section Five means section 5 of the Inflation Adjustment Act. (e) Department means the Department...

Diffusion Monte Carlo studies of MB-pol (H2O)2-6 and (D2O)2-6 clusters: Structures and binding energies

NASA Astrophysics Data System (ADS)

Mallory, Joel D.; Mandelshtam, Vladimir A.

2016-08-01

We employ the diffusion Monte Carlo (DMC) method in conjunction with the recently developed, ab initio-based MB-pol potential energy surface to characterize the ground states of small (H2O)2-6 clusters and their deuterated isotopomers. Observables, other than the ground state energies, are computed using the descendant weighting approach. Among those are various spatial correlation functions and relative isomer fractions. Interestingly, the ground states of all clusters considered in this study, except for the dimer, are delocalized over at least two conformations that differ by the orientation of one or more water monomers with the relative isomer populations being sensitive to the isotope substitution. Most remarkably, the ground state of the (H2O)6 hexamer is represented by four distinct cage structures, while that of (D2O)6 is dominated by the prism, i.e., the global minimum geometry, with a very small contribution from a prism-book geometry. In addition, for (H2O)6 and (D2O)6, we performed DMC calculations to compute the ground states constrained to the cage and prism geometries. These calculations compared results for three different potentials, MB-pol, TTM3/F, and q-TIP4P/F.

Dissemination--Task 5. [And] Social Studies Educators Rate the NAEP Social Studies Exercises--Task 6. Final Reports.

ERIC Educational Resources Information Center

Fair, Jean; Chapin, June

Tasks 5 and 6 describe the dissemination activities and a rating of the National Assessment for Educational Progress social studies exercises by members of the National Council for the Social Studies (NCSS). The dissemination activities, described in a one page report, include a special issue of the NCSS journal "Social Education," May…

In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.

PubMed

Gurley, Bill J; Gardner, Stephanie F; Hubbard, Martha A; Williams, D Keith; Gentry, W Brooks; Khan, Ikhlas A; Shah, Amit

2005-05-01

Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic

Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

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

Sachse, C.; Brockmoeller, J.; Bauer, S.

Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015,more » respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.« less

17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act shall...

An observational study of Venlafaxine and CYP2D6 in clinical practice.

PubMed

Rolla, R; Gramaglia, Carla; Dalò, Valentina; Ressico, Francesca; Prosperini, Pierluigi; Vidali, Matteo; Meola, Silvia; Pollarolo, Paola; Bellomo, Giorgio; Torre, Eugenio; Zeppegno, Patrizia

2014-01-01

Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.

Analysis of the 3d(sup 6)4s((sup 6)D)4f-5g supermultiplet of Fe I in laboratory and solar infrared spectra

NASA Technical Reports Server (NTRS)

Johansson, S.; Nave, G.; Geller, M.; Sauval, A. J.; Grevesse, N.; Schoenfeld, W. G.; Change, E. S.; Farmer, C. B.

1994-01-01

The combined laboratory and solar analysis of the highly excited subconfigurations 3d(sup 6)4s((sup 6)D)4f and 3d(sup 6)4s((sup 6)D)5g of Fe I has allowed us to classify 87 lines of the 4f-5g supermultiplet in the spectral region 2545-2585 per cm. The level structure of these JK-coupled configurations is predicted by semiempirical calculations and the quardrupolic approximation. Semiempirical gf-values have been calculated and are compared to gf-values derived from the solar spectrum. The solar analysis has shown that these lines, which should be much less sensitive than lower excitation lines to departures from Local Thermal Equilibrium (LTE) and to temperature uncertanties, lead to a solar abundance of iron which is consistent with the meteoritic value (A(sub Fe) = 7.51).

TRPC6 G757D Loss-of-Function Mutation Associates with FSGS

PubMed Central

Riehle, Marc; Büscher, Anja K.; Gohlke, Björn-Oliver; Kaßmann, Mario; Kolatsi-Joannou, Maria; Bräsen, Jan H.; Nagel, Mato; Becker, Jan U.; Winyard, Paul; Hoyer, Peter F.; Preissner, Robert; Krautwurst, Dietmar; Gollasch, Maik

2016-01-01

FSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of FSGS have been linked to mutations in the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene encoding a nonselective cation channel. Most of these TRPC6 mutations cause a gain-of-function phenotype, leading to calcium–triggered podocyte cell death, but the underlying molecular mechanisms are unclear. We studied the molecular effect of disease-related mutations using tridimensional in silico modeling of tetrameric TRPC6. Our results indicated that G757 is localized in a domain forming a TRPC6-TRPC6 interface and predicted that the amino acid exchange G757D causes local steric hindrance and disruption of the channel complex. Notably, functional characterization of model interface domain mutants suggested a loss-of-function phenotype. We then characterized 19 human FSGS–related TRPC6 mutations, the majority of which caused gain-of-function mutations. However, five mutations (N125S, L395A, G757D, L780P, and R895L) caused a loss-of-function phenotype. Coexpression of wild-type TRPC6 and TRPC6 G757D, mimicking heterozygosity observed in patients, revealed a dominant negative effect of TRPC6 G757D. Our comprehensive analysis of human disease–causing TRPC6 mutations reveals loss of TRPC6 function as an additional concept of hereditary FSGS and provides molecular insights into the mechanism responsible for the loss-of-function phenotype of TRPC6 G757D in humans. PMID:26892346

29 CFR 1905.11 - Variances and other relief under section 6(d).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Variances and other relief under section 6(d). 1905.11... section 6(d). (a) Application for variance. Any employer, or class of employers, desiring a variance authorized by section 6(d) of the Act may file a written application containing the information specified in...

42 CFR 52d.6 - Grant awards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.6 Grant awards. (a) Within the limits of funds available, after... the cancer education committee is broadly representative of the disciplines concerned with cancer care...

From 6D superconformal field theories to dynamic gauged linear sigma models

NASA Astrophysics Data System (ADS)

Apruzzi, Fabio; Hassler, Falk; Heckman, Jonathan J.; Melnikov, Ilarion V.

2017-09-01

Compactifications of six-dimensional (6D) superconformal field theories (SCFTs) on four- manifolds generate a large class of novel two-dimensional (2D) quantum field theories. We consider in detail the case of the rank-one simple non-Higgsable cluster 6D SCFTs. On the tensor branch of these theories, the gauge group is simple and there are no matter fields. For compactifications on suitably chosen Kähler surfaces, we present evidence that this provides a method to realize 2D SCFTs with N =(0 ,2 ) supersymmetry. In particular, we find that reduction on the tensor branch of the 6D SCFT yields a description of the same 2D fixed point that is described in the UV by a gauged linear sigma model (GLSM) in which the parameters are promoted to dynamical fields, that is, a "dynamic GLSM" (DGLSM). Consistency of the model requires the DGLSM to be coupled to additional non-Lagrangian sectors obtained from reduction of the antichiral two-form of the 6D theory. These extra sectors include both chiral and antichiral currents, as well as spacetime filling noncritical strings of the 6D theory. For each candidate 2D SCFT, we also extract the left- and right-moving central charges in terms of data of the 6D SCFT and the compactification manifold.

A Non-oncogenic HPV 16 E6/E7 Vaccine Enhances Treatment of HPV Expressing Tumors

PubMed Central

Wieking, Bryant G.; Vermeer, Daniel W.; Spanos, William C.; Lee, Kimberly M.; Vermeer, Paola; Lee, Walter T.; Xu, Younong; Gabitzsch, Elizabeth S.; Balcaitis, Stephanie; Balint, Joseph P.; Jones, Frank R.; Lee, John H.

2012-01-01

Human papillomaviruses (HPVs) are the causative factor for greater than 90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas (HNSCCs) has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long term survival in preclinical models. Here we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6Δ/E7Δ) expressed as a stable integrant, or in the [E1-, E2b-] adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV specific immune response. Moreover, E6Δ/E7Δ plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo. PMID:22918471

Hydrophysical Evaluation of Wells TW-B, TW-7, UE-6d, U-2gg PSE 3A, U-10L 1, and UE-6e in Yucca Flat

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

Pohlmann, Karl; Healey, John; Lyles, Bred

This study evaluated six wells in Yucca Flat in support of the Underground Test Area (UGTA) Activity conducted by the U.S. Department of Energy (DOE) at the Nevada National Security Site (NNSS). Accessibility and groundwater sampling conditions were assessed and if conditions permitted, samples were collected for tritium analysis. Four of the wells, TW-B, UE-6d, UE-6e, and TW-7 were sampled in support of UGTA responses to recommendations made by the Yucca Flat/Climax Mine External Peer Review Committee (Navarro, 2016). In addition to its role in support of these responses, TW-7 was included because it is listed in the NNSS Integratedmore » Groundwater Sampling Plan (DOE, 2014) as a required sampling location, although it had not been sampled since 1994. U-2gg PSE 3A and U-10L 1 were evaluated to determine whether deteriorating well conditions can be addressed so that these wells can be used as additional sampling points in Yucca Flat.« less

Structural Basis for Proficient Incorporation of dTTP Opposite O[superscript 6]-Methylguanine by Human DNA Polymerase [iota

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

Pence, Matthew G.; Choi, Jeong-Yun; Egli, Martin

2012-03-15

O{sup 6}-Methylguanine (O{sup 6}-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase L core enzyme was determined for nucleoside triphosphate incorporation opposite O{sup 6}-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol L, which showed that dTTP incorporation occurs with high efficiency opposite O{sup 6}-methylG. Misincorporation of dTTP opposite O{sup 6}-methylG occurred with {approx}6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol L with O{sup 6}-methylG asmore » the template base and incoming dCTP or dTTP were solved and showed that O{sup 6}-methylG is rotated into the syn conformation in the pol L active site and that dTTP misincorporation by pol L is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O{sup 6}-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O{sup 6}-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O{sup 6} atoms of O{sup 6}-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O{sup 6}-methylG by human pol L, in contrast to the mispairing modes observed previously for O{sup 6}-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.« less

Microwave spectrum of 2,6-dimethylcyclohexanone

NASA Astrophysics Data System (ADS)

Jang, Heesu; Shim, Jae-Seol; Oh, Jung Jin

2017-07-01

The rotational spectrum of 2,6-dimethylcyclohexanone (DMCHO) was measured in the frequency region from 6 to 12 GHz. Among three possible conformational isomers, two conformers were identified where two methyl groups are aligned in the equatorial/equatorial (ee) and the equatorial/axial (ea) positions. Both b-type and c-type transitions for (e,e)-2,6-DMCHO, and a-type, b-type, and c-type transitions for (e,a)-2,6-DMCHO were assigned to determine the rotational constants and quartic centrifugal distortion constants based on the Watson-A reduction Hamiltonian: (ee) A = 2150.95789(48) MHz, B = 1578.76212(40) MHz, C = 990.19141(45) MHz, ΔJ = 0.086(11) kHz, ΔJK = -0.134(20) kHz, ΔK = 0.298(15) kHz, δJ = 23.4(24) Hz, and δK = 101.4(77) Hz; and (ea) A = 2082.62538(83) MHz, B = 1566.59564(59) MHz, C = 1113.90153(75) MHz, ΔJ = 0.066(23) kHz. In addition, dipole moment components of the two isomers were determined by Stark effect measurements: (ee) μb = 2.6673(12) D, μc = 1.0379(11) D, μtotal = 2.8621(12) D; and (ea) μa = 1.385(253) D, μb = 2.358(104) D, μc = 1.172(21) D, μtotal = 2.975(144) D. Ab initio calculations for all three isomers were compared with each other and with experimental results.

POLYCYCLIC AROMATIC HYDROCARBONS WITH STRAIGHT EDGES AND THE 7.6/6.2 AND 8.6/6.2 INTENSITY RATIOS IN REFLECTION NEBULAE.

PubMed

Ricca, Alessandra; Bauschlicher, Charles W; Roser, Joseph E; Peeters, Els

2018-01-01

We have investigated the mid-infrared spectral characteristics of a series of polycyclic aromatic hydrocarbons (PAHs) with straight edges and containing an even or odd number of carbons using density functional theory (DFT). For several even and odd-carbon PAHs, the 8.6/6.2 and 7.6/6.2 intensity ratios computed in emission after the absorption of a 8 eV photon match the observed ratios obtained for three reflection nebulae (RNe), namely NGC 1333, NGC 7023, and NGC 2023. Odd-carbon PAHs are favored, particularly for NGC 1333. Both cations and anions are present with the cations being predominant. Relevant PAHs span sizes ranging from 46 to 103-113 carbons for NGC 7023 and NGC 2023 and from 38 to 127 carbons for NGC 1333 and have symmetries ranging from D 2 h to C s . Our work suggests that even and odd-carbon PAHs with straight edges are viable candidates for the PAH emission seen towards irradiated Photo-Dissociation Regions (PDRs).

Polycyclic Aromatic Hydrocarbons with Straight Edges and the 7.6/6.2 and 8.6/6.2 Intensity Ratios in Reflection Nebulae

NASA Astrophysics Data System (ADS)

Ricca, Alessandra; Bauschlicher, Charles W., Jr.; Roser, Joseph E.; Peeters, Els

2018-02-01

Using density functional theory, we have investigated the mid-infrared spectral characteristics of a series of polycyclic aromatic hydrocarbons (PAHs) that have straight edges and that contain an even or odd number of carbons. For several even and odd-carbon PAHs, the 8.6/6.2 and 7.6/6.2 intensity ratios computed in emission after the absorption of a 8 eV photon match the observed ratios obtained for three reflection nebulae (RNe), namely NGC 1333, NGC 7023, and NGC 2023. Odd-carbon PAHs are favored, particularly for NGC 1333. Both cations and anions are present, with the cations being predominant. Relevant PAHs span sizes ranging from 46 to 113 carbons for NGC 7023 and NGC 2023 and from 38 to 127 carbons for NGC 1333, and have symmetries ranging from D2h to C s . Our work suggests that even- and odd-carbon PAHs with straight edges are viable candidates for the PAH emission seen toward irradiated photodissociation regions.

Partial reactions of d-glucose 6-phosphate–1 l-myoinositol 1-phosphate cyclase

PubMed Central

Barnett, J. E. G.; Rasheed, A.; Corina, D. L.

1973-01-01

After removal of tightly bound NAD+ by using charcoal, a preparation of d-glucose 6-phosphate–1 l-myoinositol 1-phosphate cyclase catalysed the reduction of 5-keto-d-glucitol 6-phosphate and 5-keto-d-glucose 6-phosphate by [4-3H]NADH to give [5-3H]-glucitol 6-phosphate and [5-3H]glucose 6-phosphate respectively. The position of the tritium atom in the latter was shown by degradation. Both enzyme-catalysed reductions were strongly inhibited by 2-deoxy-d-glucose 6-phosphate, a powerful competitive inhibitor of inositol cyclase. The charcoal-treated enzyme preparation also converted 5-keto-d-glucose 6-phosphate into [3H]myoinositol 1-phosphate in the presence of [4-3H]NADH, but less effectively. These partial reactions of inositol cyclase are interpreted as providing strong evidence for the formation of 5-keto-d-glucose 6-phosphate as an enzyme-bound intermediate in the conversion of d-glucose 6-phosphate into 1 l-myoinositol 1-phosphate. The enzyme was partially inactivated by NaBH4 in the presence of NAD+. Glucose 6-phosphate did not increase the inactivation, and there was no inactivation in the absence of NAD+. There was no evidence for Schiff base formation during the cyclization. d-Glucitol 6-phosphate (l-sorbitol 1-phosphate) was a good inhibitor of the overall reaction. It did not inactivate the enzyme. The apparent molecular weight of inositol cyclase as determined by Sephadex chromatography was 2.15×105. PMID:4352864

Clinical and microbiological characterization of serotype 6D pneumococcal infections in South Korea.

PubMed

Cheong, Hee Jin; Song, Joon Young; Choi, Min Joo; Jeon, Ji Ho; Kang, Seong Hee; Jeong, Eun Joo; Noh, Ji Yun; Kim, Woo Joo

2016-08-01

The prevalence of Serotype 6D Streptococcus pneumoniae was reported relatively high in South Korea. Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), serotype replacement was observed. This study was designed to better clarify genetic diversity of pneumococcal serotype 6D and its clinical characteristics after introduction of PCV7 in 2000. We performed serotyping analysis with 1298 pneumococcal isolates from clinical specimens in South Korea from 2004 to 2011. Multilocus sequence typing was performed, and minimal inhibitory concentration was determined for the available serotype 6D and nontypeable (NT) pneumococcal isolates during the 2006-2007 period. The proportion of serotype 6D pneumococci increased from 0.8% (2004-2007) to 2.9% (2008-2011) of all clinical pneumococcal isolates, accounting for 14.9% of serogroup 6 pneumococci in South Korea. NT pneumococci markedly increased to 13.3% during 2006-2007 in advance of the increase in serotype 6D. Among the 26 available serotype 6D pneumococcal isolates, ST282 was predominant (23 isolates, 88.5%). The STs of NT pneumococci (26 isolates) were diverse, but clonal complex 271 was the dominant clone. The oral penicillin non-susceptibility rate was 92.3% (24 among 26 isolates) for both serotype 6D and NT pneumococci. The ceftriaxone non-susceptibility rates of serotype 6D and NT pneumococci were 7.7% and 3.8%, respectively. ST228(6D) strain expanded, particularly among old adults with comorbidities in South Korea. Both antibiotic and PCV7 pressure might have contributed to the selective increase of NT and serotype 6D pneumococci. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Penicilones A-D, Anti-MRSA Azaphilones from the Marine-Derived Fungus Penicillium janthinellum HK1-6.

PubMed

Chen, Min; Shen, Nan-Xing; Chen, Zhi-Qi; Zhang, Feng-Min; Chen, Yang

2017-04-28

Four new azaphilones, penicilones A-D (1-4), were isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6. Their planar structures and absolute configurations were determined by extensive analysis of NMR spectroscopic data, ECD spectra, the modified Mosher's method, and chemical conversions. Interestingly, 1 and 2 had the opposite configuration at C-7 compared to the closely related chloro analogues 3 and 4. Ester hydrolysis of 2 and 4 afforded their parental azaphilones, named penicilones E (5) and F (6). Compounds 1-6 were evaluated for their antibacterial activities in vitro. Penicilones B-D (2-4) showed potent anti-MRSA (Staphylococcus aureus ATCC 43300, ATCC 33591) activities with MIC values ranging from 3.13 to 6.25 μg/mL.

Bi–Mn mixed metal organic oxide: A novel 3d-6p mixed metal coordination network

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

Shi, Fa-Nian, E-mail: fshi@ua.pt; Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro; Rosa Silva, Ana

2015-05-15

A new terminology of metal organic oxide (MOO) was given a definition as a type of coordination polymers which possess the feature of inorganic connectivity between metals and the direct bonded atoms and show 1D, 2D or 3D inorganic sub-networks. One such compound was shown as an example. A 3d-6p (Mn–Bi. Named MOOMnBi) mixed metals coordination network has been synthesized via hydrothermal method. The new compound with the molecular formula of [MnBi{sub 2}O(1,3,5-BTC){sub 2}]{sub n} (1,3,5-BTC stands for benzene-1,3,5-tricarboxylate) was characterized via single crystal X-ray diffraction technique that revealed a very interesting 3-dimensional (3D) framework with Bi{sub 4}O{sub 2}(COO){sub 12}more » clusters which are further connected to Mn(COO){sub 6} fragments into a 2D MOO. The topology study indicates an unprecedented topological type with the net point group of (4{sup 13}.6{sup 2})(4{sup 13}.6{sup 8})(4{sup 16}.6{sup 5})(4{sup 18}.6{sup 10})(4{sup 22}.6{sup 14})(4{sup 3}) corresponding to 3,6,7,7,8,9-c hexa-nodal net. MOOMnBi shows catalytic activity in the synthesis of (E)-α,β-unsaturated ketones. - Graphical abstract: This metal organic framework (MOF) is the essence of a 2D metal organic oxide (MOO). - Highlights: • New concept of metal organic oxide (MOO) was defined and made difference from metal organic framework. • New MOO of MOOMnBi was synthesized by hydrothermal method. • Crystal structure of MOOMnBi was determined by single crystal X-ray analysis. • The catalytic activity of MOOMnBi was studied showing reusable after 2 cycles.« less

Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells.

