Sample records for vanstar 7

  1. Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2018-03-02

    Advanced Bile Duct Carcinoma; Stage II Esophageal Cancer AJCC v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIB Pancreatic Cancer AJCC v6 and v7; Stage III Colon Cancer AJCC v7; Stage III Esophageal Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage III Liver Cancer; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Rectal Cancer AJCC v7; Stage III Small Intestinal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIA Small Intestinal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIB Small Intestinal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Esophageal Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Stage IV Liver Cancer; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Rectal Cancer AJCC v7; Stage IV Small Intestinal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Liver Cancer; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Liver Cancer; Stage IVB Rectal Cancer AJCC v7

  2. Medical Separation Among Careerists

    DTIC Science & Technology

    2013-03-01

    Observations 18,314 18,314 18,314 18,314 Adjusted7R&squared 0.0210 0.0210 0.0211 0.0212 Robust7standard7errors7in7parentheses *** 7p ɘ.01,7** 7p ...0.05,7* 7p ɘ.1 Medical7Separation Medical7Separation Medical7Separation Medical7Separation (i) (j) (k) (l) 58 The factors with the highest magnitude are

  3. Korat Royal Thai AFB, Thailand. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1973-08-08

    7 9.5 93.8 94.0 9 40 , .0 940 00 94.0 94 0 94 0 9 94.0 94o. 94. 9W.0 > 7000 93.2 9:iv 95,11 95 5 95o5 96,5 9505 95.5 91’,5 9 . 9’o*5 95,5 95*5 q345 95...9 95, 95o ! 1 9545 95051 9905 9505 9395 9505 9505 9565 9505 > 6000 93P ’a,o 9 .n 9,7 95.7 q5o7 94o7 95,7 957 95o7 95.7 95.7 9Io7 15,1 95o7� -1 9o 4...80.7 8.7 80,7 80,7 80,7 80,7 80,7 80. 40.7 80.7 nO.7 8007 -10000 614,6 85, i 85, ,5 15,5 5 5 85,5 055, 8505 85,6 9505 8.5 1!5,05 821 > 9000 05 , 5 60,4

  4. Trametinib and TAS-102 in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2018-05-07

    RAS Family Gene Mutation; Stage III Colon Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

  5. Surface Observation Climatic Summaries (SOCS) for Rickenbacker ANGB, Ohio

    DTIC Science & Technology

    1989-02-01

    86.9 90.5 91.8 93.2 94.9 95.3 96.7 98.2 98.5 91.7 GE 103 72. 7 77 .’ 62. 1 86. 9 40.5 91.6 93. Z 94.9 95.3 96. 7 98.2 96. 5 93.7 1) () 0 71 o 77.9...I 95.’s 97.1 7. 6 97.7 97. 93.0 9.0 9.I1 98.1 9 ! 95.1 49.4 103 . 5 q7.7 Z33 1 hi.4 ml.s 95.6 9P.6 99.7 93.7 9R.7 98.7 9. 5 4 96.5 9;.1 98. t 99.7 95.9...19339 ;7. )0.2 3.3 63.4 63.6 63.7 )3. 7 63.7 53.7 ’,3.7 63.7 63.7 rF 103 . 57.5 5 .q 5 ". 5 ".4.3 64.1 64.2 𔃾._ A4.? 64.2 64.? 64.2 G C 00o 51.? 5 ,. 6

  6. Ginseng in Decreasing Cancer-Related Fatigue After Treatment in Cancer Survivors

    ClinicalTrials.gov

    2018-03-15

    Cancer Survivor; Stage I Breast Cancer AJCC v7; Stage I Colon Cancer AJCC v6 and v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage II Colon Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIA Colon Cancer AJCC v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIB Colon Cancer AJCC v7; Stage IIC Colon Cancer AJCC v7; Stage III Breast Cancer AJCC v7; Stage III Colon Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7

  7. Pulse Shaping and Energy Storage Capabilities of Angularly-Multiplexed KrF Laser Fusion Drivers

    DTIC Science & Technology

    2009-01-01

    6&-7 9)%:5?𔄃%1706-?1 6%5&1-J.% 5?./2 (% %x9%)-’%160//C -𔄃/%’%16%2 -1 )%0/ 6-’% ?1 0 )%9:)06%2 /07%) 7C76%’" 8&% 7-’./06-? 17 7&?K 6&06 6&-7 ’./6-(%0...8217 7C76%’ 501 05&-%=% 0 &-*& L2%/-6C 9./7% 7&09-1* 5090(-/-6CG %=%1 >?) 0 &-*& *0-1 7&?5B -*1-6-?1 9./7% K&?7% L10/ 79-B% )%J.-)%7 ?.69.6 -16% 17 -6-%7...K-26&7  " 17 " <?) 6&% 5&?7%1 9./7%G K&-5& *-=%7 0 9)%2-56%2 >.7-?1 %1%)*C *0-1  "#$G 6&% 7-’./06-? 17 9)%2-56 6&% ɠ< 501 2%/-=%) 0 6?60/ ?1:60)*%6

  8. 40 CFR 180.116 - Ziram; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....0 1 Blueberry 7.0 1 Cherry, sweet 7.0 1 Cherry, tart 7.0 1 Grape 7.0 Huckleberry 7.0 Peach 7.0 Pear 7.0 1 Pecan 0.1 Quince 7.0 1 Strawberry 7.0 Tomato 7.0 1 1 Some of these tolerances were established...

  9. 40 CFR 180.116 - Ziram; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....0 1 Blueberry 7.0 1 Cherry, sweet 7.0 1 Cherry, tart 7.0 1 Grape 7.0 Huckleberry 7.0 Peach 7.0 Pear 7.0 1 Pecan 0.1 Quince 7.0 1 Strawberry 7.0 Tomato 7.0 1 1 Some of these tolerances were established...

  10. MAGNA (Materially and Geometrically Nonlinear Analysis). Part I. Finite Element Analysis Manual.

    DTIC Science & Technology

    1982-12-01

    provided for operating the program, modifying storage caoacity, preparing input data, estimating computer run times , and interpreting the output...7.1.3 Reserved File Names 7.1.16 7.1.4 Typical Execution Times on CDC Computers 7.1.18 7.2 CRAY PROGRAM VERSION 7.2.1 7.2.1 Job Control Language 7.2.1...7.2.2 Modification of Storage Capacity 7.2.8 7.2.3 Execution Times on the CRAY-I Computer 7.2.12 7.3 VAX PROGRAM VERSION 7.3.1 8 INPUT DATA 8.0.1 8.1

  11. A self-initiating eukaryotic transient gene expression system based on contransfection of bacteriophage T7 RNA polymerase and DNA vectors containing a T7 autogene.

    PubMed Central

    Chen, X; Li, Y; Xiong, K; Wagner, T E

    1994-01-01

    A novel cytoplasmic gene expression system has been developed. This system differs from other expression systems in that it relies on the co-delivery of plasmid DNA and T7 RNA polymerase (RNAP) during transfection. The plasmid contains a T7 RNAP gene driven by the T7 promoter (T7 autogene) and a functional/reporter gene driven by another T7 promoter (T7T7/T7-gene construct). Once this DNA-enzyme complex is introduced into eukaryotic cells, the transcription of the T7 RNAP and the functional/reporter genes is initiated by the co-delivered T7 RNAP. The T7 RNAP, which is responsible for the initiation and maintenance of expression of both T7 and functional/reporter genes, is replenished by translation of newly synthesized T7 mRNA. This T7 system was designed in such a manner that the expression of the functional/reporter genes can occur in the cytoplasm and does not require any nuclear involvement. When transfected by either a pT7T7/T7Luc or a pT7T7/T7hGH plasmids with the cointroduced T7 RNAP, mouse L cells were found to express high levels of luciferase immediately after transfection, apparently due to the cytoplasmic gene expression; the expression of human growth hormone (hGH) could be sustained for at least 6 days. Both T7 and hGH mRNA were expressed by the cells transfected with pT7T7/T7hGH. These results suggest that this cytoplasmic expression system may be used for certain targets of somatic gene therapy. Images PMID:8029020

  12. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    ClinicalTrials.gov

    2018-04-02

    Glioma; Lymphoma; Metastatic Malignant Solid Neoplasm; Neuroendocrine Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Breast Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Prostate Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Solid Neoplasm

  13. Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

    ClinicalTrials.gov

    2018-04-27

    Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

  14. Effects of 7,8-benzoflavone of skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7,12-dimenthylbenz(a)anthracene in mice

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

    DiGiovanni, J.; Slaga, T.J.; Viaje, A.

    1978-07-01

    The skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7,12-dimethylbenz(a)anthracene (DMBA) were investigated in female outbred Charles River CD-1 mice. 7-Formyl-12-methylbenz(a)anthracene (7-CHO-12-MBA) at 740 nmoles/mouse was an effective tumor initiator, at a dose 74-fold greater than that of DMBA. 7,8-Benzoflavone (7,8-BF) inhibited the tumor-initiating activity of 7-CHO-12-MBA by 51%. 12-Formyl-7-methylbenz(a)anthranene and 7,12-diformylbenz(a)anthracene, applied at initiating doses of 740 nmoles and 704 nmoles/mouse, respectively, were much less active than 7-CHO-12-MBA. 7-Bromomethyl-12-methylbenz(a)anthracene (7-BRME-12-MBA) and 7-bromomethylbenz(a)anthracene (7-BRMEBA) were also investigated. 7-BRME-12-MBA was a more effective tumor initiator than 7-BRMEBA, but both were less active than DMBA. 7,8-BF inhibited the tumor-initiating activitymore » of 7-BRME- 12-MBA and 7-BRMEBA by 34 and 54%, respectively. 12-Bromomethyl-7-methylbenz(a)anthracene (12-BRME-7-MBA) was as active an initiator as 7-BRME-12-MBA. 7,8-BF inhibited tumor initiation with 12-BRME-7-MBA by 29%. Three naturally occurring flavones, quercetin, myricetin, and 4',5,7-trihydroxyflavonone, and the cytochrome P/sub 450/, inhibitor 1-benzylimidazole were investigated after topical application(100 ..mu..g) for their effects on tumor initiation with DMBA. Quercetin inhibited tumor initiation with DMBA. Quercetin inhibited tumor initiation with DMBA by 22%, whereas myricetin and 4',5,7-trihydroxyflavanone enhanced tumor initiation with DMBA by 54 and 29%, respectively. 1-Benzylimidazole had no effect. The abilities of the flavones and 1-benzylimidazole to inhibit aryl hydrocarbon hydroxylase in vitro did not correlate with their effects on tumor initiation with DMBA.« less

  15. Differential Protein Kinase C-dependent Modulation of Kv7.4 and Kv7.5 Subunits of Vascular Kv7 Channels*

    PubMed Central

    Brueggemann, Lioubov I.; Mackie, Alexander R.; Cribbs, Leanne L.; Freda, Jessica; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L.

    2014-01-01

    The Kv7 family (Kv7.1–7.5) of voltage-activated potassium channels contributes to the maintenance of resting membrane potential in excitable cells. Previously, we provided pharmacological and electrophysiological evidence that Kv7.4 and Kv7.5 form predominantly heteromeric channels and that Kv7 activity is regulated by protein kinase C (PKC) in response to vasoconstrictors in vascular smooth muscle cells. Direct evidence for Kv7.4/7.5 heteromer formation, however, is lacking. Furthermore, it remains to be determined whether both subunits are regulated by PKC. Utilizing proximity ligation assays to visualize single molecule interactions, we now show that Kv7.4/Kv.7.5 heteromers are endogenously expressed in vascular smooth muscle cells. Introduction of dominant-negative Kv7.4 and Kv7.5 subunits in mesenteric artery myocytes reduced endogenous Kv7 currents by 84 and 76%, respectively. Expression of an inducible protein kinase Cα (PKCα) translocation system revealed that PKCα activation is sufficient to suppress endogenous Kv7 currents in A7r5 rat aortic and mesenteric artery smooth muscle cells. Arginine vasopressin (100 and 500 pm) and the PKC activator phorbol 12-myristate 13-acetate (1 nm) each inhibited human (h) Kv7.5 and hKv7.4/7.5, but not hKv7.4 channels expressed in A7r5 cells. A decrease in hKv7.5 and hKv7.4/7.5 current densities was associated with an increase in PKC-dependent phosphorylation of the channel proteins. These findings provide further evidence for a differential regulation of Kv7.4 and Kv7.5 channel subunits by PKC-dependent phosphorylation and new mechanistic insights into the role of heteromeric subunit assembly for regulation of vascular Kv7 channels. PMID:24297175

  16. Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology.

    PubMed

    Oliveras, Anna; Roura-Ferrer, Meritxell; Solé, Laura; de la Cruz, Alicia; Prieto, Angela; Etxebarria, Ainhoa; Manils, Joan; Morales-Cano, Daniel; Condom, Enric; Soler, Concepció; Cogolludo, Angel; Valenzuela, Carmen; Villarroel, Alvaro; Comes, Núria; Felipe, Antonio

    2014-07-01

    Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fail to modulate smooth muscle reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form functional heterotetrameric channels increasing the channel diversity in vascular smooth muscles. Kv7.1 and Kv7.5 currents elicited in arterial myocytes, oocyte, and mammalian expression systems suggest the formation of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5 associations were confirmed by coimmunoprecipitation, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching experiments. Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum. Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles demonstrated that the predominant presence of Kv7.5 stimulates release of Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological studies supported that KCNE1 and KCNE3 regulatory subunits further increased the channel diversity. Finally, the analysis of rat isolated myocytes and human blood vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression, which may lead to channel diversity. Kv7.1 and Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. Because the lipid raft localization of ion channels is crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient spatial and temporal regulation of smooth muscle function. Our results shed light on the debate about the contribution of Kv7 channels to vasoconstriction and hypertension. © 2014 American Heart Association, Inc.

  17. Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value?

    PubMed

    Ademà, Vera; Hernández, Jesús María; Abáigar, María; Lumbreras, Eva; Such, Esperanza; Calull, Anna; Dominguez, Esther; Arenillas, Leonor; Mallo, Mar; Cervera, José; Marugán, Isabel; Tormo, Mar; García, Francisca; González, Teresa; Luño, Elisa; Sanzo, Carmen; Martín, María Luisa; Fernández, Manuela; Costa, Dolors; Blázquez, Beatriz; Barreña, Beatriz; Marco, Fernando; Batlle, Ana; Buño, Ismael; Martínez-Laperche, Carolina; Noriega, Víctor; Collado, Rosa; Ivars, David; Carbonell, Félix; Vallcorba, Isabel; Melero, Josefa; Delgado, Elena; Vargas, María Teresa; Grau, Javier; Salido, Marta; Espinet, Blanca; Melero, Carme; Florensa, Lourdes; Pedro, Carmen; Solé, Francesc

    2013-04-01

    Chromosomal abnormalities are detected in 40-60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (-7) or 7q deletion (7q-) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected -7/7q- in 5.2% of patients. Presence of -7/7q- was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of -7/7q- by CC. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Adavosertib, External Beam Radiation Therapy, and Cisplatin in Treating Patients With Cervical, Vaginal, or Uterine Cancer

    ClinicalTrials.gov

    2018-06-06

    Endometrioid Adenocarcinoma; Recurrent Cervical Carcinoma; Stage I Uterine Corpus Cancer AJCC v7; Stage I Vaginal Cancer AJCC v6 and v7; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Cervical Cancer AJCC v6 and v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Cervical Cancer AJCC v6 and v7; Stage III Uterine Corpus Cancer AJCC v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7

  19. Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents.

    PubMed

    Mani, Bharath K; Robakowski, Christina; Brueggemann, Lyubov I; Cribbs, Leanne L; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L

    2016-03-01

    Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K(+) currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 > Kv7.4/Kv7.5 > Kv7.4. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

    PubMed Central

    Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

    2016-01-01

    Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

  1. Veliparib and Irinotecan Hydrochloride in Treating Patients With Cancer That Is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2018-04-12

    Advanced Malignant Solid Neoplasm; Estrogen Receptor Negative; HER2/Neu Negative; Hodgkin Lymphoma; Metastatic Malignant Neoplasm; Metastatic Malignant Solid Neoplasm; Non-Hodgkin Lymphoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Colon Cancer AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Colon Cancer AJCC v7; Stage IV Lung Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colon Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Malignant Neoplasm; Unresectable Solid Neoplasm

  2. Differential Activation of Vascular Smooth Muscle Kv7.4, Kv7.5, and Kv7.4/7.5 Channels by ML213 and ICA-069673

    PubMed Central

    Brueggemann, Lyubov I.; Haick, Jennifer M.; Cribbs, Leanne L.

    2014-01-01

    Recent research suggests that smooth muscle cells express Kv7.4 and Kv7.5 voltage-activated potassium channels, which contribute to maintenance of their resting membrane voltage. New pharmacologic activators of Kv7 channels, ML213 (N-mesitybicyclo[2.2.1]heptane-2-carboxamide) and ICA-069673 N-(6-chloropyridin-3-yl)-3,4-difluorobenzamide), have been reported to discriminate among channels formed from different Kv7 subtypes. We compared the effects of ML213 and ICA-069673 on homomeric human Kv7.4, Kv7.5, and heteromeric Kv7.4/7.5 channels exogenously expressed in A7r5 vascular smooth muscle cells. We found that, despite its previous description as a selective activator of Kv7.2 and Kv7.4, ML213 significantly increased the maximum conductance of homomeric Kv7.4 and Kv7.5, as well as heteromeric Kv7.4/7.5 channels, and induced a negative shift of their activation curves. Current deactivation rates decreased in the presence of the ML213 (10 μM) for all three channel combinations. Mutants of Kv7.4 (W242L) and Kv7.5 (W235L), previously found to be insensitive to another Kv7 channel activator, retigabine, were also insensitive to ML213 (10 μM). In contrast to ML213, ICA-069673 robustly activated Kv7.4 channels but was significantly less effective on homomeric Kv7.5 channels. Heteromeric Kv7.4/7.5 channels displayed intermediate responses to ICA-069673. In each case, ICA-069673 induced a negative shift of the activation curves without significantly increasing maximal conductance. Current deactivation rates decreased in the presence of ICA-069673 in a subunit-specific manner. Kv7.4 W242L responded to ICA-069673-like wild-type Kv7.4, but a Kv7.4 F143A mutant was much less sensitive to ICA-069673. Based on these results, ML213 and ICA-069673 likely bind to different sites and are differentially selective among Kv7.4, Kv7.5, and Kv7.4/7.5 channel subtypes. PMID:24944189

  3. A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries.

    PubMed

    Lasala, Matías; Corradi, Jeremías; Bruzzone, Ariana; Esandi, María Del Carmen; Bouzat, Cecilia

    2018-05-21

    The cholinergic α7 nicotinic receptor gene, CHRNA7, encodes a subunit that forms the homopentameric α7 receptor, involved in learning and memory. In humans, exons 5-10 in CHRNA7 are duplicated and fused to the FAM7A genetic element, giving rise to the hybrid gene CHRFAM7A. Its product, dupα7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation.We combined dupα7 expression on mammalian cells with patch clamp recordings to understand its functional role. Transfected cells expressed dupα7 protein, but they exhibited neither surface binding of the α7 antagonist α-bungarotoxin nor responses to acetylcholine (ACh) or to an allosteric agonist that binds to the conserved transmembrane region. To determine if dupα7 assembles with α7, we generated receptors comprising α7 and dupα7 subunits, one of which was tagged with conductance substitutions that report subunit stoichiometry and monitored ACh-elicited channel openings elicited by ACh in the presence of a positive allosteric α7 modulator. We found that α7 and dupα7 subunits co-assemble into functional heteromeric receptors, that at least two α7 subunits are required for channel opening, and that dupα7's presence in the pentameric arrangement does not affect the duration of the potentiated events compare with that of α7. Using an α7 subunit mutant, we found that activation of (α7)2(dupα7)3 receptors occurs through ACh binding at the α7/α7 interfacial binding site. Our study contributes to the understanding of the modulation of α7 function by the human specific, duplicated subunit, associated with human disorders. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  4. 41 CFR 302-7.7 - May the origin and destination points be other than that prescribed in § 302-7.6?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... destination points be other than that prescribed in § 302-7.6? 302-7.7 Section 302-7.7 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF... EQUIPMENT (PBP&E) General Rules § 302-7.7 May the origin and destination points be other than that...

  5. Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

    ClinicalTrials.gov

    2018-04-02

    Clear Cell Renal Cell Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Penile Carcinoma; Renal Pelvis Urothelial Carcinoma; Squamous Cell Carcinoma of the Penis; Stage III Bladder Adenocarcinoma AJCC v6 and v7; Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Penile Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IIIa Penile Cancer AJCC v7; Stage IIIb Penile Cancer AJCC v7; Stage IV Bladder Adenocarcinoma AJCC v7; Stage IV Bladder Squamous Cell Carcinoma AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

  6. 40 CFR 439.16 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Xylenes 3.0 0.7 n-Heptane 3.0 0.7 n-Hexane 3.0 0.7 Methylene chloride 3.0 0.7 Chloroform 0.1 0.03 1,2... 1 Ammonia (as N) 2 84.1 29.4 Acetone 20.7 8.2 4-methyl-2-pentanone 20.7 8.2 Isobutyraldehyde 20.7 8.2 n-Amyl acetate 20.7 8.2 n-Butyl acetate 20.7 8.2 Ethyl acetate 20.7 8.2 Isopropyl acetate 20.7 8.2...

  7. 40 CFR 439.16 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Xylenes 3.0 0.7 n-Heptane 3.0 0.7 n-Hexane 3.0 0.7 Methylene chloride 3.0 0.7 Chloroform 0.1 0.03 1,2... 1 Ammonia (as N) 2 84.1 29.4 Acetone 20.7 8.2 4-methyl-2-pentanone 20.7 8.2 Isobutyraldehyde 20.7 8.2 n-Amyl acetate 20.7 8.2 n-Butyl acetate 20.7 8.2 Ethyl acetate 20.7 8.2 Isopropyl acetate 20.7 8.2...

  8. 40 CFR 439.16 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Xylenes 3.0 0.7 n-Heptane 3.0 0.7 n-Hexane 3.0 0.7 Methylene chloride 3.0 0.7 Chloroform 0.1 0.03 1,2... 1 Ammonia (as N) 2 84.1 29.4 Acetone 20.7 8.2 4-methyl-2-pentanone 20.7 8.2 Isobutyraldehyde 20.7 8.2 n-Amyl acetate 20.7 8.2 n-Butyl acetate 20.7 8.2 Ethyl acetate 20.7 8.2 Isopropyl acetate 20.7 8.2...

  9. The colour degradation of anthocyanin-rich extract from butterfly pea (Clitoria ternatea L.) petal in various solvents at pH 7.

    PubMed

    Marpaung, Abdullah Muzi; Andarwulan, Nuri; Hariyadi, Purwiyatno; Nur Faridah, Didah

    2017-10-01

    A spectroscopic study was conducted to evaluate the colour degradation mechanism of anthocyanin-rich extract from butterfly pea petal. The extract was diluted in four different solvent systems, which were buffer solution pH 7 (AQ7) and the mixture of organic solvent with buffer solution pH 7 (4:1 v/v). The organic cosolvent involved were methanol (ME7), ethanol (ET7) and acetone (AC7). The samples were stored in containers with 0% and 50% headspace, and their colour intensity, total anthocyanin and hypsochromic shift were evaluated periodically. The rank of colour and anthocyanin degradation from the biggest was AQ7 > ME7 > ET7 > AC7. The longest hypsochromic shift was AQ7 > ME7 > ET7, while in AC7 the shift was absent. There was evidence that the volume of package headspace provoked colour stability. The colour degradation in AC7 was proposed to occur through hydrophobic interaction unfolding, and in AQ7 was through the deacylation, while in ME7 and ET7 was due to both mechanisms.