PubMed

Gillis, L D; Lewis, S M

2013-08-01

eIF3e/Int6 is a component of the multi-subunit eIF3 complex, which binds directly to the 40S ribosome to facilitate ribosome recruitment to mRNA and hence protein synthesis. Reduced expression of eIF3e/Int6 has been found in up to 37% of human breast cancers, and expression of a truncated mutant version of the mouse eIF3e/Int6 protein leads to malignant transformation of normal mammary cells. These findings suggest that eIF3e/Int6 is a tumor suppressor; however, a recent study has reported that a reduction of eIF3e/Int6 expression in breast cancer cells leads to reduced translation of oncogenes, suggesting that eIF3e/Int6 may in fact have an oncogenic role in breast cancer. To gain a better understanding of the role of eIF3e/Int6 in breast cancer, we have examined the effects of decreased eIF3e/Int6 expression in an immortalized breast epithelial cell line, MCF-10A. Surprisingly, we find that decreased expression of eIF3e/Int6 causes breast epithelial cells to undergo epithelial-to-mesenchymal transition (EMT). We show that EMT induced by a decrease in eIF3e/Int6 expression imparts invasive and migratory properties to breast epithelial cells, suggesting that regulation of EMT by eIF3e/Int6 may have an important role in breast cancer metastasis. Furthermore, we show that reduced eIF3e/Int6 expression in breast epithelial cells causes a specific increase in the expression of the key EMT regulators Snail1 and Zeb2, which occurs at both the transcriptional and post-transcriptional levels. Together, our data indicate a novel role of eIF3e/Int6 in the regulation of EMT in breast epithelial cells and support a tumor suppressor role of eIF3e/Int6.

Mapping the Dark Matter with 6dFGS

NASA Astrophysics Data System (ADS)

Mould, Jeremy R.; Magoulas, C.; Springob, C.; Colless, M.; Jones, H.; Lucey, J.; Erdogdu, P.; Campbell, L.

2012-05-01

Fundamental plane distances from the 6dF Galaxy Redshift Survey are fitted to a model of the density field within 200/h Mpc. Likelihood is maximized for a single value of the local galaxy density, as expected in linear theory for the relation between overdensity and peculiar velocity. The dipole of the inferred southern hemisphere early type galaxy peculiar velocities is calculated within 150/h Mpc, before and after correction for the individual galaxy velocities predicted by the model. The former agrees with that obtained by other peculiar velocity studies (e.g. SFI++). The latter is only of order 150 km/sec and consistent with the expectations of the standard cosmological model and recent forecasts of the cosmic mach number, which show linearly declining bulk flow with increasing scale.

Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility

PubMed Central

Nam, Hyungwoo; Engeln, Michel; Konkalmatt, Prasad; Iniguez, Sergio D.

2017-01-01

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection.

PubMed

Cardoso, Rita; Lacerda, Pedro C; Costa, Paulo P; Machado, Ana; Carvalho, André; Bordalo, Adriano; Fernandes, Ruben; Soares, Raquel; Richter, Joachim; Alves, Helena; Botelho, Monica C

2017-11-28

Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium -infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6 G-174C (13.3%) variants were frequent in S. haematobium -infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.

Synthesis of 7-(2,4-dichlorophenyl)-D-erythro-3-hydroxy-5-heptanolide, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexane-1-sulfonic acid, and 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexylphosphonic acid.

PubMed

Hodosi, G; Galambos, G; Podányi, B; Kuszmann, J

1992-03-02

6-(2,4-Dichlorophenyl)-D-erythro-1,2,4-hexanetriol, synthesised from D-glucose, was partially silylated, then reacted with 2-methoxypropene to afford 1-O-tert-butyldimethylsilyl-6-(2,4- dichlorophenyl)-2,4-O-isopropylidene-D-erythro-1,2,4-hexanetriol (17). Desilylation of 17 gave 6-(2,4-dichlorophenyl)-2,4-O-isopropylidene-D- erythro-1,2,4-hexanetriol, which was converted into the 1-tosylate 18 and the 1-bromo derivative 19. Reaction of 18 with potassium thiolbenzoate gave, after debenzoylation, oxidation, and deprotection, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexane-1-sulfonic acid (4). Reaction of 18 or 19 with triethyl phosphite gave, after deprotection, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexyl-phosphonic acid (5), and reaction of 19 with potassium cyanide gave, after subsequent hydrolysis and deprotection, 7-(2,4-dichlorophenyl)-D-erythro-3-hydroxy-5-heptanolide (3).

Computing the scalar field couplings in 6D supergravity

NASA Astrophysics Data System (ADS)

Saidi, El Hassan

2008-11-01

Using non-chiral supersymmetry in 6D space-time, we compute the explicit expression of the metric the scalar manifold SO(1,1)×{SO(4,20)}/{SO(4)×SO(20)} of the ten-dimensional type IIA superstring on generic K3. We consider as well the scalar field self-couplings in the general case where the non-chiral 6D supergravity multiplet is coupled to generic n vector supermultiplets with moduli space SO(1,1)×{SO(4,n)}/{SO(4)×SO(n)}. We also work out a dictionary giving a correspondence between hyper-Kähler geometry and the Kähler geometry of the Coulomb branch of 10D type IIA on Calabi-Yau threefolds. Others features are also discussed.

Task Parallel Incomplete Cholesky Factorization using 2D Partitioned-Block Layout

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

Kim, Kyungjoo; Rajamanickam, Sivasankaran; Stelle, George Widgery

We introduce a task-parallel algorithm for sparse incomplete Cholesky factorization that utilizes a 2D sparse partitioned-block layout of a matrix. Our factorization algorithm follows the idea of algorithms-by-blocks by using the block layout. The algorithm-byblocks approach induces a task graph for the factorization. These tasks are inter-related to each other through their data dependences in the factorization algorithm. To process the tasks on various manycore architectures in a portable manner, we also present a portable tasking API that incorporates different tasking backends and device-specific features using an open-source framework for manycore platforms i.e., Kokkos. A performance evaluation is presented onmore » both Intel Sandybridge and Xeon Phi platforms for matrices from the University of Florida sparse matrix collection to illustrate merits of the proposed task-based factorization. Experimental results demonstrate that our task-parallel implementation delivers about 26.6x speedup (geometric mean) over single-threaded incomplete Choleskyby- blocks and 19.2x speedup over serial Cholesky performance which does not carry tasking overhead using 56 threads on the Intel Xeon Phi processor for sparse matrices arising from various application problems.« less

The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

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

Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela, E-mail: lizanosoberon@gmail.com

The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins tomore » recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.« less

Evaluation of anti-melanoma activities of (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol from the Red Sea soft coral Sarcophyton glaucum.

PubMed

Szymanski, Pawel T; Ahmed, Safwat A; Radwan, Mohamed M; Khalifa, Sherief I; Fahmy, Hesham

2014-08-01

Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were evaluated for their inhibitory effects on mouse melanoma B16F10 cell growth. Results show that all the cembranoids strongly inhibit viability of melanoma cells particularly during 48 -72 hrs treatment and also inhibit de novo DNA synthesis and PARP activity and stimulate fragmentation of DNA. (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol was not cytotoxic to monkey kidney CV-1 cells at the concentration that produces the anti-melanoma effects which indicates that this compound may be a good candidate for further development. (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were found to be cytotoxic to healthy cells.

Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

PubMed

Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

2017-07-05

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

The electronic structure of d{sup 6} metal-acetylides

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

Renshaw, S.K.; Uplinger, A.B.; Bullock, R.M.

1997-12-31

Gas-phase ultraviolet photoelectron spectroscopy has been used to investigate the electronic structure and bonding interactions of d{sup 6} piano-stool metal-acetylides of the general formulas CpML{sub 2}C{triple_bond} C-R [M = Ru, L = PMe{sub 3}, R = H, Me, {sup t}Bu, C{sub 6}H{sub 5}] and CpML{sub 2}C{triple_bond}C-p-C{sub 6}H{sub 4}-NO{sub 2} [M = Fe, Ru, L = CO; M = Ru, L = PMe{sub 3}]. Previous studies of analogous CpFe(CO){sub 2}C{triple_bond}C-R complexes found that the filled-filled interaction between the metal d electrons and the acetylide {pi} bond electrons dominates the shift of the first valence ionizations, and that backbonding of the metalmore » d electrons into the acetylide {pi}* orbitals is very small. It is found here that the change to the second row transition metal and the substitution of phosphines for the carbonyls makes the metal more electron rich, but does not change the basic description of the metal interaction with the acetylide.« less

Neutron diffraction study, magnetic properties and thermal stability of YMn 2D 6 synthesized under high deuterium pressure

NASA Astrophysics Data System (ADS)

Paul-Boncour, V.; Filipek, S. M.; Dorogova, M.; Bourée, F.; André, G.; Marchuk, I.; Percheron-Guégan, A.; Liu, R. S.

2005-01-01

A new phase YMn 2D 6 was synthesized by submitting YMn 2 to 1.7 kbar deuterium pressure at 473 K. According to X-ray and neutron powder diffraction experiments, YMn 2D 6 crystallizes in the Fm3¯m space group with a=6.709(1) Å at 300 K. The Y and half of the Mn atoms occupy statistically the 8 c site whereas the other Mn atoms are located in 4 a site and surrounded by 6 D atoms (24 e). This corresponds to a K 2PtCl 6-type structure with a partially disordered substructure which can be written as [YMn]MnH 6. No ordered magnetic moment is observed in the NPD patterns and the magnetization measurements display a paramagnetic behavior. The study of the thermal stability by Differential Scanning Calorimetry and XRD experiments indicates that this phase decomposes in YD 2 and Mn at 625 K, and is more stable than YMn 2H 4.5.

Separate analysis of human papillomavirus E6 and E7 messenger RNAs to predict cervical neoplasia progression

PubMed Central

Liu, Shuling; Lachkar, Bouchra; Zhang, Shuang; Xu, Chenyang; Tenjimbayashi, Yuri; Shikama, Ayumi; Tasaka, Nobutaka; Akiyama, Azusa; Sakurai, Manabu; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Matsumoto, Koji; Yoshikawa, Hiroyuki; Satoh, Toyomi

2018-01-01

A few studies previously suggested that human papillomavirus (HPV) E6 messenger RNA (mRNA) may exist uniformly in all grades of cervical intraepithelial neoplasia (CIN), whereas the detection rate of E7 mRNA may increase with disease progression from low-grade CIN to invasive carcinoma. The aim of this study was to clarify the different roles of E6 and E7 mRNAs in cervical carcinogenesis. The presence of each E6 and E7 mRNA was analyzed in 171 patients with pathologically-diagnosed CIN or cervical carcinoma. We utilized a RT-PCR assay based on consensus primers which could detect E6 mRNA (full-length E6/E7 transcript) and E7 mRNAs (spliced E6*/E7 transcripts) separately for various HPV types. E7 mRNAs were detected in 6% of CIN1, 12% of CIN2, 24% of CIN3, and 54% of cervical carcinoma. The presence of E7 mRNAs was significantly associated with progression from low-grade CIN to invasive carcinoma in contrast with E6 mRNA or high-risk HPV (HR-HPV) DNA (p = 0.00011, 0.80 and 0.54). The presence of both E6 and E7 mRNAs was significantly associated with HPV16/18 DNA but not with HR-HPV DNA (p = 0.0079 and 0.21), while the presence of E6 mRNA was significantly associated with HR-HPV DNA but not with HPV16/18 DNA (p = 0.036 and 0.089). The presence of both E6 and E7 mRNAs showed high specificity and low sensitivity (100% and 19%) for detecting CIN2+ by contrast with the positivity for HR-HPV DNA showing low specificity and high sensitivity (19% and 89%). The positive predictive value for detecting CIN2+ was even higher by the presence of both E6 and E7 mRNAs than by the positivity for HR-HPV DNA (100% vs. 91%). In 31 patients followed up for CIN1-2, the presence of both E6 and E7 mRNAs showed significant association with the occurrence of upgraded abnormal cytology in contrast with E6 mRNA, HR-HPV DNA, or HPV16/18 DNA (p = 0.034, 0.73, 0.53, and 0.72). Our findings support previous studies according to which E7 mRNA is more closely involved in cervical carcinogenesis than

N.m.r. studies of the conformation of analogues of methyl beta-lactoside in methyl sulfoxide-d6.

PubMed

Rivera-Sagredo, A; Jiménez-Barbero, J; Martín-Lomas, M

1991-12-16

The 1H- and 13C-n.m.r. spectra of solutions of methyl beta-lactoside (1), all of its monodeoxy derivatives (2, 3, 6-10), the 3-O-methyl derivative (4), and methyl 4-O-beta-D-galactopyranosyl-D-xylopyranoside (5) in methyl sulfoxide-d6 have been analysed. The n.O.e.'s and specific desheildings indicate similar distributions of low-energy conformers, comparable to those in aqueous solution. The major conformer has torsion angles phi H and psi H of 49 degrees and 5 degrees, respectively, with contributions of conformers with phi/psi 24 degrees/-59 degrees, 22 degrees/32 degrees, and 6 degrees/44 degrees.

29 CFR 2530.200b-6 - Maritime industry.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Maritime industry. 2530.200b-6 Section 2530.200b-6 Labor... Provisions § 2530.200b-6 Maritime industry. (a) General. Sections 202(a)(3)(D), 203(b)(2)(D) and 204(b)(3)(E... provisions applicable to the maritime industry. In general, those provisions permit statutory standards...

29 CFR 2530.200b-6 - Maritime industry.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Maritime industry. 2530.200b-6 Section 2530.200b-6 Labor... Provisions § 2530.200b-6 Maritime industry. (a) General. Sections 202(a)(3)(D), 203(b)(2)(D) and 204(b)(3)(E... provisions applicable to the maritime industry. In general, those provisions permit statutory standards...

29 CFR 2530.200b-6 - Maritime industry.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Maritime industry. 2530.200b-6 Section 2530.200b-6 Labor... Provisions § 2530.200b-6 Maritime industry. (a) General. Sections 202(a)(3)(D), 203(b)(2)(D) and 204(b)(3)(E... provisions applicable to the maritime industry. In general, those provisions permit statutory standards...

29 CFR 2530.200b-6 - Maritime industry.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Maritime industry. 2530.200b-6 Section 2530.200b-6 Labor... Provisions § 2530.200b-6 Maritime industry. (a) General. Sections 202(a)(3)(D), 203(b)(2)(D) and 204(b)(3)(E... provisions applicable to the maritime industry. In general, those provisions permit statutory standards...

29 CFR 2530.200b-6 - Maritime industry.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false Maritime industry. 2530.200b-6 Section 2530.200b-6 Labor... Provisions § 2530.200b-6 Maritime industry. (a) General. Sections 202(a)(3)(D), 203(b)(2)(D) and 204(b)(3)(E... provisions applicable to the maritime industry. In general, those provisions permit statutory standards...

New Generation of Photosensitizers: Conjugates of Chlorin e 6 With Diamond Nanoparticles

NASA Astrophysics Data System (ADS)

Lapina, V. A.; Bushuk, S. B.; Pavich, T. A.; Vorobey, A. V.

2016-07-01

Conjugates of chlorin e 6 with diamond nanoparticles were synthesized by two methods. The spectral and luminescent properties of the obtained conjugates were studied. It was shown that chlorin e 6 retained its photosensitizing activity in the conjugate. It was established that chlorin e 6 immobilized directly on diamond nanoparticles had higher photosensitizing activity than that conjugated using a spacer. It was observed that chlorin e 6 in the conjugate had higher photolytic stability than the free form.

40 CFR 721.10269 - [5,6]Fullerene-C84-D2.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10269 [5,6]Fullerene-C84-D2. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C84-D2 (PMN P-09-56; CAS No. 145809-19-4...

40 CFR 721.10269 - [5,6]Fullerene-C84-D2.

Code of Federal Regulations, 2014 CFR

2014-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10269 [5,6]Fullerene-C84-D2. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as [5,6]Fullerene-C84-D2 (PMN P-09-56; CAS No. 145809-19-4...

Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

PubMed

Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

2011-11-01

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

Lines in the spectrum of /sup 6/LiD (3086--5156 A)

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

Li, K.C.

1976-01-01

The emission spectra of A/sup 1/..sigma../sup +/--X/sup 1/..sigma../sup +/ bands of /sup 6/LiD were photographed in the 3086 A - 5156 A region with a 3.4 meter Ebert Spectrograph of theoretical resolution of about 0.07 cm/sup -1/. High-purity /sup 6/LiD crystals were obtained from Oak Ridge National Laboratory. The atomic percent of /sup 6/Li in /sup 6/LiD was 95.58 percent. The discharge source is a demountable stainless steel hollow cathode lamp. The lithium deuteride crystals were packed into the cathode. Pressure in the discharge tube was about 10 to 20 torr of D/sub 2/. The discharge was run at aboutmore » 600 volts and 1.25 to 1.75 amperes. Acceptable spectra were obtained with exposure time of 6 hours. A Westinghouse iron hollow cathode was used to produce the iron spectrum for calibration. The plates were measured on the Gaertner photoplate comparator with an encoder system and on-line computer service at Argonne National Laboratory. The measured lines in the spectra of /sup 6/LiD are given in this report (COO-2326-18). Similar spectra for /sup 6/LiH and /sup 7/LiH are given in companion reports (COO-2326-17) and (COO-2326-19), respectively. The relative intensities of the lines are applicable only to short regions and do not extend over the whole spectrum.« less

Psychometric properties of responses by clinicians and older adults to a 6-item Hebrew version of the Hamilton Depression Rating Scale (HAM-D6)

PubMed Central

2013-01-01

Background The Hamilton Depression Rating Scale (HAM-D) is commonly used as a screening instrument, as a continuous measure of change in depressive symptoms over time, and as a means to compare the relative efficacy of treatments. Among several abridged versions, the 6-item HAM-D6 is used most widely in large degree because of its good psychometric properties. The current study compares both self-report and clinician-rated versions of the Hebrew version of this scale. Methods A total of 153 Israelis 75 years of age on average participated in this study. The HAM-D6 was examined using confirmatory factor analytic (CFA) models separately for both patient and clinician responses. Results Reponses to the HAM-D6 suggest that this instrument measures a unidimensional construct with each of the scales’ six items contributing significantly to the measurement. Comparisons between self-report and clinician versions indicate that responses do not significantly differ for 4 of the 6 items. Moreover, 100% sensitivity (and 91% specificity) was found between patient HAM-D6 responses and clinician diagnoses of depression. Conclusion These results indicate that the Hebrew HAM-D6 can be used to measure and screen for depressive symptoms among elderly patients. PMID:23281688

D-tagatose 1,6-diphosphate aldolase from lactic streptococci: purification, properties, and use in measuring intracellular tagatose 1,6-diphosphate.

PubMed Central

Crow, V L; Thomas, T D

1982-01-01

Two D-ketohexose 1,6-diphosphate aldolases are present in Streptococcus cremoris E8 and S. lactis C10. One aldolase, which was induced by growth on either lactose or galactose, was active with both tagatose 1,6-diphosphate (TDP) and fructose 1,6-diphosphate (FDP), having a lower Km and a higher Vmax with TDP as the substrate. This enzyme, named TDP aldolase, had properties typical of a class I aldolase, being insensitive to EDTA and showing substrate-dependent inactivation by sodium borohydride. Sodium dodecyl sulfate-gel electrophoresis indicated a subunit molecular weight of 34,500. The amino acid composition of TDP aldolase is reported. When the enzyme was incubated with either triose phosphates or FDP, the equilibrium mixture contained an FDP/TDP ratio of 6.9:1. The other aldolase, which had properties typical of a class II aldolase, showed activity with FDP but not with TDP. The intracellular TDP concentration, measured with the purified TDP aldolase, was 0.4 to 4.0 mM in cells growing on lactose or galactose and was lower (0 to 1.0 mM) in cells growing on glucose. The intracellular concentration of FDP was always higher than that of TDP. The role of ketohexose diphosphates in the regulation of end product fermentation by lactic streptococci is discussed. PMID:6807956

E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China

PubMed Central

Wen, Qiang; Wang, Tao; Mu, Xuemei; Chenzhang, Yuwei; Cao, Man

2017-01-01

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6. PMID:28141822

Impact of CYP2D6 polymorphisms on clinical efficacy & tolerability of metoprolol tartrate

PubMed Central

Hamadeh, Issam S.; Langaee, Taimour Y.; Dwivedi, Ruti; Garcia, Sofia; Burkley, Ben M.; Chapman, Arlene B.; Gums, John G.; Turner, Stephen T.; Gong, Yan; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

2014-01-01

Metoprolol is a selective β-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme, CYP2D6. Our objective was to investigate the influence of CYP2D6 polymorphisms on efficacy and tolerability of metoprolol tartrate. 281 study participants with uncomplicated hypertension received 50 mg of metoprolol twice daily followed by response guided titration to 100 mg twice daily. Phenotypes were assigned based on results of CYP2D6 genotyping and copy number variation assays. Clinical response to metoprolol and adverse effect rates were analyzed in relation to CYP2D6 phenotypes by using appropriate statistical tests. Heart rate response differed significantly by CYP2D6 phenotype (p-value <0.0001) with poor metabolizers & intermediate metabolizers showing greater HR reduction. However, blood pressure response and adverse effect rates were not significantly different by CYP2D6 phenotype. Other than a significant difference in heart rate response, CYP2D6 polymorphisms were not a determinant of the variability in response or tolerability to metoprolol. PMID:24637943

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-d-glucose gold nanoparticles in vivo

NASA Astrophysics Data System (ADS)

Roa, Wilson; Xiong, Yeping; Chen, Jie; Yang, Xiaoyan; Song, Kun; Yang, Xiaohong; Kong, Beihua; Wilson, John; Xing, James Z.

2012-09-01

We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-d-glucose (6-FDG) to gold nanoparticles (6-FDG-GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG-GNPs in vivo using a murine model. At 2 h, following intravenous injection of 6-FDG-GNPs into the murine model, approximately 30% of the 6-FDG-GNPs were distributed to three major organs: the liver, the spleen and the kidney. PEGylation of the 6-FDG-GNPs was found to significantly improve the bio-distribution of 6-FDG-GNPs by avoiding unintentional uptake into these organs, while simultaneously doubling the cellular uptake of GNPs in implanted breast MCF-7 adenocarcinoma. When combined with radiation, PEG-6-FDG-GNPs were found to increase the apoptosis of the MCF-7 breast adenocarinoma cells by radiation both in vitro and in vivo. Pharmacokinetic data indicate that GNPs reach their maximal concentrations at a time window of two to four hours post-injection, during which optimal radiation efficiency can be achieved. PEG-6-FDG-GNPs are thus novel nanoparticles that preferentially accumulate in targeted cancer cells where they act as potent radiosensitizing agents. Future research will aim to substitute the 18F atom into the 6-FDG molecule so that the PEG-6-FDG-GNPs can also function as radiotracers for use in positron emission tomography scanning to aid cancer diagnosis and image guided radiation therapy planning.

META-ANALYSIS OF CYP2D6 METABOLIZER PHENOTYPE AND METOPROLOL PHARMACOKINETICS

PubMed Central

Blake, CM; Kharasch, ED; Schwab, M; Nagele, P

2013-01-01

Metoprolol, a commonly prescribed beta-blocker, is primarily metabolized by cytochrome P450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Several smaller studies have shown that metoprolol pharmacokinetics is influenced by CYP2D6 genotype and metabolizer phenotype. To increase robustness of metoprolol pharmacokinetic estimates, a systematic review and meta-analysis of pharmacokinetic studies that administered a single oral dose of immediate release metoprolol was performed. Pooled analysis (n= 264) demonstrated differences in peak plasma metoprolol concentration, area under the concentration-time curve, elimination half-life, and apparent oral clearance that were 2.3-, 4.9-, 2.3-, and 5.9-fold between extensive and poor metabolizers, respectively, and 5.3-, 13-, 2.6-, and 15-fold between ultra-rapid and poor metabolizers (all p<0.001). Enantiomer-specific analysis revealed genotype-dependent enantio-selective metabolism, with nearly 40% greater R- vs S-metoprolol metabolism in ultra-rapid and extensive metabolizers. This study demonstrates a marked effect of CYP2D6 metabolizer phenotype on metoprolol pharmacokinetics and confirms enantiomer specific metabolism of metoprolol. PMID:23665868

GENETIC MAPPING OF VOCALIZATION TO A SERIES OF INCREASING ACUTE FOOTSHOCKS USING B6.A CONSOMIC AND B6.D2 CONGENIC MOUSE STRAINS

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

Matthews, Douglas B; Chesler, Elissa J; Cook, Melloni N.

2008-01-01

Footshock response is used to study biological functions in mammals. However, the genetics underlying variability in footshock sensitivity are not well understood. In the current studies, a panel of B6.A consomic mouse strains, two B6.D2 congenic mouse strains and the progenitor strains were screened for footshock sensitivity as measured by audible vocalization. It was found that A/J (A) mice and C57BL/6J (B6) mice with an A Chromosome 1 (Chr 1) were less sensitive to footshock compared to B6 animals. Furthermore, the offspring of Chr 1 consomic mice crossed with B6 mice had vocalization levels that were intermediate to A/J andmore » B6 animals. A F2 mapping panel revealed two significant QTLs for footshock vocalization centered around D1Mit490 and D1Mit206 on Chr 1. The role of these Chr 1 loci in footshock sensitivity was confirmed in B6.D2 congenic mice. These data identify genetic regions involved in footshock sensitivity and establish additional mouse resources for use in investigating complex behaviors.« less

CYP2D6 Genetic Polymorphisms and Phenotypes in Different Ethnicities of Malaysian Breast Cancer Patients.

PubMed

Chin, Fee Wai; Chan, Soon Choy; Abdul Rahman, Sabariah; Noor Akmal, Sharifah; Rosli, Rozita

2016-01-01

The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the

Photodynamic tissue adhesion with chlorin(e6) protein conjugates.

PubMed

Khadem, J; Veloso, A A; Tolentino, F; Hasan, T; Hamblin, M R

1999-12-01

To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. Both covalent conjugates and noncovalent mixtures showed a light dose-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology.

Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study.

PubMed

Molloy, J; Koplin, J J; Allen, K J; Tang, M L K; Collier, F; Carlin, J B; Saffery, R; Burgner, D; Ranganathan, S; Dwyer, T; Ward, A C; Moreno-Betancur, M; Clarke, M; Ponsonby, A L; Vuillermin, P

2017-08-01

Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D 3 (25(OH)D 3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D 3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.

PubMed

Huang, Chin-Wei; Lai, Ming-Liang; Lin, Min-Shung; Lee, Hwei-Ling; Huang, Jin-Ding

2003-01-01

For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the beta-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the beta-blockade effect of propranolol in Chinese subjects.

4,2':6',4"- and 3,2':6',3"-Terpyridines: The Conflict between Well-Defined Vectorial Properties and Serendipity in the Assembly of 1D-, 2D- and 3D-Architectures.

PubMed

Klein, Y Maximilian; Prescimone, Alessandro; Constable, Edwin C; Housecroft, Catherine E

2017-06-30

A comparative investigation of the coordination assemblies formed between Co(NCS)₂ and two monotopic 4,2':6',4''-terpyridine (4,2':6',4"-tpy) ligands or two related ditopic ligands is reported. Crystals were grown by layering MeOH solutions of Co(NCS)₂ over a CHCl₃ or 1,2-C₆H₄Cl₂ solution of the respective ligand at room temperature. With 4'-(2-methylpyrimidin-5-yl)-4,2':6',4"-terpyridine ( 6 ), the 1D-coordination polymer {[Co₂(NCS)₄(MeOH)₄( 6 )₂]∙2MeOH∙8H₂O} n assembles with 6 coordinating only through the outer N-donors of the 4,2':6',4"-tpy unit; coordination by the MeOH solvent blocks two cobalt coordination sites preventing propagation in a higher-dimensional network. A combination of Co(NCS)₂ and 1-(4,2':6',4"-terpyridin-4'-yl)ferrocene ( 7 ) leads to {[Co(NCS)₂( 7 )₂]∙4CHCl₃} n which contains a (4,4) net; the 2D-sheets associate through π-stacking interactions between ferrocenyl and pyridyl units. A 3D-framework is achieved through use of the ditopic ligand 1,4-bis( n propoxy)-2,5-bis(4,2':6',4"-terpyridin-4'-yl)benzene ( 8 ) which acts as a 4-connecting node in {[Co(NCS)₂( 8 )₂] . 2C₆H₄Cl₂} n ; the combination of metal and ligand planar 4-connecting nodes results in a {6⁵.8} cds net. For a comparison with the coordinating abilities of the previously reported 1,4-bis( n octoxy)-2,5-bis(4,2':6',4"-terpyridin-4'-yl)benzene ( 3 ), a more flexible analogue 9 was prepared. {[Co(NCS)₂( 9 )]∙2CHCl₃} n contains a (4,4) net defined by both metal and ligand planar 4-connecting nodes. The n octoxy tails of 9 protrude from each side of the (4,4) net and thread through adjacent sheets; the arene-attached n octoxy chains associate through a combination of van der Waals and C-H...π interactions.

Helical FOFO Snake for 6D Ionization Cooling of Muons

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

Alexahin, Y.

2010-03-30

A channel for 6D ionization cooling of muons is described which consists of periodically inclined solenoids of alternating polarity, liquid hydrogen absorbers placed inside the solenoids and RF cavities between them. An important feature of such a channel (called Helical FOFO snake) is that it can cool simultaneously muons of both signs. Theoretical considerations as well as results of simulations with G4beamline are presented which show that a 200 MHz HFOFO snake has sufficient acceptance to be used for initial 6D cooling in muon colliders and neutrino factories.

Novel mode of inhibition by D-tagatose 6-phosphate through a Heyns rearrangement in the active site of transaldolase B variants.

PubMed

Stellmacher, Lena; Sandalova, Tatyana; Schneider, Sarah; Schneider, Gunter; Sprenger, Georg A; Samland, Anne K

2016-04-01

Transaldolase B (TalB) and D-fructose-6-phosphate aldolase A (FSAA) from Escherichia coli are C-C bond-forming enzymes. Using kinetic inhibition studies and mass spectrometry, it is shown that enzyme variants of FSAA and TalB that exhibit D-fructose-6-phosphate aldolase activity are inhibited covalently and irreversibly by D-tagatose 6-phosphate (D-T6P), whereas no inhibition was observed for wild-type transaldolase B from E. coli. The crystal structure of the variant TalB(F178Y) with bound sugar phosphate was solved to a resolution of 1.46 Å and revealed a novel mode of covalent inhibition. The sugar is bound covalently via its C2 atom to the ℇ-NH2 group of the active-site residue Lys132. It is neither bound in the open-chain form nor as the closed-ring form of D-T6P, but has been converted to β-D-galactofuranose 6-phosphate (D-G6P), a five-membered ring structure. The furanose ring of the covalent adduct is formed via a Heyns rearrangement and subsequent hemiacetal formation. This reaction is facilitated by Tyr178, which is proposed to act as acid-base catalyst. The crystal structure of the inhibitor complex is compared with the structure of the Schiff-base intermediate of TalB(E96Q) formed with the substrate D-fructose 6-phosphate determined to a resolution of 2.20 Å. This comparison highlights the differences in stereochemistry at the C4 atom of the ligand as an essential determinant for the formation of the inhibitor adduct in the active site of the enzyme.

Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.

PubMed

Xu, Rui; Zhang, Yujie; Gu, Luo; Zheng, Jianchao; Cui, Jie; Dong, Jing; Du, Jun

2015-01-01

E-cadherin internalization facilitates dissolution of adherens junctions and promotes tumor cell epithelial-mesenchymal transition (EMT) and migration. Our previous results have shown that Arf6 exerts pro-migratory action in breast cancer cells after EGF stimulation. Despite the fact that EGF signaling stimulates EMT of breast cancer cells, the effect of Arf6 on internalization of E-cadherin of breast cancer cells under EGF treatment remains to be determined. Here, we showed that EGF dose-dependently stimulated E-cadherin internalization by MCF-7 cells with the maximal effect at 50 ng/ml. Meanwhile, EGF treatment markedly increased Arf6 activation. Arf6 was involved in complexes of E-cadherin, and more E-cadherin was pulled down with Arf6 when the activity of the latter was increased. Immunoblotting and immunofluorescence assays showed that transfection breast cancer cells with Arf6-T27N or Arf6 siRNA suppressed EGF-induced E-cadherin internalization. Taken together, our study demonstrated that Arf6 activation plays a potential role in EGF-induced E-cadherin internalization, providing new mechanism underlying the effect of Arf6 on promoting breast cancer cell metastasis.

Identification of RNA Aptamers that Internalize into HPV-16 E6/E7 Transformed Tonsillar Epithelial Cells

PubMed Central

Gourronc, Francoise A.; Rockey, William M.; Thiel, William H.; Giangrande, Paloma H.; Klingelhutz, Aloysius J.

2013-01-01

Human papillomavirus type 16 (HPV-16) associated oropharyngeal cancers are on a significant increase and better therapeutic strategies are needed. The HPV-16 oncogenes E6 and E7 are expressed in HPV-associated cancers and are able to transform human tonsillar epithelial cells (HTECs). We used cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to select for RNA aptamers that entered into HPV-16 E6/E7-HTECs. After 12 rounds of cell-SELEX, a pool of aptamers was obtained that had significantly greater internalization capacity (~5-fold) into E6/E7-HTECs as compared to primary HTECs or fibroblasts. Analysis of individual aptamers from the pool indicated variable internalization into E6/E7-HTECs (1 to 8-fold as compared to a negative control). Most of the individual aptamers internalized into E6/E7 and primary HTECs with similar efficiency, while one aptamer exhibited ~3-fold better internalization into E6/E7-HTECs. Aptamers that internalize into cells may be useful for delivering therapeutic agents to HPV-16 associated malignancies. PMID:24074596

Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system.

PubMed

Poirson, Juline; Biquand, Elise; Straub, Marie-Laure; Cassonnet, Patricia; Nominé, Yves; Jones, Louis; van der Werf, Sylvie; Travé, Gilles; Zanier, Katia; Jacob, Yves; Demeret, Caroline; Masson, Murielle

2017-10-01

Protein ubiquitination and its reverse reaction, deubiquitination, regulate protein stability, protein binding activity, and their subcellular localization. These reactions are catalyzed by the enzymes E1, E2, and E3 ubiquitin (Ub) ligases and deubiquitinases (DUBs). The Ub-proteasome system (UPS) is targeted by viruses for the sake of their replication and to escape host immune response. To identify novel partners of human papillomavirus 16 (HPV16) E6 and E7 proteins, we assembled and screened a library of 590 cDNAs related to the UPS by using the Gaussia princeps luciferase protein complementation assay. HPV16 E6 was found to bind to the homology to E6AP C terminus-type Ub ligase (E6AP), three really interesting new gene (RING)-type Ub ligases (MGRN1, LNX3, LNX4), and the DUB Ub-specific protease 15 (USP15). Except for E6AP, the binding of UPS factors did not require the LxxLL-binding pocket of HPV16 E6. LNX3 bound preferentially to all high-risk mucosal HPV E6 tested, whereas LNX4 bound specifically to HPV16 E6. HPV16 E7 was found to bind to several broad-complex tramtrack and bric-a-brac domain-containing proteins (such as TNFAIP1/KCTD13) that are potential substrate adaptors of Cullin 3-RING Ub ligases, to RING-type Ub ligases implicated in innate immunity (RNF135, TRIM32, TRAF2, TRAF5), to the substrate adaptor DCAF15 of Cullin 4-RING Ub ligase and to some DUBs (USP29, USP33). The binding to UPS factors did not require the LxCxE motif but rather the C-terminal region of HPV16 E7 protein. The identified UPS factors interacted with most of E7 proteins across different HPV types. This study establishes a strategy for the rapid identification of interactions between host or pathogen proteins and the human ubiquitination system. © 2017 Federation of European Biochemical Societies.

Mathematical Modeling of E6-p53 interactions in Cervical Cancer

PubMed

Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

2017-04-01

Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

Mathematical Modeling of E6-p53 interactions in Cervical Cancer

PubMed Central

Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, AI; Ullah, Mukhtar

2017-01-01

Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. PMID:28547941

Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

PubMed Central

Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

2011-01-01

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

40 CFR 721.2076 - D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false D-Glucuronic acid, polymer with 6...-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium potassium sodium... identified as D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium...

The vaccinia virus E6 protein influences virion protein localization during virus assembly

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

Condit, Richard C., E-mail: condit@mgm.ufl.edu; Moussatche, Nissin

2015-08-15

Vaccinia virus mutants in which expression of the virion core protein gene E6R is repressed are defective in virion morphogenesis. E6 deficient infections fail to properly package viroplasm into viral membranes, resulting in an accumulation of empty immature virions and large aggregates of viroplasm. We have used immunogold electron microscopy and immunofluorescence confocal microscopy to assess the intracellular localization of several virion structural proteins and enzymes during E6R mutant infections. We find that during E6R mutant infections virion membrane proteins and virion transcription enzymes maintain a normal localization within viral factories while several major core and lateral body proteins accumulatemore » in aggregated virosomes. The results support a model in which vaccinia virions are assembled from at least three substructures, the membrane, the viroplasm and a “pre-nucleocapsid”, and that the E6 protein is essential for maintaining proper localization of the seven-protein complex and the viroplasm during assembly. - Highlights: • Mutation of E6 disrupts association of viral membranes with viral core proteins • Mutation of E6 does not perturb viral membrane biosynthesis • Mutation of E6 does not perturb localization of viral transcription enzymes • Mutation of E6 causes mis-localization and aggregation of viral core proteins • Vaccinia assembly uses three subassemblies: membranes, viroplasm, prenucleocapsid.« less

Leptogenesis in the E{sub 6}SSM: Flavour Dependent Lepton Asymmetries

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

King, S. F.; Luo, R.; Miller, D. J.

2008-11-23

We discuss flavour dependent lepton asymmetries in the Exceptional Supersymmetric Standard Model (E{sub 6}SSM). In the E{sub 6}SSM, the right-handed neutrinos do not participate in gauge interactions, and they decay into leptons and leptoquarks. Their Majorana nature allows violation of lepton number. New particles and interactions can result in substantial lepton asymmetries, even for scales as low as 10{sup 6} GeV.

Valproic acid-inducible Arl4D and cytohesin-2/ARNO, acting through the downstream Arf6, regulate neurite outgrowth in N1E-115 cells.

PubMed

Yamauchi, Junji; Miyamoto, Yuki; Torii, Tomohiro; Mizutani, Reiko; Nakamura, Kazuaki; Sanbe, Atsushi; Koide, Hiroshi; Kusakawa, Shinji; Tanoue, Akito

2009-07-15

The mood-stabilizing agent valproic acid (VPA) potently promotes neuronal differentiation. As yet, however, little is known about the underlying molecular mechanism. Here, we show that VPA upregulates cytohesin-2 and mediates neurite outgrowth in N1E-115 neuroblastoma cells. Cytohesin-2 is the guanine-nucleotide exchange factor (GEF) for small GTPases of the Arf family; it regulates many aspects of cellular functions including morphological changes. Treatment with the specific cytohesin family inhibitor SecinH3 or knockdown of cytohesin-2 with its siRNA results in blunted induction of neurite outgrowth in N1E-115 cells. The outgrowth is specifically inhibited by siRNA knockdown of Arf6, but not by that of Arf1. Furthermore, VPA upregulates Arl4D, an Arf-like small GTPase that has recently been identified as the regulator that binds to cytohesin-2. Arl4D knockdown displays an inhibitory effect on neurite outgrowth resulting from VPA, while expression of constitutively active Arl4D induces outgrowth. We also demonstrate that the addition of cell-permeable peptide, coupling the cytohesin-2-binding region of Arl4D into cells, reduces the effect of VPA. Thus, Arl4D is a previously unknown regulator of neurite formation through cytohesin-2 and Arf6, providing another example that the functional interaction of two different small GTPases controls an important cellular function.

β decay of He 6 into the α + d continuum

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

Pfutzner, M.; Dominik, W.; Janas, Z.

2015-07-23

Here, the rare β-decay channel of 6He into the α+d continuum was investigated at the REX-ISOLDE facility. Bunches of postaccelerated 6He ions were implanted into the optical time projection chamber (OTPC), where the decays with emission of charged particles were recorded. This novel technique allowed us to extend the low-energy end of the spectrum down to 150 keV in α+d center of mass, corresponding to a deuteron energy of 100 keV. The branching ratio for this process amounts to [2.78±0.07(stat)±0.17(sys)]×10 –6. The shape of the spectrum is found to be in a good agreement with a three-body model, while themore » total intensity is about 20% larger than the predicted one.« less

Chilean population norms derived from the health-related quality of Life SF-6D.

PubMed

Garcia-Gordillo, Miguel A; Collado-Mateo, Daniel; Olivares, Pedro R; Adsuar, José C

2018-06-01

The Health-Related Quality of Life Short Form 6D (HRQoL SF-6D) provides utility values for health status. Utilities generated have a number of potentially valuable applications in economic evaluations and not only to ensure comparability between studies. Reference values can be useful to estimate the effect on patients' HRQoL as a result of interventions in the absence of control groups. Thus, the purpose of this study was to provide normative values in the SF-6D in relation to the Chilean population. A cross-sectional study was conducted evaluating 5293 people. SF-6D utilities were derived from the SF-12 questions. Mean SF-6D utility index for the whole sample was 0.74. It was better for men (0.78) than for women (0.71). The ceiling effect was much higher for men (11.16%) than for women (5.31%). Women were more likely to show problems in any dimension than were men. Chilean population norms for the SF-6D help in the decision-making process around health policies. Men reported higher health status than women in all subcategories analyzed. Likewise, men also reported higher scores than women in overall SF-6D dimensions.

A precursor to the beta-pyranosides of 3-amino-3,6-dideoxy-D-mannose (mycosamine).