  10. Air Force Research Laboratory’s 2006 Technology Milestones

    DTIC Science & Technology

    2006-01-01

    3 $*( )RUP$SSURYHG 20%1R 5(3257’$7( ’󈧄<<<< 5(32577< 3 ( 7,7/($1󈨈%7,7/( D&2175$&7180%(5...87+25 6 3 (5)250,1*25*$1,=$7,211$0( 6 $1’$’𔃿(66 (6 6321625,1*021,725,1*$*(1&ə$0( 6 $1’$’𔃿(66 (6 3 (5)250,1*25*$1,=$7,21...180%(5 2) 3 $*(6 D1$0(2)5(63216,%/( 3 (5621 D5(3257 E$%675$&7 F7+,6 3 $*( /,0,7$7,212) $%675$&7

  11. Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses

    PubMed Central

    Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

    2016-01-01

    The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses. PMID:26907865

  12. Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses.

    PubMed

    Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

    2016-02-24

    The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses.

  13. Molecular and Cytological Comparisons of Chromosomes 7el₁, 7el₂, 7E(e), and 7E ⁱ Derived from Thinopyrum.

    PubMed

    Guo, Jun; He, Fang; Cai, Jin-Jin; Wang, Hong-Wei; Li, An-Fei; Wang, Hong-Gang; Kong, Ling-Rang

    2015-01-01

    Thinopyrum chromosomes 7el1, 7el2, 7E(e), and 7E(i), homoeologous to group 7 chromosomes of common wheat (Triticum aestivum), were determined to have many useful agronomical traits for wheat improvement. To analyze the genetic relationships among the 4 Thinopyrum 7E chromosomes, the conserved orthologous set markers, genomic in situ hybridization (GISH), and meiotic chromosome pairing were used in this study. The unweighted pair-group method with arithmetical averages (UPGMA) analysis indicated that 7el1, derived from T. ponticum, and 7E(i), derived from T. intermedium, were the most closely related. 7el2, derived from T. ponticum, was relatively distant from the 7el1-7E(i) complex. While 7E(e), derived from T. elongatum, was more distantly related to 7el1, 7el2, and 7E(i). This is the first report showing that 7el1 and 7E(i) may be similar, which could be explained by the similar chromosome signal distribution revealed by GISH as well as UPGMA analysis revealed by both molecular markers and the highest frequency of meiotic pairing. The newly developed genome-specific molecular markers may be useful for marker-assisted selection of Lr19, Bdv3, and Fhblop. © 2015 S. Karger AG, Basel.

  14. 7-Deazapurine containing DNA: efficiency of c7GdTP, c7AdTP and c7IdTP incorporation during PCR-amplification and protection from endodeoxyribonuclease hydrolysis.

    PubMed Central

    Seela, F; Röling, A

    1992-01-01

    The enzymatic synthesis of 7-deazapurine nucleoside containing DNA (501 bp) is performed by PCR-amplification (Taq polymerase) using a pUC18 plasmid DNA as template and the triphosphates of 7-deaza-2'-deoxyguanosine (c7Gd), -adenosine (c7Ad) and -inosine (c7Id). c7GdTP can fully replace dGTP resulting in a completely modified DNA-fragment of defined size and sequence. The other two 7-deazapurine triphosphates (c7AdTP) and (c7IdTP) require the presence of the parent purine 2'-deoxyribonucleotides. In purine/7-deazapurine nucleotide mixtures Taq polymerase prefers purine over 7-deazapurine nucleotides but accepts c7GdTP much better than c7AdTP or c7IdTP. As incorporation of 7-deazapurine nucleotides represents a modification of the major groove of DNA it can be used to probe DNA/protein interaction. Regioselective phosphodiester hydrolysis of the modified DNA-fragments was studied with 28 endodeoxyribonucleases. c7Gd is able to protect the DNA from the phosphodiester hydrolysis in more than 20 cases, only a few enzymes (Mae III, Rsa I, Hind III, Pvu II or Taq I) do still hydrolyze the modified DNA. c7Ad protects DNA less efficiently, as this DNA could only be modified in part. The absence of N-7 as potential binding position or a geometric distortion of the recognition duplex caused by the 7-deazapurine base can account for protection of hydrolysis. Images PMID:1738604

  15. Bioconversion of 7-hydroxyflavanone: isolation, characterization and bioactivity evaluation of twenty-one phase I and phase II microbial metabolites.

    PubMed

    Mikell, Julie Rakel; Khan, Ikhlas Ahmad

    2012-01-01

    Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8-dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7-hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and 8, flavanone 7-O-β-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7-O-β-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195) also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'-trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7-O-α-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19). The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3, 16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A metabolite of 1, flavanone 7-O-β-D-O-glucopyranoside (22) was produced by Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. Metabolites 4 and 16 showed weak antileishmanial activity.

  16. Fibroblast growth factor 7 inhibits cholesterol 7{alpha}-hydroxylase gene expression in hepatocytes

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

    Sun, Zhichao; Yu, Xuemei; Wu, Weibin

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer FGF7 strongly and rapidly down-regulates the expression of CYP7A1 in hepatocytes. Black-Right-Pointing-Pointer FGF7 suppresses the expression of CYP7A1 via FGFR2 and downstream JNK activation. Black-Right-Pointing-Pointer Blocking FGF7 abrogates HSC-induced inhibition of CYP7A1 expression in hepatocytes. -- Abstract: Cholesterol 7{alpha}-hydroxylase (CYP7A1) is the initial and rate-limiting enzyme for bile acid synthesis. Transcription of the CYP7A1 gene is regulated by bile acids, nuclear receptors and cytokines. Fibroblast growth factor 7 (FGF7) secreted from activated hepatic stellate cells (HSC) during chronic liver fibrosis regulates hepatocyte survival and liver regeneration. In the carbon tetrachloride (CCl{sub 4})-induced fibrotic mouse liver, we demonstrated thatmore » the expression of CYP7A1 was largely decreased while the expression of FGF7 was significantly increased. We further demonstrated that FGF7 inhibited CYP7A1 gene expression in hepatocytes. Knockdown study by short interfering RNA, kinase inhibition and phosphorylation assays revealed that the suppression of CYP7A1 expression by FGF7 was mediated by FGFR2 and its downstream JNK signaling cascade. The FGF7 neutralizing antibody restored CYP7A1 expression in Hep3B cells treated with conditioned medium from HSC. In summary, the data suggest that FGF7 is a novel regulator of CYP7A1 expression in hepatocytes and may prevent hepatocytes from accumulating toxic bile acids during liver injury and fibrosis.« less

  17. S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2018-04-09

    Colon Adenocarcinoma; ERBB2 Gene Amplification; Rectal Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage III Colon Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

  18. Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

    ClinicalTrials.gov

    2018-05-23

    Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

  19. Tamoxifen Inhibition of Kv7.2/Kv7.3 Channels

    PubMed Central

    Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S.; Tristani-Firouzi, Martin; Sanchez-Chapula, José A.

    2013-01-01

    KCNQ genes encode five Kv7 K+ channel subunits (Kv7.1–Kv7.5). Four of these (Kv7.2–Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels. PMID:24086693

  20. Tamoxifen inhibition of kv7.2/kv7.3 channels.

    PubMed

    Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S; Tristani-Firouzi, Martin; Sanchez-Chapula, José A

    2013-01-01

    KCNQ genes encode five Kv7 K(+) channel subunits (Kv7.1-Kv7.5). Four of these (Kv7.2-Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels.

  1. Characteristics and molecular basis of celecoxib modulation on Kv7 potassium channels

    PubMed Central

    Du, XN; Zhang, X; Qi, JL; An, HL; Li, JW; Wan, YM; Fu, Y; Gao, HX; Gao, ZB; Zhan, Y; Zhang, HL

    2011-01-01

    BACKGROUND AND PURPOSE Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used for the treatment of pain and inflammation. Emerging and accumulating evidence suggests that celecoxib can affect cellular targets other than COX, such as ion channels. In this study, we characterized the effects of celecoxib on Kv7 K+ channels and compared its effects with the well-established Kv7 channel opener retigabine. EXPERIMENTAL APPROACH A perforated whole-cell patch technique was used to record Kv7currents expressed in HEK 293 cells and M-type currents from rat superior cervical ganglion neurons. KEY RESULTS Celecoxib enhanced Kv7.2–7.4, Kv7.2/7.3 and Kv7.3/7.5 currents but inhibited Kv7.1 and Kv7.1/KCNE1 currents and these effects were concentration dependent. The IC50 value for inhibition of Kv7.1 channels was approximately 4 µM and the EC50 values for activation of Kv7.2–7.4, Kv7.2/Kv7.3 and Kv7.3/Kv7.5 channels were approximately 2–5 µM. The effects of celecoxib were manifested by increasing current amplitudes, shifting the voltage-dependent activation curve in a more negative direction and slowing the deactivation of Kv7 currents. 2,5-Dimethyl-celecoxib, a celecoxib analogue devoid of COX inhibition activity, has similar but greater effects on Kv7currents. Kv7.2(A235T) and Kv7.2(W236L) mutant channels, which have greatly attenuated responses to retigabine, showed a reversed response to celecoxib, from activation to inhibition. CONCLUSIONS AND IMPLICATIONS These results suggest that Kv7 channels are targets of celecoxib action and provide new mechanistic evidence for understanding the effects of celecoxib. They also provide a new approach to developing Kv7 modulators and for studying the structure–function relationship of Kv7 channels. PMID:21564087

  2. Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2018-06-18

    Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

  3. B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4–dependent Mechanism

    PubMed Central

    Stremmel, C.; Greenfield, E.A.; Howard, E.; Freeman, G.J.; Kuchroo, V.K.

    1999-01-01

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the “second signal” pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4–B7-1 cells are completely rejected in syngeneic mice. Unlike EL4–B7-1 cells, we find that EL4–B7-2 cells are not rejected but progressively grow in the mice. A B7-1– and B7-2–EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4–B7-1 tumor line that regressed in vivo. The EL4–B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti–B7-1 antibodies, anti–B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti–B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4–B7-2 and EL4–B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response. PMID:10075975

  4. B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism.

    PubMed

    Stremmel, C; Greenfield, E A; Howard, E; Freeman, G J; Kuchroo, V K

    1999-03-15

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we find that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response.

  5. 30 CFR 7.7 - Quality assurance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Quality assurance. 7.7 Section 7.7 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY General § 7.7 Quality assurance. Applicants granted...

  6. Climate of Remote Areas in North-Central Alaska: 1975-1979 Summary,

    DTIC Science & Technology

    1982-11-01

    The altitudinal and lati- *Defined as the period between the first and last day when tudinal timberline of the white spruce forest occurs the...11.7 12.6 2.0 .10.2 -18.1 -19.6 - 5.9 1189 3173 Timberline - 7.5 4.1 11.5 14.5 12.4 2.3 - 7.7 1428 Dietrich - 7.7 5.1 13.0 15.4 13.7 5.1 6.6 1626...3.3 1.5 8.1 610 Chandalar Shelf -14.5 -18.0 - 8.3 0.5 7.6 13.2 10.7 1.7 -10.9 1107 Timberline 2.8 7.8 17.3 10.9 4.7 1223 Dietrich 3.7 9.4 15.8 12.8 5.2

  7. Analysing Blast and Fragment Penetration Effects on Composite Helicopter Structures

    DTIC Science & Technology

    2005-03-01

    7.3 BC/AC 10 -45 7.2/7.3 DE/AE - 4.9/5.0 E/AE - 11 45 8.5/8.6 DE/AE 7.4/7. A’,E’ 4.8/8.5 E/AE 7.4/7.7 A’/E’ = very 9 local12 7.2/7.3 DE/AE - 7.2/7.5 D...6 ±45 7 ±45 8 0/90 9 45 10 0/90 11 ±45 12 0/90 Table 11 : Laminate lay-up for the tensile and in-plane shear test specimen O)2004 Advanced...onderling gevolgen voor de manier van construeren, vergeleken. maar ook voor de kwetsbaarbeid. Schet fins/a~g Deze ontwvikkelingen vereisen aanpassing

  8. 40 CFR 180.549 - Diflufenzopyr; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Cattle, kidney 4.0 7/31/05 Cattle, meat 0.60 7/31/05 Cattle, meat byproducts, except kidney 0.50 7/31/05 Goat, fat 0.30 7/31/05 Goat, kidney 4.0 7/31/05 Goat, meat 0.60 7/31/05 Goat, meat byproducts, except kidney 0.50 7/31/05 Hog, fat 0.30 7/31/05 Hog, kidney 4.0 7/31/05 Hog, meat 0.60 7/31/05 Hog, meat...

  9. Four new sesqui-lignans isolated from Acanthopanax senticosus and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

    PubMed

    Li, Jia-Lin; Li, Na; Lee, Hyun-Sun; Xing, Shan-Shan; Qi, Shi-Zhou; Tuo, Zhen-Dong; Zhang, Le; Li, Ban-Ban; Chen, Jian-Guang; Cui, Long

    2016-03-01

    Four new sesqui-lignans, (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (1), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',3″-dihydroxy-3,5,3',5',4″-pentamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (2), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-3',4″-dihydroxy-3,5,4',5″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (3) and acanthopanax A (7) together with three known compounds (4-6) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.1 ± 1.3 to 97.7 ± 1.1 μM and compound 7 showed selective inhibition of DGAT2 with IC50 value 93.2 ± 1.2. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Molecular dynamic simulations for FOX-7 and FOX-7 based PBXs.

    PubMed

    Wang, Junying; Jin, Shaohua; Chen, Shusen; Li, Lijie; Wang, Dongxu; Lu, Zhiyan; Wang, Na; Wang, Junfeng

    2018-06-01

    Molecular dynamic (MD) simulations were applied to investigate the binding energies and mechanical properties of 1,1-diamino-2,2-dinitroethene (FOX-7) based polymer bonded explosives (PBXs) with ethylenevinylacetate copolymer (EVA), fluorine (F2641), hydroxyl-terminated polybutadiene (HTPB), and styrene butadiene styrene block copolymer (SBS). The binding energies between FOX-7 and the four polymer binders are different, of which the descending order is FOX-7/HTPB ≈ FOX-7/SBS > FOX-7/EVA > FOX-7/F2641. Furthermore, the (002) surface of FOX-7 has the strongest interaction with the four polymers. The mechanical properties (elastic moduli and Poisson's ratio) of pure FOX-7 and FOX-7 based PBXs were obtained. The results show that the descending order of the ability of polymer binders to improve plasticity of PBXs is SBS > F2641 > EVA > HTPB. The formability of FOX-7 based PBXs is better than that of pure FOX-7, as the order of FOX-7/SBS > FOX-7/EVA > FOX-7/F2641 > FOX-7/HTPB > FOX-7 shows. Poisson's ratio of SBS is the highest. The calculated detonation performances for pure FOX-7 and FOX-7 based PBXs show that the detonation properties of explosives slightly decreases when the mass ratio of binder is about 5%. All the theoretical detonation velocities of FOX-7 based PBXs are higher than 8500 m/s.

  11. Olfactory discrimination varies in mice with different levels of α7-nicotinic acetylcholine receptor expression.

    PubMed

    Hellier, Jennifer L; Arevalo, Nicole L; Blatner, Megan J; Dang, An K; Clevenger, Amy C; Adams, Catherine E; Restrepo, Diego

    2010-10-28

    Previous studies have shown that schizophrenics have decreased expression of α7-nicotinic acetylcholine (α7) receptors in the hippocampus and other brain regions, paranoid delusions, disorganized speech, deficits in auditory gating (i.e., inability to inhibit neuronal responses to repetitive auditory stimuli), and difficulties in odor discrimination and detection. Here we use mice with decreased α7 expression that also show a deficit in auditory gating to determine if these mice have similar deficits in olfaction. In the adult mouse olfactory bulb (OB), α7 expression localizes in the glomerular layer; however, the functional role of α7 is unknown. We show that inbred mouse strains (i.e., C3H and C57) with varying α7 expressions (e.g., α7 wild-type [α7+/+], α7 heterozygous knock-out [α7+/-] and α7 homozygous knock-out mice [α7-/-]) significantly differ in odor discrimination and detection of chemically-related odorant pairs. Using [(125)I] α-bungarotoxin (α-BGT) autoradiography, α7 expression was measured in the OB. As previously demonstrated, α-BGT binding was localized to the glomerular layer. Significantly more expression of α7 was observed in C57 α7+/+ mice compared to C3H α7+/+ mice. Furthermore, C57 α7+/+ mice were able to detect a significantly lower concentration of an odor in a mixture compared to C3H α7+/+ mice. Both C57 and C3H α7+/+ mice discriminated between chemically-related odorants sooner than α7+/- or α7-/- mice. These data suggest that α7-nicotinic-receptors contribute strongly to olfactory discrimination and detection in mice and may be one of the mechanisms producing olfactory dysfunction in schizophrenics. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. 10 CFR 7.7 - Termination, renewal, and rechartering of advisory committees.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Termination, renewal, and rechartering of advisory committees. 7.7 Section 7.7 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.7 Termination, renewal, and rechartering of advisory committees. (a) Except as provided in paragraph (b)(1) of this...

  13. 10 CFR 7.7 - Termination, renewal, and rechartering of advisory committees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Termination, renewal, and rechartering of advisory committees. 7.7 Section 7.7 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.7 Termination, renewal, and rechartering of advisory committees. (a) Except as provided in paragraph (b)(1) of this...

  14. 10 CFR 7.7 - Termination, renewal, and rechartering of advisory committees.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Termination, renewal, and rechartering of advisory committees. 7.7 Section 7.7 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.7 Termination, renewal, and rechartering of advisory committees. (a) Except as provided in paragraph (b)(1) of this...

  15. 10 CFR 7.7 - Termination, renewal, and rechartering of advisory committees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Termination, renewal, and rechartering of advisory committees. 7.7 Section 7.7 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.7 Termination, renewal, and rechartering of advisory committees. (a) Except as provided in paragraph (b)(1) of this...

  16. 10 CFR 7.7 - Termination, renewal, and rechartering of advisory committees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Termination, renewal, and rechartering of advisory committees. 7.7 Section 7.7 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.7 Termination, renewal, and rechartering of advisory committees. (a) Except as provided in paragraph (b)(1) of this...

  17. Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Chen, Jianjun; Nguyen, Minh N.; Li, Wei; Yates, Charles R.; Sweatman, Trevor; Janjetovic, Zorica; Tuckey, Robert C.

    2012-01-01

    The discovery that 7-dehydrocholesterol (7DHC) is an excellent substrate for cytochrome P450scc (CYP11A1) opens up new possibilities in biochemistry. To elucidate its biological significance we tested ex-vivo P450scc-dependent metabolism of 7DHC by tissues expressing high and low levels of P450scc activity, placenta and epidermal keratinocytes, respectively. Incubation of human placenta fragments with 7DHC led to its conversion to 7-dehydropregnenolone (7DHP), which was inhibited by DL-aminoglutethimide, and stimulated by forskolin. Final proof for P450scc involvement was provided in isolated placental mitochondria where production of 7DHP was almost completely inhibited by 22R-hydroxycholesterol. 7DHC was metabolized by placental mitochondria at a faster rate than exogenous cholesterol, under both limiting and saturating conditions of substrate transport, consistent with higher catalytic efficiency (kcat/Km) with 7DHC as substrate than with cholesterol. Ex-vivo experiments showed five 5,7-dienal intermediates with MS spectra of dihydroxy and mono-hydroxy-7DHC and retention time corresponding to 20,22(OH)27DHC and 22(OH)7DHC. The chemical structure of 20,22(OH)27DHC was defined by NMR. 7DHP was further metabolized by either placental fragments or placental microsomes to 7-dehydroprogesterone as defined by UV, MS and NMR, and to an additional product with a 5,7-dienal structure and MS corresponding to hydroxy-7DHP. Furthermore, epidermal keratinocytes transformed either exogenous or endogenous 7DHC to 7DHP. 7DHP inhibited keratinocytes proliferation, while the product of its pholytic transformation, pregcalciferol, lost this capability. In conclusion, tissues expressing P450scc can metabolize 7DHC to biologically active 7DHP with 22(OH)7DHC and 20,22(OH)27DHC serving as intermediates, and with further metabolism to 7-dehydroprogesterone and (OH)7DHP. PMID:22877869

  18. Molecular expression and pharmacological evidence for a functional role of kv7 channel subtypes in Guinea pig urinary bladder smooth muscle.

    PubMed

    Afeli, Serge A Y; Malysz, John; Petkov, Georgi V

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction.

  19. Biochemical and structural characterizations of two Dictyostelium cellobiohydrolases from the amoebozoa kingdom reveal a high level of conservation between distant phylogenetic trees of life

    DOE PAGES

    Hobdey, Sarah E.; Knott, Brandon C.; Momeni, Majid Haddad; ...

    2016-04-01

    Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes often employed in plant cell wall degradation across eukaryotic kingdoms of life, as they provide significant hydrolytic potential in cellulose turnover. To date, many fungal GH7 CBHs have been examined, yet many questions regarding structure-activity relationships in these important natural and commercial enzymes remain. Here, we present the crystal structures and a biochemical analysis of two GH7 CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The structures of DdiCel7Amore » and DpuCel7A, resolved to 2.1 Å and 2.7 Å, respectively, are homologous to those of other GH7 CBHs with an enclosed active-site tunnel. Two primary differences between the Dictyostelium CBHs and the archetypal model GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active site and the product-binding sites. To compare the activities of these enzymes with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to the C terminus of each of the Dictyostelium enzymes, creating DdiCel7A CBM and DpuCel7A CBM, which were recombinantly expressed in T. reesei. DdiCel7A CBM and DpuCel7A CBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid-swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at their temperature optima. The K i of cellobiose was significantly higher for DdiCel7A CBM and DpuCel7A CBM than for TreCel7A: 205, 130, and 29 μM, respectively. Finally, taken together, the present study highlights the remarkable degree of conservation of the activity of these key natural and industrial enzymes across quite distant phylogenetic trees of life.« less

  20. Biochemical and structural characterizations of two Dictyostelium cellobiohydrolases from the amoebozoa kingdom reveal a high level of conservation between distant phylogenetic trees of life

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

    Hobdey, Sarah E.; Knott, Brandon C.; Momeni, Majid Haddad

    Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) are enzymes often employed in plant cell wall degradation across eukaryotic kingdoms of life, as they provide significant hydrolytic potential in cellulose turnover. To date, many fungal GH7 CBHs have been examined, yet many questions regarding structure-activity relationships in these important natural and commercial enzymes remain. Here, we present the crystal structures and a biochemical analysis of two GH7 CBHs from social amoeba: Dictyostelium discoideum Cel7A (DdiCel7A) and Dictyostelium purpureum Cel7A (DpuCel7A). DdiCel7A and DpuCel7A natively consist of a catalytic domain and do not exhibit a carbohydrate-binding module (CBM). The structures of DdiCel7Amore » and DpuCel7A, resolved to 2.1 Å and 2.7 Å, respectively, are homologous to those of other GH7 CBHs with an enclosed active-site tunnel. Two primary differences between the Dictyostelium CBHs and the archetypal model GH7 CBH, Trichoderma reesei Cel7A (TreCel7A), occur near the hydrolytic active site and the product-binding sites. To compare the activities of these enzymes with the activity of TreCel7A, the family 1 TreCel7A CBM and linker were added to the C terminus of each of the Dictyostelium enzymes, creating DdiCel7A CBM and DpuCel7A CBM, which were recombinantly expressed in T. reesei. DdiCel7A CBM and DpuCel7A CBM hydrolyzed Avicel, pretreated corn stover, and phosphoric acid-swollen cellulose as efficiently as TreCel7A when hydrolysis was compared at their temperature optima. The K i of cellobiose was significantly higher for DdiCel7A CBM and DpuCel7A CBM than for TreCel7A: 205, 130, and 29 μM, respectively. Finally, taken together, the present study highlights the remarkable degree of conservation of the activity of these key natural and industrial enzymes across quite distant phylogenetic trees of life.« less

  1. Preparation and characterization of three 7Be targets for the measurement of the 7Be(n, p)7Li and 7Be(n, α)7Li reaction cross sections

    NASA Astrophysics Data System (ADS)

    Maugeri, E. A.; Heinitz, S.; Dressler, R.; Barbagallo, M.; Ulrich, J.; Schumann, D.; Colonna, N.; Köster, U.; Ayranov, M.; Vontobel, P.; Mastromarco, M.; Schell, J.; Correia, J. Martins; Stora, T.; n TOF Collaboration

    2018-05-01

    This manuscript describes the production of three targets obtained by implantation of different activities of 7Be into thin aluminium disks. Two of the produced targets were used to measure the 7Be(n, p)7Li cross section in the energy range of interest for the Big-Bang Nucleosynthesis. A third target was used to measure the cross sections of 7Be(n, p)7Li and 7Be(n, α)7Li nuclear reactions with cold and thermal neutrons, respectively. This paper describes also the characterization of the first two targets, performed after the neutron irradiation, in terms of implanted 7Be activities and spatial distributions.