PubMed

Alais, J; David, S

1992-06-04

SN2-type reaction of 3-O-(1-imidazyl)sulfonyl-1,2:5,6-di-O-isopropylidene-alpha-D-gluco furanose with benzoate gave the 3-O-benzoyl-alpha-D-allo derivative 2, which was hydrolysed to give the 5,6-diol 3. Compound 3 was converted into the 6-deoxy-6-iodo derivative 4 which was reduced with tributylstannane, and then position 5 was protected by benzyloxymethylation, to give 3-O-benzoyl-5-O-benzyloxymethyl-6-deoxy-1,2-O-isopropylidene-alpha -D- allofuranose (6). Debenzoylation of 6 gave 7, (1-imidazyl)sulfonylation gave 8, and azide displacement gave 3-azido-5-O-benzyloxymethyl-3,6-dideoxy- 1,2-O-isopropylidene-alpha-D-glucofuranose (9, 85%). Acetolysis of 9 gave 1,2,4-tri-O-acetyl-3-azido-3,6-dideoxy-alpha,beta-D-glucopyranose (10 and 11). Selective hydrolysis of AcO-1 in the mixture of 10 and 11 with hydrazine acetate (----12), followed by conversion into the pyranosyl chloride 13, treatment with N,N-dimethylformamide dimethyl acetal in the presence of tetrabutylammonium bromide, and benzylation gave 3-azido-4-O-benzyl-3,6-dideoxy-1,2-O-(1-methoxyethylidene)-alpha-D -glucopyranose (15). Treatment of 15 with dry acetic acid gave 1,2-di-O-acetyl-3-azido-4-O-benzyl-3,6-dideoxy-beta-D-glucopyranose (16, 86% yield) that was an excellent glycosyl donor in the presence of trimethylsilyl triflate, allowing the synthesis of cyclohexyl 2-O-acetyl-3-azido-4-O-benzyl-3,6-dideoxy-beta-D-glucopyranoside (17, 90%).(ABSTRACT TRUNCATED AT 250 WORDS)

A molecular beam photoionization mass spectrometric study of Cr(CO){sub 6}, Mo(CO){sub 6}, and W(CO){sub 6}

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

Chen, Y.; Liao, C.; Ng, C.Y.

1997-09-01

The photoionization efficiency (PIE) spectra for M(CO){sub n}{sup +} (n=0{endash}6) from M(CO){sub 6}, M=Cr, Mo, and W, have been measured in the photon energy range of 650{endash}1600 {Angstrom}. Based on the ionization energies for M(CO){sub 6} and appearance energies (AEs) for M(CO){sub n}{sup +} (n=0{endash}5) determined here, we have obtained estimates for the sequential bond dissociation energies (D{sub 0}) for CO{endash}M(CO){sub n{minus}1}{sup +} (n=1{endash}6). The comparison between the D{sub 0} values for the Cr(CO){sub 6}{sup +} system obtained here and in the recent collisional induced dissociation and theoretical studies suggests that D{sub 0} values for CO{endash}M(CO){sub n{minus}1}{sup +} (n=3{endash}6) basedmore » on this PIE experiment are reliable. The PIE results reveal the general trend for individual D{sub 0} values that D{sub 0}[CO{endash}Cr(CO){sub n{minus}1}{sup +}]{lt}D{sub 0}[CO{endash}Mo(CO){sub n{minus}1}{sup +}]{lt}D{sub 0}[CO{endash}W(CO){sub n{minus}1}{sup +}] (n=3{endash}6). The comparison of the first D{sub 0} values for M(CO){sub 6}{sup +} obtained here and those for M(CO){sub 6} reported previously provides strong support for the theoretical analysis that the importance of relativistic effects, which give rise to more efficient M to CO {pi}-back-donation in M(CO){sub 6}, is in the order W(CO){sub 6}{gt}Mo(CO){sub 6}{gt}Cr(CO){sub 6}. {copyright} {ital 1997 American Institute of Physics.}« less

Biological characterization of bovine mammary epithelial cell lines immortalized by HPV16 E6/E7 and SV40T.

PubMed

Zhan, Kang; Lin, Miao; Zhao, Qian-Ming; Zhan, Jin-Shun; Zhao, Guo-Qi

2016-10-01

Primary bovine mammary epithelial cells are not ideal models for long-term studies, because primary cells undergo a limited number of proliferations in vitro and enter into a growth-arrest stage called cell replicative senescence; we therefore must establish the immortalized bovine mammary epithelial cells (BMECs) in vitro. More importantly, the mechanisms of the relationship between immortalized and apoptotic cell remain unknown in BMECs. We therefore sought to elucidate the mechanisms of which immortalized cells escape the pathway of apoptotic signal. These cells were successfully immortalized without any signs of senescence. The maximum number of BMEC and E6E7 immortalized cells were reached after 6 d of culture. At this point, there were significantly more E6E7 immortalized cells than primary BMECs (P < 0.01). The population-doubling times of the E6E7 and SV40T immortalized cells were lowest at 48 and 72 h. We failed to detect the expression of the epithelial cell marker E-cadherin in BMECs; however, immortalized cells had low expression of E-cadherin. The expression of β-catenin was markedly expressed in immortalized cells than in BMECs (P < 0.01). Caspase-3, caspase-9, and poly ADP-ribose polymerase (PARP) were detected; however, the cleavage of caspase-3 and PARP was not observed. Our data demonstrate that the expressions of caspase-9, caspase-3, and PARP are not sufficient for the apoptosis of immortalized cells and suggest that E-cadherin and β-catenin might be an important indicator of the development of cancer.

Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study.

PubMed

Zhang, Jinling; Zhu, Xuebin; Li, Yuhong; Zhu, Lingyan; Li, Shiming; Zheng, Guoying; Ren, Qi; Xiao, Yonghong; Feng, Fumin

2016-08-01

This study investigated the role of CpG island methylation of the CYP2E1 and CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic perspective in a Chinese cohort. A 1:1 matched nested case-control study design was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB therapy and developed liver injury were defined as cases, while those who did not develop liver injury were defined as control. The two groups were matched in terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of anti-TB drug-induced liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively (p < 0.01). Moreover, through multivariate logistic regression analysis, CpG island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of ADLI, with adjusted OR values of 4.390 (95% confidence interval (CI): 1.982-9.724) and 9.193 (95% CI: 3.624-25.888), respectively (p < 0.001). These results suggest that aberrantly elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA may increase the risk of ADLI in Chinese TB patients.

Proteomic analysis of the gamma human papillomavirus type 197 E6 and E7 associated cellular proteins

PubMed Central

Grace, Miranda; Munger, Karl

2016-01-01

Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing. To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex. Despite lacking a canonical retinoblastoma (RB1) tumor suppressor binding site, HPV197 E7 binds RB1 and activates E2F transcription. Hence, HPV197 E6 and E7 proteins interact with a similar set of cellular proteins as E6 and E7 proteins encoded by HPVs that have been linked to human carcinogenesis and/or have transforming activities in vitro. PMID:27771561

Discoloration of the wetted surface in the 6.1D dissolver

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

Rudisill, T.; Mickalonis, J.; Crapse, K.

During a camera inspection of a failed coil in the 6.1D dissolver, an orange discoloration was observed on a portion of the dissolver wall and coils. At the request of H-Canyon Engineering, the inspection video of the dissolver was reviewed by SRNL to assess if the observed condition (a non-uniform, orange-colored substance on internal surfaces) was a result of corrosion. Although the dissolver vessel and coil corrode during dissolution operations, the high acid conditions are not consistent with the formation of ferrous oxides (i.e., orange/rust-colored corrosion products). In a subsequent investigation, SRNL performed dissolution experiments to determine if residues frommore » the nylon bags used for Pu containment could have generated the orange discoloration following dissolution. When small pieces of a nylon bag were placed in boiling 8 M nitric acid solutions containing other components representative of the H-Canyon process, complete dissolution occurred almost immediately. No residues were obtained even when a nylon mass to volume ratio greater than 100 times the 6.1D dissolver value was used. Degradation products from the dissolution of nylon bags are not responsible for the discoloration observed in the dissolver.« less

Facilitation of extinction of operant behaviour in C57Bl/6 mice by chlordiazepoxide and D-cycloserine.

PubMed

Leslie, Julian C; Norwood, Kelly; Kennedy, Paul J; Begley, Michael; Shaw, David

2012-09-01

Effects on the extinction of GABAergic drug, chlordiazepoxide (CDP), and glutamatergic drug, D: -cycloserine (DCS), in C57BL/6 mice were compared. Following a palatability test (Experiment 1), Experiments 2-6 involved food-reinforced lever press training followed by extinction sessions at 1- or 4-day intervals. The effects of drugs were examined. Experiment 7 involved a two-lever task. CDP did not affect food palatability (Experiment 1), but facilitated extinction when administered prior to extinction sessions via intracerebral (Experiment 2) or peripheral administration at 1-day (Experiments 3-7) or 4-day intervals (Experiment 6). Reducing the amount of training prior to extinction reduced the delay in the effect of CDP typically seen, and CDP had a larger effect in early sessions on mice that had received less training (Experiment 3). There was some evidence that CDP could be blocked by flumazenil (Experiment 4), and CDP withdrawal reversed extinction facilitation (Experiments 5 and 7). With 4-day intervals, DCS administered immediately following extinction sessions, or pre-session CDP, facilitated extinction with 48-trial sessions (experiment 6B). With six-trial sessions, the co-administration of post-session DCS enhanced facilitation produced by pre-session CDP (experiment 6A). Finally, CDP facilitated extinction in a dose-related fashion following training on a two-lever food-reinforced task (Experiment 7). The findings are consistent with the hypotheses that two neurotransmitter systems have different roles in operant extinction and that glutamatergic systems are involved in extinction learning and GABAergic systems involved in the expression of that learning. This parallels findings with extinction following Pavlovian conditioning, which has been more extensively investigated.

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PubMed

Wang, P; Fu, A Z; Wee, H L; Lee, J; Tai, E S; Thumboo, J; Luo, N

2013-09-01

To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

CFL3D Version 6.4-General Usage and Aeroelastic Analysis

NASA Technical Reports Server (NTRS)

Bartels, Robert E.; Rumsey, Christopher L.; Biedron, Robert T.

2006-01-01

This document contains the course notes on the computational fluid dynamics code CFL3D version 6.4. It is intended to provide from basic to advanced users the information necessary to successfully use the code for a broad range of cases. Much of the course covers capability that has been a part of previous versions of the code, with material compiled from a CFL3D v5.0 manual and from the CFL3D v6 web site prior to the current release. This part of the material is presented to users of the code not familiar with computational fluid dynamics. There is new capability in CFL3D version 6.4 presented here that has not previously been published. There are also outdated features no longer used or recommended in recent releases of the code. The information offered here supersedes earlier manuals and updates outdated usage. Where current usage supersedes older versions, notation of that is made. These course notes also provides hints for usage, code installation and examples not found elsewhere.

Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells

PubMed Central

Mann, Amandeep; Tyndale, Rachel F.

2016-01-01

Cytochrome P450 (CYP) 2D6 is an enzyme that is expressed in liver and brain. It can inactivate neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroisoquinoline and β-carbolines. Genetically slow CYP2D6 metabolizers are at higher risk for developing Parkinson’s disease, a risk that increases with exposure to pesticides. The goal of this study was to investigate the neuroprotective role of CYP2D6 in an in-vitro neurotoxicity model. SH-SY5Y human neuroblastoma cells express CYP2D6 as determined by western blotting, immunocytochemistry and enzymatic activity. CYP2D6 metabolized 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin and the CYP2D6-specific inhibitor quinidine (1 μM) blocked 96 ± 1% of this metabolism, indicating that CYP2D6 is functional in this cell line. Treatment of cells with CYP2D6 inhibitors (quinidine, propanolol, metoprolol or timolol) at varying concentrations significantly increased the neurotoxicity caused by 1-methyl-4-phenylpyridinium (MPP+) at 10 and 25 μM by between 9 ± 1 and 22 ± 5% (P < 0.01). We found that CYP3A is also expressed in SH-SY5Y cells and inhibiting CYP3A with ketoconazole significantly increased the cell death caused by 10 and 25 μM of MPP+ by between 8 ± 1 and 30 ± 3% (P < 0.001). Inhibiting both CYP2D6 and CYP3A showed an additive effect on MPP+ neurotoxicity. These data further support a possible role for CYP2D6 in neuroprotection from Parkinson’s disease-causing neurotoxins, especially in the human brain where expression of CYP2D6 is high in some regions (e.g. substantia nigra). PMID:20345925

Correlation of P16 (Ink4a) and CK17 to HPV (16E6+18E6) in Premalignant and Malignant Lesions of Uterine Cervix: A Clinicopathologic Study

PubMed Central

Chaloob, Mohammed K.; Hussein, Alaa G.; Qasim, Ban J.

2016-01-01

Background: This research was accomplished to evaluate the IHC expression of p16 (ink4a) and CK17 in low grade cervical intraepithelial lesions (LSIL), high grade cervical intraepithelial lesions (HSIL) and invasive cervical carcinomas and to assess their correlation to HPV (16E6+18E6). Methods: The study included (127) formalin-fixed paraffin-embedded cervical biopsies; of which 22 cases were chronic cervicitis, 24 cases were LSIL, 28 cases were HSIL and 53 cases were invasive cervical carcinomas. Sections were immunohistochemically stained for p16 (ink4a), CK17 and HPV (16E6+18E6). Results: The study established a highly significant increase in IHC of expression of p16 (ink4a), CK17 and HPV (16E6+18E6) from LSIL through HSIL to invasive carcinomas (P-value˂0.001). There was non-significant association between IHC expression of all makers with age of patients; types, grade and stage of cervical carcinomas (P-value˃0.05). HPV (16E6+18E6) revealed a significantly positive correlation with p16 (ink4a) (P-value˂0.05) and a non- significant correlation with CK17 (P-value˃0.05); in LSIL, HSIL and invasive carcinoma cases. Conclusion: p16 (ink4a) expression directly reflects infection with high risk HPV in cervical lesions and can add a significant diagnostic accuracy in the evaluation of CIN. CK 17 is a good marker of malignant transformation, with increasing in its expression according to the severity of cervical lesions; however, it is not related to HPV infection. Both markers are not related to prognostic variables of patients with cervical carcinoma. PMID:28855930

Synthesis, spectroscopic investigations (FT-IR, NMR, UV-Vis, and TD-DFT), and molecular docking of (E)-1-(benzo[d][1, 3]dioxol-6-yl)-3-(6-methoxynaphthalen-2-yl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Therasa Alphonsa, A.; Loganathan, C.; Athavan Alias Anand, S.; Kabilan, S.

2017-02-01

The compound (E)-1-(benzo [d] [1, 3] dioxol-6-yl)-3-(6-methoxy naphthalen-2-yl) prop-2-en-1-one (AKN) was synthesized and characterized by FT-IR, NMR, and UV-Vis spectrometer. The optimized molecular geometry, bond lengths, bond angles, atomic charges, harmonic vibrational wave numbers and intensities of vibrational bonds of the title compound have been investigated by Time dependent- Density Functional Theory (TD-DFT) using a standard B3LYP method with 6-31 G (d, p) basis set available in the Gaussian 09W package. 1H and 13C NMR chemical shifts of the molecule were calculated using Gauge-independent atomic orbital method (GIAO). Experimental excitation energies of the molecules were matched with the theoretically calculated energies. The atomic charge distributions of the various atoms present in the AKN were obtained by Mulliken charge population analysis. The Molecular Electrostatic Potential (MEP) analysis reveals the sites for electrophilic attack and nucleophilic reactions in the molecule. The difference between the observed and scaled frequencies was small. The HOMO to LUMO transition implies an electron density transfer. The intramolecular contacts have been interpreted using Natural Bond Orbital (NBO) analysis. The calculation results were applied to simulate spectra of the title compound, which show excellent agreement with observed spectra. To provide information about the interactions between human cytochrome protein and the novel compound theoretically, docking studies were carried out using Schrödinger software.

Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

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

Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim

Highlights: {yields} Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. {yields} BAF53 is essential for higher-order chromatin structure. {yields} BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. {yields} BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. {yields} BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways,more » respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher

Pharmacophore, QSAR, and binding mode studies of substrates of human cytochrome P450 2D6 (CYP2D6) using molecular docking and virtual mutations and an application to chinese herbal medicine screening.

PubMed

Mo, Sui-Lin; Liu, Wei-Feng; Li, Chun-Guang; Zhou, Zhi-Wei; Luo, Hai-Bin; Chew, Helen; Liang, Jun; Zhou, Shu-Feng

2012-07-01

The highly polymorphic human cytochrome P450 2D6 (CYP2D6) metabolizes about 25% of currently used drugs. In this study, we have explored the interaction of a large number of substrates (n = 120) with wild-type and mutated CYP2D6 by molecular docking using the CDOCKER module. Before we conducted the molecular docking and virtual mutations, the pharmacophore and QSAR models of CYP2D6 substrates were developed and validated. Finally, we explored the interaction of a traditional Chinese herbal formula, Fangjifuling decoction, with CYP2D6 by virtual screening. The optimized pharmacophore model derived from 20 substrates of CYP2D6 contained two hydrophobic features and one hydrogen bond acceptor feature, giving a relevance ratio of 76% when a validation set of substrates were tested. However, our QSAR models gave poor prediction of the binding affinity of substrates. Our docking study demonstrated that 117 out of 120 substrates could be docked into the active site of CYP2D6. Forty one out of 117 substrates (35.04%) formed hydrogen bonds with various active site residues of CYP2D6 and 53 (45.30%) substrates formed a strong π-π interaction with Phe120 (53/54), with only carvedilol showing π-π interaction with Phe483. The active site residues involving hydrogen bond formation with substrates included Leu213, Lys214, Glu216, Ser217, Gln244, Asp301, Ser304, Ala305, Phe483, and Phe484. Furthermore, the CDOCKER algorithm was further applied to study the impact of mutations of 28 active site residues (mostly non-conserved) of CYP2D6 on substrate binding modes using five probe substrates including bufuralol, debrisoquine, dextromethorphan, sparteine, and tramadol. All mutations of the residues examined altered the hydrogen bond formation and/or aromatic interactions, depending on the probe used in molecular docking. Apparent changes of the binding modes have been observed with the Glu216Asp and Asp301Glu mutants. Overall, 60 compounds out of 130 from Fangjifuling decoction

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2017-12-01

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane.

PubMed

Muratori, L; Parola, M; Ripalti, A; Robino, G; Muratori, P; Bellomo, G; Carini, R; Lenzi, M; Landini, M P; Albano, E; Bianchi, F B

2000-04-01

Liver/kidney microsomal antibody type 1 (LKM1) is the marker of type 2 autoimmune hepatitis (AIH) and is detected in up to 6% of patients with hepatitis C virus (HCV) infection. It recognises linear and conformational epitopes of cytochrome P450IID6 (CYP2D6) and may have liver damaging activity, provided that CYP2D6 is accessible to effector mechanisms of autoimmune attack. The presence of LKM1 in the plasma membrane was investigated by indirect immunofluorescence and confocal laser microscopy of isolated rat hepatocytes probed with 10 LKM1 positive sera (five from patients with AIH and five from patients with chronic HCV infection) and a rabbit polyclonal anti-CYP2D6 serum. Serum from both types of patient stained the plasma membrane of non-permeabilised cells, where the fluorescent signal could be visualised as discrete clumps. Conversely, permeabilised hepatocytes showed diffuse submembranous/cytoplasmic staining. Adsorption with recombinant CYP2D6 substantially reduced plasma membrane staining and LKM1 immunoblot reactivity. Plasma membrane staining of LKM1 colocalised with that of anti-CYP2D6. Immunoprecipitation experiments showed that a single 50 kDa protein recognised by anti-CYP2D6 can be isolated from the plasma membrane of intact hepatocytes. AIH and HCV related LKM1 recognise CYP2D6 exposed on the plasma membrane of isolated hepatocytes. This observation supports the notion that anti-CYP2D6 autoreactivity may be involved in the pathogenesis of liver damage.

CYP2B6, CYP2D6, and CYP3A4 catalyze the primary oxidative metabolism of perhexiline enantiomers by human liver microsomes.

PubMed

Davies, Benjamin J; Coller, Janet K; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

2007-01-01

The cytochrome P450 (P450)-mediated 4-monohydroxylations of the individual enantiomers of the racemic antianginal agent perhexiline (PHX) were investigated in human liver microsomes (HLMs) to identify stereoselective differences in metabolism and to determine the contribution of the polymorphic enzyme CYP2D6 and other P450s to the intrinsic clearance of each enantiomer. The cis-, trans1-, and trans2-4-monohydroxylation rates of (+)- and (-)-PHX by human liver microsomes from three extensive metabolizers (EMs), two intermediate metabolizers (IMs), and two poor metabolizers (PMs) of CYP2D6 were measured with a high-performance liquid chromatography assay. P450 isoform-specific inhibitors, monoclonal antibodies directed against P450 isoforms, and recombinantly expressed human P450 enzymes were used to define the P450 isoform profile of PHX 4-monohydroxylations. The total in vitro intrinsic clearance values (mean +/- S.D.) of (+)- and (-)-PHX were 1376 +/- 330 and 2475 +/- 321, 230 +/- 225 and 482 +/- 437, and 63.4 +/- 1.6 and 54.6 +/- 1.2 microl/min/mg for the EM, IM, and PM HLMs, respectively. CYP2D6 catalyzes the formation of cis-OH-(+)-PHX and trans1-OH-(+)-PHX from (+)-PHX and cis-OH-(-)-PHX from (-)-PHX with high affinity. CYP2B6 and CYP3A4 each catalyze the trans1- and trans2-4-monohydroxylation of both (+)- and (-)-PHX with low affinity. Both enantiomers of PHX are subject to significant polymorphic metabolism by CYP2D6, although this enzyme exhibits distinct stereoselectivity with respect to the conformation of metabolites and the rate at which they are formed. CYP2B6 and CYP3A4 are minor contributors to the intrinsic P450-mediated hepatic clearance of both enantiomers of PHX, except in CYP2D6 PMs.

Probing 6D operators at future e - e + colliders

NASA Astrophysics Data System (ADS)

Chiu, Wen Han; Leung, Sze Ching; Liu, Tao; Lyu, Kun-Feng; Wang, Lian-Tao

2018-05-01

We explore the sensitivities at future e - e + colliders to probe a set of six-dimensional operators which can modify the SM predictions on Higgs physics and electroweak precision measurements. We consider the case in which the operators are turned on simultaneously. Such an analysis yields a "conservative" interpretation on the collider sensitivities, complementary to the "optimistic" scenario where the operators are individually probed. After a detail analysis at CEPC in both "conservative" and "optimistic" scenarios, we also considered the sensitivities for FCC-ee and ILC. As an illustration of the potential of constraining new physics models, we applied sensitivity analysis to two benchmarks: holographic composite Higgs model and littlest Higgs model.

Triacetonide of Glucoheptonic Acid in the Scalable Syntheses of d-Gulose, 6-Deoxy-d-gulose, l-Glucose, 6-Deoxy-l-glucose, and Related Sugars.

PubMed

Liu, Zilei; Yoshihara, Akihide; Jenkinson, Sarah F; Wormald, Mark R; Estévez, Ramón J; Fleet, George W J; Izumori, Ken

2016-08-19

Ease of separation of petrol-soluble acetonides derived from the triacetonide of methyl glucoheptonate allows scalable syntheses of rare sugars containing the l-gluco or d-gulo structural motif with any oxidation level at the C6 or C1 position of the hexose, usually without chromatography: meso-d-glycero-d-guloheptitol available in two steps is an ideal entry point for the study of the biotechnological production of heptoses.

The chemokine decoy receptor D6 prevents excessive inflammation and adverse ventricular remodeling after myocardial infarction.

PubMed

Cochain, Clément; Auvynet, Constance; Poupel, Lucie; Vilar, José; Dumeau, Edouard; Richart, Adèle; Récalde, Alice; Zouggari, Yasmine; Yin, Kiave Yune Ho Wang; Bruneval, Patrick; Renault, Gilles; Marchiol, Carmen; Bonnin, Philippe; Lévy, Bernard; Bonecchi, Raffaella; Locati, Massimo; Combadière, Christophe; Silvestre, Jean-Sébastien

2012-09-01

Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming infiltration of innate immune cells has been shown to promote adverse remodeling and cardiac rupture. Recruitment of inflammatory cells in the ischemic heart depends highly on the family of CC-chemokines and their receptors. Here, we hypothesized that the chemokine decoy receptor D6, which specifically binds and scavenges inflammatory CC-chemokines, might limit inflammation and adverse cardiac remodeling after infarction. D6 was expressed in human and murine infarcted myocardium. In a murine model of myocardial infarction, D6 deficiency led to increased chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 3 levels in the ischemic heart. D6-deficient (D6(-/-)) infarcts displayed increased infiltration of pathogenic neutrophils and Ly6Chi monocytes, associated with strong matrix metalloproteinase-9 and matrix metalloproteinase-2 activities in the ischemic heart. D6(-/-) mice were cardiac rupture prone after myocardial infarction, and functional analysis revealed that D6(-/-) hearts had features of adverse remodeling with left ventricle dilation and reduced ejection fraction. Bone marrow chimera experiments showed that leukocyte-borne D6 had no role in this setting, and that leukocyte-specific chemokine (C-C motif) receptor 2 deficiency rescued the adverse phenotype observed in D6(-/-) mice. We show for the first time that the chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction.

(1-->6)-beta-D-glucan as cell wall receptor for Pichia membranifaciens killer toxin.

PubMed

Santos, A; Marquina, D; Leal, J A; Peinado, J M

2000-05-01

The killer toxin from Pichia membranifaciens CYC 1106, a yeast isolated from fermenting olive brines, binds primarily to the (1-->6)-beta-D-glucan of the cell wall of a sensitive yeast (Candida boidinii IGC 3430). The (1-->6)-beta-D-glucan was purified from cell walls of C. boidinii by alkali and hot-acetic acid extraction, a procedure which solubilizes glucans. The major fraction of receptor activity remained with the alkali-insoluble (1-->6)-beta- and (1-->3)-beta-D-glucans. The chemical (gas-liquid chromatography) and structural (periodate oxidation, infrared spectroscopy, and (1)H nuclear magnetic resonance) analyses of the fractions obtained showed that (1-->6)-beta-D-glucan was a receptor. Adsorption of most of the killer toxin to the (1-->6)-beta-D-glucan was complete within 2 min. Killer toxin adsorption to the linear (1-->6)-beta-D-glucan, pustulan, and a glucan from Penicillium allahabadense was observed. Other polysaccharides with different linkages failed to bind the killer toxin. The specificity of the killer toxin for its primary receptor provides an effective means to purify the killer toxin, which may have industrial applications for fermentations in which salt is present as an adjunct, such as olive brines. This toxin shows its maximum killer activity in the presence of NaCl. This report is the first to identify the (1-->6)-beta-D-glucan as a receptor for this novel toxin.

Equivalence of several descriptions for 6d SCFT

NASA Astrophysics Data System (ADS)

Hayashi, Hirotaka; Kim, Sung-Soo; Lee, Kimyeong; Yagi, Futoshi

2017-01-01

We show that the three different looking BPS partition functions, namely the elliptic genus of the 6d N=(1, 0) Sp(1) gauge theory with 10 flavors and a tensor multiplet, the Nekrasov partition function of the 5d N=1 Sp(2) gauge theory with 10 flavors, and the Nekrasov partition function of the 5d N=1 SU(3) gauge theory with 10 flavors, are all equal to each other under specific maps among gauge theory parameters. This result strongly suggests that the three gauge theories have an identical UV fixed point. Type IIB 5-brane web diagrams play an essential role to compute the SU(3) Nekrasov partition function as well as establishing the maps.

Geospace Plasma Dynamics Laboratory Annual Task Report (FY11)

DTIC Science & Technology

2012-03-01

Site Contractors: Nagendra Singh, Ph.D., Physicist , 0.5 MY Neil Grossbard, M.S., Mathematician , 0.7 MY Visitors: Publications: Articles in...PhD Project Manager Division Chief, RVB This report is published in the interest of scientific and technical...Annual Task Report (FY11) 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) 5d. PROJECT NUMBER 2311 Daniel Ober 5e. TASK NUMBER

HPV16 E6 Promotes Breast Cancer Proliferation via Upregulation of COX-2 Expression

PubMed Central

Li, Y. Z.; Zhang, Z. Y.; Wang, J. Q.

2017-01-01

Background. Breast cancer remains the leading cause of cancer-related mortality worldwide. It has been indicated that human papillomaviruses 16 (HPV16) might participate in the pathogenesis and development of breast cancer. However, the detected rate of HPV16 varies with region. We will investigate HPV16 E6 expression in North China and explore the effects and mechanism of HPV16 E6 on breast cancer proliferation in this study. Methods. The expressions of HPV16 E6 and COX-2 in paraffin-embedded tissues of the invasive ductal breast cancer were detected by qPCR and IHC. The effects of HPV16 E6 on breast cancer proliferation were determined by function studies. The mechanism of HPV16 E6 in promoting breast cancer proliferation was explored by Western blot and Dual-Luciferase Reporter Assay. Results. HPV16 E6 was positive in 28% invasive ductal breast carcinoma in North China; HPV16 E6 promoted breast cancer proliferation. Inhibition of COX-2 by siCOX-2 or Celecoxib attenuated the proliferation of breast cancer cells with HPV16 E6 expression; and the upregulation of COX-2 could be suppressed by the inhibition of NF-κB activity. Conclusion. HPV16 E6 promotes breast cancer proliferation by activation of NF-κB signaling pathway and increase of COX-2 expression. COX-2 will be a potential target for HPV16 E6-associated breast cancer. PMID:29250535

A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6.

PubMed

Marchiò, Serena; Soster, Marco; Cardaci, Sabrina; Muratore, Andrea; Bartolini, Alice; Barone, Vanessa; Ribero, Dario; Monti, Maria; Bovino, Paola; Sun, Jessica; Giavazzi, Raffaella; Asioli, Sofia; Cassoni, Paola; Capussotti, Lorenzo; Pucci, Piero; Bugatti, Antonella; Rusnati, Marco; Pasqualini, Renata; Arap, Wadih; Bussolino, Federico

2012-11-01

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α(6) integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α(6) integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α(6) integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC. Copyright © 2012 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6

PubMed Central

Marchiò, Serena; Soster, Marco; Cardaci, Sabrina; Muratore, Andrea; Bartolini, Alice; Barone, Vanessa; Ribero, Dario; Monti, Maria; Bovino, Paola; Sun, Jessica; Giavazzi, Raffaella; Asioli, Sofia; Cassoni, Paola; Capussotti, Lorenzo; Pucci, Piero; Bugatti, Antonella; Rusnati, Marco; Pasqualini, Renata; Arap, Wadih; Bussolino, Federico

2012-01-01

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α6 integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α6 integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α6 integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC. PMID:23070965

Construct validity of SF-6D health state utility values in an employed population.

PubMed

Baxter, Siyan; Sanderson, Kristy; Venn, Alison; Otahal, Petr; Palmer, Andrew J

2015-04-01

Health utility values permit cost utility analysis in workplace health promotion; however, utility measures of working populations have not been validated. To investigate construct validity of SF-6D health utility in a public service workforce. SF-12v2 Health Survey was administered to 3,408 randomly selected public service employees in Australia in 2010. SF-12 scores were converted to SF-6D health utility values. Associations and correlates of SF-6D with health, socio-demographic and work characteristics [comorbidities, body mass index (BMI), Kessler-10 psychological distress (K10), education, salary, effort-reward imbalance (ERI), absenteeism] were explored. Ceiling effects were analysed. Nationally representative employee SF-6D values from the Household, Income and Labour Dynamics in Australia (HILDA) survey (n = 11,234) were compared. All analyses were stratified by sex. Mean (SE) age was 45.7 (0.35) males; 44.5 (0.22) females. Females represented 72 % of the sample. Mean (SE) health utility 0.792 (0.004); 0.771 (0.003) was higher in males. SF-6D demonstrated both a significant inverse association (p < 0.01) and negative correlations (female; male) with K10 (r = -0.63; r = -0.66), comorbidity count (r = -0.40; r = -0.33), ERI (r = -0.37; r = -0.34) and absenteeism (p < 0.005, r = -0.25; r = -0.21). Mean (SE) SF-6D in HILDA was 0.792 (0.002); 0.775 (0.003) males; females. Correlates and associations in all samples were similar. The general employed demonstrated a significant inverse association with age and positive association with salary. SF-6D was independent of BMI. Psychological distress, comorbidity, effort-reward imbalance and absenteeism are negatively associated with employee health. SF-6D is a valid measure of perceived health states in working populations.

MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb repressive complex PRC1.6

PubMed Central

Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten

2018-01-01

Diverse Polycomb repressive complexes 1 (PRC1) play essential roles in gene regulation, differentiation and development. Six major groups of PRC1 complexes that differ in their subunit composition have been identified in mammals. How the different PRC1 complexes are recruited to specific genomic sites is poorly understood. The Polycomb Ring finger protein PCGF6, the transcription factors MGA and E2F6, and the histone-binding protein L3MBTL2 are specific components of the non-canonical PRC1.6 complex. In this study, we have investigated their role in genomic targeting of PRC1.6. ChIP-seq analysis revealed colocalization of MGA, L3MBTL2, E2F6 and PCGF6 genome-wide. Ablation of MGA in a human cell line by CRISPR/Cas resulted in complete loss of PRC1.6 binding. Rescue experiments revealed that MGA recruits PRC1.6 to specific loci both by DNA binding-dependent and by DNA binding-independent mechanisms. Depletion of L3MBTL2 and E2F6 but not of PCGF6 resulted in differential, locus-specific loss of PRC1.6 binding illustrating that different subunits mediate PRC1.6 loading to distinct sets of promoters. Mga, L3mbtl2 and Pcgf6 colocalize also in mouse embryonic stem cells, where PRC1.6 has been linked to repression of germ cell-related genes. Our findings unveil strikingly different genomic recruitment mechanisms of the non-canonical PRC1.6 complex, which specify its cell type- and context-specific regulatory functions. PMID:29381691

Non-Abelian black string solutions of N = (2,0) , d = 6 supergravity

NASA Astrophysics Data System (ADS)

Cano, Pablo A.; Ortín, Tomás; Santoli, Camilla

2016-12-01

We show that, when compactified on a circle, N = (2, 0), d = 6 supergravity coupled to 1 tensor multiplet and n V vector multiplets is dual to N = (2 , 0) , d = 6 supergravity coupled to just n T = n V + 1 tensor multiplets and no vector multiplets. Both theories reduce to the same models of N = 2 , d = 5 supergravity coupled to n V 5 = n V + 2 vector fields. We derive Buscher rules that relate solutions of these theories (and of the theory that one obtains by dualizing the 3-form field strength) admitting an isometry. Since the relations between the fields of N = 2 , d = 5 supergravity and those of the 6-dimensional theories are the same with or without gaugings, we construct supersymmetric non-Abelian solutions of the 6-dimensional gauged theories by uplifting the recently found 5-dimensional supersymmetric non-Abelian black-hole solutions. The solutions describe the usual superpositions of strings and waves supplemented by a BPST instanton in the transverse directions, similar to the gauge dyonic string of Duff, Lü and Pope. One of the solutions obtained interpolates smoothly between two AdS3× S3 geometries with different radii.

Quantitation of Human Cytochrome P450 2D6 Protein with Immunoblot and Mass Spectrometry Analysis

PubMed Central

Yu, Ai-Ming; Qu, Jun; Felmlee, Melanie A.; Cao, Jin; Jiang, Xi-Ling

2009-01-01

Accurate quantification of cytochrome P450 (P450) protein contents is essential for reliable assessment of drug safety, including the prediction of in vivo clearance from in vitro metabolism data, which may be hampered by the use of uncharacterized standards and existence of unknown allelic isozymes. Therefore, this study aimed to delineate the variability in absolute quantification of polymorphic CYP2D6 drug-metabolizing enzyme and compare immunoblot and nano liquid chromatography coupled to mass spectrometry (nano-LC/MS) methods in identification and relative quantification of CYP2D6.1 and CYP2D6.2 allelic isozymes. Holoprotein content of in-house purified CYP2D6 isozymes was determined according to carbon monoxide difference spectrum, and total protein was quantified with bicinchoninic acid protein assay. Holoprotein/total CYP2D6 protein ratio was markedly higher for purified CYP2D6.1 (71.0%) than that calculated for CYP2D6.1 Supersomes (35.5%), resulting in distinct linear calibration range (0.05–0.50 versus 0.025–0.25 pmol) that was determined by densitometric analysis of immunoblot bands. Likewise, purified CYP2D6.2 and CYP2D6.10 and the CYP2D6.10 Supersomes all showed different holoprotein/total CYP2D6 protein ratios and distinct immunoblot linear calibration ranges. In contrast to immunoblot, nano-LC/MS readily distinguished CYP2D6.2 (R296C and S486T) from CYP2D6.1 by isoform-specific proteolytic peptides that contain the altered amino acid residues. In addition, relative quantitation of the two allelic isozymes was successfully achieved with label-free protein quantification, consistent with the nominated ratio. Because immunoblot and nano-LC/MS analyses measure total P450 protein (holoprotein and apoprotein) in a sample, complete understanding of holoprotein and apoprotein contents in P450 standards is desired toward reliable quantification. Our data also suggest that nano-LC/MS not only facilitates P450 quantitation but also provides genotypic

A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.

PubMed

Maffie, Jonathon; Blenkinsop, Timothy; Rudy, Bernardo

2009-01-16

The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

The DEP-6D, a new preference-based measure to assess health states of dependency.

PubMed

Rodríguez-Míguez, E; Abellán-Perpiñán, J M; Alvarez, X C; González, X M; Sampayo, A R

2016-03-01

In medical literature there are numerous multidimensional scales to measure health states for dependence in activities of daily living. However, these scales are not preference-based and are not able to yield QALYs. On the contrary, the generic preference-based measures are not sensitive enough to measure changes in dependence states. The objective of this paper is to propose a new dependency health state classification system, called DEP-6D, and to estimate its value set in such a way that it can be used in QALY calculations. DEP-6D states are described as a combination of 6 attributes (eat, incontinence, personal care, mobility, housework and cognition problems), with 3-4 levels each. A sample of 312 Spanish citizens was surveyed in 2011 to estimate the DEP-6D preference-scoring algorithm. Each respondent valued six out of the 24 states using time trade-off questions. After excluding those respondents who made two or more inconsistencies (6% out of the sample), each state was valued between 66 and 77 times. The responses present a high internal and external consistency. A random effect model accounting for main effects was the preferred model to estimate the scoring algorithm. The DEP-6D describes, in general, more severe problems than those usually described by means of generic preference-based measures. The minimum score predicted by the DEP-6D algorithm is -0.84, which is considerably lower than the minimum value predicted by the EQ-5D and SF-6D algorithms. The DEP-6D value set is based on community preferences. Therefore it is consistent with the so-called 'societal perspective'. Moreover, DEP-6D preference weights can be used in QALY calculations and cost-utility analysis. Copyright © 2016. Published by Elsevier Ltd.

Telomerase activation by the E6 gene product of human papillomavirus type 16.

PubMed

Klingelhutz, A J; Foster, S A; McDougall, J K

1996-03-07

Activation of telomerase, a ribonucleoprotein complex that synthesizes telomere repeat sequences, is linked to cell immortalization and is characteristic of most cell lines and tumours. Here we show that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells. This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6. Studies using HPV-16 E6 mutants showed that there was no correlation between the ability of the mutants to activate telomerase and their ability to target p53 for degradation, suggesting that telomerase activation by HPV-16 E6 is p53 independent. Keratinocytes expressing wild-type HPV-16 E6 have an extended lifespan, but do not become immortal, indicating that telomerase activation and E6-mediate degradation of p53 are insufficient for their immortalization. These results show that telomerase activation is an intrinsic, but insufficient, component of transformation by HPV.

Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics

PubMed Central

Cacabelos, Ramón; Martínez, Rocío; Fernández-Novoa, Lucía; Carril, Juan C.; Lombardi, Valter; Carrera, Iván; Corzo, Lola; Tellado, Iván; Leszek, Jerzy; McKay, Adam; Takeda, Masatoshi

2012-01-01

Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of the APOE gene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. The APOE and CYP2D6 genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs, CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6 may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics. PMID:22482072

Lack of association between schizophrenia and the CYP2D6 gene polymorphisms

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

Pirmohamed, M.; Wild, M.J.; Kitteringham, N.R.

1996-04-09

Approximately 5-10% of the Caucasian population lack the P450 isoform, CYP2D6. This polymorphism may be of importance in determining individual susceptibility to Parkinson`s disease. In this journal, Daniels et al. recently reported a negative association between the CYP2D6 gene locus and schizophrenia, a disease characterized by dopamine overactivity. It is important to exclude such an association because CYP2D6 is expressed in the brain and it is involved in dopamine catabolism. Between 1992 and 1993, we also performed a study similar to that, and reached the same conclusion. 7 refs., 1 tab.

Comparing the performance of the SF-6D and the EQ-5D in different patient groups.