  2. 49 CFR 173.436 - Exempt material activity concentrations and exempt consignment activity limits for radionuclides.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...×102 2.7×10−9 1.0×106 2.7×10−5 N-13 Nitrogen (7) 1.0×102 2.7×10−9 1.0×109 2.7×10−2 Na-22 Sodium (11) 1.0×101 2.7×10−10 1.0×106 2.7×10−5 Na-24 1.0×101 2.7×10−10 1.0×105 2.7×10−6 Nb-93m Niobium (41) 1.0... 1.0×104 2.7×10−7 1.0×107 2.7×10−4 Si-31 Silicon (14) 1.0×103 2.7×10−8 1.0×106 2.7×10−5 Si-32 1.0×103...

  3. Lenvatinib and Pembrolizumab in DTC

    ClinicalTrials.gov

    2018-05-21

    Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

  4. Water and Sediment Quality in the Yukon River Basin, Alaska, During Water Year 2005

    DTIC Science & Technology

    2007-01-01

    Disordered Kaolinite 0.6 0.5 0.4 0.7 0.6 1.0 0.4 Ferruginous smectite 7.4 9.5 6.1 4.9 9.4 10.6 12.4 Illite + Smectite 6.8 4.8 5.2 6.6 6.6 5.5 4.9...64.7 Clays: Goethite 0.1 0.1 0.3 0.1 0.1 0.3 0.1 Disordered Kaolinite 0.6 0.9 0.3 0.7 0.9 0.6 0.7 Ferruginous smectite 7.0 6.8 7.1...7.9 7.6 16.4 15.7 Illite + Smectite 10.2 7.7 8.1 7.9 6.8 1.2 3.2 Chlorite 8.0 9.5 9.6 9.4 10.7 10.8 12.2 Muscovite (2M1) 4.1 6.0 5.2 4.8 4.1 4.8

  5. Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2018-02-14

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

  6. A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

    ClinicalTrials.gov

    2018-06-04

    Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Small Cell Lung Carcinoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Small Cell Lung Carcinoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Small Cell Lung Carcinoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Small Cell Lung Carcinoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Pancreatic Carcinoma

  7. Mechanisms of Polymer Curing and Thermal Degradation

    DTIC Science & Technology

    1979-12-01

    respectively. 29 0)- Fi . J . IR S e t u f i ( - 3 E hy y p e o y Ph n l S f n .30 z Iii 41 rI2P6i4000 3500 3000 42500 §200010 6010 2010 0 0 0 0...Polymer X Obs.6(_pm) Obs.(ppmA H 7.9,8.0 g,h 7.8 g,h 7.5 I ,e 7.5 i ,c,2 7.3 b,e 6.0-7.2 b,d,f,j,=CH 7.2 d 7.0 f,j 3.1 a HC C =- T O" 7.9 g 7.9 g 7.3 b...e 7.4 b,e 7.1 d 6.0-7.1 c,d,f,=CH 7.0 f,c 3.1 a 3.1 a aFor X 0 H, ggh, f= i b Based on first-order analysis of multiplets. 37 t TABLE 4. SUMMARY OF 13C

  8. 45 CFR 7.7 - Notice to employee of determination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Notice to employee of determination. 7.7 Section 7.7 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.7 Notice to employee of determination. The employee-inventor shall be notified in writing of the...

  9. 34 CFR 7.7 - Notice to employee of determination.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Notice to employee of determination. 7.7 Section 7.7 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.7 Notice to employee of determination. The employee-inventor shall be notified in writing of the Department's determination of the...

  10. 17 CFR 7.200-7.201 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false [Reserved] 7.200-7.201 Section 7.200-7.201 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION CONTRACT MARKET RULES ALTERED OR SUPPLEMENTED BY THE COMMISSION Board of Trade of the City of Chicago Rules § 7.200-7...

  11. 17 CFR 7.200-7.201 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false [Reserved] 7.200-7.201 Section 7.200-7.201 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION CONTRACT MARKET RULES ALTERED OR SUPPLEMENTED BY THE COMMISSION Board of Trade of the City of Chicago Rules § 7.200-7...

  12. The Intelligibility of Words, Sentences, and Continuous Discourse Using the Articulation Index

    DTIC Science & Technology

    1992-10-01

    21.4 sub5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 28.4 sub6 0.0 0.0 0.0 0.0 0.0 0.0 14.3 7.1 sub7 0.0 0.0 0.0 0.0 0.0 0.0 7.1 7.1 sub8 0.0 0.0 0.0 7.1 0.0 0.0 0.0...0.0 28.4 0.0 0.0 50.0 42.9 sub6 0.0 7.1 7.1 35.7 0.0 28.6 28.6 64.3 sub7 0.0 0.0 7.1 28.6 0.0 0.0 50.0 71.4 sub8 0.0 7.1 14.3 35.6 0.0 7.1 28.6 64.6... sub7 0.0 64.3 85.7 100.0 14.3 78.6 100.0 92.8 sub8 14.3 64.6 100.0 92.9 0.0 64.6 92.9 78.6 sub9 0.0 35.7 64.3 92.9 21.4 42.9 85.7 92.9 sublO 7.1 28.6

  13. Evaluation of the efficacy and safety of a lidocaine and tetracaine (7%/7%) cream for induction of local dermal anesthesia for facial soft tissue augmentation with hyaluronic Acid.

    PubMed

    Cohen, Joel L; Gold, Michael H

    2014-10-01

    Injection of dermal fillers for soft tissue augmentation is a minimally invasive cosmetic procedure with growing popularity. However, patients often express concern about pain with such procedures. A topical anesthetic cream formulated with lidocaine/tetracaine 7%7% was approved by the United States Food and Drug Administration in 2006 and recently reintroduced to the market for use during superficial dermatological procedures. A Phase 3 study was conducted to assess the efficacy and safety of lidocaine/tetracaine 7%7% cream versus placebo cream when used to induce local dermal anesthesia during injections with hyaluronic acid. Mean visual analog scale scores significantly favored lidocaine/tetracaine 7%7% cream. A significant percent of subjects also indicated that lidocaine/tetracaine 7%7% cream provided adequate pain relief and that they would use lidocaine/tetracaine 7%7% cream again. Investigators also rated lidocaine/tetracaine 7%7% cream significantly better than placebo cream for providing adequate pain relief and on the assessment of pain scale. Lidocaine/tetracaine 7%7% cream was safe and well tolerated with most subjects reporting no erythema, edema, or blanching. No related adverse events were reported with lidocaine/tetracaine 7%7% cream; one related adverse event of erythema was reported with placebo cream. The results of this study indicate that lidocaine/tetracaine 7%7% cream is efficacious and safe at providing pain relief for soft tissue augmentation with hyaluronic acid.

  14. Evaluation of the Efficacy and Safety of a Lidocaine and Tetracaine (7%/7%) Cream for Induction of Local Dermal Anesthesia for Facial Soft Tissue Augmentation with Hyaluronic Acid

    PubMed Central

    Gold, Michael H.

    2014-01-01

    Injection of dermal fillers for soft tissue augmentation is a minimally invasive cosmetic procedure with growing popularity. However, patients often express concern about pain with such procedures. A topical anesthetic cream formulated with lidocaine/tetracaine 7%7% was approved by the United States Food and Drug Administration in 2006 and recently reintroduced to the market for use during superficial dermatological procedures. A Phase 3 study was conducted to assess the efficacy and safety of lidocaine/tetracaine 7%7% cream versus placebo cream when used to induce local dermal anesthesia during injections with hyaluronic acid. Mean visual analog scale scores significantly favored lidocaine/tetracaine 7%7% cream. A significant percent of subjects also indicated that lidocaine/tetracaine 7%7% cream provided adequate pain relief and that they would use lidocaine/tetracaine 7%7% cream again. Investigators also rated lidocaine/tetracaine 7%7% cream significantly better than placebo cream for providing adequate pain relief and on the assessment of pain scale. Lidocaine/tetracaine 7%7% cream was safe and well tolerated with most subjects reporting no erythema, edema, or blanching. No related adverse events were reported with lidocaine/tetracaine 7%7% cream; one related adverse event of erythema was reported with placebo cream. The results of this study indicate that lidocaine/tetracaine 7%7% cream is efficacious and safe at providing pain relief for soft tissue augmentation with hyaluronic acid. PMID:25371769

  15. Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity.

    PubMed

    Leng, Tian-Dong; Lin, Jun; Sun, Hua-Wei; Zeng, Zhao; O'Bryant, Zaven; Inoue, Koichi; Xiong, Zhi-Gang

    2015-01-01

    Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn(2+) accumulation may represent a promising strategy in the treatment of stroke. To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn(2+) imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn(2+) accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn(2+) accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn(2+) toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. © 2014 John Wiley & Sons Ltd.

  16. 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

    PubMed

    Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

    2012-10-09

    Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

  17. Regulation of Kv7.2/Kv7.3 channels by cholesterol: Relevance of an optimum plasma membrane cholesterol content.

    PubMed

    Delgado-Ramírez, Mayra; Sánchez-Armass, Sergio; Meza, Ulises; Rodríguez-Menchaca, Aldo A

    2018-05-01

    Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment. Surprisingly, Kv7.2/Kv7.3 channels were also inhibited by membrane cholesterol loading with the MβCD/cholesterol complex. Depletion or enrichment of plasma membrane cholesterol differentially affected the biophysical parameters of the macroscopic Kv7.2/Kv7.3 currents. These results indicate a complex mechanism of Kv7.2/Kv7.3 channels modulation by membrane cholesterol. We propose that inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol depletion involves a loss of a direct cholesterol-channel interaction. However, the inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol enrichment could include an additional direct cholesterol-channel interaction, or changes in the physical properties of the plasma membrane. In summary, our results indicate that an optimum cholesterol level in the plasma membrane is required for the proper functioning of Kv7.2/Kv7.3 channels. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Digital genotyping of avian influenza viruses of H7 subtype detected in central Europe in 2007-2011.

    PubMed

    Nagy, Alexander; Cerníková, Lenka; Křivda, Vlastimil; Horníčková, Jitka

    2012-05-01

    The objective of our study was to provide a genotype analysis of H7N7 and H7N9 influenza A viruses (IAV) and infer their relationships to co-circulating non-H7 IAV genomes. The H7N7 strains were collected in central Europe (Hungary-1, Czech Republic-1, Slovenia-1 and Poland-4) and the H7N9 in the Czech Republic and Spain between 2007 and 2011. Hand in hand with this effort, a novel IAV genotype visualization approach called digital genotyping was developed. This approach relies on phylogenetic data summarization and transformation into a pixel array called a segment identity matrix. The digital genotyping revealed a complicated genetic interplay between the H7 and co-circulating non-H7 IAV genotypes. At the H7 IAV level the most obvious relationships were observed between one Polish H7N7/446/09 and Czech H7N7/11 viruses which, despite the special and temporal distance of 800 km and 15 months, retained at least 6/8 genome segments. Close relationships were also observed between the Czech H7N9, Polish and Slovenian H7N7 on one hand and Hungarian and Slovenian H7N7 isolates on the other. In addition the former genomes exhibited close interplays with the Czech H6N2/09 and H11N9/10-like viruses. The Czech and Spanish H7N9 genomes were completely different and 6/8 of the Czech H7N9-like segments were traced to either the Czech H3N8/07, H11N9/09 and Polish H7N7/09-like viruses. The results of digital genotyping correlated with the previous observations obtained on the Polish H7N7 isolates. As was demonstrated, the digital genotyping provides a well-arranged and easily interpretable output and may serve as an alternative genotyping tool useful for handling and analysing even a large panel of IAV genomes. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 49 CFR 7.7 - Access to materials and indices.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Access to materials and indices. 7.7 Section 7.7... To Be Made Public by DOT § 7.7 Access to materials and indices. (a) Except as provided in paragraph... unnecessary and impracticable to publish the index of materials in the Federal Register. Information as to the...

  20. 37 CFR 7.41 - Renewal of international registration and extension of protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and charges 2.6, 2.206-2.209, 7.6, 7.7 For filing an application 2.6(a)(1) For TEAS Plus application 2....14 Must be filed through TEAS or on International Bureau's form 7.11(a) Must be in English 7.3... transmission does not apply 2.197(a)(2) Fees for 7.7, 7.21(a)(8) Must be filed through TEAS or on International...

  1. 78 FR 17598 - Special Local Regulation; Southern California Annual Marine Events for the San Diego Captain of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ....1101 will be enforced from 7 a.m. to 7 p.m. on April 6, 2013 and 7 a.m. to 7 p.m. on April 7, 2013. FOR... Regulation for the 2013 San Diego Crew Classic in 33 CFR 100.1101 from 7 a.m. to 7 p.m. on April 6, 2013 and from 7 a.m. to 7 p.m. on April 7, 2013. Under provisions of 33 CFR 100.1101, a vessel may not enter the...

  2. Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2018-06-28

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

  3. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2018-04-24

    Non-Squamous Non-Small Cell Lung Carcinoma; Stage III Large Cell Lung Carcinoma AJCC v7; Stage III Lung Adenocarcinoma AJCC v7; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Large Cell Lung Carcinoma AJCC v7; Stage IIIA Lung Adenocarcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Large Cell Lung Carcinoma AJCC v7; Stage IIIB Lung Adenocarcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Large Cell Lung Carcinoma AJCC v7; Stage IV Lung Adenocarcinoma AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

  4. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2018-04-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Vulvar Cancer AJCC v7; Stage IIA1 Cervical Cancer AJCC v7; Stage IIA2 Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vulvar Cancer AJCC v7; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  5. Antigenic Fingerprinting of Antibody Response in Humans following Exposure to Highly Pathogenic H7N7 Avian Influenza Virus: Evidence for Anti-PA-X Antibodies.

    PubMed

    Khurana, Surender; Chung, Ka Yan; Coyle, Elizabeth M; Meijer, Adam; Golding, Hana

    2016-10-15

    Infections with H7 highly pathogenic avian influenza (HPAI) viruses remain a major public health concern. Adaptation of low-pathogenic H7N7 to highly pathogenic H7N7 in Europe in 2015 raised further alarm for a potential pandemic. An in-depth understanding of antibody responses to HPAI H7 virus following infection in humans could provide important insight into virus gene expression as well as define key protective and serodiagnostic targets. Here we used whole-genome gene fragment phage display libraries (GFPDLs) expressing peptides of 15 to 350 amino acids across the complete genome of the HPAI H7N7 A/Netherlands/33/03 virus. The hemagglutinin (HA) antibody epitope repertoires of 15 H7N7-exposed humans identified clear differences between individuals with no hemagglutination inhibition (HI) titers (<1:10) and those with HI titers of >1:40. Several potentially protective H7N7 epitopes close to the HA receptor binding domain (RBD) and neuraminidase (NA) catalytic site were identified. Surface plasmon resonance (SPR) analysis identified a strong correlation between HA1 (but not HA2) binding antibodies and H7N7 HI titers. A proportion of HA1 binding in plasma was contributed by IgA antibodies. Antibodies against the N7 neuraminidase were less frequent but targeted sites close to the sialic acid binding site. Importantly, we identified strong antibody reactivity against PA-X, a putative virulence factor, in most H7N7-exposed individuals, providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human influenza A virus infection. This knowledge can help inform the development and selection of the most effective countermeasures for prophylactic as well as therapeutic treatments of HPAI H7N7 avian influenza virus. An outbreak of pathogenic H7N7 virus occurred in poultry farms in The Netherlands in 2003. Severe outcome included conjunctivitis, influenza-like illness, and one lethal infection. In this study, we investigated convalescent-phase sera from H7N7-exposed individuals by using a whole-genome phage display library (H7N7-GFPDL) to explore the complete repertoire of post-H7N7-exposure antibodies. PA-X is a recently identified influenza virus virulence protein generated by ribosomal frameshifting in segment 3 of influenza virus coding for PA. However, PA-X expression during influenza virus infection in humans is unknown. We identified strong antibody reactivity against PA-X in most H7N7-exposed individuals (but not in unexposed adults), providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human infection with pathogenic H7N7 avian influenza virus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. 7 CFR 1774.7 - Environmental requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Environmental requirements. 1774.7 Section 1774.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF...) General Provisions § 1774.7 Environmental requirements. The policies and regulations contained in 7 CFR...

  7. CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS

    PubMed Central

    Dang, Xitong; Eliceiri, Brian P.; Baird, Andrew; Costantini, Todd W.

    2015-01-01

    The human genome contains a unique, distinct, and human-specific α7-nicotinic acetylcholine receptor (α7nAChR) gene [CHRNA7 (gene-encoding α7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-α7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5′ upstream from the “wild-type” CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type α7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific α7nAChR response that might regulate gut epithelial function in a human-specific fashion.—Dang, X., Eliceiri, B. P., Baird, A., Costantini, T. W. CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. PMID:25681457

  8. Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

    ClinicalTrials.gov

    2018-05-23

    Recurrent Colon Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Rectal Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Rectal Cancer AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  9. Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

    PubMed Central

    Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

  10. Activation energies for dissociation of double strand oligonucleotide anions: evidence for watson-crick base pairing in vacuo.

    PubMed

    Schnier, P D; Klassen, J S; Strittmatter, E F; Williams, E R

    1998-09-23

    The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)(2) (3-), (CCGG)(2) (3-), (AATTAAT)(2) (3-), (CCGGCCG)(2) (3-), A(7)*T(7) (3-), A(7)*A(7) (3-), T(7)*T(7) (3-), and A(7)*C(7) (3-) were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 10(13) to 10(19) s(-1). Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a - base) and w ions. Four pieces of evidence are presented which indicate that Watson-Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A(7)*T(7) (3-), to the single strands is significantly higher than that for the related noncomplementary A(7)*A(7) (3-) and T(7)*T(7) (3-) dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A(7)*A(7) (3-) and A(7)*C(7) (3-) but not for A(7)*T(7) (3-) consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (-DeltaH(d)) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A(7)*T(7) (3-) duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent.

  11. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-06-19

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  12. Evolution of the B7 family: co-evolution of B7H6 and NKp30, identification of a new B7 family member, B7H7, and of B7's historical relationship with the MHC.

    PubMed

    Flajnik, Martin F; Tlapakova, Tereza; Criscitiello, Michael F; Krylov, Vladimir; Ohta, Yuko

    2012-08-01

    The B7 family of genes is essential in the regulation of the adaptive immune system. Most B7 family members contain both variable (V)- and constant (C)-type domains of the immunoglobulin superfamily (IgSF). Through in silico screening of the Xenopus genome and subsequent phylogenetic analysis, we found novel genes belonging to the B7 family, one of which is the recently discovered B7H6. Humans and rats have a single B7H6 gene; however, many B7H6 genes were detected in a single large cluster in the Xenopus genome. The B7H6 expression patterns also varied in a species-specific manner. Human B7H6 binds to the activating natural killer receptor, NKp30. While the NKp30 gene is single-copy and maps to the MHC in most vertebrates, many Xenopus NKp30 genes were found in a cluster on a separate chromosome that does not harbor the MHC. Indeed, in all species so far analyzed from sharks to mammals, the number of NKp30 and B7H6 genes correlates well, suggestive of receptor-ligand co-evolution. Furthermore, we identified a Xenopus-specific B7 homolog (B7HXen) and revealed its close linkage to B2M, which we have demonstrated previously to have been originally encoded in the MHC. Thus, our study provides further proof that the B7 precursor was included in the proto MHC. Additionally, the comparative analysis revealed a new B7 family member, B7H7, which was previously designated in the literature as an unknown gene, HHLA2.

  13. SLC7 family transporters control the establishment of left-right asymmetry during organogenesis in medaka by activating mTOR signaling.

    PubMed

    Asaoka, Yoichi; Nagai, Yoko; Namae, Misako; Furutani-Seiki, Makoto; Nishina, Hiroshi

    2016-05-20

    The precise government of the left-right (LR) specification of an organ is an essential aspect of its morphogenesis. Multiple signaling cascades have been implicated in the establishment of vertebrate LR asymmetry. Recently, mTOR signaling was found to critically regulate the development of LR asymmetry in zebrafish. However, the upstream factor(s) that activate mTOR signaling in the context of LR specification are as yet unknown. In this study, we identify the SLC7 amino acid transporters Slc7a7 and Slc7a8 as novel regulators of LR asymmetry development in the small fish medaka. Knockdown of Slc7a7 and/or Slc7a8 in medaka embryos disrupted LR organ asymmetries. Depletion of Slc7a7 hindered left-sided expression of the southpaw (spaw) gene, which is responsible for LR axis determination. Work at the cellular level revealed that Slc7a7 coordinates ciliogenesis in the epithelium of Kupffer's vesicle and thereby the generation of the nodal fluid flow required for LR asymmetry. Interestingly, knockdown of Slc7a7 depressed mTOR signaling activity in medaka embryos. Treatment with rapamycin, an inhibitor of mTOR signaling, together with Slc7a7 knockdown synergistically perturbed spaw expression, indicating an interaction between Slc7a7 and mTOR signaling affecting gene expression required for LR specification. Taken together, our results demonstrate that Slc7a7 governs the regulation of LR asymmetry development via the activation of mTOR signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Derivatives of dibenzothiophene for PET imaging of α7-Nicotinic Acetylcholine Receptors

    PubMed Central

    Gao, Yongjun; Kellar, Kenneth J.; Yasuda, Robert P.; Tran, Thao; Xiao, Yingxian; Dannals, Robert F.; Horti, Andrew G.

    2013-01-01

    A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for α7-nicotinic acetylcholine receptors (α7-nAChRs) (Ki = 0.4 – 20 nM) has been synthesized for PET imaging of α7-nAChRs. Two radiolabeled members of the series [18F]7a (Ki = 0.4 nM) and [18F]7c (Ki = 1.3 nM) were synthesized. [18F]7a and [18F]7c readily entered the mouse brain and specifically labeled α7-nAChRs. The α7-nAChR selective ligand 1 (SSR180711) blocked the binding of [18F]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-α7-nAChR CNS drugs demonstrated that [18F]7a is highly α7-nAChR selective. In agreement with its binding affinity the binding potential of [18F]7a (BPND = 5.3 – 8.0) in control mice is superior to previous α7-nAChR PET radioligands. Thus, [18F]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of α7-nAChR in non-human primates. PMID:24050653

  15. The Human CHRNA7 and CHRFAM7A Genes: A Review of the Genetics, Regulation, and Function

    PubMed Central

    Sinkus, Melissa L.; Graw, Sharon; Freedman, Robert; Ross, Randal G.; Lester, Henry A.; Leonard, Sherry

    2015-01-01

    The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer’s disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene. Exons 5-10 of CHRNA7 on chromosome 15 were duplicated and inserted 1.6 Mb upstream of CHRNA7, interrupting an earlier partial duplication of two other genes. The chimeric CHRFAM7A gene product, dupα7, assembles with α7 subunits, resulting in a dominant negative regulation of function. The duplication is human specific, occurring neither in primates nor in rodents. The duplicated α7 sequence in exons 5-10 of CHRFAM7A is almost identical to CHRNA7, and thus is not completely queried in high throughput genetic studies (GWAS). Further, pre-clinical animal models of the α7nAChR utilized in drug development research do not have CHRFAM7A (dupα7) and cannot fully model human drug responses. The wide expression of CHRNA7, its multiple functions and modes of regulation present challenges for study of this gene in disease. PMID:25701707

  16. Identification of the antigenic region of Neospora caninum dense granule protein 7 using ELISA.

    PubMed

    Abdelbaky, Hanan H; Fereig, Ragab M; Nishikawa, Yoshifumi

    2018-06-26

    Dense granule protein 7 (NcGRA7) is a potent diagnostic antigen of Neospora caninum. Some studies have reported on the difficult expression, low yield, and variable degree of solubility of recombinant NcGRA7. We aimed to unravel the possible causes for these issues and tested NcGRA7 antigenicity in enzyme linked immunosorbent assays (ELISAs). The NcGRA7 coding sequence (217 amino acids) was split into five amino acid regions: NcGRA7m (27-217), NcGRA7m3 (27-160), NcGRA7m4 (27-135), NcGRA7m5 (161-190), and NcGRA7m6 (188-217). Three fragments, NcGRA7m, NcGRA7m3 and NcGRA7m4, exhibited high antigenic properties when tested against experimentally-infected mice and dog sera by ELISA. High levels of IgG2 antibodies against NcGRA7m were observed in field dog sera. In experimentally and naturally-infected cattle, the N. caninum-specific sera only reacted with NcGRA7m, indicating that this antigenic region differs among the three animal species. This study presents valuable information about the antigenic properties and topology of NcGRA7, and highlights its suitability for diagnostic purposes. Copyright © 2018. Published by Elsevier B.V.

  17. 7 CFR 755.7 - Transportation rates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Transportation rates. 755.7 Section 755.7 Agriculture... SPECIAL PROGRAMS REIMBURSEMENT TRANSPORTATION COST PAYMENT PROGRAM FOR GEOGRAPHICALLY DISADVANTAGED FARMERS AND RANCHERS § 755.7 Transportation rates. (a) Payments may be based on fixed, set, or actual...

  18. 7 CFR 755.7 - Transportation rates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Transportation rates. 755.7 Section 755.7 Agriculture... SPECIAL PROGRAMS REIMBURSEMENT TRANSPORTATION COST PAYMENT PROGRAM FOR GEOGRAPHICALLY DISADVANTAGED FARMERS AND RANCHERS § 755.7 Transportation rates. (a) Payments may be based on fixed, set, or actual...

  19. 7 CFR 755.7 - Transportation rates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Transportation rates. 755.7 Section 755.7 Agriculture... SPECIAL PROGRAMS REIMBURSEMENT TRANSPORTATION COST PAYMENT PROGRAM FOR GEOGRAPHICALLY DISADVANTAGED FARMERS AND RANCHERS § 755.7 Transportation rates. (a) Payments may be based on fixed, set, or actual...

  20. 7 CFR 755.7 - Transportation rates.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Transportation rates. 755.7 Section 755.7 Agriculture... SPECIAL PROGRAMS REIMBURSEMENT TRANSPORTATION COST PAYMENT PROGRAM FOR GEOGRAPHICALLY DISADVANTAGED FARMERS AND RANCHERS § 755.7 Transportation rates. (a) Payments may be based on fixed, set, or actual...

  1. ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment

    ClinicalTrials.gov

    2018-03-02

    Oral Cavity Neoplasm; Oropharyngeal Neoplasm; Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

  2. 49 CFR 173.436 - Exempt material activity concentrations and exempt consignment activity limits for radionuclides.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....0×102 2.7×10−9 1.0×109 2.7×10−2 Na-22 Sodium (11) 1.0×101 2.7×10−10 1.0×106 2.7×10−5 Na-24 1.0×101 2...×10−6 Se-75 Selenium (34) 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Se-79 1.0×104 2.7×10−7 1.0×107 2.7×10−4 Si-31 Silicon (14) 1.0×103 2.7×10−8 1.0×106 2.7×10−5 Si-32 1.0×103 2.7×10−8 1.0×106 2.7×10−5 Sm-145...

  3. 49 CFR 173.436 - Exempt material activity concentrations and exempt consignment activity limits for radionuclides.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....0×102 2.7×10−9 1.0×109 2.7×10−2 Na-22 Sodium (11) 1.0×101 2.7×10−10 1.0×106 2.7×10−5 Na-24 1.0×101 2...×10−6 Se-75 Selenium (34) 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Se-79 1.0×104 2.7×10−7 1.0×107 2.7×10−4 Si-31 Silicon (14) 1.0×103 2.7×10−8 1.0×106 2.7×10−5 Si-32 1.0×103 2.7×10−8 1.0×106 2.7×10−5 Sm-145...

  4. Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2018-04-23

    Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  5. Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

    ClinicalTrials.gov

    2018-05-08

    Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Thyroglobulin Antibody Negative; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

  6. Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2018-06-08

    Advanced Malignant Solid Neoplasm; KRAS Gene Mutation; Metastatic Malignant Solid Neoplasm; NRAS Gene Mutation; Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Malignant Neoplasm

  7. China’s Exchange Rate Peg: Economic Issues and Options for U.S. Trade Policy

    DTIC Science & Technology

    2005-05-10

    in 2004) and has hurt U.S. production and employment in several U.S. manufacturing sectors (such as textiles and apparel and furniture) that are forced...countries is mixed. From 1980 to 1997, Korea, Malaysia , Philippines, Indonesia, and Thailand typically ran current account deficits, while Hong Kong...64.0 73.9 7.9 China 8.3 8.2 12.0 18.7 29.5 255.4 Malaysia 4.9 5/0 7.1 8.0 8.7 77.6 Mexico 6.9 8.5 7.9 7.0 7.4 7.2 Singapore 8.7 7.1 7.1 6.9 6.6 -24.1

  8. Analysis of Body Size Measurements for U.S. Navy Women’s Clothing and Pattern Design

    DTIC Science & Technology

    1979-03-01

    due Charles E . Clauser, of the Aerospace Medical Research Laboratory at Wright-Patterson Air Force Base, Ohio and Robert M. White of the U.S. Army...Distribution of Samples by Race ..... e 155 6 Distribution of Samples by Handedness. 155 7 Number of Subjects at Each Site ....... 156 C FREQUENCY...20TH 7.86 -.. .. .. ... .. ... e - s ......... 7-65 15TH 7,* 77 ! ADJUSTED COMPOSITE VALUE 1 7.54 10TH 7,66 1 I 7,37 5TH 7.50 ! MEAN 8.23 1 7o26 3TH 7e40

  9. 7 CFR 783.7 - Obligations of a participant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Obligations of a participant. 783.7 Section 783.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS TREE ASSISTANCE PROGRAM § 783.7 Obligations of a participant. (a) Eligible...

  10. 7 CFR 784.7 - Availability of funds.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Availability of funds. 784.7 Section 784.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS 2004 EWE LAMB REPLACEMENT AND RETENTION PAYMENT PROGRAM § 784.7 Availability of funds...

  11. Cabozantinib and Nivolumab in Treating Patients With Advanced, Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2018-06-13

    Recurrent Uterine Corpus Carcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IIIC1 Uterine Corpus Cancer AJCC v7; Stage IIIC2 Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

  12. Recombinant human B7.2 IgV-like domain expressed in bacteria maintains its co-stimulatory activity in vitro.

    PubMed

    Yan, Xiaocai; Ma, Jun; Zheng, Jin; Lai, Baochang; Geng, Yiping; Wang, Yili; Si, Lüsheng

    2002-07-01

    To investigate which of the two immunoglobulin (Ig)-like domains, the immunoglobulin variable region homologous domain IgV (hB7.2 IgV) and the immunoglobulin constant region homologous domain IgC (hB7.2 IgC) on the human B7.2 molecule contains receptor binding sites, and to evaluate whether the B7.2 protein expressed in bacteria has biological activity in vitro. Three fragments of hB7.2 IgV,hB7.2 IgC and the complete extracellular region of human B7.2 containing both the IgV and IgC domains,hB7.2 Ig (V+C), were amplified by PCR and subcloned into pGEM-Teasy. Three recombinants,pGEX-4T-3-hB7.2 IgV,pGEX-4T-3-hB7.2 IgC and pGEX-4T-3-hB7.2 Ig (V+C), were generated by cloning the fragments into a prokaryote expression plasmid (pGEX-4T-3) and transformed into the host strain E. coli DH5alpha. The relevant target fusion proteins consisting of GST and hB7.2 IgV,hB7.2 IgC and hB7.2 Ig (V+C), were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7.2 fusion proteins by [(3)H]-TdR incorporation. Three recombinant fusion proteins of human B7.2, GST-hB7.2 IgV, GST-hB7.2 IgC and GST-hB7.2 Ig (V+C) were produced and detected in inclusion body form from engineered bacteria. With the first signal present,T lymphocytes proliferated when co-stimulated by bacterially-produced either GST-hB7.2 Ig (V+C) or GST-hB7.2 IgV fusion proteins, but not by GST-hB7.2 IgC. Functional human B7.2 fusion protein can be produced in bacteria. The IgV-like domain of human B7.2 is sufficient for B7.2 to interact with its counter-receptors and co-stimulate T lymphocytes.

  13. 11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo.

    PubMed

    Mitić, Tijana; Shave, Steven; Semjonous, Nina; McNae, Iain; Cobice, Diego F; Lavery, Gareth G; Webster, Scott P; Hadoke, Patrick W F; Walker, Brian R; Andrew, Ruth

    2013-07-01

    11β-Hydroxysteroid dehydrogenase 1 (11βHSD1; EC 1.1.1.146) generates active glucocorticoids from inert 11-keto metabolites. However, it can also metabolize alternative substrates, including 7β-hydroxy- and 7-keto-cholesterol (7βOHC, 7KC). This has been demonstrated in vitro but its consequences in vivo are uncertain. We used genetically modified mice to investigate the contribution of 11βHSD1 to the balance of circulating levels of 7KC and 7βOHC in vivo, and dissected in vitro the kinetics of the interactions between oxysterols and glucocorticoids for metabolism by the mouse enzyme. Circulating levels of 7KC and 7βOHC in mice were 91.3±22.3 and 22.6±5.7 nM respectively, increasing to 1240±220 and 406±39 nM in ApoE(-/-) mice receiving atherogenic western diet. Disruption of 11βHSD1 in mice increased (p<0.05) the 7KC/7βOHC ratio in plasma (by 20%) and also in isolated microsomes (2 fold). The 7KC/7βOHC ratio was similarly increased when NADPH generation was restricted by disruption of hexose-6-phosphate dehydrogenase. Reduction and oxidation of 7-oxysterols by murine 11βHSD1 proceeded more slowly and substrate affinity was lower than for glucocorticoids. in vitro 7βOHC was a competitive inhibitor of oxidation of corticosterone (Ki=0.9 μM), whereas 7KC only weakly inhibited reduction of 11-dehydrocorticosterone. However, supplementation of 7-oxysterols in cultured cells, secondary to cholesterol loading, preferentially slowed reduction of glucocorticoids, rather than oxidation. Thus, in mouse, 11βHSD1 influenced the abundance and balance of circulating and tissue levels of 7βOHC and 7KC, promoting reduction of 7KC. In health, 7-oxysterols are unlikely to regulate glucocorticoid metabolism. However, in hyperlipidaemia, 7-oxysterols may inhibit glucocorticoid metabolism and modulate signaling through corticosteroid receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Expression of Kir7.1 and a Novel Kir7.1 Splice Variant in Native Human Retinal Pigment Epithelium

    PubMed Central

    Yang, Dongli; Swaminathan, Anuradha; Zhang, Xiaoming; Hughes, Bret A.

    2009-01-01

    Previous studies on bovine retinal pigment epithelium (RPE) established that Kir7.1 channels compose this epithelium’s large apical membrane K+ conductance. The purpose of this study was to determine whether Kir7.1 and potential Kir7.1 splice variants are expressed in native adult human RPE and, if so, to determine their function and how they are generated. RT-PCR analysis indicated that human RPE expresses full-length Kir7.1 and a novel Kir7.1 splice variant, designated Kir7.1S. Analysis of the human Kir7.1 gene (KCNJ13) organization revealed that it contains 3 exons, 2 introns, and a novel alternative 5′ splice site in exon 2. In human RPE, the alternative usage of two competing 5′ splice sites in exon 2 gives rise to transcripts encoding full-length Kir7.1 and Kir7.1S, which is predicted to encode a truncated protein. Real-time PCR indicated that Kir7.1 transcript is nearly as abundant as GAPDH mRNA in human RPE whereas Kir7.1S transcript expression is 4-fold lower. Western blot analysis showed that the splice variant is translated in Xenopus oocytes injected with Kir7.1S cRNA and revealed the expression of full-length Kir7.1 but not Kir7.1S in adult human RPE. Co-expression of Kir7.1 with Kir7.1S in Xenopus oocytes had no effect on either the kinetics or amplitude of Kir7.1 currents. This study confirms the expression of Kir7.1 in human RPE, identifies a Kir7.1 splice variant resulting in predicted changes in protein sequence, and indicates that there no functional interaction between this splice variant and full-length Kir7.1. PMID:18035352

  15. Regulator of G Protein Signaling 7 (RGS7) Can Exist in a Homo-oligomeric Form That Is Regulated by Gαo and R7-binding Protein.

    PubMed

    Tayou, Junior; Wang, Qiang; Jang, Geeng-Fu; Pronin, Alexey N; Orlandi, Cesare; Martemyanov, Kirill A; Crabb, John W; Slepak, Vladlen Z

    2016-04-22

    RGS (regulator of G protein signaling) proteins of the R7 subfamily (RGS6, -7, -9, and -11) are highly expressed in neurons where they regulate many physiological processes. R7 RGS proteins contain several distinct domains and form obligatory dimers with the atypical Gβ subunit, Gβ5 They also interact with other proteins such as R7-binding protein, R9-anchoring protein, and the orphan receptors GPR158 and GPR179. These interactions facilitate plasma membrane targeting and stability of R7 proteins and modulate their activity. Here, we investigated RGS7 complexes using in situ chemical cross-linking. We found that in mouse brain and transfected cells cross-linking causes formation of distinct RGS7 complexes. One of the products had the apparent molecular mass of ∼150 kDa on SDS-PAGE and did not contain Gβ5 Mass spectrometry analysis showed no other proteins to be present within the 150-kDa complex in the amount close to stoichiometric with RGS7. This finding suggested that RGS7 could form a homo-oligomer. Indeed, co-immunoprecipitation of differentially tagged RGS7 constructs, with or without chemical cross-linking, demonstrated RGS7 self-association. RGS7-RGS7 interaction required the DEP domain but not the RGS and DHEX domains or the Gβ5 subunit. Using transfected cells and knock-out mice, we demonstrated that R7-binding protein had a strong inhibitory effect on homo-oligomerization of RGS7. In contrast, our data indicated that GPR158 could bind to the RGS7 homo-oligomer without causing its dissociation. Co-expression of constitutively active Gαo prevented the RGS7-RGS7 interaction. These results reveal the existence of RGS protein homo-oligomers and show regulation of their assembly by R7 RGS-binding partners. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Selective activation of vascular Kv7.4/Kv7.5 K+ channels by fasudil contributes to its vasorelaxant effect

    PubMed Central

    Zhang, Xuan; An, Hailong; Li, Junwei; Zhang, Yuanyuan; Liu, Yang; Jia, Zhanfeng; Zhang, Wei

    2016-01-01

    Background and Purpose Kv7 (Kv7.1–7.5) channels play an important role in the regulation of neuronal excitability and the cardiac action potential. Growing evidence suggests Kv7.4/Kv7.5 channels play a crucial role in regulating vascular smooth muscle contractility. Most of the reported Kv7 openers have shown poor selectivity across these five subtypes. In this study, fasudil – a drug used for cerebral vasospasm – has been found to be a selective opener of Kv7.4/Kv7.5 channels. Experimental Approach A perforated whole‐cell patch technique was used to record the currents and membrane potential. Homology modelling and a docking technique were used to investigate the interaction between fasudil and the Kv7.4 channel. An isometric tension recording technique was used to assess the vascular tension. Key Results Fasudil selectively and potently enhanced Kv7.4 and Kv7.4/Kv7.5 currents expressed in HEK293 cells, and shifted the voltage‐dependent activation curve in a more negative direction. Fasudil did not affect either Kv7.2 and Kv7.2/Kv7.3 currents expressed in HEK293 cells, the native neuronal M‐type K+ currents, or the resting membrane potential in small rat dorsal root ganglia neurons. The Val248 in S5 and Ile308 in S6 segment of Kv7.4 were critical for this activating effect of fasudil. Fasudil relaxed precontracted rat small arteries in a concentration‐dependent fashion; this effect was antagonized by the Kv7 channel blocker XE991. Conclusions and Implications These results suggest that fasudil is a selective Kv7.4/Kv7.5 channel opener and provide a new dimension for developing selective Kv7 modulators and a new prospective for the use, action and mechanism of fasudil. PMID:27677924

  17. Microbial Metabolism. Part 10. Metabolites of 7,8 Dimethoxyflavone and 5-Methoxyflavone

    USDA-ARS?s Scientific Manuscript database

    Microbial transformation of 7, 8-dimethoxyflavone (1) by Mucor ramannianus (ATCC 9628) produced five metabolites: 7, 8-dimethoxy-4'-hydroxyflavone (2), 3', 4'-dihydroxy-7, 8-dimethoxyflavone (3), 7, 3'-dihydroxy-8-methoxyflavone (4), 7, 4'-dihydroxy-8-methoxyflavone (5) and 8-methoxy-7, 3', 4'-trihy...

  18. Characterization of Small DC Brushed and Brushless Motors

    DTIC Science & Technology

    2013-03-01

    8 Figure 6. Torque vs. RPM for a SS7 -1.7-1 brushed motor...9 Figure 7. Efficiency vs. motor power output for SS7 -1.7-1 brushed motor...10 Figure 8. Efficiency vs. RPM for SS7 -1.7-1 brushed motor. ........................................................10 Figure 9

  19. 7 CFR 770.7 - Security requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Security requirements. 770.7 Section 770.7 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.7 Security requirements. (a) The applicant will take appropriate action to obtain and provide security for the loan. (b) A mortgage or deed of...

  20. 7 CFR 770.7 - Security requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Security requirements. 770.7 Section 770.7 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.7 Security requirements. (a) The applicant will take appropriate action to obtain and provide security for the loan. (b) A mortgage or deed of...

  1. 7 CFR 1436.7 - Loan term.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Loan term. 1436.7 Section 1436.7 Agriculture... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS FARM STORAGE FACILITY LOAN PROGRAM REGULATIONS § 1436.7 Loan term. (a) For eligible facility loan commodities other than sugar, the term of the loan will be 7...

  2. 7 CFR 784.7 - Availability of funds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Availability of funds. 784.7 Section 784.7 Agriculture... SPECIAL PROGRAMS 2004 EWE LAMB REPLACEMENT AND RETENTION PAYMENT PROGRAM § 784.7 Availability of funds... amount available, FSA shall prorate the available funds by a national factor to reduce the expected...

  3. Long term effects of low protein diet on depressive symptoms and quality of life in elderly Type 2 diabetic patients.

    PubMed

    Ciarambino, Tiziana; Castellino, Pietro; Paolisso, Giuseppe; Coppola, Ludovico; Ferrara, Nicola; Signoriello, Giuseppe; Giordano, Mauro

    2012-08-01

    The long term effects of a low protein diet (LPD) on depressive symptoms and the quality of life in elderly Type 2 diabetic are unclear. 38 elderly Type 2 diabetic patients with CRD (Stage 3 - 4) were enrolled in the study. After 4 weeks on a normal protein diet regimen (NPD) providing 1.0 g/kg per day, all participants were assigned for 30 months, randomly, to a LPD (0.7 g/kg per day), either 7 days a week (LPD 7/7) or 6 days a week (LPD 6/7). Mini mental state examination (MMSE), activities daily living (ADL), cumulative illness severity (CIRS-IS), geriatric depression scale (GDS-15) and short-form healthy survey (SF- 36) were evaluated every 3 months. Before the LPD regimen creatinine clearance (CrCl), MMSE, ADL, CIRS-IS, GDS-15 and SF-36 were similar in both LPD 7/7 and LPD 6/7 groups. After 30 months, the mean GDS- 15 increased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). Both mean SF-36 MCS and SF-36 PCS were decreased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). After 30 months, the decline in CrCl observed was similar in LPD 7/7 and LPD 6/7 groups (2.77 ± 0.3 and 2.84 ± 0.3 ml/min/year, respectively). In elderly Type 2 diabetic patients, long term effects of LPD 6/7 regimen in comparison to LPD 7/7 are associated with a similar decline in CrCl, but with decreased depressive symptoms and a better quality of life.

  4. Overexpression of Escherichia coli udk mimics the absence of T7 Gp2 function and thereby abrogates successful infection by T7 phage.

    PubMed

    Shadrin, Andrey; Sheppard, Carol; Savalia, Dhruti; Severinov, Konstantin; Wigneshweraraj, Sivaramesh

    2013-02-01

    Successful infection of Escherichia coli by bacteriophage T7 relies upon the transcription of the T7 genome by two different RNA polymerases (RNAps). The bacterial RNAp transcribes early T7 promoters, whereas middle and late T7 genes are transcribed by the T7 RNAp. Gp2, a T7-encoded transcription factor, is a 7 kDa product of an essential middle T7 gene 2, and is a potent inhibitor of the host RNAp. The essential biological role of Gp2 is to inhibit transcription of early T7 genes that fail to terminate efficiently in order to facilitate the coordinated usage of the T7 genome by both host and phage RNAps. Overexpression of the E. coli udk gene, which encodes a uridine/cytidine kinase, interferes with T7 infection. We demonstrate that overexpression of udk antagonizes Gp2 function in E. coli in the absence of T7 infection and thus independently of T7-encoded factors. It seems that overexpression of udk reduces Gp2 stability and functionality during T7 infection, which consequently results in inadequate inhibition of host RNAp and in the accumulation of early T7 transcripts. In other words, overexpression of udk mimics the absence of Gp2 during T7 infection. Our study suggests that the transcriptional regulation of the T7 genome is surprisingly complex and might potentially be affected at many levels by phage- and host-encoded factors.

  5. Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Stage III-IVB Head and Neck Cancer Who Cannot Take Cisplatin

    ClinicalTrials.gov

    2018-06-15

    Head and Neck Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  6. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-05-18

    CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  7. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2018-02-14

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  8. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2018-03-22

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Tumor; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Direct and inverted reciprocal chromosome insertions between chromosomes 7 and 14 in a woman with recurrent miscarriages

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

    Ying-Tai Wang; Zhao-Cai Wang; Bajalica, S.