PubMed

Ferreira, Lara N; Ferreira, Pedro L; Pereira, Luis N

2014-01-01

This research aims to explore the performance of the SF-6D and the EQ-5D in patients suffering from asthma, chronic obstructive pulmonary disease, cataracts, and rheumatoid arthritis. In particular, the aim of this research is twofold: 1) to study the level of agreement between the indexes and the descriptive systems of the dimensions of the SF-6D and the EQ-5D, and 2) to analyze the discriminative ability of the instruments. A sample of 643 patients completed both the SF-36v2 and the EQ-5D. The discriminative ability of the instruments was analyzed. Furthermore, the level of agreement between the indexes and the descriptive systems of the dimensions of the SF-6D and the EQ-5D were studied. The level of agreement between instruments was investigated using correlation coefficients and the Bland-Altman plots, while the influence of medical condition and other socio-demographic variables was analyzed using nonparametric tests. Paired-samples tests were used to identify differences between the scores. The results show a strong correlation and agreement between both indexes. Overall, questionnaire indexes differ by medical condition and socio-demographic groups and both instruments are able to discriminate between socio-demographic groups. This study confirmed the hypothesis that the SF-6D generates higher utility values in less healthy individuals. The SF-6D and the EQ-5D seem to perform differently in each of the diseases studied since the descriptive statistics differ between instruments and the level of correlation is not uniform. Results show that the instruments generate different utility values, but there is a strong agreement between both indexes. Thus, the two instruments are not interchangeable and their results cannot be directly comparable.

LETTER TO THE EDITOR: Cross sections of 6Li(t,d1)7Li*[0.478] and 6Li(t,p1)8Li*[0.981] nuclear reactions in the 0-2 MeV energy range

NASA Astrophysics Data System (ADS)

Voronchev, V. T.; Kukulin, V. I.

2000-12-01

An original extrapolation technique developed previously is modified and applied to study nuclear reactions in the 6Li + T system at energies E = 0-2 MeV. Cross sections of gamma-ray-producing reactions 6Li(t,d1)7Li*[0.478] and 6Li(t,p1)8Li*[0.981] with important diagnostic implications are calculated. The (t,d1) nuclear data found exceed those accepted elsewhere by 2.5-3.5 times at sub-barrier energies. The cross sections of the (t,p1) reaction are calculated for the first time.

Relatedness of the O-polysaccharide structures of Escherichia coli O123 and Salmonella enterica O58, both containing 4,6-dideoxy-4-{N-[(S)-3-hydroxybutanoyl]-D-alanyl}amino-D-glucose; revision of the E. coli O123 O-polysaccharide structure.

PubMed

Perepelov, Andrei V; Liu, Bin; Shevelev, Sergei D; Senchenkova, Sof'ya N; Shashkov, Alexander S; Feng, Lu; Knirel, Yuriy A; Wang, Lei

2010-04-19

O-Polysaccharides were isolated by mild acid degradation of the lipopolysaccharides of Escherichia coli O123 and Salmonella enterica O58 and studied by chemical methods and 2D (1)H and (13)C NMR spectroscopy, including experiments in a H(2)O/D(2)O mixture, which enabled observation of correlations for nitrogen-linked protons. The following structure of the O-polysaccharide of E. coli O123 was established: -->3)-beta-D-Quip4NAlaHb-(1-->6)-alpha-D-GlcpNAc-(1-->3)-alpha-L-QuipNAc-(1-->3)-alpha-D-Glcp (6)(approx. 30% OAc)NAc-(1--> where L-QuipNAc stands for 2-acetamido-2,6-dideoxy-L-glucose and D-Qui4NAlaHb for 4-{N-[(S)-3-hydroxybutanoyl]-D-alanyl}amino-4,6-dideoxy-D-glucose. The latter was isolated as an ethylene glycol glycoside by three sequential Smith degradations of the O-deacetylated O-polysaccharide. The structure established in this work is at variance with the E. coli O123-polysaccharide structure reported earlier [Clark, C. G.; Kropinski, A. M.; Parolis, H.; Grant, C. C.; Trout-Yakel, K. M.; Franklin, K.; Ng, L. K.; Paramonov, N. A.; Parolis, L. A.; Rahn, K.; Tabor, H. J. Med. Microbiol.2009, 58, 884-894]. In accordance with the genetic data, the O-polysaccharide of S. enterica O58 has the same structure, except for it lacks the O-acetylation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

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

Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16more » E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.« less

The 6dF Galaxy Survey: Mass and Motions in the Local Universe

NASA Astrophysics Data System (ADS)

Colless, M.; Jones, H.; Campbell, L.; Burkey, D.; Taylor, A.; Saunders, W.

2005-01-01

The 6dF Galaxy Survey will provide 167000 redshifts and about 15000 peculiar velocities for galaxies over most of the southern sky out to about cz = 30000 km/s. The survey is currently almost half complete, with the final observations due in mid-2005. An initial data release was made public in December 2002; the first third of the dataset will be released at the end of 2003, with the remaining thirds being released at the end of 2004 and 2005. The status of the survey, the survey database and other relevant information can be obtained from the 6dFGS web site at http://www.mso.anu.edu.au/6dFGS. In terms of constraining cosmological parameters, combining the 6dFGS redshift and peculiar velocity surveys will allow us to: (1) break the degeneracy between the redshift-space distortion parameter beta = Omega_m0.6b/b and the galaxy-mass correlation parameter rg; (2) measure the four parameters Ag, Gamma, beta and rg with precisions of between 1% and 3%; (3) measure the variation of rg and b with scale to within a few percent over a wide range of scales.

New phenylpropanoid and 6H-dibenzo[b,d]pyran-6-one derivatives from the stems of Dasymaschalon rostratum.

PubMed

Yu, Zhang-Xin; Niu, Zhi-Gang; Li, Xiao-Bao; Zheng, Cai-Juan; Song, Xin-Ming; Chen, Guang-Ying; Song, Xiao-Ping; Han, Chang-Ri; Wu, Shu-Xian

2017-04-01

Three new phenylpropanoid derivatives, dasymaroacid A (1), dasymaroesters B and C (2 and 3), and one new polyoxygenated 6H-dibenzo[b,d]pyran-6-one derivative dasymarolactone D (4), together with seven known compounds (5-11), were isolated from the stems of Dasymaschalon rostratum Merr. Compounds 1 and 2 are unusual phenylpropanoid derivatives with a polymethyl substituted cyclopentene conjugated diketone as a substituent, and 3 is a unique cinnamic acid detective with a polymethyl substituted cyclohexene conjugated triketone as a substituent. Their structures were elucidated by extensive spectroscopic methods and chemical method, and 4 was further confirmed by the single crystal X-ray diffraction method. Compounds 1-4 and 7 showed weak anti-HIV-1 activities with EC 50 values ranged from 16.44 to 25.91μM. Copyright © 2017 Elsevier B.V. All rights reserved.

Proceedings of the Annual RAND-China Reform Forum Conference (6th) Held in Santa Monica, California on August 28-29, 2003

DTIC Science & Technology

2005-01-01

documents for commercial use. Limited Electronic Distribution Rights For More Information CHILD POLICY CIVIL JUSTICE EDUCATION ENERGY AND ENVIRONMENT HEALTH...Reform Forum Conference. August 28-29, 2003 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...have been reviewed and approved by RAND Science and Technology. Proceedings of the 6th Annual RAND–China Reform Forum Conference August 28–29

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites.

PubMed

Byeon, Ji-Yeong; Kim, Young-Hoon; Na, Han-Sung; Jang, Jong-Hwa; Kim, Se-Hyung; Lee, Yun-Jeong; Bae, Jung-Woo; Kim, In Su; Jang, Choon-Gon; Chung, Myeon-Woo; Lee, Seok-Yong

2015-11-01

To investigate the effect of the variant CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites, 4-hydroxyatomoxetine (4-HAT) and N-desmethylatomoxetine (NAT), in healthy subjects, a single oral dose of atomoxetine was administered to 62 subjects with a CYP2D6*wt/*wt (*wt = *1 or *2, n = 22), CYP2D6*wt/*10 (n = 22) or CYP2D6*10/*10 (n = 18) genotype. Plasma samples were then collected for 24 h after atomoxetine administration. The concentrations of atomoxetine and its metabolites were assayed using LC-MS/MS. For atomoxetine, the Cmax, AUC0-∞, t1/2 and CL/F showed genotype-dependent differences. The CYP2D6*10/*10 and CYP2D6*wt/*10 groups showed 1.74- and 1.15-fold higher Cmax, 3.40- and 1.33-fold higher AUC0-∞, and 69.7 and 24.6 % lower CL/F, compared to those of the CYP2D6*wt/*wt group, respectively. The Cmax and t1/2 for 4-HAT were lower and longer in the CYP2D6*10/*10 group than those in the CYP2D6*wt/*wt group, but the AUC0-∞ was not different between these groups. The Cmax, AUC0-∞ and t1/2 for NAT were profoundly greater in the CYP2D6*10/*10 group than they were in the CYP2D6*wt/*wt group. The concentration of active moieties of atomoxetine (atomoxetine + 4-HAT) in the CYP2D6*10/*10 group was 3.32-fold higher than that in the CYP2D6*wt/*wt group. The mean exposure to active moieties of atomoxetine was markedly higher in subjects with the CYP2D6*10/*10 genotype compared to that in those with the CYP2D6*wt/*wt genotype. The higher systemic exposure of the active atomoxetine moieties in CYP2D6*10/*10 individuals may increase the risk of concentration-related adverse events of atomoxetine, although this has not yet been clinically confirmed.

Spectrometric characteristics and tumor-affinity of a novel photosensitizer: mono-l-aspartyl aurochlorin e6 (Au-NPe6).

PubMed

Ishizumi, Taichiro; Aizawa, Katsuo; Tsuchida, Takaaki; Okunaka, Tetsuya; Kato, Harubumi

2004-12-01

Photodiagnosis and photodynamic therapy with photosensitizers can be indicated only for tumors of the superficial type, because these approaches utilizing visible light are limited by said light penetrability. To overcome this disadvantage, we innovated a novel photosensitizer, mono-l-aspartyl aurochlorin e6 (Au-NPe6), by incorporating a gold atom in the center of tetrapyrrole ring of NPe6 with a coordination bond. The gold atom in Au-NPe6 plays a role as an X-ray interceptor to detect deeply sited tumors. In this study, the absorption spectrum of novel Au-NPe6 in the diagnosis of deeply sited tumors was investigated, and the results were compared with the parent photosensitizer NPe6. Furthermore, the tumor-affinity of Au-NPe6 was evaluated using atomic absorption spectrometry. Despite the fact that both photosensitizers display a difference in the absorption spectrum, waveform changes of either photosensitizer with human serum albumin established a saturation point at a molar ratio of 1:1. The results indicate that it is highly possible that Au-NPe6 bound with albumin at a molar ratio (1:1) similar to NPe6. The accumulation rate of gold in tumor tissues was always significantly (p<0.05) higher than that in normal muscle tissues during the observation terms. Moreover, absorption spectra of tumor-tissue homogenates obtained from tumor-bearing mice after Au-NPe6 administration revealed a common peak with a wavelength equivalent to that of albumin-bond Au-NPe. This result suggests that the gold atom and NPe6 probably remained bonded even when Au-NPe6 was incorporated in tumor tissues.

26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... amendments with the same applicable amendment date are treated as one amendment. Thus, if two amendments have the same applicable amendment date and one amendment, standing alone, increases participants' accrued... are treated as one amendment and will only violate section 411(d)(6) if, for any participant, the net...

Cytochrome P450 2D6 and Parkinson's Disease: Polymorphism, Metabolic Role, Risk and Protection.

PubMed

Ur Rasheed, Mohd Sami; Mishra, Abhishek Kumar; Singh, Mahendra Pratap

2017-12-01

Cytochrome P450 (CYP) 2D6 is one of the most highly active, oxidative and polymorphic enzymes known to metabolize Parkinsonian toxins and clinically established anti-Parkinson's disease (PD) drugs. Albeit CYP2D6 gene is not present in rodents, its orthologs perform almost the similar function with imprecise substrate and inhibitor specificity. CYP2D6 expression and catalytic activity are found to be regulated at every stage of the central dogma except replication as well as at the epigenetic level. CYP2D6 gene codes for a set of alternate splice variants that give rise to a range of enzymes possessing variable catalytic activity. Case-control studies, meta-analysis and systemic reviews covering CYP2D6 polymorphism and PD risk have demonstrated that poor metabolizer phenotype possesses a considerable genetic susceptibility. Besides, ultra-rapid metabolizer offers protection against the risk in some populations while lack of positive or inverse association is also reported in other inhabitants. CYP2D6 polymorphisms resulting into deviant protein products with differing catalytic activity could lead to inter-individual variations, which could be explained to certain extent on the basis of sample size, life style factors, food habits, ethnicity and tools used for statistical analysis across various studies. Current article describes the role played by polymorphic CYP2D6 in the metabolism of anti-PD drugs/Parkinsonian toxins and how polymorphisms determine PD risk or protection. Moreover, CYP2D6 orthologs and their roles in rodent models of Parkinsonism have also been mentioned. Finally, a perspective on inconsistency in the findings and futuristic relevance of CYP2D6 polymorphisms in disease diagnosis and treatment has also been highlighted.

EQ-5D-5L and SF-6D Utility Measures in Symptomatic benign Thyroid Nodules: Acceptability and Psychometric Evaluation.

PubMed

Wong, Carlos K H; Lang, Brian H H; Yu, Hill M S; Lam, Cindy L K

2017-08-01

The aim of this study was to examine the acceptability, validity, and reliability of the EuroQoL Five-Dimension Five-Level (EQ-5D-5L) and Short-Form Six-Dimension (SF-6D) health utility measures in patients with symptomatic benign thyroid nodules. Data from a randomized controlled trial (ClinicalTrials.gov identifier: NCT02398721) of 294 patients with symptomatic benign thyroid nodules were utilized for this psychometric evaluation of health-related quality of life (HR-QOL) measurement. Three HR-QOL questionnaires-the generic 12-item Short Form Health Survey (SF-12v2), EQ-5D-5L, and SF-6D-were interviewer-administered at baseline and 2 weeks afterwards. Responses to SF-6D were transformed to SF-6D utility scores using a Hong Kong population scoring algorithm derived by standard gamble, whereas responses to EQ-5D-5L were mapped onto EQ-5D-3L response via interim mapping algorithms and then converted to EQ-5D-5L utility scores using a Chinese-specific value set. Construct validity was determined by evaluating Spearman correlation between SF-12v2 scores and utility scores. Two-week test-retest reliability was assessed using intra-class correlation coefficient. No significant (>15%) floor and ceiling effects were observed for SF-6D utility scores. The SF-6D utility scores had a moderate Spearman rank correlation with the SF-12v2 domain score providing evidence for adequate construct validity. The SF-6D utility scores showed good test-retest reliability (0.794; range 0.696-0.860). Better reliability was observed in SF-6D utility scores than in EQ-5D-5L utility scores. While the EQ-5D-5L instrument was less reproducible, the SF-6D instrument appeared to be an applicable, valid, and reliable measure in assessing the HR-QOL of Chinese patients with symptomatic benign thyroid nodules. The impact of utility score selection on the effectiveness and cost effectiveness of clinical interventions targeted to these patients needs further exploration. NCT02398721, ClinicalTrials.gov.

Establishment of immunoassay for detecting HPV16 E6 and E7 RNA

PubMed Central

Ding, Sen; Qian, Steven Y.; Zhang, Yang; Wu, Wenlei; Lu, Gensheng; Lu, Yan; Feng, Xiujing; Li, Li; Shen, Pingping

2015-01-01

Cervical carcinoma is the most prevalent malignancy second only to breast cancer among women worldwide. Since more than 99% of cervical cancers are caused by human papilloma virus (HPV), measurement of HPV (HPV test) was commonly used in screening risk and/or early stage of cervical cancer as well as assessing the efficacies of the treatments that can decrease the incidence of cervical cancer. Many approaches that diagnose HPV infections have been developed, while most of them have distinct shortcomings. We here established a novel immunoassay method in which the pairs of unlabeled DNA probes firstly bind to HPV16 E6 and E7 RNAs to form the DNA-RNA hybrids, and the hybrids will subsequently be identified by S9.6 antibody. The sensitivity of this highly specific method can reach ~0.923 pg/mL and ~0.424 pg/mL of in vitro transcribed HPV16 E6 and E7 RNA, respectively, and reverse transcription and polymerase chain reaction (PCR) amplification were no longer needed. Thus, our immunoassay approaches can precisely reflect the actually viral load that is related to the course of HPV infection. In addition, it has also fast and low cost characteristic feature. PMID:26333509

Task 6 -- Advanced turbine systems program conceptual design and product development

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

NONE

1996-01-10

The Allison Engine Company has completed the Task 6 Conceptual Design and Analysis of Phase 2 of the Advanced Turbine System (ATS) contract. At the heart of Allison`s system is an advanced simple cycle gas turbine engine. This engine will incorporate components that ensure the program goals are met. Allison plans to commercialize the ATS demonstrator and market a family of engines incorporating this technology. This family of engines, ranging from 4.9 MW to 12 MW, will be suitable for use in all industrial engine applications, including electric power generation, mechanical drive, and marine propulsion. In the field of electricmore » power generation, the engines will be used for base load, standby, cogeneration, and distributed generation applications.« less

Performance of OncoE6 cervical test with collection methods enabling self-sampling.

PubMed

Krings, Amrei; Dückelmann, Anna M; Moser, Lutz; Gollrad, Johannes; Wiegerinck, Maarten; Schweizer, Johannes; Kaufmann, Andreas M

2018-05-21

The paradigm shift from cytological screening to Human Papillomavirus (HPV)-based screening for cervical cancer allows the introduction of new technologies in sample collection and diagnostics. The OncoE6™ Cervical Test (OncoE6 Test) is a rapid, easy-to-use lateral flow method detecting HPV16/18 E6 oncoproteins that has proven to detect high-grade cervical lesions with high specificity. If compatible with self-collection samples, this technology might allow for decentralized screening of hard-to-reach populations. For technical validation, cervicovaginal lavages were collected from 20 patients with confirmed HPV16+ or HPV18+ invasive cervical cancer. Cervical smears were collected by polyester-tipped swabs and cytobrushes. All samples were applied to the OncoE6 Test and cytobrush samples additionally genotyped. Lavage, swab, and cytobrush revealed concordant outcome in 18/20 samples. HPV types corresponded with the HPV genotyping by GP5+/6+ PCR analyses. Due to a rare mutation found in the E6 antibody binding site one sample was not detected, another sample had very low cellularity. Overall, vaginal lavages are technically adequate for the OncoE6 Test. Combining self-sampling with oncoprotein rapid testing to detect women with highest risk for severe dysplasia or cancer may allow for secondary cancer prevention in settings where other screening modalities were unsuccessful to date.

The metabolism of primaquine to its active metabolite is dependent on CYP 2D6.

PubMed

Pybus, Brandon S; Marcsisin, Sean R; Jin, Xiannu; Deye, Gregory; Sousa, Jason C; Li, Qigui; Caridha, Diana; Zeng, Qiang; Reichard, Gregory A; Ockenhouse, Christian; Bennett, Jason; Walker, Larry A; Ohrt, Colin; Melendez, Victor

2013-06-20

The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites. In the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity. PQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice. These results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers.

PubMed

Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J; Beelen, Andrew P; Kongpatanakul, Supornchai; Möhrle, Jörg J; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A

2017-09-01

Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol 487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose-response was evident in G6PD-heterozygous subjects ( N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [ N = 3]) and primaquine (-1.25 to -3.0 g/dL [ N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61-80% ( N = 2) and > 80% ( N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days.

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers

PubMed Central

Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J.; Beelen, Andrew P.; Kongpatanakul, Supornchai; Möhrle, Jörg J.; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H.; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A.

2017-01-01

Abstract. Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40–60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose–response was evident in G6PD-heterozygous subjects (N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (−2.65 to −2.95 g/dL [N = 3]) and primaquine (−1.25 to −3.0 g/dL [N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61–80% (N = 2) and > 80% (N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days. PMID:28749773

E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6

PubMed Central

Hibbert, Richard G.; Huang, Anding; Boelens, Rolf; Sixma, Titia K.

2011-01-01

In ubiquitin conjugation, different combinations of E2 and E3 enzymes catalyse either monoubiquitination or ubiquitin chain formation. The E2/E3 complex Rad6/Rad18 exclusively monoubiquitinates the proliferating cell nuclear antigen (PCNA) to signal for “error prone” DNA damage tolerance, whereas a different set of conjugation enzymes is required for ubiquitin chain formation on PCNA. Here we show that human E2 enzyme Rad6b is intrinsically capable of catalyzing ubiquitin chain formation. This activity is prevented during PCNA ubiquitination by the interaction of Rad6 with E3 enzyme Rad18. Using NMR and X-ray crystallography we show that the R6BD of Rad18 inhibits this activity by competing with ubiquitin for a noncovalent “backside” binding site on Rad6. Our findings provide mechanistic insights into how E3 enzymes can regulate the ubiquitin conjugation process. PMID:21422291

Aqueous stress-corrosion cracking of high-toughness D6AC steel

NASA Technical Reports Server (NTRS)

Gilbreath, W. P.; Adamson, M. J.