    We present the first case of direct and inverted reciprocal chromosome insertions between human chromosomes 7 and 14, ascertained because of repeated spontaneous abortions. Prometaphase GTG banding analysis showed the karyotype to be 46, XX, inv ins (7;14)(7pter {yields} 7q11.23::14q32.2 {yields} 14q22::7q21.2 {yields} 7qter), dir ins(14;7)(14pter {yields} 14q22::7q11.23 {yields} 7q21.2::14q32.2 {yields} 14qter). Origins of the insertion have been confirmed by chromosome painting with libraries specific for chromosomes 7 and 14 using fluorescence in situ hybridization. 5 refs., 3 figs.

  10. Democratization as a United States Strategy for Middle East Security

    DTIC Science & Technology

    2005-03-18

    the Middle East presents a wide variety of governments across the region. Republics exists in Algeria, Egypt, Lebanon , Syria, Tunisia, and Yemen...PF 4 5 PF 4 5 PF 4 5 PF 4 5 PF Lebanon 6 5 NF 6 5 NF 6 5 NF 6 5 NF 6 5 NF Libya 7 7 NF 7 7 NF 7 7 NF 7 7 NF 7 7 NF Morocco 5 4 PF 5 5 PF 5 5 PF 5 5...more open discussion of previously taboo topics.17 Syria’s firm control continues to be the greatest impediment to freedom in Lebanon . The Lebanese

  11. Four new neolignans isolated from Eleutherococcus senticosus and their protein tyrosine phosphatase 1B inhibitory activity (PTP1B).

    PubMed

    Zhang, Le; Li, Ban-Ban; Li, Hao-Ze; Meng, Xiao; Lin, Xin; Jiang, Yi-Yu; Ahn, Jong-Seog; Cui, Long

    2017-09-01

    Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the compounds were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, compounds 1-4 and 6-8 were found to exhibit selective inhibitory activity on PTP1B with IC 50 values ranging from 17.2±1.6 to 32.7±1.2μM. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Gene 1.7 of bacteriophage T7 confers sensitivity of phage growth to dideoxythymidine.

    PubMed

    Tran, Ngoc Q; Rezende, Lisa F; Qimron, Udi; Richardson, Charles C; Tabor, Stanley

    2008-07-08

    Bacteriophage T7 DNA polymerase efficiently incorporates dideoxynucleotides into DNA, resulting in chain termination. Dideoxythymidine (ddT) present in the medium at levels not toxic to Escherichia coli inhibits phage T7. We isolated 95 T7 phage mutants that were resistant to ddT. All contained a mutation in T7 gene 1.7, a nonessential gene of unknown function. When gene 1.7 was expressed from a plasmid, T7 phage resistant to ddT still arose; analysis of 36 of these mutants revealed that all had a single mutation in gene 5, which encodes T7 DNA polymerase. This mutation changes tyrosine-526 to phenylalanine, which is known to increase dramatically the ability of T7 DNA polymerase to discriminate against dideoxynucleotides. DNA synthesis in cells infected with wild-type T7 phage was inhibited by ddT, suggesting that it resulted in chain termination of DNA synthesis in the presence of gene 1.7 protein. Overexpression of gene 1.7 from a plasmid rendered E. coli cells sensitive to ddT, indicating that no other T7 proteins are required to confer sensitivity to ddT.

  13. Bioconversion of 7-hydroxyflavanone: isolation, characterization and bioactivity evaluation of twenty-one phase I and phase II microbial metaboites

    USDA-ARS?s Scientific Manuscript database

    Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4’-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 1330...

  14. 48 CFR 6302.7 - Motions (Rule 7).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Motions (Rule 7). 6302.7... APPEALS RULES OF PROCEDURE 6302.7 Motions (Rule 7). (a) Motions are made by filing an original and two copies, together with any supporting papers, with the Board. Motions may also be made upon the record, in...

  15. 48 CFR 6302.7 - Motions (Rule 7).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Motions (Rule 7). 6302.7... APPEALS RULES OF PROCEDURE 6302.7 Motions (Rule 7). (a) Motions are made by filing an original and two copies, together with any supporting papers, with the Board. Motions may also be made upon the record, in...

  16. Fatigue Interventions in Cancer (Exercise Intervention)

    ClinicalTrials.gov

    2018-01-29

    Sedentary Lifestyle; Stage III Breast Cancer AJCC v7; Stage III Prostate Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7

  17. The effect of angiotensin 1-7 on tyrosine kinases activity in rat anterior pituitary

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

    Rebas, Elzbieta; Zabczynska, Joanna; Lachowicz, Agnieszka

    2006-09-01

    Angiotensin 1-7 (Ang 1-7) is a peptide originated from Ang II. It is known that in vessels Ang 1-7 shows opposite effects to Ang II. Ang 1-7 can modify processes of proliferation. However, Ang 1-7 action in pituitary gland cells was never studied. Moreover, the specific binding sites for Ang 1-7 are still unknown. The aim of this study was to examine the effects of Ang 1-7 on tyrosine kinases (PTKs) activity in the anterior pituitary. The reaction of phosphorylation was carrying out in presence of different concentration of Ang 1-7 and losartan (antagonist of AT1 receptor) and PD123319 (antagonistmore » of AT2). Our results show that Ang 1-7 inhibited activity of PTK to 60% of basic activity. Losartan did not change the Ang 1-7-induced changes in PTKs activity. The presence of PD123319 together with Ang 1-7 caused stronger inhibition PTKs activity than Ang 1-7 alone. These observations suggest that Ang 1-7 binds to the novel, unknown, specific for this peptide receptor.« less

  18. Characterization of the canine mda-7 gene, transcripts and expression patterns

    PubMed Central

    Sandey, Maninder; Bird, R. Curtis; Das, Swadesh K.; Sarkar, Devanand; Curiel, David T.; Fisher, Paul B.; Smith, Bruce F.

    2014-01-01

    Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) displays potent growth suppressing and cell killing activity against a wide variety of human and rodent cancer cells. In this study, we identified a canine ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family members on chromosome 7. The full-length mRNA sequence of canine mda-7 was determined, which encodes a 186-amino acid protein that has 66% similarity to human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal canine epidermal keratinocytes (NCEKs), and its expression levels are increased after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5′-splice donor sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus (signal peptide sequence) and are dissimilar in amino acid sequences at their C-terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most tumor derived cancer cell lines tested, like its human counterpart. Unlike human MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA) stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in-silico analysis revealed that canonical canine MDA-7 has a potential 28 amino acid signal peptide sequence that can target it for active secretion. This data suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its protein product has high amino acid similarity to human MDA-7/IL-24 protein and it may possess similar biological properties to human MDA-7/IL-24, but its expression pattern is more restricted than its human ortholog. PMID:24865935

  19. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    PubMed

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm

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

    Masuda, Kouhei; Katagiri, Chiaki; Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo

    2010-03-05

    MAPK phosphatase-7 (MKP-7) was identified as a JNK-specific phosphatase. However, despite its high specificity for JNK, MKP-7 interacts also with ERK. We previously showed that as a physiological consequence of their interaction, activated ERK phosphorylates MKP-7 at Ser-446, and stabilizing MKP-7. In the present study, we analyzed MKP-7 function in activation of ERK. A time-course experiment showed that both MKP-7 and its phosphatase-dead mutant prolonged mitogen-induced ERK phosphorylation, suggesting that MKP-7 functions as a scaffold for ERK. An important immunohistological finding was that nuclear translocation of phospho-ERK following PMA stimulation was blocked by co-expressed MKP-7 and, moreover, that phospho-ERK co-localizedmore » with MKP-7 in the cytoplasm. Reporter gene analysis indicated that MKP-7 blocks ERK-mediated transcription. Overall, our data indicate that MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK.« less

  1. Camp Casey, Tongduchon, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1981-02-10

    76.,a41 7S.4 ?R.4’ 7B.q. .4 . I 78.uf 7-.t- . .I 2 V_𔃻 77.71 77.71 72.2 f6 . I 7 -.. 4 78. . ,= , 9Ss 7. 7. ’ 7 .Z 7 7 79.Z 79.2 79.1-3; 77. 7 79.a: 75...cof-. .4r E0C >j a- -- =* C.j C . = ± (i3e!’ afl o oc- g Nta.. a .o.r3azdflloD2Coa.aoc a- f~ie~~z. n.!. G a 4 . ACca . . rx Co.--&Z3Er,0C i1DaI Da...6-=.1 66.4 ;-’ -0 o-b 915 c.01 is 99.2i 90.7 99.7 9 9. 1 99.7s. JO 200 1 5 01 6 ,. 1 66.4! .69 F6 . 1 ? 1 .61 976.1if 97.r1 99. 1 9gs 999 .39 a c .3 c

  2. Modulation of Kv7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58

    PubMed Central

    Zhang, F; Mi, Y; Qi, JL; Li, JW; Si, M; Guan, BC; Du, XN; An, HL; Zhang, HL

    2013-01-01

    Background and Purpose Modulation of Kv7/M channel function represents a relatively new strategy to treat neuronal excitability disorders such as epilepsy and neuropathic pain. We designed and synthesized a novel series of pyrazolo[1,5-a] pyrimidin-7(4H)-one compounds, which activate Kv7 channels. Here, we characterized the effects of the lead compound, QO-58, on Kv7 channels and investigated its mechanism of action. Experimental Approach A perforated whole-cell patch technique was used to record Kv7 currents expressed in mammalian cell lines and M-type currents from rat dorsal root ganglion neurons. The effects of QO-58 in a rat model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve, were also examined. Key Results QO-58 increased the current amplitudes, shifted the voltage-dependent activation curve in a more negative direction and slowed the deactivation of Kv7.2/Kv7.3 currents. QO-58 activated Kv7.1, Kv7.2, Kv7.4 and Kv7.3/Kv7.5 channels with a more selective effect on Kv7.2 and Kv7.4, but little effect on Kv7.3. The mechanism of QO-58's activation of Kv7 channels was clearly distinct from that used by retigabine. A chain of amino acids, Val224Val225Tyr226, in Kv7.2 was important for QO-58 activation of this channel. QO-58 enhanced native neuronal M currents, resulting in depression of evoked action potentials. QO-58 also elevated the pain threshold of neuropathic pain in the sciatic nerve CCI model. Conclusions and Implications The results indicate that QO-58 is a potent modulator of Kv7 channels with a mechanism of action different from those of known Kv7 openers. Hence, QO-58 shows potential as a treatment for diseases associated with neuronal hyperexcitability. PMID:23013484

  3. Kindness Interventions in Enhancing Well-Being in Breast Cancer Survivors

    ClinicalTrials.gov

    2018-06-18

    Cancer Survivor; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

  4. 40 CFR 439.16 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-Heptane 3.0 0.7 n-Hexane 3.0 0.7 Methylene chloride 3.0 0.7 Chloroform 0.1 0.03 1,2-dichloroethane 20.7 8...: Pretreatment Standards (PSES) Regulated parameter Maximum daily 1 Maximum monthly average 1 Ammonia (as N) 2 84.1 29.4 Acetone 20.7 8.2 4-methyl-2-pentanone 20.7 8.2 Isobutyraldehyde 20.7 8.2 n-Amyl acetate 20.7...

  5. Ching Chuan Kang AB, Kung Kuan, Formosa. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1972-04-11

    jt: PERCENTAGE FREQUENCY OF OCCURRENCE Iso - 1 4Qo (FROM HOURLY OBSERVATIONS) VISIBILITY (STATUTE MILES) CEIUNG ,FEET, [ 0 >_6 :>5 -4 _3 2 -2 I I >_I...73,1 76,7 79,2 8o?0, 81,4 81,7 82,1 8628 82,8 82,8 2,a 82.8 82.8 >- 1500 52@ 7i),3 7,6 79, 8 s7 83,s 83,9 64,2 84.6 8a5,3 8j,1 8583 85:3 8503 85,3 1 200...19,0 46,0 7Z 252 06.06 7v9 00 7.9 ).,Z 1 4,8 3.2 17,9 42,5 7,2 252 Ol-L1 70 11,5 7.5 o.3 .#0 7,.1 7,5 23,0 25.0 6,4 252 12-14 4- iso , 9o,1 ,3 0,3 4.0

  6. TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

    ClinicalTrials.gov

    2018-05-14

    Adult Glioblastoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Solid Neoplasm; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

  7. Navy Career Sea Pay: Is it Still a Viable Compensating Wage Program? A Historical and Financial Analysis

    DTIC Science & Technology

    2007-06-01

    220 | E7 5 262 | E7 5 468 | E7 6 118 | E7 6 147 | E7 6 267 | E7 7 17 | E7 7 37 | E7 7 81 | E8 1 61 | E8 1 64 | E8 1 57 | E8 2 62 | E8 2 76 | E8 2 70...5027 4923 4932 4640 E7-E9 451 405 387 445 447 462 453 454 448 441 441 489 MA E1-E3 1 1 1 2 12 22 33 108 135 137 160 189 E4-E6 429 414 407 416 444 483...20 262 12 24 970 8 4.60% 5.80% 1.33% 60.00% 1.60% 33.33% Apr-03 1593 10 342 4 42 467 15 26 1023 11 0.63% 40.00% 2.64% 35.71% 1.63% 42.31% Oct-03 1711

  8. Pembrolizumab in Treating Patients With HIV and Relapsed, Refractory, or Disseminated Malignant Neoplasms

    ClinicalTrials.gov

    2018-03-22

    AIDS-Related Non-Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Locally Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Malignant Neoplasm; Recurrent Melanoma of the Skin; Recurrent Non-Hodgkin Lymphoma; Recurrent Non-Small Cell Lung Carcinoma; Refractory Hodgkin Lymphoma; Refractory Malignant Neoplasm; Solid Neoplasm; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7

  9. Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells.

    PubMed

    Martin, Christopher E; Spasova, Darina S; Frimpong-Boateng, Kwesi; Kim, Hee-Ok; Lee, Minji; Kim, Kwang Soon; Surh, Charles D

    2017-07-18

    Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4 + and CD8 + T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R. Unexpectedly, innate lymphoid cells were found to have a potent influence on IL-7 amounts in the primary and secondary lymphoid tissues. These results demonstrate that IL-7 homeostasis is achieved through consumption by multiple subsets of innate and adaptive immune cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Grissom AFB, Indiana. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

    DTIC Science & Technology

    1987-11-01

    PERIOD OF RECORD: 78-B7 MONTH: MAR HOUSILSTI: ISO -1700 CE ILIOO V|SIBIL1TV IN SIATUTE MILES IN I GE GE GE GE GE GE GE GE GE GE GE GE GE GC GE GE FEET I...77.9 77.9 77.9 77.9 77.9 77.9 77.9 GE200:52 14 748 7.3 7. 79:1 79.4 79.4 79.6 79:7 79:7 79:7 79.7 79.7 79.7 79.74E 27001 25. 7 T4.7 78.2, 91.1 62.4...82175. ’.1. 1 *- I. p ’X k,’ 33U-CS I SD 13.712 15.2?’. 51.51. 10 09? 1k I-j6; b.Z* b.6i k.450,~ 9 Ia..’ I * ISO ? 0S1 921 646 #;v 9: 𔄃 $0 49 vs t7 * P LAN

  11. Transition-state destabilization reveals how human DNA polymerase β proceeds across the chemically unstable lesion N7-methylguanine

    PubMed Central

    Ouzon-Shubeita, Hala; Lee, Seongmin

    2014-01-01

    N7-Methyl-2′-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2′-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2′-fluoro-m7dG (Fm7dG), by human DNA polymerase β (polβ) and solved three X-ray structures of polβ in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polβ catalysis ∼300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson–Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polβ-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polβ. In addition, the polβ-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polβ catalysis across m7dG is slow, yet highly accurate. PMID:24966350

  12. Synthesis by ring-closing alkyne metathesis with selective hydrogenation, and olfactory comparison of (7E)- and (7Z)-cyclohexadec-7-enone (Aurelione(®) ).

    PubMed

    Mathys, Marion; Kraft, Philip

    2014-10-01

    Both C=C-bond isomers of cyclohexadec-7-enone (6, Aurelione(®) ) were selectively synthesized via cyclohexadec-7-ynol (16) by ring-closing alkyne metathesis of icosa-2,18-diyn-9-ol (15), employing an in situ-formed catalyst from Mo(CO)6 and 4-(trifluoromethyl)phenol. Pyridinium chlorochromate (PCC) oxidation and subsequent Lindlar hydrogenation afforded the (7Z)-configured isomer (7Z)-6, while hydrosilylation of the intermediate cyclohexadec-7-ynone (17), followed by desilylation, provided the (7E)-configured cyclohexadec-7-enone ((7E)-6). The substrate for the alkyne metathesis was prepared from cycloheptanone (7) by cycloaddition of chloromethylcarbene to its trimethylsilyl enol ether 8, and subsequent ring enlargement of the adduct 9 under rearrangement to 2-methylcyclooct-2-enone (10), which was subjected to Weitz-Scheffer epoxidation and Eschenmoser-Ohloff fragmentation to non-7-ynal (12). Its reaction with the Grignard reagent of 11-bromoundec-2-yne (14), prepared from the corresponding alcohol 13 by Appel-Lee bromination, furnished the icosa-2,18-diyn-9-ol (15). While both isomers of cyclohexadec-7-enone (6) possess warm and powdery musk odors with tobacco-type ambery accents, (7Z)-6 is more animalic and waxy, whereas (7E)-6 was found to be more floral, sweet, and hay-like in tonality. Interestingly, however, with odor detection thresholds of 2.0 ng/l air and 2.3 ng/l air, respectively, both (7Z)-6 and (7E)-6 were found to be almost identical in their odor strength, with the (7Z)-6 being only very slightly more powerful. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  13. IL-7 splicing variant IL-7{delta}5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway

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

    Pan, Deshun; Department of Pharmaceutical science, Guangdong Pharmaceutical University, Guangzhou, Guangdong; Liu, Bing

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer This study confirms the role of IL-7{delta}5 in breast cancer cell proliferation. Black-Right-Pointing-Pointer IL-7{delta}5 promotes breast cancer cell proliferation and cell cycle progression. Black-Right-Pointing-Pointer IL-7{delta}5 promotes cell proliferation via activation of PI3K/Akt pathway. -- Abstract: Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7{delta}5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The resultsmore » showed that IL-7{delta}5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27{sup kip1} expression. Mechanistically, we found that IL-7{delta}5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7{delta}5. In conclusion, our findings demonstrate that IL-7{delta}5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7{delta}5 may be a potential target for human breast cancer therapeutics intervention.« less

  14. Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7α-hydroxy dehydroepiandrosterone and 7α-hydroxy pregnenolone

    PubMed Central

    Rose, Ken A.; Stapleton, Genevieve; Dott, Karin; Kieny, Marie Paule; Best, Ruth; Schwarz, Margrit; Russell, David W.; Björkhem, Ingemar; Seckl, Jonathan; Lathe, Richard

    1997-01-01

    Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 μM) and pregnenolone (Km, 4.0 μM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17β-estradiol and 5α-androstane-3β,17β-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7α-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7α-hydroxy DHEA but not with 7β-hydroxy DHEA; when [7α-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7α position. Brain extracts also efficiently liberated tritium from [7α-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7α-hydroxy DHEA. We conclude that Cyp7b is a 7α-hydroxylase participating in the synthesis, in brain, of neurosteroids 7α-hydroxy DHEA, and 7α-hydroxy pregnenolone. PMID:9144166

  15. Prevalence of naturally occurring antibodies against dog erythrocyte antigen 7 in a population of dog erythrocyte antigen 7-negative dogs from Spain and Italy.

    PubMed

    Spada, Eva; Proverbio, Daniela; Viñals Flórez, Luis Miguel; Del Rosario Perlado Chamizo, Maria; Serra Y Gómez de la Serna, Blanca; Perego, Roberta; Baggiani, Luciana

    2016-08-01

    OBJECTIVE To determine the prevalence of naturally occurring anti-dog erythrocyte antigen (DEA) 7 antibodies in DEA 7-negative dogs from Spain and Italy. ANIMALS 252 DEA 7-negative dogs from a population of 312 dogs that were previously tested for DEA 1, DEA 4, and DEA 7. PROCEDURES A plasma sample was obtained from each dog and evaluated for anti-DEA 7 antibodies by the use of gel column agglutination. Each plasma sample underwent major crossmatching with RBCs from DEA 7-positive dogs. Samples that resulted in agglutination were then crossmatched with RBCs from DEA 1-negative, DEA 4-positive, and DEA 7-negative dogs to confirm the presence of anti-DEA 7 antibodies. Results were then used to calculate the risk for a delayed transfusion reaction in a DEA 7-negative dog with anti-DEA 7 antibodies after a transfusion with blood that was not crossmatched or typed for DEA 7. RESULTS 96 of 252 (38.1%) plasma samples contained anti-DEA 7 antibodies. A DEA 7-negative dog with anti-DEA 7 antibodies had a 5.9% chance of developing a delayed hemolytic reaction after transfusion with blood not crossmatched or typed for DEA 7. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that canine blood used for transfusion should be crossmatched with the blood or plasma of the intended recipient prior to transfusion to minimize the likelihood that the recipient will develop a hemolytic reaction associated with anti-DEA 7 antibodies. Ideal canine blood donors should be negative for both DEA 1 and DEA 7.

  16. Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7.

    PubMed

    Eichhorn, Catherine D; Yang, Yuan; Repeta, Lucas; Feigon, Juli

    2018-06-26

    The La and the La-related protein (LARP) superfamily is a diverse class of RNA binding proteins involved in RNA processing, folding, and function. Larp7 binds to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein (RNP) assembly and function. The 7SK RNP sequesters a pool of the positive transcription elongation factor b (P-TEFb) in an inactive state; on release, P-TEFb phosphorylates RNA Polymerase II to stimulate transcription elongation. Despite its essential role in transcription, limited structural information is available for the 7SK RNP, particularly for protein-RNA interactions. Larp7 contains an N-terminal La module that binds UUU-3'OH and a C-terminal atypical RNA recognition motif (xRRM) required for specific binding to 7SK and P-TEFb assembly. Deletion of the xRRM is linked to gastric cancer in humans. We report the 2.2-Å X-ray crystal structure of the human La-related protein group 7 (hLarp7) xRRM bound to the 7SK stem-loop 4, revealing a unique binding interface. Contributions of observed interactions to binding affinity were investigated by mutagenesis and isothermal titration calorimetry. NMR 13 C spin relaxation data and comparison of free xRRM, RNA, and xRRM-RNA structures show that the xRRM is preordered to bind a flexible loop 4. Combining structures of the hLarp7 La module and the xRRM-7SK complex presented here, we propose a structural model for Larp7 binding to the 7SK 3' end and mechanism for 7SK RNP assembly. This work provides insight into how this domain contributes to 7SK recognition and assembly of the core 7SK RNP.

  17. Development of rapid immunochromatographic test for hemagglutinin antigen of H7 subtype in patients infected with novel avian influenza A (H7N9) virus.

    PubMed

    Kang, Keren; Chen, Li; Zhao, Xiang; Qin, Chengfeng; Zhan, Zanwu; Wang, Jihua; Li, Wenmei; Dzakah, Emmanuel E; Huang, Weijuang; Shu, Yuelong; Jiang, Tao; Cao, Wuchun; Xie, Mingquan; Luo, Xiaochun; Tang, Shixing

    2014-01-01

    Since human infection with the novel H7N9 avian influenza virus was identified in China in March 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of H7N9 infection. We developed a rapid diagnostic test for the novel avian influenza A (H7N9) virus using anti-hemagglutinin (HA) monoclonal antibodies specifically targeting H7 in an immunochromatographic assay system. The assay limit of detection was 103.5 pfu/ml or 103TCID50 of H7N9 virus. The assay specifically detected H7N9 viral isolates and recombinant HA proteins of H7 subtypes including H7N7 and H7N9, but did not react with non-H7 subtypes including H1N1, H3N2, H5N1, H5N9, and H9N2. The detection sensitivity was 59.4% (19/32) for H7N9 patients confirmed by RT-PCR. Moreover, the highest sensitivity of 61.5% (16/26) was obtained when testing H7N9 positive sputum samples while 35.7% (5/14) of nasopharyngeal swabs and 20% (2/10) of fecal samples tested positive. No false positive detection was found when testing 180 H7N9 negative samples. Our novel rapid assay can specifically detect H7 HA antigen, facilitating rapid diagnosis for prevention and control of the on-going H7N9 epidemic.