1976-01-01

The crack growth behavior of D6AC steel as a function of stress intensity, stress and corrosion history, and test technique, under sustained load in filtered natural seawater, 3.3 per cent sodium chloride solution, and distilled water, was investigated. Reported investigations of D6AC were considered in terms of the present study with emphasis on thermal treatment, specimen configuration, fracture toughness, crack-growth rates, initiation period, and threshold. Both threshold and growth kinetics were found to be relatively insensitive to these test parameters. The apparent incubation period was dependent on technique, both detection sensitivity and precracking stress intensity level.

CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of Durango, Mexico.

PubMed

Sosa-Macías, Martha; Elizondo, Guillermo; Flores-Pérez, Carmen; Flores-Pérez, Janet; Bradley-Alvarez, Francisco; Alanis-Bañuelos, Ruth E; Lares-Asseff, Ismael

2006-05-01

Although the drug-metabolizing enzyme CYP2D6 has been studied extensively in subjects of differing ethnicities, limited CYP2D6 pharmacogenetic data are available for the Amerindian population and Mestizos of Mexico. Dextromethorphan hydroxylation phenotype was studied in Tepehuano Amerindian (n = 58) and Mestizo (n = 88) subjects, and 195 individuals (85 Tepehuano Amerindians and 110 Mestizos) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods to identify the frequencies of the CYP2D6*3, *4, *6, and *10 alleles. Tepehuano Amerindian subjects lacked the poor metabolizer (PM) phenotype, whereas in Mestizos the PM phenotype frequency was 6.8%. The CYP2D6*3, *6, and *10 alleles were not found in Tepehuano Amerindians. The CYP2D6*4 allele had a low frequency (0.006) in this Amerindian group. In the Mestizo group, the CYP2D6*3, *4, and *10 alleles had frequencies of 0.009, 0.131, and 0.023, respectively. The CYP2D6*6 allele was not found in Mestizos. The genotype-phenotype association was strongly statistically significant (r(2) = .45; P = .005) in Mestizos. The Tepehuano population was found to have a low phenotypic and genotypic CYP2D6 diversity and differed from other Amerindian groups. On the other hand, the frequencies of the CYP2D6 variant alleles in Mestizos were similar to those reported for whites.

Mission Design and Concept of Operations of a 6U CubeSat Mission for Proximity Operations and RSO Imaging

DTIC Science & Technology

2013-05-29

Design and Concept of Operations of a 6U Cube Sat Mission for NIA Proximity Oper111ions and RSO Imaging 5b. GRANT NUMBER NIA 5c. PROGRAM ELEMENT...NUMBER NIA 6. AUTHOR(S) 5d. PROJECT NUMBER B. Udrea, M. Nayak, M. Ryle, N. Martini, S. Gillespie, T. Grande, S. Caicedo, S. NIA Wilette, A. Baba...K. , Harri s, J. DiGregorio, S. Salzburger, P. Patel , A. Huang 5e. TASK NUMBER NIA 5f. WORK UNIT NUMBER NIA T. PERFORMING ORGANIZATION NAME(S

Ground-state properties of H 5 from the He 6 ( d , He 3 ) H 5 reaction

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

Wuosmaa, A. H.; Bedoor, S.; Brown, K. W.

2017-01-01

We have studied the ground state of the unbound, very neutron-rich isotope of hydrogen 5H, using the 6He(d,3He)5H reaction in inverse kinematics at a bombarding energy of E(6He)=55A MeV. The present results suggest a ground-state resonance energy ER=2.4±0.3 MeV above the 3H+2n threshold, with an intrinsic width of Γ=5.3±0.4 MeV in the 5H system. Both the resonance energy and width are higher than those reported in some, but not all previous studies of 5H. The previously unreported 6He(d,t)5Heg.s. reaction is observed in the same measurement, providing a check on the understanding of the response of the apparatus. The data aremore » compared to expectations from direct two-neutron and dineutron decay. The possibility of excited states of 5H populated in this reaction is discussed using different calculations of the 6He→5H+p spectroscopic overlaps from shell-model and ab initio nuclear-structure calculations.« less

6-phospho-alpha-D-glucosidase from Fusobacterium mortiferum: cloning, expression, and assignment to family 4 of the glycosylhydrolases.

PubMed Central

Bouma, C L; Reizer, J; Reizer, A; Robrish, S A; Thompson, J

1997-01-01

The Fusobacterium mortiferum malH gene, encoding 6-phospho-alpha-glucosidase (maltose 6-phosphate hydrolase; EC 3.2.1.122), has been isolated, characterized, and expressed in Escherichia coli. The relative molecular weight of the polypeptide encoded by malH (441 residues; Mr of 49,718) was in agreement with the estimated value (approximately 49,000) obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the enzyme purified from F. mortiferum. The N-terminal sequence of the MalH protein obtained by Edman degradation corresponded to the first 32 amino acids deduced from the malH sequence. The enzyme produced by the strain carrying the cloned malH gene cleaved [U-14C]maltose 6-phosphate to glucose 6-phosphate (Glc6P) and glucose. The substrate analogs p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alphaGlc6P) and 4-methylumbelliferyl-alpha-D-glucopyranoside 6-phosphate (4MU alphaGlc6P) were hydrolyzed to yield Glc6P and the yellow p-nitrophenolate and fluorescent 4-methylumbelliferyl aglycons, respectively. The 6-phospho-alpha-glucosidase expressed in E. coli (like the enzyme purified from F. mortiferum) required Fe2+, Mn2+, Co2+, or Ni2+ for activity and was inhibited in air. Synthesis of maltose 6-phosphate hydrolase from the cloned malH gene in E. coli was modulated by addition of various sugars to the growth medium. Computer-based analyses of MalH and its homologs revealed that the phospho-alpha-glucosidase from F. mortiferum belongs to the seven-member family 4 of the glycosylhydrolase superfamily. The cloned 2.2-kb Sau3AI DNA fragment from F. mortiferum contained a second partial open reading frame of 83 residues (designated malB) that was located immediately upstream of malH. The high degree of sequence identity of MalB with IIB(Glc)-like proteins of the phosphoenol pyruvate dependent:sugar phosphotransferase system suggests participation of MalB in translocation of maltose and related alpha-glucosides in F. mortiferum. PMID:9209025

In silico modeling of the cryptic E2∼ubiquitin-binding site of E6-associated protein (E6AP)/UBE3A reveals the mechanism of polyubiquitin chain assembly.

PubMed

Ronchi, Virginia P; Kim, Elizabeth D; Summa, Christopher M; Klein, Jennifer M; Haas, Arthur L

2017-11-03

To understand the mechanism for assembly of Lys 48 -linked polyubiquitin degradation signals, we previously demonstrated that the E6AP/UBE3A ligase harbors two functionally distinct E2∼ubiquitin-binding sites: a high-affinity Site 1 required for E6AP Cys 820 ∼ubiquitin thioester formation and a canonical Site 2 responsible for subsequent chain elongation. Ordered binding to Sites 1 and 2 is here revealed by observation of UbcH7∼ubiquitin-dependent substrate inhibition of chain formation at micromolar concentrations. To understand substrate inhibition, we exploited the PatchDock algorithm to model in silico UbcH7∼ubiquitin bound to Site 1, validated by chain assembly kinetics of selected point mutants. The predicted structure buries an extensive solvent-excluded surface bringing the UbcH7∼ubiquitin thioester bond within 6 Å of the Cys 820 nucleophile. Modeling onto the active E6AP trimer suggests that substrate inhibition arises from steric hindrance between Sites 1 and 2 of adjacent subunits. Confirmation that Sites 1 and 2 function in trans was demonstrated by examining the effect of E6APC820A on wild-type activity and single-turnover pulse-chase kinetics. A cyclic proximal indexation model proposes that Sites 1 and 2 function in tandem to assemble thioester-linked polyubiquitin chains from the proximal end attached to Cys 820 before stochastic en bloc transfer to the target protein. Non-reducing SDS-PAGE confirms assembly of the predicted Cys 820 -linked 125 I-polyubiquitin thioester intermediate. Other studies suggest that Glu 550 serves as a general base to generate the Cys 820 thiolate within the low dielectric binding interface and Arg 506 functions to orient Glu 550 and to stabilize the incipient anionic transition state during thioester exchange. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

E6-associated transcription patterns in human papilloma virus 16-positive cervical tissues.

PubMed

Lin, Kezhi; Lu, Xulian; Chen, Jun; Zou, Ruanmin; Zhang, Lifang; Xue, Xiangyang

2015-01-01

The change in transcription pattern induced by post-transcriptional RNA splicing is an important mechanism in the regulation of the early gene expression of human papilloma virus (HPV). The present study was conducted to establish a method to specifically amplify HPV-16 E6-associated transcripts. The E6-related transcripts from 63 HPV-16-positive cervical tumor tissue samples were amplified, consisting of eight cases of low-risk intraepithelial lesions, 38 cases of high-risk intraepithelial lesions and 17 cases of cervical cancer (CxCa). The appropriate amplified segments were recovered following agarose gel electrophoresis, and subjected to further sequencing and sequence alignment analysis. Six groups of E6 transcription patterns were identified from HPV-16-positive cervical tumor tissue, including five newly-discovered transcripts. Different HPV-16 E6-associated transcription patterns were detected during the development of CxCa. Over the course of the progression of the low-grade squamous intraepithelial lesions to CxCa, the specific HPV-16 E6-associated transcription patterns and the dominant transcripts were all different. As indicated by this study, the transcription pattern of the E6 early gene of HPV-16 was closely associated with the stages of cervical carcinogenesis, and may also be involved in the development of CxCa.

In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential.

PubMed Central

Barbosa, M S; Vass, W C; Lowy, D R; Schiller, J T

1991-01-01

Human papillomavirus type 16 (HPV-16) and HPV-18 are often detected in cervical carcinomas, while HPV-6, although frequently present in benign genital lesions, is only rarely present in cancers of the cervix. Therefore, infections with HPV-16 and HPV-18 are considered high risk and infection with HPV-6 is considered low risk. We found, by using a heterologous promoter system, that expression of the E7 transforming protein differs between high- and low-risk HPVs. In high-risk HPV-16, E7 is expressed from constructs containing the complete upstream E6 open reading frame. In contrast, HPV-6 E7 was efficiently translated only when E6 was deleted. By using clones in which the coding regions of HPV-6, HPV-16, and HPV-18 E7s were preceded by identical leader sequences, we found that the ability of the E7 gene products to induce anchorage-independent growth in rodent fibroblasts correlated directly with the oncogenic association of the HPV types. By using an immortalization assay of normal human keratinocytes that requires complementation of E6 and E7, we found that both E6 and E7 of HPV-18 could complement the corresponding gene from HPV-16. However, neither E6 nor E7 from HPV-6 was able to substitute for the corresponding gene of HPV-16 or HPV-18. Our results suggest that multiple factors, including lower intrinsic biological activity of E6 and E7 and differences in the regulation of their expression, account for the low activity of HPV-6, in comparison with HPV-16 and HPV-18, in in vitro assays. These same factors may, in part, account for the apparent difference in oncogenic potential between these viruses. Images PMID:1845889

3-D Image Encryption Based on Rubik's Cube and RC6 Algorithm

NASA Astrophysics Data System (ADS)

Helmy, Mai; El-Rabaie, El-Sayed M.; Eldokany, Ibrahim M.; El-Samie, Fathi E. Abd

2017-12-01

A novel encryption algorithm based on the 3-D Rubik's cube is proposed in this paper to achieve 3D encryption of a group of images. This proposed encryption algorithm begins with RC6 as a first step for encrypting multiple images, separately. After that, the obtained encrypted images are further encrypted with the 3-D Rubik's cube. The RC6 encrypted images are used as the faces of the Rubik's cube. From the concepts of image encryption, the RC6 algorithm adds a degree of diffusion, while the Rubik's cube algorithm adds a degree of permutation. The simulation results demonstrate that the proposed encryption algorithm is efficient, and it exhibits strong robustness and security. The encrypted images are further transmitted over wireless Orthogonal Frequency Division Multiplexing (OFDM) system and decrypted at the receiver side. Evaluation of the quality of the decrypted images at the receiver side reveals good results.

Cutaneous Papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling

PubMed Central

Brimer, Nicole; Lyons, Charles; Wallberg, Annika E.; Vande Pol, Scott B.

2011-01-01

Papillomavirus E6 oncoproteins associate with LXXLL motifs on target cellular proteins to alter their function. Using a proteomic approach, we found the E6 oncoproteins of cutaneous papillomaviruses Bovine Papillomavirus Type 1 (BE6) and HPV types 1 and 8 (1E6 and 8E6) associated with the MAML1 transcriptional co-activator. All three E6 proteins bind to an acidic LXXLL motif at the carboxy-terminus of MAML1 and repress transactivation by MAML1. MAML1 is best known as the co-activator and effector of NOTCH induced transcription, and BPV-1 E6 represses synthetic NOTCH responsive promoters, endogenous NOTCH responsive promoters, and is found in a complex with MAML1 in stably transformed cells. BPV-1 induced papillomas show characteristics of repressed NOTCH signal transduction, including suprabasal expression of integrins, talin, and basal type keratins, and delayed expression of the NOTCH dependent HES1 transcription factor. These observations give rise to a model whereby papillomavirus oncoproteins including BPV-1 E6 and the cancer associated HPV-8 E6 repress Notch induced transcription, thereby delaying keratinocyte differentiation. PMID:22249263

Phthalocyaninatoruthenium(II), Hexakis(dimethylsulfoxide)Phthalocyaninatoruthenium(II), and Hexadis(dimethylsulfoxide-d6)phthalocyanin-atoruthenium(II), Three Highly Selective NMR Shift Reagents.

DTIC Science & Technology

1977-07-18

dimethylsu lfoxi de-d6) phthalocyanin — atoruthenium (II), Three Highly Selective NMR Shift Reagents ( ~‘ iby j \\ / Clement K. Choy and F•lalcolm E. Kenney...Running head : Phthalocyaninatorut henium( II) Shift Reagents I NTRODUCT ION Previously, work on FePc (Pc = phthalocyanine li gand , C32H16N8) show- ing...RuPc and dimethylsulfoxide -d 6 were re cted together and the product isolated, An nmr spectrum of the product showed only phthalocyanine resorar.ces

21 CFR 74.2306 - D&C Red No. 6.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Red No. 6. 74.2306 Section 74.2306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... coloring cosmetics generally in amounts consistent with current good manufacturing practice. (c) Labeling...

3D printed e-tongue

NASA Astrophysics Data System (ADS)

Gaál, Gabriel; da Silva, Tatiana A.; Gaál, Vladimir; Hensel, Rafael C.; Amaral, Lucas R.; Rodrigues, Varlei; Riul, Antonio

2018-05-01

Nowadays, one of the biggest issues addressed to electronic sensor fabrication is the build-up of efficient electrodes as an alternative way to the expensive, complex and multistage processes required by traditional techniques. Printed electronics arises as an interesting alternative to fulfill this task due to the simplicity and speed to stamp electrodes on various surfaces. Within this context, the Fused Deposition Modeling 3D printing is an emerging, cost-effective and alternative technology to fabricate complex structures that potentiates several fields with more creative ideas and new materials for a rapid prototyping of devices. We show here the fabrication of interdigitated electrodes using a standard home-made CoreXY 3D printer using transparent and graphene-based PLA filaments. Macro 3D printed electrodes were easily assembled within 6 minutes with outstanding reproducibility. The electrodes were also functionalized with different nanostructured thin films via dip-coating Layer-by-Layer technique to develop a 3D printed e-tongue setup. As a proof of concept, the printed e-tongue was applied to soil analysis. A control soil sample was enriched with several macro-nutrients to the plants (N, P, K, S, Mg and Ca) and the discrimination was done by electrical impedance spectroscopy of water solution of the soil samples. The data was analyzed by Principal Component Analysis and the 3D printed sensor distinguished clearly all enriched samples despite the complexity of the soil chemical composition. The 3D printed e-tongue successfully used in soil analysis encourages further investments in developing new sensory tools for precision agriculture and other fields exploiting the simplicity and flexibility offered by the 3D printing techniques.

Clinical inhibition of CYP2D6-catalysed metabolism by the antianginal agent perhexiline

PubMed Central

Davies, Benjamin J L; Coller, Janet K; James, Heather M; Gillis, David; Somogyi, Andrew A; Horowitz, John D; Morris, Raymond G; Sallustio, Benedetta C

2004-01-01

Aims Perhexiline is an antianginal agent that displays both saturable and polymorphic metabolism via CYP2D6. The aim of this study was to determine whether perhexiline produces clinically significant inhibition of CYP2D6-catalysed metabolism in angina patients. Methods The effects of perhexiline on CYP2D6-catalysed metabolism were investigated by comparing urinary total dextrorphan/dextromethorphan metabolic ratios following a single dose of dextromethorphan (16.4 mg) in eight matched control patients not taking perhexiline and 24 patients taking perhexiline. All of the patients taking perhexiline had blood drawn for CYP2D6 genotyping as well as to measure plasma perhexiline and cis-OH-perhexiline concentrations. Results Median (range) dextrorphan/dextromethorphan metabolic ratios were significantly higher (P < 0.0001) in control patients, 271.1 (40.3–686.1), compared with perhexiline-treated patients, 5.0 (0.3–107.9). In the perhexiline-treated group 10/24 patients had metabolic ratios consistent with poor metabolizer phenotypes; however, none was a genotypic poor metabolizer. Interestingly, 89% of patients who had phenocopied to poor metabolizers had only one functional CYP2D6 gene. There was a significant negative linear correlation between the log of the dextrorphan/dextromethorphan metabolic ratio and plasma perhexiline concentrations (r2 = 0.69, P < 0.0001). Compared with patients with at least two functional CYP2D6 genes, those with one functional gene were on similar perhexiline dosage regimens but had significantly higher plasma perhexiline concentrations, 0.73 (0.21–1.00) vs. 0.36 (0.04–0.69) mg l−1 (P = 0.04), lower cis-OH-perhexiline/perhexiline ratios, 2.85 (0.35–6.10) vs. 6.51 (1.84–11.67) (P = 0.03), and lower dextrorphan/dextromethorphan metabolic ratios, 2.51 (0.33–39.56) vs. 11.80 (2.90–36.93) (P = 0.005). Conclusions Perhexiline significantly inhibits CYP2D6-catalysed metabolism in angina patients. The plasma cis

Valuing SF-6D Health States Using a Discrete Choice Experiment.

PubMed

Norman, Richard; Viney, Rosalie; Brazier, John; Burgess, Leonie; Cronin, Paula; King, Madeleine; Ratcliffe, Julie; Street, Deborah

2014-08-01

SF-6D utility weights are conventionally produced using a standard gamble (SG). SG-derived weights consistently demonstrate a floor effect not observed with other elicitation techniques. Recent advances in discrete choice methods have allowed estimation of utility weights. The objective was to produce Australian utility weights for the SF-6D and to explore the application of discrete choice experiment (DCE) methods in this context. We hypothesized that weights derived using this method would reflect the largely monotonic construction of the SF-6D. We designed an online DCE and administered it to an Australia-representative online panel (n = 1017). A range of specifications investigating nonlinear preferences with respect to additional life expectancy were estimated using a random-effects probit model. The preferred model was then used to estimate a preference index such that full health and death were valued at 1 and 0, respectively, to provide an algorithm for Australian cost-utility analyses. Physical functioning, pain, mental health, and vitality were the largest drivers of utility weights. Combining levels to remove illogical orderings did not lead to a poorer model fit. Relative to international SG-derived weights, the range of utility weights was larger with 5% of health states valued below zero. s. DCEs can be used to investigate preferences for health profiles and to estimate utility weights for multi-attribute utility instruments. Australian cost-utility analyses can now use domestic SF-6D weights. The comparability of DCE results to those using other elicitation methods for estimating utility weights for quality-adjusted life-year calculations should be further investigated. © The Author(s) 2013.