  18. Development of Rapid Immunochromatographic Test for Hemagglutinin Antigen of H7 Subtype in Patients Infected with Novel Avian Influenza A (H7N9) Virus

    PubMed Central

    Kang, Keren; Chen, Li; Zhao, Xiang; Qin, Chengfeng; Zhan, Zanwu; Wang, Jihua; Li, Wenmei; Dzakah, Emmanuel E.; Huang, Weijuang; Shu, Yuelong; Jiang, Tao; Cao, Wuchun; Xie, Mingquan; Luo, Xiaochun; Tang, Shixing

    2014-01-01

    Background Since human infection with the novel H7N9 avian influenza virus was identified in China in March 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of H7N9 infection. Methodology/Principal Findings We developed a rapid diagnostic test for the novel avian influenza A (H7N9) virus using anti-hemagglutinin (HA) monoclonal antibodies specifically targeting H7 in an immunochromatographic assay system. The assay limit of detection was 103.5 pfu/ml or 103TCID50 of H7N9 virus. The assay specifically detected H7N9 viral isolates and recombinant HA proteins of H7 subtypes including H7N7 and H7N9, but did not react with non-H7 subtypes including H1N1, H3N2, H5N1, H5N9, and H9N2. The detection sensitivity was 59.4% (19/32) for H7N9 patients confirmed by RT-PCR. Moreover, the highest sensitivity of 61.5% (16/26) was obtained when testing H7N9 positive sputum samples while 35.7% (5/14) of nasopharyngeal swabs and 20% (2/10) of fecal samples tested positive. No false positive detection was found when testing 180 H7N9 negative samples. Conclusions/Significance Our novel rapid assay can specifically detect H7 HA antigen, facilitating rapid diagnosis for prevention and control of the on-going H7N9 epidemic. PMID:24647358

  19. Reading Grade Level (RGL) Data for Air Force Specialties (1988)

    DTIC Science & Technology

    1990-08-01

    10.7 10.5 9.8 452X2 814 11.3 9.8 10.7 10.5 9.6 452X3 740 11.3 10.1 10.7 10.5 9.6 452X4 7804 10.5 9.3 9.8 9.4 8.9 454X0 5376 10.5 9.3 9.6 9.3 8.9 454X1 ...9.7 10.3 9.7 9.1 454X1 4520 11.2 9.7 10.6 10.0 9.4 454X2 410 10.9 9.7 10.3 9.7 8.8 454X3 1261 11.2 9.7 10.6 1U.0 9.1 454X4 1829 11,2 9,7 10.3 9.7 9.1

  20. Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

    PubMed Central

    Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

    2014-01-01

    Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

  1. Genomic DNA Copy-Number Alterations of the let-7 Family in Human Cancers

    PubMed Central

    Greshock, Joel; Shen, Liang; Yang, Xiaojun; Shao, Zhongjun; Liang, Shun; Tanyi, Janos L.; Sood, Anil K.; Zhang, Lin

    2012-01-01

    In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients. However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear. Since an alteration in copy-number is one of the causes of gene deregulation in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset. We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner. Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e), breast cancer (let-7a-2), and ovarian cancer (let-7a-3/let-7b). For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients. We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer. Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of cancer. PMID:22970210

  2. Photophysical Property and Photocatalytic Activity of New Gd2InSbO7 and Gd2FeSbO7 Compounds under Visible Light Irradiation

    PubMed Central

    Luan, Jingfei; Xu, Yong

    2013-01-01

    Gd2InSbO7 and Gd2FeSbO7 were synthesized first, and their structural and photocatalytic properties were studied. The lattice parameters and the band gaps for Gd2InSbO7 and Gd2FeSbO7 were 10.449546 Å, 10.276026 Å, 2.897 eV and 2.151 eV. The photocatalytic degradation of rhodamine B was performed with Gd2InSbO7 and Gd2FeSbO7 under visible light irradiation. Gd2InSbO7 and Gd2FeSbO7 had higher catalytic activity compared with Bi2InTaO7. Gd2FeSbO7 exhibited higher catalytic activity than Gd2InSbO7. The photocatalytic degradation of rhodamine B followed with the first-order reaction kinetics, and the first-order rate constant k was 0.01606, 0.02220 or 0.00329 min−1 with Gd2InSbO7, Gd2FeSbO7 or Bi2InTaO7 as photocatalyst. Complete removal of rhodamine B was observed after visible light irradiation for 225 min or 260 min with Gd2FeSbO7 or Gd2InSbO7 as photocatalyst. The evolution of CO2 was realized, and it indicated continuous mineralization of rhodamine B during the photocatalytic process. The possible photocatalytic degradation pathway of rhodamine B was proposed. PMID:23296275

  3. 1,2,3-Triazole Tagged 3H-Pyrano[2,3-d]pyrimidine-6-carboxylate Derivatives: Synthesis, in Vitro Cytotoxicity, Molecular Docking and DNA Interaction Studies.

    PubMed

    Boda, Sathish Kumar; Pishka, Vasantha; Lakshmi, P V Anantha; Chinde, Srinivas; Grover, Paramjit

    2018-06-01

    A series of novel ethyl 2,7-dimethyl-4-oxo-3-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carboxylate derivatives 7a - 7m were efficiently synthesized employing click chemistry approach and evaluated for in vitro cytotoxic activity against four tumor cell lines: A549 (human lung adenocarcinoma cell line), HepG2 (human hematoma), MCF-7 (human breast adenocarcinoma), and SKOV3 (human ovarian carcinoma cell line). Among the compounds tested, the compounds 7a, 7b, 7f, 7l, and 7m have shown potential and selective activity against human lung adenocarcinoma cell line (A549) with IC 50 ranging from 0.69 to 6.74 μm. Molecular docking studies revealed that the compounds 7a, 7b, 7f, 7l, and 7m are potent inhibitors of human DNA topoisomerase-II and also showed compliance with stranded parameters of drug likeness. The calculated binding constants, k b , from UV/VIS absorptional binding studies of 7a and 7l with CT-DNA were 10.77 × 10 4 , 6.48 × 10 4 , respectively. Viscosity measurements revealed that the binding could be surface binding mainly due to groove binding. DNA cleavage study showed that 7a and 7l have the potential to cleave pBR322 plasmid DNA without any external agents. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  4. Tannic acid activates the Kv7.4 and Kv7.3/7.5 K(+) channels expressed in HEK293 cells and reduces tension in the rat mesenteric arteries.

    PubMed

    Zhang, Yuanyuan; Chu, Xi; Liu, Ling; Zhang, Nan; Guo, Hui; Yang, Fan; Liu, Zhenyi; Dong, Yongsheng; Bao, Yifan; Zhang, Xuan; Zhang, Jianping

    2016-04-01

    This study investigated the effect of tannic acid (TA), a plant-derived hydrolyzable polyphenol, on Kv7.4 and Kv7.5 K(+) channels and rat mesenteric artery. Whole-cell patch clamp experiments were used to record the Kv7.4 and Kv7.3/7.5 K(+) currents expressed in HEK293 cells; and the tension changes of mesenteric arteries isolated from rats were recorded using small vessel myography apparatus. Tannic acid increases the Kv7.4 and Kv7.3/7.5 K(+) currents in a concentration-dependent manner (median effective concentration (EC50 ) = 27.3 ± 3.6 μm and EC50 = 23.1 ± 3.9 μm, respectively). In addition, 30 μm TA shifts the G-V curve of Kv7.4 and Kv7.3/7.5 K(+) currents to the left by 14.18 and 25.24 mV, respectively, and prolongs the deactivation time constants by 184.44 and 154.77 ms, respectively. Moreover, TA relaxes the vascular tension of rat mesenteric arteries in a concentration-dependent manner (half inhibitory concentration (IC50 ) = 148.7 ± 13.4 μm). These results confirms the vasodilatory effects of TA on rat mesenteric artery and the activating effects on the Kv7.4 and Kv7.3/7.5 K(+) channels, which may be a mechanism to explain the vasodilatory effect and this mechanism can be used in the research of antihypertension. © 2016 Royal Pharmaceutical Society.

  5. Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2018-03-22

    Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  6. 7 CFR 600.7 - Specialized field offices.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Specialized field offices. 600.7 Section 600.7..., DEPARTMENT OF AGRICULTURE GENERAL ORGANIZATION § 600.7 Specialized field offices. Other field offices serve... direction and supervision of these offices. ...

  7. Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts.

    PubMed

    Gálvez-Ruiz, Juan Carlos; Holl, Gerhard; Karaghiosoff, Konstantin; Klapötke, Thomas M; Löhnwitz, Karolin; Mayer, Peter; Nöth, Heinrich; Polborn, Kurt; Rohbogner, Christoph J; Suter, Max; Weigand, Jan J

    2005-06-13

    1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b-d were calculated using the empirical equations of Kamlet and Jacobs: D(2b) = 8383 m s(-)(1), P(2b) = 32.2 GPa; D(7b) = 7682 m s(-)(1), P(7b) = 23.4 GPa; D(7c) = 8827 m s(-)(1), P(7c) = 33.6 GPa; and D(7d) = 7405 m s(-)(1), P(7d) = 20.8 GPa. For all compounds, a structure determination by single-crystal X-ray diffraction was performed. 2a and 2b crystallize in the monoclinic space groups C2/c and P2(1)/n, respectively. The salts of 7 crystallize in the orthorhombic space groups Pna2(1) (7a, 7d) and Fdd2 (7b). The hydrogen-bonded ring motifs are discussed in the formalism of graph-set analysis of hydrogen-bond patterns and compared in the case of 2a, 2b, and 7b.

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

    Ogami, Koichi; Cho, Rihe; Hoshino, Shin-ichi, E-mail: hoshino@phar.nagoya-cu.ac.jp

    Highlights: ► So far, only an enzymatically inactive isoform of PAPD7 was reported. ► The novel isoform: PAPD7 l shows robust nucleotidyl transferase activity. ► The newly identified amino terminal region is required for the activity. ► PAPD7 l localizes to the nucleoplasm. ► The N terminal region identified is also required for the nuclear localization. - Abstract: Non-canonical poly(A) polymerases (ncPAPs) catalyze the addition of poly(A) tail to the 3′ end of RNA to play pivotal roles in the regulation of gene expression and also in quality control. Here we identified a novel isoform of the 7th member ofmore » ncPAPs: PAPD7 (PAPD7 l), which contains 230 extra amino acids at the amino terminus of the previously identified PAPD7 (PAPD7 s). In sharp contrast to the inactive PAPD7 s, PAPD7 l showed robust nucleotidyl transferase activity when tethered to an RNA. A region required for the activity was localized to 187–219 aa, and this region was also required for the nuclear retention of PAPD7 l. Western blot analysis revealed that 94 kDa band (corresponding to PAPD7 l) but not 62 kDa band (corresponding to PAPD7 s) detected by PAPD7 antibody was specifically depleted by treatment with PAPD7 siRNA in both HeLa and U2OS cells. These results suggest that PAPD7 l is the major and active isoform of PAPD7 expressed in cells.« less

  9. Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target.

    PubMed

    Watson, Gabrielle M; Lucas, William A H; Gunzburg, Menachem J; Wilce, Jacqueline A

    2017-01-01

    Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

  10. Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7)*

    PubMed Central

    Valinsky, William C.; Jolly, Anna; Miquel, Perrine

    2016-01-01

    Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg2+-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg2+ levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. PMID:27466368

  11. Efficacy of a Parainfluenza Virus 5 (PIV5)-Based H7N9 Vaccine in Mice and Guinea Pigs: Antibody Titer towards HA Was Not a Good Indicator for Protection

    PubMed Central

    Johnson, Scott; Dlugolenski, Daniel; Phan, Shannon; Tompkins, S. Mark; He, Biao

    2015-01-01

    H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5), an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7) and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9) in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP) conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively. PMID:25803697

  12. Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

    PubMed Central

    Watson, Gabrielle M.; Lucas, William A. H.; Gunzburg, Menachem J.; Wilce, Jacqueline A.

    2017-01-01

    Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors. PMID:29018805

  13. Electronic Reliability Design Handbook. Volume 1

    DTIC Science & Technology

    1988-10-12

    greater use of proven designs , more design attention to non -random failures, design sim- plicity, improved quality control , more effective development and...RELIABILITY ENGINEERING DESIGN GUIDELINES 7-1 7.1 INTRODUCTION 7-1 7.2 PART SELECTION AND CONTROL 7-1 7.3 DERATING 7-4 7.3.1 DERATING OF MECHANICAL STRUCTURAL...11-58 11.3.1 INTRODUCTION 11-58 11.3.2 MAINTAINABILITY DESIGN ATTRIBUTES 11-59 11.3.3 MAINTAINABILITY CONTROL PARAMETERS 11-59 11.3.4 MAINTAINABILITY

  14. Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients With Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer

    ClinicalTrials.gov

    2017-11-15

    Epstein-Barr Virus Positive; Gastric Adenocarcinoma; Mismatch Repair Protein Deficiency; Stage IB Gastric Cancer AJCC v7; Stage II Gastric Cancer AJCC v7; Stage IIA Gastric Cancer AJCC v7; Stage IIB Gastric Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7

  15. Prostate Cancer Evaluation: Design, Synthesis and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents

    DTIC Science & Technology

    2008-10-01

    3$*(6 D1$0(2)5(63216,%/(3(5621 D5(3257 E $%675$&7 F7+,63$*( /,0,7$7,212) $%675$&7 6WDQGDUG)RUP 5HY 3UHVFULEHG... E \\$16,6WG= 7KHSXEOLFUHSRUWLQJEXUGHQIRUWKLVFROOHFWLRQRI LQIRUPDWLRQLVHVWLPDWHGWRDYHUDJHKRXUSHUUHVSRQVH LQFOXGLQJWKHWLPH...FRQWUROQXPEHU 3/($6(�(7851)250727+($%29($’𔃿(66 ’$7(6&29(5(’ )URP7R E *5$17180%(5 F352*5$0(/(0(17180%(5 G

  16. Design, Build and Test of an Axial Flow Hydrokinetic Turbine with Fatigue Analysis

    DTIC Science & Technology

    2010-06-01

    180%(5 2) 3$*(6 D1$0(2)5(63216,%/(3(5621 D5(3257 E $%675$&7 F7+,63$*( /,0,7$7,212) $%675$&7 6WDQGDUG)RUP...5HY 3UHVFULEHG E \\$16,6WG= 7KHSXEOLFUHSRUWLQJEXUGHQIRUWKLVFROOHFWLRQRI LQIRUPDWLRQLVHVWLPDWHGWRDYHUDJHKRXUSHUUHVSRQVH...FXUUHQWO\\YDOLG20%FRQWUROQXPEHU 3/($6(�(7851)250727+($%29($’𔃿(66 ’$7(6&29(5(’ )URP7R E *5$17180%(5 F352*5$0

  17. Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders.

    PubMed

    Kristensen, J H; Larsen, L; Dasgupta, B; Brodmerkel, C; Curran, M; Karsdal, M A; Sand, J M B; Willumsen, N; Knox, A J; Bolton, C E; Johnson, S R; Hägglund, P; Svensson, B; Leeming, D J

    2015-11-01

    Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer. Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls. The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls. MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA

    DOE PAGES

    Eichhorn, Catherine D.; Chug, Rahul; Feigon, Juli

    2016-09-26

    The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD andmore » show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study thus confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.« less

  19. Effects of Doping on Thermal Conductivity of Pyrochlore Oxides for Advanced Thermal Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Bansal, Narottam P.; Zhu, Dongming; Eslamloo-Grami, Maryam

    2006-01-01

    Pyrochlore oxides of general composition, A2B2O7, where A is a 3(+) cation (La to Lu) and B is a 4(+) cation (Zr, Hf, Ti, etc.) have high melting point, relatively high coefficient of thermal expansion, and low thermal conductivity which make them suitable for applications as high-temperature thermal barrier coatings. The effect of doping at the A site on the thermal conductivity of a pyrochlore oxide La2Zr2O7, has been investigated. Oxide powders of various compositions La2Zr2O7, La(1.7)Gd(0.3)Zr2O7, La(1.7)Yb(0.3)Zr2O7 and La(1.7)Gd(0.15)Yb(0.15)Zr2O7 were synthesized by the citric acid sol-gel method. These powders were hot pressed into discs and used for thermal conductivity measurements using a steady-state laser heat flux test technique. The rare earth oxide doped pyrochlores La(1.7)Gd(0.3)Zr2O7, La(1.7)Yb(0.3)Zr2O7 and La(1.7)Gd(0.15)Yb(0.15)Zr2O7 had lower thermal conductivity than the un-doped La2Zr2O7. The Gd2O3 and Yb2O3 co-doped composition showed the lowest thermal conductivity.

  20. hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA

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

    Eichhorn, Catherine D.; Chug, Rahul; Feigon, Juli

    The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD andmore » show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study thus confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.« less

  1. Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-02-02

    Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

  2. Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases from Trichoderma atroviride, T. reesei and T. harzianum.

    PubMed

    Borisova, Anna S; Eneyskaya, Elena V; Jana, Suvamay; Badino, Silke F; Kari, Jeppe; Amore, Antonella; Karlsson, Magnus; Hansson, Henrik; Sandgren, Mats; Himmel, Michael E; Westh, Peter; Payne, Christina M; Kulminskaya, Anna A; Ståhlberg, Jerry

    2018-01-01

    The ascomycete fungus Trichoderma reesei is the predominant source of enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase family 7 cellobiohydrolase (GH7 CBH) Tre Cel7A constitutes nearly half of the enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis process. The orthologs from Trichoderma atroviride ( Tat Cel7A) and Trichoderma harzianum ( Tha Cel7A) show high sequence identity with Tre Cel7A, ~ 80%, and represent naturally evolved combinations of cellulose-binding tunnel-enclosing loop motifs, which have been suggested to influence intrinsic cellobiohydrolase properties, such as endo-initiation, processivity, and off-rate. The Tat Cel7A, Tha Cel7A, and Tre Cel7A enzymes were characterized for comparison of function. The catalytic domain of Tat Cel7A was crystallized, and two structures were determined: without ligand and with thio-cellotriose in the active site. Initial hydrolysis of bacterial cellulose was faster with Tat Cel7A than either Tha Cel7A or Tre Cel7A. In synergistic saccharification of pretreated corn stover, both Tat Cel7A and Tha Cel7A were more efficient than Tre Cel7A, although Tat Cel7A was more sensitive to thermal inactivation. Structural analyses and molecular dynamics (MD) simulations were performed to elucidate important structure/function correlations. Moreover, reverse conservation analysis (RCA) of sequence diversity revealed divergent regions of interest located outside the cellulose-binding tunnel of Trichoderma spp. GH7 CBHs. We hypothesize that the combination of loop motifs is the main determinant for the observed differences in Cel7A activity on cellulosic substrates. Fine-tuning of the loop flexibility appears to be an important evolutionary target in Trichoderma spp., a conclusion supported by the RCA data. Our results indicate that, for industrial use, it would be beneficial to combine loop motifs from Tat Cel7A with the thermostability features of Tre Cel7A. Furthermore, one region implicated in thermal unfolding is suggested as a primary target for protein engineering.

  3. Crystal structures, vibrational spectra and DFT calculations of five halogeno-derivatives of 7-azaindole (3Br7AI, 4Br7AI, 4Cl7AI, 3Br4Cl7AI and 5Br3Cl7AI): a comparative study

    NASA Astrophysics Data System (ADS)

    Morzyk-Ociepa, Barbara; Dysz, Karolina; Turowska-Tyrk, Ilona; Michalska, Danuta

    2018-01-01

    Structures and vibrational spectra of 3-bromo-7-azaindole (3Br7AI), 4-bromo-7-azaindole (4Br7AI), 4-chloro-7-azaindole (4Cl7AI), 5-bromo-3-chloro-7-azaindole (5Br3Cl7AI) and 3-bromo-4-chloro-7-azaindole (3Br4Cl7AI) have been investigated. For the first time a single crystal analysis is reported for the three compounds: 3Br7AI (P21/n space group; a = 12.6586(3), b = 3.98664(12), c = 14.1189(4)Å, β = 100.901(2)o, Z = 4); 4Br7AI (P21/n space group; a = 5.38136 (13), b = 9.2262 (2), c = 13.9806 (4)Å, β = 90.052 (2)o, Z = 4); and 5Br3Cl7AI (C2/c space group; a = 22.9444(10), b = 3.91953(12), c = 17.8500(6)Å, β = 102.621(4)o, Z = 8). In the crystal structure, a pair of molecules forms a centrosymmetric dimer connected by dual nearly linear Nsbnd H⋯N hydrogen bonds between the pyrrole and pyridine rings. In addition, the structures of 4Br7AI and 5Br3Cl7AI are stabilized by C2sbnd H2⋯Br hydrogen bonds. The IR and Raman spectra of all compounds and their N-deuterated derivatives were recorded in the solid state. The theoretical molecular structures and vibrational spectra of the centrosymmetric dimers of five investigated compounds were calculated using the B3LYP method with the 6-311G++(d,p) basis set. The optimized structural parameters and the calculated vibrational spectra reproduce well the experiment. Detailed vibrational assignments for all these compounds have been made on the basis of the calculated potential energy distributions (PEDs). The characteristic marker bands for the chloro- and bromo-derivativeds of 7-azaindoles are reported.

  4. Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer.

    PubMed

    Hu, Jianguo; Zhang, Luo; Mei, Zhiqiang; Jiang, Yuan; Yi, Yuan; Liu, Li; Meng, Ying; Zhou, Lili; Zeng, Jianhua; Wu, Huan; Jiang, Xingwei

    2018-05-22

    Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-β-smad2/3 pathway by interacting with TGFβR2. MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-β-smad2/3 pathway by interacting with TGFβR2. Inhibition of TGF-β-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-β induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-β induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-β-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. These findings suggested that TGFβR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

  5. Bacterially produced human B7-1 protein encompassing its complete extracellular domain maintains its costimulatory activity in vitro.

    PubMed

    Shen, W; Wang, Y; Geng, Y; Si, L

    2000-08-01

    To investigate which of the two immunoglobulin (Ig)-like domains, immunoglobulin variable region homologous domain IgV (hB7-1 IgV), or immunoglobulin constant region homologous domain IgC (hB7-1 IgC) on human B7-1 molecule contain the receptor binding sites, and to evaluate if the B7-1 molecule expressed in bacteria has biological activity. PCR was used to amplify three fragments of hB7-1 IgV, hB7-1 IgC and complete extracellular region of human B7-1 containing both the IgV and IgC domains (hB7-1 IgV + IgC). Three recombinants, pQE9-hB7-1 IgV, pQE9-hB7-1 IgC and pQE9-Hb7-1 (IgV + IgC) were generated by cloning the PCR products into a prokaryote expression plasmid (pQE-9) and were introduced into the host stain M15. The relevant target hexahistidine-tagged proteins were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7-1 proteins and [3H]-TdR incorporation. Three recombinant proteins of human B7-1, hB7-1 IgV, hB7-1 IgC and hB7-1 (IgV + IgC) were produced and detected in both soluble and inclusive body forms from engineered bacterial cells. With the presence of anti-CD3 antibody, T lymphocytes proliferated when co-stimulated by bacterially produced hB7-1 (IgV + IgC), but not by either hB7-1 IgV or hB7-1 IgC. Functional glycoprotein human B7-1 could be produced in bacterial cells. Both extracellular immunoglobulin-like domains are necessary for B7-1 to react with its counter receptors.

  6. Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases from Trichoderma atroviride, T. reesei and T. harzianum

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

    Borisova, Anna S.; Eneyskaya, Elena V.; Jana, Suvamay

    The ascomycete fungus Trichoderma reesei is the predominant source of enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase family 7 cellobiohydrolase (GH7 CBH) TreCel7A constitutes nearly half of the enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis process. The orthologs from Trichoderma atroviride (TatCel7A) and Trichoderma harzianum (ThaCel7A) show high sequence identity with TreCel7A, ~ 80%, and represent naturally evolved combinations of cellulose-binding tunnel-enclosing loop motifs, which have been suggested to influence intrinsic cellobiohydrolase properties, such as endo-initiation, processivity, and off-rate. The TatCel7A, ThaCel7A, and TreCel7A enzymes were characterized for comparison of function. Themore » catalytic domain of TatCel7A was crystallized, and two structures were determined: without ligand and with thio-cellotriose in the active site. Initial hydrolysis of bacterial cellulose was faster with TatCel7A than either ThaCel7A or TreCel7A. In synergistic saccharification of pretreated corn stover, both TatCel7A and ThaCel7A were more efficient than TreCel7A, although TatCel7A was more sensitive to thermal inactivation. Structural analyses and molecular dynamics (MD) simulations were performed to elucidate important structure/function correlations. Moreover, reverse conservation analysis (RCA) of sequence diversity revealed divergent regions of interest located outside the cellulose-binding tunnel of Trichoderma spp. GH7 CBHs. We hypothesize that the combination of loop motifs is the main determinant for the observed differences in Cel7A activity on cellulosic substrates. Fine-tuning of the loop flexibility appears to be an important evolutionary target in Trichoderma spp., a conclusion supported by the RCA data. Our results indicate that, for industrial use, it would be beneficial to combine loop motifs from TatCel7A with the thermostability features of TreCel7A. Furthermore, one region implicated in thermal unfolding is suggested as a primary target for protein engineering.« less

  7. Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases from Trichoderma atroviride, T. reesei and T. harzianum

    DOE PAGES

    Borisova, Anna S.; Eneyskaya, Elena V.; Jana, Suvamay; ...

    2018-01-13

    The ascomycete fungus Trichoderma reesei is the predominant source of enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase family 7 cellobiohydrolase (GH7 CBH) TreCel7A constitutes nearly half of the enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis process. The orthologs from Trichoderma atroviride (TatCel7A) and Trichoderma harzianum (ThaCel7A) show high sequence identity with TreCel7A, ~ 80%, and represent naturally evolved combinations of cellulose-binding tunnel-enclosing loop motifs, which have been suggested to influence intrinsic cellobiohydrolase properties, such as endo-initiation, processivity, and off-rate. The TatCel7A, ThaCel7A, and TreCel7A enzymes were characterized for comparison of function. Themore » catalytic domain of TatCel7A was crystallized, and two structures were determined: without ligand and with thio-cellotriose in the active site. Initial hydrolysis of bacterial cellulose was faster with TatCel7A than either ThaCel7A or TreCel7A. In synergistic saccharification of pretreated corn stover, both TatCel7A and ThaCel7A were more efficient than TreCel7A, although TatCel7A was more sensitive to thermal inactivation. Structural analyses and molecular dynamics (MD) simulations were performed to elucidate important structure/function correlations. Moreover, reverse conservation analysis (RCA) of sequence diversity revealed divergent regions of interest located outside the cellulose-binding tunnel of Trichoderma spp. GH7 CBHs. We hypothesize that the combination of loop motifs is the main determinant for the observed differences in Cel7A activity on cellulosic substrates. Fine-tuning of the loop flexibility appears to be an important evolutionary target in Trichoderma spp., a conclusion supported by the RCA data. Our results indicate that, for industrial use, it would be beneficial to combine loop motifs from TatCel7A with the thermostability features of TreCel7A. Furthermore, one region implicated in thermal unfolding is suggested as a primary target for protein engineering.« less

  8. Recombinant influenza H7 hemagglutinin containing CFLLC minidomain in the transmembrane domain showed enhanced cross-protection in mice.

    PubMed

    Wang, Yang; Zhang, Yun; Wu, Jialing; Lin, Ying; Wu, Zhihui; Wei, Ying; Wei, Xiaona; Qin, Jianru; Xue, Chunyi; Liu, George Dacai; Cao, Yongchang

    2017-10-15

    Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection. In this study, we used Sf9 insect cell expression system to express recombinant H7 HA proteins H7-53WT, in which HA gene was derived from H7N9-53 strain, and H7-53TM containing CFLLC minidomian by replacing its TM domain with H3 HA TM. We investigated whether introduction of CFLLC minidomain into H7 HA (H7-53TM) could increase its cross-reactivity and cross-protection against different genotypes of H7N9 viruses. The results showed that the H7-53TM either with or without squalene adjuvant induced increased HI antibodies, serum IgG antibodies, and IFN-γ production to a panel of 7 H7N9 viruses in mice. Vaccinated animals with H7-53TM alone showed complete protection against challenge with heterologous H7N9-MCX strain, while H7-53WT alone showed incomplete protection (80%). Furthermore, mice vaccinated with H7-53TM HA showed less body weight loss and less pulmonary lesions and inflammation after challenge with homologous or heterologous H7N9 viruses, comparing to H7-53WT. In summary, this study presents a better subunit vaccine candidate (H7-53TM) against potential H7N9 pandemic. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

    PubMed Central

    Costantini, Todd W; Dang, Xitong; Yurchyshyna, Maryana V; Coimbra, Raul; Eliceiri, Brian P; Baird, Andrew

    2015-01-01

    The human genome contains a variant form of the α7-nicotinic acetylcholine receptor (α7nAChR) gene that is uniquely human. This CHRFAM7A gene arose during human speciation and recent data suggests that its expression alters ligand tropism of the normally homopentameric human α7-AChR ligand-gated cell surface ion channel that is found on the surface of many different cell types. To understand its possible significance in regulating inflammation in humans, we investigated its expression in normal human leukocytes and leukocyte cell lines, compared CHRFAM7A expression to that of the CHRNA7 gene, mapped its promoter and characterized the effects of stable CHRFAM7A overexpression. We report here that CHRFAM7A is highly expressed in human leukocytes but that the levels of both CHRFAM7A and CHRNA7 mRNAs were independent and varied widely. To this end, mapping of the CHRFAM7A promoter in its 5′-untranslated region (UTR) identified a unique 1-kb sequence that independently regulates CHRFAM7A gene expression. Because overexpression of CHRFAM7A in THP1 cells altered the cell phenotype and modified the expression of genes associated with focal adhesion (for example, FAK, P13K, Akt, rho, GEF, Elk1, CycD), leukocyte transepithelial migration (Nox, ITG, MMPs, PKC) and cancer (kit, kitL, ras, cFos cyclinD1, Frizzled and GPCR), we conclude that CHRFAM7A is biologically active. Most surprisingly however, stable CHRFAM7A overexpression in THP1 cells upregulated CHRNA7, which, in turn, led to increased binding of the specific α7nAChR ligand, bungarotoxin, on the THP1 cell surface. Taken together, these data confirm the close association between CHRFAM7A and CHRNA7 expression, establish a biological consequence to CHRFAM7A expression in human leukocytes and support the possibility that this human-specific gene might contribute to, and/or gauge, a human-specific response to inflammation. PMID:25860877

  10. 7 CFR 353.7 - Certificates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Certificates. 353.7 Section 353.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORT CERTIFICATION § 353.7 Certificates. (a) Phytosanitary certificate (PPQ Form...

  11. 7 CFR 1775.7 - Environmental requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Environmental requirements. 1775.7 Section 1775.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) TECHNICAL ASSISTANCE GRANTS General Provisions § 1775.7 Environmental requirements...

  12. 7 CFR 1775.7 - Environmental requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Environmental requirements. 1775.7 Section 1775.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) TECHNICAL ASSISTANCE GRANTS General Provisions § 1775.7 Environmental requirements...

  13. 7 CFR 1924.7 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] 1924.7 Section 1924.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... CONSTRUCTION AND REPAIR Planning and Performing Construction and Other Development § 1924.7 [Reserved] ...

  14. 49 CFR 173.436 - Exempt material activity concentrations and exempt consignment activity limits for radionuclides.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Nd-147 Neodymium (60) 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Nd-149 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Ni-59 Nickel (28) 1.0×104 2.7×10−7 1.0×108 2.7×10−3 Ni-63 1.0×105 2.7×10−6 1.0×108 2.7×10−3 Ni-65 1.0...

  15. 49 CFR 173.436 - Exempt material activity concentrations and exempt consignment activity limits for radionuclides.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Nd-147 Neodymium (60) 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Nd-149 1.0×102 2.7×10−9 1.0×106 2.7×10−5 Ni-59 Nickel (28) 1.0×104 2.7×10−7 1.0×108 2.7×10−3 Ni-63 1.0×105 2.7×10−6 1.0×108 2.7×10−3 Ni-65 1.0...

  16. Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer

    ClinicalTrials.gov

    2018-05-23

    Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  17. Osteoblast Specific Overexpression of Human Interleukin-7 Rescues the Bone Mass Phenotype of Interleukin-7 Deficient Female Mice

    PubMed Central

    Aguila, Hector L.; Mun, Se Hwan; Kalinowski, Judith; Adams, Douglas J.; Lorenzo, Joseph A.; Lee, Sun-Kyeong

    2012-01-01

    Interleukin-7 is a critical cytokine for lymphoid development and a direct inhibitor of in vitro osteoclastogenesis in murine bone marrow cultures. To explore the role of IL-7 in bone, we generated transgenic mouse lines bearing the 2.3 Kb rat collagen 1A1 promoter driving the expression of human IL-7 specifically in osteoblasts. In addition we crossed these mice with IL-7 deficient mice to determine if the alterations in lymphopoiesis, bone mass and osteoclast formation observed in the IL-7 KO mice could be rescued by osteoblast-specific overexpression of IL-7. Here we show that mice overexpressing human IL-7 in the osteoblast lineage demonstrated increased trabecular bone volume in vivo by µCT and decreased osteoclast formation in vitro. Furthermore, targeted overexpression of IL-7 in osteoblasts rescued the osteopenic bone phenotype and B cell development of IL-7 KO mice but did not have an effect on T lymphopoiesis, which occurs in the periphery. The bone phenotypes in IL-7 KO mice and targeted IL-7 overexpressing mouse models were observed only in females. These results likely reflect both a direct inhibitory effects of IL-7 on osteoclastogenesis in vivo and gender specific differences in responses to IL-7. PMID:22258693

  18. Preparation of crystals for characterizing the Grb7 SH2 domain before and after complex formation with a bicyclic peptide antagonist.

    PubMed

    Ambaye, Nigus D; Gunzburg, Menachem J; Traore, Daouda A K; Del Borgo, Mark P; Perlmutter, Patrick; Wilce, Matthew C J; Wilce, Jacqueline A

    2014-02-01

    Human growth factor receptor-bound protein 7 (Grb7) is an adapter protein involved in cell growth, migration and proliferation. It is now recognized that Grb7 is an emerging therapeutic target in specific cancer subtypes. Recently, the discovery of a bicyclic peptide inhibitor that targets the Grb7 SH2 domain, named G7-B1, was reported. In an attempt to probe the foundation of its interaction with Grb7, the crystallization and preliminary data collection of both the apo and G7-B1-bound forms of the Grb7 SH2 domain are reported here. Diffraction-quality crystals were obtained using the hanging-drop vapour-diffusion method. After several rounds of microseeding, crystals of the apo Grb7 SH2 domain were obtained that diffracted to 1.8 Å resolution, while those of the G7-B1-Grb7 SH2 domain complex diffracted to 2.2 Å resolution. The apo Grb7 SH2 domain crystallized in the trigonal space group P63, whereas the G7-B1-Grb7 SH2 domain complex crystallized in the monoclinic space group P21. The experimental aspects of crystallization, crystal optimization and data collection and the preliminary data are reported.

  19. Comparison of sagittal parameters for anterior cervical discectomy and fusion, hybrid surgery, and total disc replacement for three levels of cervical spondylosis.

    PubMed

    Hung, Che-Wei; Wu, Ming-Fang; Yu, Gwo-Fane; Ko, Chin-Chu; Kao, Cheng-Hsing

    2018-05-01

    To analyze sagittal balance of the cervical spine after three operative methods for three consecutive levels. A retrospective case selection and observational study was performed from December 2012 to December 2015: 20 patients underwent anterior cervical discectomy and fusion, 22 patients underwent hybrid surgery (HS), and 20 patients underwent total disc replacement (TDR). Perioperative parameters, clinical outcomes, and preoperative and postoperative sagittal parameters were recorded. Clinical outcomes improved. Fusion and hybrid groups were associated with more postoperative focal lordosis than the TDR group (no significant difference). The postoperative C2-7 sagittal vertical axis (SVA) was greater in the TDR group (no significant difference). In the fusion group, the postoperative C2-7 SVA was highly correlated with the preoperative C2-7 SVA and postoperative C7 slope (C7SL). Postoperative C2-7 lordosis (C2-7L) was highly correlated with the preoperative C2-7 SVA and preoperative and postoperative C7SL. In the hybrid group, postoperative C2-7L was highly correlated with preoperative C2-7L, preoperative and postoperative focal lordosis, and C7SL. In the TDR group, the postoperative C2-7 SVA was highly correlated with the preoperative C2-7 SVA and postoperative C7 slope. The postoperative C2-7 SVA was also negatively correlated with postoperative C2-7L and focal lordosis. Postoperative C2-7L was highly correlated with postoperative focal lordosis. For three or more levels of cervical degenerative disease, good clinical outcomes can be achieved. TDR may not be a good choice for large preoperative C2-7 SVA. HS provides good cervical range of motion and restores cervical lordosis and C2-7 SVA. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related peptide-induced cerebral reactivity.

    PubMed

    Chadha, Preet S; Jepps, Thomas A; Carr, Georgina; Stott, Jennifer B; Zhu, Hei-Lei; Cole, William C; Greenwood, Iain A

    2014-04-01

    Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) participate in the myogenic control of MCA diameter. The present study investigated the contribution of Kv7.4 and Kv7.5 isoforms to myogenic and CGRP regulation of MCA diameter and determined whether they were affected in hypertensive animals. Isometric tension recordings performed on MCA from normotensive rats produced CGRP vasodilations that were inhibited by the pan-Kv7 channel blocker linopirdine (P<0.01) and after transfection of arteries with siRNA against KCNQ4 (P<0.01) but not KCNQ5. However, isobaric myography revealed that myogenic constriction in response to increases in intravascular pressure (20-80 mm Hg) was affected by both KCNQ4 and KCNQ5 siRNA. Proximity ligation assay signals were equally abundant for Kv7.4/Kv7.4 or Kv7.4/Kv7.5 antibody combinations but minimal for Kv7.5/Kv7.5 antibodies or Kv7.4/7.1 combinations. In contrast to systemic arteries, Kv7 function and Kv7.4 abundance in MCA were not altered in hypertensive rats. This study reveals, for the first time to our knowledge, that in cerebral arteries, Kv7.4 and Kv7.5 proteins exist predominantly as a functional heterotetramer, which regulates intrinsic myogenicity and vasodilation attributed to CGRP. Surprisingly, unlike systemic arteries, Kv7 activity in MCAs is not affected by the development of hypertension, and CGRP-mediated vasodilation is well maintained. As such, cerebrovascular Kv7 channels could be amenable for therapeutic targeting in conditions such as cerebral vasospasm.

  1. Talimogene Laherparepvec, Capecitabine, and Chemoradiation Before Surgery in Treating Patients With Locally Advanced or Metastatic Rectal Cancer

    ClinicalTrials.gov

    2018-04-30

    Rectal Adenocarcinoma; Stage III Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

  2. Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

    ClinicalTrials.gov

    2018-02-08

    Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

  3. 78 FR 49207 - Airworthiness Directives; Maule Aerospace Technology, Inc. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... Technology, Inc. Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... certain Maule Aerospace Technology, Inc. M-4, M-5, M-6, M-7, MT-7, MX-7, MXT-7, and M-8 airplanes that are... Technology Corp. (currently Maule Aerospace Technology, Inc.) M-4, M-5, M-6, M-7, MX-7, and MXT-7 series...

  4. Overexpression of Activin Receptor-like Kinase 7 in Breast Cancer Cells Is Associated with Decreased Cell Growth and Adhesion.

    PubMed

    Hu, Tingting; Su, Fengxi; Jiang, Wenguo; Dart, D Alwyn

    2017-07-01

    To examine the expression and function of activin receptor-like kinase 7 (ALK7) in breast cancer, its association with disease prognosis, and its impact on breast cancer cell function. A cohort of patients with breast cancer were examined for ALK7 expression in association with pathological and clinical aspects. In vitro cell assays of ALK7 were investigated using an expression plasmid. Overall higher levels of ALK7 transcripts were seen in the breast cancer samples vs. normal tissue. However, within the cancer cohort, lower levels of ALK7 transcript were associated with poor prognosis. Patients with lower expression of ALK7 also had shorter survival. Overexpression of ALK7 reduced proliferation and adhesion of breast cancer cells in vitro. We found that overexpressed ALK7 had complex effects on the MCF-7 cell sensitivity to chemotherapy drugs. Decreased expression of ALK7 in breast cancer is correlated with poor prognosis. ALK7 is a negative regulator of adhesion and proliferation of breast cancer cells. This suggests that ALK7 is a potential tumor suppressor in breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Bismuth-Indium-Sodium two-dimensional compounds on Si(111) surface

    NASA Astrophysics Data System (ADS)

    Denisov, N. V.; Alekseev, A. A.; Utas, O. A.; Azatyan, S. G.; Zotov, A. V.; Saranin, A. A.

    2017-12-01

    Using scanning tunneling microscopy (STM) observations, it has been found that room temperature (RT) deposition of Na onto the (Bi,In)/Si(111) surfaces, namely the 2 × 2 and √7 × √7, induces formation of a joint bismuth-indium-sodium structure without changing of the initial periodicity. For the 2 × 2-(Bi,In), Na atoms ;conceal; defects and domain boundaries, while the √7 × √7-(Bi,In) is reconstructed into the new Si(111)√7 × √7-(Bi,In,Na) structure. The first structure is temperature unstable, but the √7 × √7-(Bi,In,Na) is thermostable and can be formed by ordinary codeposition of the metals onto the Si(111)7 × 7 surface followed by annealing at 350-360 °C. Scanning tunneling spectroscopy (STS) has demonstrated that the √7 × √7-(Bi,In,Na) is semiconductor with a ∼0.5 eV energy gap. The structural model of the √7 × √7-(Bi,In,Na) has been proposed on the basis of DFT calculations and comparison of simulated and experimental STM images as well as density of states (DOS) and STS spectra.

  6. The predominant bacteria isolated from radicular cysts

    PubMed Central

    2013-01-01

    Purpose To detect predominant bacteria associated with radicular cysts and discuss in light of the literature. Material and methods Clinical materials were obtained from 35 radicular cysts by aspiration. Cultures were made from clinical materials by modern laboratory techniques, they underwent microbiologic analysis. Results The following are microorganisms isolated from cultures: Streptococcus milleri Group (SMG) (23.8%) [Streptococcus constellatus (19.1%) and Streptococcus anginosus (4.7%)], Streptococcus sanguis (14.3%), Streptococcus mitis (4.7%), Streptococcus cremoris (4.7%), Peptostreptococcus pevotii (4.7%), Prevotella buccae (4.7%), Prevotella intermedia (4.7%), Actinomyces meyeri (4.7%), Actinomyces viscosus (4.7%), Propionibacterium propionicum (4.7%), Bacteroides capillosus (4.7%), Staphylococcus hominis (4.7%), Rothia denticariosa (4.7%), Gemella haemolysans (4.7%), and Fusobacterium nucleatum (4.7%). Conclusions Results of this study demonstrated that radicular cysts show a great variety of anaerobic and facultative anaerobic bacterial flora. It was observed that all isolated microorganisms were the types commonly found in oral flora. Although no specific microorganism was found, Streptococcus spp. bacteria (47.5%) – especially SMG (23.8%) – were predominantly found in the microorganisms isolated. Furthermore, radicular cysts might be polymicrobial originated. Although radicular cyst is an inflammatory cyst, some radicular cyst fluids might be sterile. PMID:24011184

  7. 7 CFR 248.7 - Nondiscrimination.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Nondiscrimination. 248.7 Section 248.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.7...

  8. 7 CFR 248.7 - Nondiscrimination.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Nondiscrimination. 248.7 Section 248.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.7...

  9. 7 CFR 248.7 - Nondiscrimination.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Nondiscrimination. 248.7 Section 248.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.7...

  10. 7 CFR 248.7 - Nondiscrimination.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Nondiscrimination. 248.7 Section 248.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.7...

  11. 7 CFR 248.7 - Nondiscrimination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Nondiscrimination. 248.7 Section 248.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS WIC FARMERS' MARKET NUTRITION PROGRAM (FMNP) Recipient Eligibility § 248.7...

  12. 7 CFR 1206.7 - Fiscal period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal period. 1206.7 Section 1206.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.7 Fiscal period. Fiscal period...

  13. 7 CFR 1230.7 - Customs Service.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Customs Service. 1230.7 Section 1230.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.7 Customs...

  14. 7 CFR 953.7 - Ship.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Ship. 953.7 Section 953.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Order Regulating Handling Definitions § 953.7 Ship. Ship is synonymous with handle and means to...

  15. 7 CFR 953.7 - Ship.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Ship. 953.7 Section 953.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Order Regulating Handling Definitions § 953.7 Ship. Ship is synonymous with handle and means to...

  16. 7 CFR 953.7 - Ship.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Ship. 953.7 Section 953.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Order Regulating Handling Definitions § 953.7 Ship. Ship is synonymous with handle and means to...

  17. 7 CFR 953.7 - Ship.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Ship. 953.7 Section 953.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND... Order Regulating Handling Definitions § 953.7 Ship. Ship is synonymous with handle and means to...

  18. 7 CFR 953.7 - Ship.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Ship. 953.7 Section 953.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND... Order Regulating Handling Definitions § 953.7 Ship. Ship is synonymous with handle and means to...