Phosphorylation of ribosomal protein S6 mediates compensatory renal hypertrophy

PubMed Central

Xu, Jinxian; Chen, Jianchun; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang

2014-01-01

The molecular mechanism underlying renal hypertrophy and progressive nephron damage remains poorly understood. Here we generated congenic ribosomal protein S6 (rpS6) knockin mice expressing non-phosphorylatable rpS6 and found that uninephrectomy-induced renal hypertrophy was significantly blunted in these knockin mice. Uninephrectomy-induced increases in cyclin D1 and decreases in cyclin E in the remaining kidney were attenuated in the knockin mice compared to their wild-type littermates. Uninephrectomy induced rpS6 phosphorylation in the wild type mice; however, no rpS6 phosphorylation was detected in uninephrectomized or sham-operated knockin mice. Nonetheless, uninephrectomy stimulated comparable 4E-BP1 phosphorylation in both knockin and wild type mice, indicating that mTORC1 was still activated in the knockin mice. Moreover, the mTORC1 inhibitor rapamycin prevented both rpS6 and 4E-BP1 phosphorylation, significantly blunted uninephrectomy-induced renal hypertrophy in wild type mice, but did not prevent residual renal hypertrophy despite inhibiting 4E-BP1 phosphorylation in uninephrectomized knockin mice. Thus, both genetic and pharmacological approaches unequivocally demonstrate that phosphorylated rpS6 is a downstream effector of the mTORC1-S6K1 signaling pathway mediating renal hypertrophy. Hence, rpS6 phosphorylation facilitates the increase in cyclin D1 and decrease in cyclin E1 that underlie the hypertrophic nature of uninephrectomy-induced kidney growth. PMID:25229342

Measurement of the differential cross sections of 6Li(d,d0) for Ion Beam Analysis purposes

NASA Astrophysics Data System (ADS)

Ntemou, E.; Aslanoglou, X.; Axiotis, M.; Foteinou, V.; Kokkoris, M.; Lagoyannis, A.; Misaelides, P.; Patronis, N.; Preketes-Sigalas, K.; Provatas, G.; Vlastou, R.

2017-09-01

In the present work, the 6Li(d,d0)6Li elastic scattering differential cross sections were measured in the energy range Ed,lab = 940-2000 keV for Elastic Backscattering Spectroscopy (EBS) purposes, using thin lithium targets, made by evaporating isotopically enriched 6LiF powder on self-supporting carbon foils, with an ultra-thin Au layer on top for normalization purposes. The experiment was carried out in deuteron beam energy steps of 20 or 30 keV and for the laboratory scattering angles of 125°, 140°, 150°, 160°, and 170°.

Expression, Polyubiquitination, and Therapeutic Potential of Recombinant E6E7 from HPV16 Antigens Fused to Ubiquitin.

PubMed

de Oliveira, Liliane M Fernandes; Morale, Mirian G; Chaves, Agtha A M; Demasi, Marilene; Ho, Paulo L

2017-01-01

Ubiquitin-proteasome system plays an essential role in the immune response due to its involvement in the antigen generation and presentation to CD8 + T cells. Hereby, ubiquitin fused to antigens has been explored as an immunotherapeutic strategy that requires the activation of cytotoxic T lymphocytes. Here we propose to apply this ubiquitin fusion approach to a recombinant vaccine against human papillomavirus 16-infected cells. E6E7 multi-epitope antigen was fused genetically at its N- or C-terminal end to ubiquitin and expressed in Escherichia coli as inclusion bodies. The antigens were solubilized using urea and purified by nickel affinity chromatography in denatured condition. Fusion of ubiquitin to E6E7 resulted in marked polyubiquitination in vitro mainly when fused to the E6E7 N-terminal. When tested in a therapeutic scenario, the fusion of ubiquitin to E6E7 reinforced the anti-tumor protection and increased the E6/E7-specific cellular immune responses. Present results encourage the investigation of the adjuvant potential of the ubiquitin fusion to recombinant vaccines requiring CD8 + T cells.

Involvement of Novel Multifunction Steroid Hormone Receptor Coactivator, E6-Associated Protein, in Prostate Gland Tumorigenesis

DTIC Science & Technology

2009-01-01

HPV infection in cervical carcinoma cells . However, this effect is E6 dependent, as p53 could only be degraded by the formation of E6 and E6-AP...and prostate cancer cell proliferation. E6-AP by itself can modulate p53 levels in prostate cancer cells independent of E6. Our data also indicates...p53 levels in prostate glands and prostate cancer cells : E6-AP was initially identified as an E3 ligase which promotes the degradation of p53 during

Confirmation of a charged charmoniumlike state Zc(3885 )∓ in e+e-→π±(D D¯ *)∓ with double D tag

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Ferroli, R. Baldini; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, H. Y.; Chen, J. C.; Chen, M. L.; Chen, S.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Duan, P. F.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, X. Y.; Gao, Y.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, J. F.; Hu, T.; Hu, Y.; Huang, G. M.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, Y.; Hussain, T.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. W.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kiese, P.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuehn, W.; Kupsc, A.; Lange, J. S.; Lara, M.; Larin, P.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. M.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, J. J.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Loehner, H.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Maas, F. E.; Maggiora, M.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Min, J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales, C. Morales; Moriya, K.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Santoro, V.; Sarantsev, A.; Savrié, M.; Schoenning, K.; Schumann, S.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Shi, M.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Ullrich, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, S. G.; Wang, W.; Wang, W. P.; Wang, X. F.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Z. Y.; Weber, T.; Wei, D. H.; Wei, J. B.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. N.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2015-11-01

We present a study of the process e+e-→π±(D D¯ *)∓ using data samples of 1092 pb-1 at √{s }=4.23 GeV and 826 pb-1 at √{s }=4.26 GeV collected with the BESIII detector at the BEPCII storage ring. With full reconstruction of the D meson pair and the bachelor π± in the final state, we confirm the existence of the charged structure Zc(3885 )∓ in the (D D¯*)∓ system in the two isospin processes e +e-→π+D0D*- and e+e-→π+D-D*0. By performing a simultaneous fit, the statistical significance of Z c (3885 )∓ signal is determined to be greater than 10 σ , and its pole mass and width are measured to be Mpole=(3881.7 ±1.6 (stat )±1.6 (syst )) MeV /c2 and Γpole=(26.6 ±2.0 (stat )±2.1 (syst )) MeV , respectively. The Born cross section times the (D D¯*)∓ branching fraction (σ (e+e-→π±Zc(3885 )∓)×B r(Zc(3885 )∓→(DD¯*)∓) ) is measured to be (141.6 ±7.9 (stat )±12.3 (syst )) pb at √{s }=4.23 GeV and (108.4 ±6.9 (stat )±8.8 (syst )) pb at √{s }=4.26 GeV . The polar angular distribution of the π±-Zc(3885 )∓ system is consistent with the expectation of a quantum number assignment of JP=1+ for Zc(3885)∓.

Developing and Evaluating the HRM Technique for Identifying Cytochrome P450 2D6 Polymorphisms.

PubMed

Lu, Hsiu-Chin; Chang, Ya-Sian; Chang, Chun-Chi; Lin, Ching-Hsiung; Chang, Jan-Gowth

2015-05-01

Cytochrome P450 2D6 is one of the important enzymes involved in the metabolism of many widely used drugs. Genetic polymorphisms of CYP2D6 can affect its activity. Therefore, an efficient method for identifying CYP2D6 polymorphisms is clinically important. We developed a high-resolution melting (HRM) analysis to investigate CYP2D6 polymorphisms. Genomic DNA was extracted from peripheral blood samples from 71 healthy individuals. All nine exons of the CYP2D6 gene were sequenced before screening by HRM analysis. This method can detect the most genotypes (*1, *2, *4, *10, *14, *21 *39, and *41) of CYP2D6 in Chinese. All samples were successfully genotyped. The four most common mutant CYP2D6 alleles (*1, *2, *10, and *41) can be genotyped. The single nucleotides polymorphism (SNP) frequencies of 100C > T (rs1065852), 1039C > T (rs1081003), 1661G > C (rs1058164), 2663G > A (rs28371722), 2850C > T (rs16947), 2988G > A (rs28371725), 3181A > G, and 4180G > C (rs1135840) were 58%, 61%, 73%, 1%, 13%, 3%, 1%, 73%, respectively. We identified 100% of all heterozygotes without any errors. The two homozygous genotypes (1661G > C and 4180G > C) can be distinguished by mixing with a known genotype sample to generate an artificial heterozygote for HRM analysis. Therefore, all samples could be identified using our HRM method, and the results of HRM analysis are identical to those obtained by sequencing. Our method achieved 100% sensitivity, specificity, positive prediction value and negative prediction value. HRM analysis is a nongel resolution method that is faster and less expensive than direct sequencing. Our study shows that it is an efficient tool for typing CYP2D6 polymorphisms. © 2014 Wiley Periodicals, Inc.

(2E,6Z,9Z)-2,6,9-Pentadecatrienal as a Male-Produced Aggregation-Sex Pheromone of the Cerambycid Beetle Elaphidion mucronatum.

PubMed

Millar, Jocelyn G; Mitchell, Robert F; Meier, Linnea R; Johnson, Todd D; Mongold-Diers, Judith A; Hanks, Lawrence M

2017-12-01

An increasing body of evidence suggests that the volatile pheromones of cerambycid beetles are much more diverse in structure than previously hypothesized. Here, we describe the identification, synthesis, and field testing of (2E,6Z,9Z)-2,6,9-pentadecatrienal as a male-produced aggregation-sex pheromone of the cerambycid Elaphidion mucronatum (Say) (subfamily Cerambycinae, tribe Elaphidiini). This novel structure is unlike any previously described cerambycid pheromone, and in field bioassays attracted only this species. Males produced about 9 μg of pheromone per 24 h period, and, in field trials, lures loaded with 10, 25, and 100 mg of synthetic pheromone attracted beetles of both sexes, whereas lures loaded with 1 mg of pheromone or less were not significantly attractive. Other typical cerambycine pheromones such as 3-hydroxy-2-hexanone, syn-2,3-hexanediol, and anti-2,3-hexanediol were not attractive to E. mucronatum, and when combined with (2E,6Z,9Z)-2,6,9-pentadecatrienal, the former two compounds appeared to inhibit attraction. Unexpectedly, adults of the cerambycine Xylotrechus colonus (F.) were attracted in significant numbers to a blend of 3-hydroxyhexan-2-one and (2E,6Z,9Z)-2,6,9-pentadecatrienal, even though there is no evidence that this species produces the latter compound. From timed pheromone trap catches, adults of E. mucronatum were determined to be active from dusk until shortly after midnight.

Genome Sequence of Lactobacillus brevis Strain D6, Isolated from Smoked Fresh Cheese

PubMed Central

Uroić, Ksenija; Hynönen, Ulla; Kos, Blaženka; Šušković, Jagoda

2016-01-01

The autochthonous Lactobacillus brevis strain D6, isolated from smoked fresh cheese, carries a 45-kDa S-layer protein. Strain D6 has shown adhesion to extracellular matrix proteins and to Caco-2 intestinal epithelial cells, as well as immunomodulatory potential and beneficial milk technological properties. Hence, it could be used as a potential probiotic starter culture for cheese production. PMID:27056237

A Portuguese value set for the SF-6D.

PubMed

Ferreira, Lara N; Ferreira, Pedro L; Pereira, Luis N; Brazier, John; Rowen, Donna

2010-08-01

The SF-6D is a preference-based measure of health derived from the SF-36 that can be used for cost-effectiveness analysis using cost-per-quality adjusted life-year analysis. This study seeks to estimate a system weight for the SF-6D for Portugal and to compare the results with the UK system weights. A sample of 55 health states defined by the SF-6D has been valued by a representative random sample of the Portuguese population, stratified by sex and age (n = 140), using the Standard Gamble (SG). Several models are estimated at both the individual and aggregate levels for predicting health-state valuations. Models with main effects, with interaction effects and with the constant forced to unity are presented. Random effects (RE) models are estimated using generalized least squares (GLS) regressions. Generalized estimation equations (GEE) are used to estimate RE models with the constant forced to unity. Estimations at the individual level were performed using 630 health-state valuations. Alternative functional forms are considered to account for the skewed distribution of health-state valuations. The models are analyzed in terms of their coefficients, overall fit, and the ability for predicting the SG-values. The RE models estimated using GLS and through GEE produce significant coefficients, which are robust across model specification. However, there are concerns regarding some inconsistent estimates, and so parsimonious consistent models were estimated. There is evidence of under prediction in some states assigned to poor health. The results are consistent with the UK results. The models estimated provide preference-based quality of life weights for the Portuguese population when health status data have been collected using the SF-36. Although the sample was randomly drowned findings should be treated with caution, given the small sample size, even knowing that they have been estimated at the individual level.

Diffusion Monte Carlo studies of MB-pol (H{sub 2}O){sub 2−6} and (D{sub 2}O){sub 2−6} clusters: Structures and binding energies

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

Mallory, Joel D.; Mandelshtam, Vladimir A.

2016-08-14

We employ the diffusion Monte Carlo (DMC) method in conjunction with the recently developed, ab initio-based MB-pol potential energy surface to characterize the ground states of small (H{sub 2}O){sub 2−6} clusters and their deuterated isotopomers. Observables, other than the ground state energies, are computed using the descendant weighting approach. Among those are various spatial correlation functions and relative isomer fractions. Interestingly, the ground states of all clusters considered in this study, except for the dimer, are delocalized over at least two conformations that differ by the orientation of one or more water monomers with the relative isomer populations being sensitivemore » to the isotope substitution. Most remarkably, the ground state of the (H{sub 2}O){sub 6} hexamer is represented by four distinct cage structures, while that of (D{sub 2}O){sub 6} is dominated by the prism, i.e., the global minimum geometry, with a very small contribution from a prism-book geometry. In addition, for (H{sub 2}O){sub 6} and (D{sub 2}O){sub 6}, we performed DMC calculations to compute the ground states constrained to the cage and prism geometries. These calculations compared results for three different potentials, MB-pol, TTM3/F, and q-TIP4P/F.« less

21 CFR 74.1306 - D&C Red No. 6.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false D&C Red No. 6. 74.1306 Section 74.1306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... medium with 3-hydroxy-2-naphthalenecarboxylic acid. The resulting dye precipitates as the disodium salt...

21 CFR 74.1306 - D&C Red No. 6.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false D&C Red No. 6. 74.1306 Section 74.1306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... medium with 3-hydroxy-2-naphthalenecarboxylic acid. The resulting dye precipitates as the disodium salt...

21 CFR 74.1306 - D&C Red No. 6.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false D&C Red No. 6. 74.1306 Section 74.1306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... medium with 3-hydroxy-2-naphthalenecarboxylic acid. The resulting dye precipitates as the disodium salt...

6. Historic American Buildings Survey E. W. Russell, Photographer, Feb. ...

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

6. Historic American Buildings Survey E. W. Russell, Photographer, Feb. 12, 1937 VIEW LOOKING UP MAIN DRIVEWAY SHOWING SO. E. (UPPER PORTION) OF BLDG. ALSO WEST ELEV. OF CHURCH. - Convent of the Visitation, 2300 Spring Hill Avenue, Mobile, Mobile County, AL

Thin limit of the 6D Cascading DGP model

NASA Astrophysics Data System (ADS)

Sbisà, Fulvio

2018-05-01

A thin limit description of the 6D Cascading DGP model is derived, starting from a configuration where both the codimension-1 and the codimension-2 branes are thick. Postulating that the thicknesses of the two branes obey a hierarchic relation, the thin limit is executed in two steps. First the thin limit of the codimension-1 brane is executed, obtaining a system where a "ribbon" codimension-2 brane is embedded inside a thin codimension-1 brane with induced gravity, and then the thin limit of the ribbon brane is considered. By proposing a geometric ansatz on the limit configuration, the junction conditions which are to hold at the thin codimension-2 brane are derived. The latters are fully non-perturbative and covariant and, together with the Israel junction conditions at the codimension-1 brane and the Einstein equations in the bulk, constitute the looked-for thin limit formulation of the 6D Cascading DGP model. It is commented on how wide is the class of thin source configurations which can be placed on the thin codimension-2 brane.

[Construction and eukaryotic expression of PVAX1-hPV58mE6E7fcGB composite gene vaccine].

PubMed

Wang, He; Yu, Jiyun; Li, Li

2013-10-01

To construct and express a composite gene vaccine for human papillomavirus 58(HPV58)-associated cervical cancer, we inserted HPV58mE6E7 fusion gene into pCI-Fc-GPI eukaryotic expression vector, constructing a recombinant plasmid named pCI-sig-HPV58mE6E7-Fc-GPI. Then we further inserted fragment of sig-HPV58mE6E7Fc-GPI into the novel vaccine vector PVAX1-IRES-GM/B7, constructing PVAX1-HPV58mE6E7FcGB composite gene vaccine. PVAX1-HPV58mE6E7FcGB vaccine was successfully constructed and identified by restriction endonuclease and sequencing analysis. Eukaryotic expression of fusion antigen sig-HPV58mE6E7-Fc-GPI and molecular ad-juvant GM-CSF and B7. 1 were proved to be realized at the same time by flow cytometry and immunofluorescence. So PVAX1-HPV58mE6E7FcGB can be taken as a candidate of therapeutic vaccine for HPV58-associated tumors and their precancerous transformations.

The Henry reaction of (1R)-(1,4:3,6-dianhydro-D-mannitol-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate. Different reactive features of nitromethane to nitroethane.

PubMed

Liu, Feng-Wu; Wang, Zhen-Ji; Song, Xiao-Ping; Zhang, Sai-Yang; Liu, Hong-Min

2009-12-14

Henry reactions of a novel higher sugar derivative, (1R)-(1,4:3,6-dianhydro-D-mannitol-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate (Alternate nomenclature: (1R)-(isomannid-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate), with nitromethane and nitroethane were studied. The kinetic and thermodynamic reactions with nitromethane under different conditions were carried out to afford (2S)- and (2R)-beta-nitroalcohols, respectively. But when using nitroethane the reaction gave a (2S)-beta-nitroalcohol with an inverted configuration at vicinal carbon C-1. Two stereogenic centers were generated, and one was altered in the reaction.

Influence of water-insoluble nonionic copolymer E(6)P(39)E(6) on the microstructure and self-aggregation dynamics of aqueous SDS solution-NMR and SANS investigations.

PubMed

Prameela, G K S; Phani Kumar, B V N; Aswal, V K; Mandal, Asit Baran

2013-10-28

The influence of water-insoluble nonionic triblock copolymer PEO-PPO-PEO [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] i.e., E6P39E6 with molecular weight 2800, on the microstructure and self-aggregation dynamics of anionic surfactant sodium dodecylsulfate (SDS) in aqueous solution (D2O) were investigated using high resolution nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS) measurements. Variable concentration and temperature proton ((1)H), carbon ((13)C) NMR chemical shifts, (1)H self-diffusion coefficients, (1)H spin-lattice and spin-spin relaxation rates data indicate that the higher hydrophobic nature of copolymer significantly influenced aggregation characteristics of SDS. The salient features of the NMR investigations include (i) the onset of mixed micelles at lower SDS concentrations (<3 mM) relative to the copolymer-free case and their evolution into SDS free micelles at higher SDS concentrations (~30 mM), (ii) disintegration of copolymer-SDS mixed aggregate at moderate SDS concentrations (~10 mM) and still binding of a copolymer with SDS and (iii) preferential localization of the copolymer occurred at the SDS micelle surface. SANS investigations indicate prolate ellipsoidal shaped mixed aggregates with an increase in SDS aggregation number, while a contrasting behavior in the copolymer aggregation is observed. The aggregation features of SDS and the copolymer, the sizes of mixed aggregates and the degree of counterion dissociation (α) extracted from SANS data analysis corroborate reasonably well with those of (1)H NMR self-diffusion and sodium ((23)Na) spin-lattice relaxation data.

Cleavage of HPV-16 E6/E7 mRNA mediated by modified 10-23 deoxyribozymes.

PubMed

Reyes-Gutiérrez, Pablo; Alvarez-Salas, Luis M

2009-09-01

Deoxyribozymes (DXZs) are small oligodeoxynucleotides capable of mediating phosphodiester bond cleavage of a target RNA in a sequence-specific manner. These molecules are a new generation of artificial catalytic nucleic acids currently used to silence many disease-related genes. The present study describes a DXZ (Dz1023-434) directed against the polycistronic mRNA from the E6 and E7 genes of human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer. Dz1023-434 showed efficient cleavage against a bona fide antisense window at nt 410-445 within HPV-16 E6/E7 mRNA even in low [Mg(2+)] conditions. Using a genetic analysis as guidance, we introduced diverse chemical modifications within Dz1023-434 catalytic core to produce a stable locked nucleic acid (LNA)-modified DXZ (Dz434-LNA) with significant cleavage activity of full E6/E7 transcripts. Cell culture testing of Dz434-LNA produced a sharp decrement of E6/E7 mRNA levels in HPV-16-positive cells resulting in decreased proliferation and considerable cell death in a specific and dose-dependent manner. No significant effects were observed with inactive or scrambled control DXZs nor from using HPV-negative cells, suggesting catalysis-dependent effect and high specificity. The biological effects of Dz434-LNA suggest a potential use for the treatment of cervical cancer.