  19. TAS-102 in Treating Advanced Biliary Tract Cancers

    ClinicalTrials.gov

    2017-10-23

    Cholangiocarcinoma; Stage III Gallbladder Cancer AJCC v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVB Gallbladder Cancer AJCC v7

  20. A Quantification of the 3D Modeling Capabilities of the Kinectfusion Algorithm

    DTIC Science & Technology

    2014-03-27

    Based on the documentation, this is based on the idea that the majority GPU cards on the market will not have the memory required to support more than...5.0 4.4 4N 520 7.9 0.4 8.6 8.2 8.0 7.6 6.6 4P 520 6.2 0.3 6.9 6.4 6.2 6.0 5.5 4Q 520 7.1 0.4 8.0 7.3 7.1 6.8 6.1 5D 520 6.4 0.4 7.0 6.6 6.4 6.1 5.5 5N...3Q 5.3 5.3 5.2 -0.1 -1.7% 4D 5.3 5.3 5.2 -0.1 -1.3% 4N 7.9 8.0 7.7 -0.2 -2.2% 4P 6.2 6.2 5.9 -0.3 -5.2% 4Q 7.1 7.1 7.0 -0.1 -1.1% 5D 6.4 6.4 6.6 0.2

  1. The IgV domain of human B7-2 (CD86) is sufficient to co-stimulate T lymphocytes and induce cytokine secretion.

    PubMed

    Rennert, P; Furlong, K; Jellis, C; Greenfield, E; Freeman, G J; Ueda, Y; Levine, B; June, C H; Gray, G S

    1997-06-01

    B7-1 (CD80) and B7-2 (CD86) are genetically and structurally related molecules expressed on antigen-presenting cells. Both bind CD28 to co-stimulate T lymphocytes, resulting in proliferation and cytokine production. The extracellular portions of B7-1 and B7-2 which bind to CD28 and CTLA-4 are related to Ig variable (V) and Ig constant (C) domain sequences. Recent reports have described splice variant forms of B7 proteins which occur in vivo and are of unknown function. Here we describe soluble recombinant forms of B7-1 and B7-2 containing either both of the Ig-like extracellular domains or the individual IgV or IgC domains coupled to an Ig Fc tail. Soluble B7-1 and B7-2 bind to CD28 and CTLA-4, and effectively co-stimulate T lymphocytes resulting in their proliferation and the secretion of cytokines. Furthermore, the IgV domain of B7-2 binds CD28 and CTLA-4, competes with B7-1 and B7-2 for binding to these receptors, and co-stimulates T lymphocytes. Cross-linked soluble B7-2v was the most potent co-stimulatory molecule tested and was active at a concentration approximately 100-fold lower than cross-linked soluble B7-1 or B7-2 proteins. When bound to tosyl-activated beads, B7-2v was capable of sustaining multiple rounds of T cell expansion. These data complement the description of naturally occurring variants to suggest that T cell co-stimulation in vivo may be regulated by soluble or truncated forms of B7 proteins.

  2. Characterization of a Drosophila ortholog of the Cdc7 kinase: a role for Cdc7 in endoreplication independent of Chiffon.

    PubMed

    Stephenson, Robert; Hosler, Marcus R; Gavande, Navnath S; Ghosh, Arun K; Weake, Vikki M

    2015-01-16

    Cdc7 is a serine-threonine kinase that phosphorylates components of the pre-replication complex during DNA replication initiation. Cdc7 is highly conserved, and Cdc7 orthologs have been characterized in organisms ranging from yeast to humans. Cdc7 is activated specifically during late G1/S phase by binding to its regulatory subunit, Dbf4. Drosophila melanogaster contains a Dbf4 ortholog, Chiffon, which is essential for chorion amplification in Drosophila egg chambers. However, no Drosophila ortholog of Cdc7 has yet been characterized. Here, we report the functional and biochemical characterization of a Drosophila ortholog of Cdc7. Co-expression of Drosophila Cdc7 and Chiffon is able to complement a growth defect in yeast containing a temperature-sensitive Cdc7 mutant. Cdc7 and Chiffon physically interact and can be co-purified from insect cells. Cdc7 phosphorylates the known Cdc7 substrates Mcm2 and histone H3 in vitro, and Cdc7 kinase activity is stimulated by Chiffon and inhibited by the Cdc7-specific inhibitor XL413. Drosophila egg chamber follicle cells deficient for Cdc7 have a defect in two types of DNA replication, endoreplication and chorion gene amplification. However, follicle cells deficient for Chiffon have a defect in chorion gene amplification but still undergo endocycling. Our results show that Cdc7 interacts with Chiffon to form a functional Dbf4-dependent kinase complex and that Cdc7 is necessary for DNA replication in Drosophila egg chamber follicle cells. Additionally, we show that Chiffon is a member of an expanding subset of DNA replication initiation factors that are not strictly required for endoreplication in Drosophila. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. New effects of a long-lived negatively charged massive particle on big bang nucleosynthesis

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

    Kusakabe, Motohiko; Kim, K. S.; Cheoun, Myung-Ki

    Primordial {sup 7}Li abundance inferred from observations of metal-poor stars is a factor of about 3 lower than the theoretical value of standard big bang nucleosynthesis (BBN) model. One of the solutions to the Li problem is {sup 7}Be destruction during the BBN epoch caused by a long-lived negatively charged massive particle, X{sup −}. The particle can bind to nuclei, and X-bound nuclei (X-nuclei) can experience new reactions. The radiative X{sup −} capture by {sup 7}Be nuclei followed by proton capture of the bound state of {sup 7}Be and X{sup −} ({sup 7}Be{sub x}) is a possible {sup 7}Be destructionmore » reaction. Since the primordial abundance of {sup 7}Li originates mainly from {sup 7}Li produced via the electron capture of {sup 7}Be after BBN, the {sup 7}Be destruction provides a solution to the {sup 7}Li problem. We suggest a new route of {sup 7}Be{sub x} formation, that is the {sup 7}Be charge exchange at the reaction of {sup 7}Be{sup 3+} ion and X{sup −}. The formation rate depends on the ionization fraction of {sup 7}Be{sup 3+} ion, the charge exchange cross section of {sup 7}Be{sup 3+}, and the probability that excited states {sup 7}Be{sub x}* produced at the charge exchange are converted to the ground state. We find that this reaction can be equally important as or more important than ordinary radiative recombination of {sup 7}Be and X{sup −}. The effect of this new route is shown in a nuclear reaction network calculation.« less

  4. The TRPM7 channel kinase regulates store-operated calcium entry.

    PubMed

    Faouzi, Malika; Kilch, Tatiana; Horgen, F David; Fleig, Andrea; Penner, Reinhold

    2017-05-15

    Pharmacological and molecular inhibition of transient receptor potential melastatin 7 (TRPM7) reduces store-operated calcium entry (SOCE). Overexpression of TRPM7 in TRPM7 -/- cells restores SOCE. TRPM7 is not a store-operated calcium channel. TRPM7 kinase rather than channel modulates SOCE. TRPM7 channel activity contributes to the maintenance of store Ca 2+ levels at rest. The transient receptor potential melastatin 7 (TRPM7) is a protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. In the present study, we report store-operated calcium entry (SOCE) as a novel target of TRPM7 kinase activity. TRPM7-deficient chicken DT40 B lymphocytes exhibit a strongly impaired SOCE compared to wild-type cells as a result of reduced calcium release activated calcium currents, and independently of potassium channel regulation, membrane potential changes or changes in cell-cycle distribution. Pharmacological blockade of TRPM7 with NS8593 or waixenicin A in wild-type B lymphocytes results in a significant decrease in SOCE, confirming that TRPM7 activity is acutely linked to SOCE, without TRPM7 representing a store-operated channel itself. Using kinase-deficient mutants, we find that TRPM7 regulates SOCE through its kinase domain. Furthermore, Ca 2+ influx through TRPM7 is essential for the maintenance of endoplasmic reticulum Ca 2+ concentration in resting cells, and for the refilling of Ca 2+ stores after a Ca 2+ signalling event. We conclude that the channel kinase TRPM7 and SOCE are synergistic mechanisms regulating intracellular Ca 2+ homeostasis. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  5. Angiopoietin-like 7 Secretion Is Induced by Glaucoma Stimuli and Its Concentration Is Elevated in Glaucomatous Aqueous Humor

    PubMed Central

    Kuchtey, John; Källberg, Maria E.; Gelatt, Kirk N.; Rinkoski, Tommy; Komàromy, András M.; Kuchtey, Rachel W.

    2010-01-01

    Purpose To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma. Methods Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor β (TGFβ), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression. Results TGFβ and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs. Conclusions Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target. PMID:18421092

  6. From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group.

    PubMed

    Blom, Sigrid Marie; Rottländer, Mario; Kehler, Jan; Bundgaard, Christoffer; Schmitt, Nicole; Jensen, Henrik Sindal

    2014-01-01

    The voltage-gated potassium channels of the KV7 family (KV7.1-5) play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2-5), aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2-5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.

  7. Lighting Study Security System Modifications

    DTIC Science & Technology

    1978-05-01

    I7, 7 ,177 uo~ 6w4, 7~% 4 1 :, 0 b17 1 7AS, ti19 1537 " 1 7Ž7 1 4bd 7c6 sP113 -oC-b 4I4 14, ൙ j 0 I ? I I I 󈧏 1 ,io i .Ž - 3?b A 1 . 󈧕 1 I t...113 j7 171k ~ 1 e~ 3 1 171~ tD 40 4’j 1 1 -0’ r17 171t d~7 In. -’Ao ?I M .4 P1 ro 4 3e" 34*v t 1~ -1 73- 1 - Itfi 3CI7 4e (.,4~?~~. 3 1i jlý A4 3 e b

  8. Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

    ClinicalTrials.gov

    2018-06-08

    Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7

  9. Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

    ClinicalTrials.gov

    2017-10-16

    Cervical Carcinoma; Esophageal Carcinoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Oral Cavity Mucosal Melanoma; Recurrent Melanoma; Stage II Vulvar Cancer AJCC v7; Stage III Vulvar Cancer AJCC v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IV Oral Cavity Cancer AJCC v6 and v7; Stage IV Vulvar Cancer AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Vaginal Carcinoma

  10. Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

    ClinicalTrials.gov

    2018-06-29

    Large Cell Lung Carcinoma; Lung Adenocarcinoma; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Squamous Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage II Squamous Cell Lung Carcinoma AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIA Squamous Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Squamous Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Squamous Cell Lung Carcinoma AJCC v7

  11. The electronic structure and optical properties of ABP 2O 7 ( A = Na, Li) double phosphates

    NASA Astrophysics Data System (ADS)

    Hizhnyi, Yu. A.; Oliynyk, A.; Gomenyuk, O.; Nedilko, S. G.; Nagornyi, P.; Bojko, R.; Bojko, V.

    2008-01-01

    Partial densities of states and reflection spectra of NaAlP 2O 7, KAlP 2O 7 and LiInP 2O 7 double phosphate crystals are calculated by the full-potential linear-augmented-plane-wave (FLAPW) method. Experimental reflection spectra of KAlP 2O 7, CsAlP 2O 7 and NaInP 2O 7 are measured in the 4-20 eV energy range. The values of band gaps, Eg, are found from a comparison of experiment and calculations to be 6.0 eV for NaAlP 2O 7 and KAlP 2O 7, and 4.6 eV for LiInP 2O 7.

  12. Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy

    PubMed Central

    Smith, Jenessa B; Lanitis, Evripidis; Dangaj, Denarda; Buza, Elizabeth; Poussin, Mathilde; Stashwick, Caitlin; Scholler, Nathalie; Powell, Daniel J

    2016-01-01

    B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6–8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo. PMID:27439899

  13. B7-H3 in tumors: friend or foe for tumor immunity?

    PubMed

    Li, Gen; Quan, Yanchun; Che, Fengyuan; Wang, Lijuan

    2018-02-01

    B7-H3 is a type I transmembrane co-stimulatory molecule of the B7 family. B7-H3 mRNA is widely distributed in most tissues; however, B7-H3 protein is not constitutively expressed. Few molecules have been shown to mediate the regulation of B7-H3 expression, and their regulatory mechanisms remain unexplored. Recently, TREM-like transcript 2 (TLT-2) has been identified as a potential receptor of B7-H3. However, TLT-2 may not be the only receptor of B7-H3, as B7-H3 has many contradictory roles. As a co-stimulatory molecule, B7-H3 increases the proliferation of both CD4+ and CD8+ T-cells and enhances cytotoxic T-cell activity. However, greatly increased T-cell proliferation and IL-2 levels have been observed in the absence of B7-H3. Thus far, it has been shown that various tumors test positive for B7-H3 expression and that B7-H3 levels correlate with tumor growth, invasion, metastasis, malignant stage, and recurrence rate. Furthermore, transfection of cells with a B7-H3 plasmid and treatment with monoclonal antibodies to block B7-H3 are the main immunotherapeutic strategies for cancer treatment. Several groups have generated anti-B7-H3 antibodies and observed tumor growth suppression in vitro and in vivo. Therefore, it is likely that B7-H3 plays an important role in cancer diagnosis and treatment, aside from its role as a co-stimulatory molecule.

  14. Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7).

    PubMed

    Valinsky, William C; Jolly, Anna; Miquel, Perrine; Touyz, Rhian M; Shrier, Alvin

    2016-09-16

    Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg(2+)-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg(2+) levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance* #

    PubMed Central

    Xu, Jian-zhong; Zhang, Wei-guo

    2017-01-01

    A menaquinone-7 (MK-7) high-producing strain needs to be isolated to increase MK-7 production, in order to meet a requirement of MK-7 given the low MK-7 content in food products. This article focuses on developing MK-7 high-producing strains via screening and mutagenesis by an atmospheric and room temperature plasma (ARTP) mutation breeding system. We isolated an MK-7-producing strain Y-2 and identified it as Bacillus amyloliquefaciens, which produced (7.1±0.5) mg/L of MK-7 with maize meal hydrolysate as carbon source. Then, an MK-7 high-producing strain B. amyloliquefaciens H.β.D.R.-5 with resistance to 1-hydroxy-2-naphthoic acid, β-2-thienylalanine, and diphenylamine was obtained from the mutation of the strain Y-2 using an ARTP mutation breeding system. Using strain H.β.D.R.-5, efficient production of MK-7 was achieved ((30.2±2.7) mg/L). In addition, the effects of nitrogen sources, prenyl alcohols, and MgSO4 on MK-7 production were investigated, suggesting that soymeal extract combined with yeast extract, isopentenol, and MgSO4 was beneficial. Under the optimized condition, the MK-7 production and biomass-specific yield reached (61.3±5.2) mg/L and 2.59 mg/L per OD600 unit respectively in a 7-L fermenter. These results demonstrated that strain H.β.D.R.-5 has the capacity to produce MK-7 from maize meal hydrolysate, which could reduce the substrate cost. PMID:28585422

  16. 7 CFR 1724.7 - Debarment and suspension.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Debarment and suspension. 1724.7 Section 1724.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC ENGINEERING, ARCHITECTURAL SERVICES AND DESIGN POLICIES AND PROCEDURES General § 1724.7...

  17. 7 CFR 503.7 - Gambling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other...

  18. 7 CFR 503.7 - Gambling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other...

  19. 7 CFR 503.7 - Gambling.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other...

  20. 7 CFR 503.7 - Gambling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other...

  1. 7 CFR 503.7 - Gambling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Gambling. 503.7 Section 503.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.7 Gambling. Participating in games for money or other...

  2. 7 CFR 624.7 - Cost-sharing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Cost-sharing. 624.7 Section 624.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WATERSHED PROTECTION § 624.7 Cost-sharing. (a) Except as provided in...

  3. 7 CFR 622.7 - Notification under Executive Order 12372.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Notification under Executive Order 12372. 622.7 Section 622.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS General § 622.7 Notification...

  4. 7 CFR 624.7 - Cost-sharing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Cost-sharing. 624.7 Section 624.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WATERSHED PROTECTION § 624.7 Cost-sharing. (a) Except as provided in...

  5. 7 CFR 622.7 - Notification under Executive Order 12372.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Notification under Executive Order 12372. 622.7 Section 622.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS General § 622.7 Notification...

  6. 7 CFR 622.7 - Notification under Executive Order 12372.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Notification under Executive Order 12372. 622.7 Section 622.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS General § 622.7 Notification...

  7. 7 CFR 622.7 - Notification under Executive Order 12372.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Notification under Executive Order 12372. 622.7 Section 622.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS General § 622.7 Notification...

  8. 7 CFR 624.7 - Cost-sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Cost-sharing. 624.7 Section 624.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WATERSHED PROTECTION § 624.7 Cost-sharing. (a) Except as provided in...

  9. 7 CFR 622.7 - Notification under Executive Order 12372.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Notification under Executive Order 12372. 622.7 Section 622.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS General § 622.7 Notification...

  10. 7 CFR 624.7 - Cost-sharing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Cost-sharing. 624.7 Section 624.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES EMERGENCY WATERSHED PROTECTION § 624.7 Cost-sharing. (a) Except as provided in...

  11. 7 CFR 305.7 - Quick freeze treatment requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Quick freeze treatment requirements. 305.7 Section 305.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE PHYTOSANITARY TREATMENTS § 305.7 Quick freeze treatment...

  12. 7 CFR 502.7 - Gambling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct...

  13. 7 CFR 502.7 - Gambling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct... 7 Agriculture 6 2010-01-01 2010-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations...

  14. 7 CFR 502.7 - Gambling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct...

  15. 7 CFR 502.7 - Gambling.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct...

  16. 7 CFR 502.7 - Gambling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Gambling. 502.7 Section 502.7 Agriculture Regulations... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.7 Gambling. Participating in games for money or other personal property, or the operation of gambling devices, the conduct...

  17. 7 CFR 281.7 - Indian tribal organization failure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Indian tribal organization failure. 281.7 Section 281.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... ON INDIAN RESERVATIONS § 281.7 Indian tribal organization failure. When Performance Reporting System...

  18. 7 CFR 281.7 - Indian tribal organization failure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Indian tribal organization failure. 281.7 Section 281.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... ON INDIAN RESERVATIONS § 281.7 Indian tribal organization failure. When Performance Reporting System...

  19. 7 CFR 281.7 - Indian tribal organization failure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Indian tribal organization failure. 281.7 Section 281.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... ON INDIAN RESERVATIONS § 281.7 Indian tribal organization failure. When Performance Reporting System...

  20. 7 CFR 612.7 - Forecast user responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Forecast user responsibility. 612.7 Section 612.7 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS SNOW SURVEYS AND WATER SUPPLY FORECASTS § 612.7 Forecast...

  1. 7 CFR 7.1 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Administration. 7.1 Section 7.1 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.1 Administration. (a) The regulations of this part are...

  2. 7 CFR 983.7 - Certified pistachios.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Certified pistachios. 983.7 Section 983.7 Agriculture... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE PISTACHIOS GROWN IN CALIFORNIA, ARIZONA, AND NEW MEXICO Definitions § 983.7 Certified pistachios. Certified pistachios are those that meet...

  3. 7 CFR 652.7 - Quality assurance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Quality assurance. 652.7 Section 652.7 Agriculture... AGRICULTURE SUPPORT ACTIVITIES TECHNICAL SERVICE PROVIDER ASSISTANCE General Provisions § 652.7 Quality assurance. (a) NRCS will review, in consultation with the Farm Service Agency, as appropriate, the quality...

  4. 7 CFR 371.7 - Animal Care.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

  5. 7 CFR 371.7 - Animal Care.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

  6. 7 CFR 371.7 - Animal Care.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

  7. 7 CFR 371.7 - Animal Care.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

  8. 7 CFR 371.7 - Animal Care.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Animal Care. 371.7 Section 371.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ORGANIZATION, FUNCTIONS, AND DELEGATIONS OF AUTHORITY § 371.7 Animal Care. (a...

  9. 7 CFR 4284.7 - Electronic submission.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Electronic submission. 4284.7 Section 4284.7... Grant Programs § 4284.7 Electronic submission. Applicants and grant awardees are encouraged, but not required, to submit applications and reports in electronic form as prescribed in requests for proposals...

  10. 7 CFR 4284.7 - Electronic submission.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Electronic submission. 4284.7 Section 4284.7... Grant Programs § 4284.7 Electronic submission. Applicants and grant awardees are encouraged, but not required, to submit applications and reports in electronic form as prescribed in requests for proposals...

  11. 7 CFR 4284.7 - Electronic submission.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Electronic submission. 4284.7 Section 4284.7... Grant Programs § 4284.7 Electronic submission. Applicants and grant awardees are encouraged, but not required, to submit applications and reports in electronic form as prescribed in requests for proposals...

  12. 7 CFR 4284.7 - Electronic submission.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Electronic submission. 4284.7 Section 4284.7... Grant Programs § 4284.7 Electronic submission. Applicants and grant awardees are encouraged, but not required, to submit applications and reports in electronic form as prescribed in requests for proposals...

  13. 7 CFR 4284.7 - Electronic submission.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Electronic submission. 4284.7 Section 4284.7... Grant Programs § 4284.7 Electronic submission. Applicants and grant awardees are encouraged, but not required, to submit applications and reports in electronic form as prescribed in requests for proposals...

  14. 7 CFR 7.1 - Administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Administration. 7.1 Section 7.1 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.1 Administration. (a) The regulations of this part are...

  15. 7 CFR 274.7 - Coupon management.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Coupon management. 274.7 Section 274.7 Agriculture... FOOD STAMP AND FOOD DISTRIBUTION PROGRAM ISSUANCE AND USE OF COUPONS § 274.7 Coupon management. (a) Coupon inventory management. State agencies shall establish coupon inventory management systems which...

  16. 7 CFR 981.7 - Edible kernel.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Edible kernel. 981.7 Section 981.7 Agriculture... Regulating Handling Definitions § 981.7 Edible kernel. Edible kernel means a kernel, piece, or particle of almond kernel that is not inedible. [41 FR 26852, June 30, 1976] ...

  17. 7 CFR 984.7 - Marketing year.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

  18. 7 CFR 984.7 - Marketing year.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

  19. 7 CFR 984.7 - Marketing year.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

  20. 7 CFR 984.7 - Marketing year.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

  1. 7 CFR 984.7 - Marketing year.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Marketing year. 984.7 Section 984.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 984.7 Marketing year. Marketing year means the twelve months from September...

  2. 7 CFR 1778.7 - Project priority.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Project priority. 1778.7 Section 1778.7 Agriculture... (CONTINUED) EMERGENCY AND IMMINENT COMMUNITY WATER ASSISTANCE GRANTS § 1778.7 Project priority. Paragraph (d... to determine the proposed project's priority for available funds. (b) State Office review. All...

  3. 7 CFR 457.7 - The contract.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false The contract. 457.7 Section 457.7 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.7 The contract. The insurance contract shall become...

  4. 7 CFR 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2000-01-01

    ... 7 Agriculture 15 2000-01-01 2000-01-01 false Title. 3200.7 Section 3200.7 Agriculture Regulations... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  5. 7 CFR 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Title. 3200.7 Section 3200.7 Agriculture Regulations... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  6. 7 CFR 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Title. 3200.7 Section 3200.7 Agriculture Regulations... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  7. 7 CFR 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2009-01-01

    ... 7 Agriculture 15 2009-01-01 2009-01-01 false Title. 3200.7 Section 3200.7 Agriculture Regulations... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  8. 7 CFR 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Title. 3200.7 Section 3200.7 Agriculture Regulations... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  9. 7 CFR 7.1 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Administration. 7.1 Section 7.1 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.1 Administration. (a) The regulations of this part are...

  10. 7 CFR 2812.7 - Costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Costs. 2812.7 Section 2812.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF OPERATIONS, DEPARTMENT OF AGRICULTURE...) § 2812.7 Costs. Donated excess personal property/equipment is free of charge. However, the donee must pay...

  11. 7 CFR 63.7 - Fund.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Fund. 63.7 Section 63.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... General Provisions Definitions § 63.7 Fund. Fund means the NSIIC Revolving Fund established in the United...

  12. 7 CFR 3434.7 - Duration of certification.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Duration of certification. 3434.7 Section 3434.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HISPANIC-SERVING AGRICULTURAL COLLEGES AND UNIVERSITIES CERTIFICATION PROCESS § 3434.7 Duration of...

  13. 7 CFR 3434.7 - Duration of certification.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Duration of certification. 3434.7 Section 3434.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE HISPANIC-SERVING AGRICULTURAL COLLEGES AND UNIVERSITIES CERTIFICATION PROCESS § 3434.7 Duration of...

  14. 7 CFR 1778.7 - Project priority.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Project priority. 1778.7 Section 1778.7 Agriculture... (CONTINUED) EMERGENCY AND IMMINENT COMMUNITY WATER ASSISTANCE GRANTS § 1778.7 Project priority. Paragraph (d... to determine the proposed project's priority for available funds. (b) State Office review. All...

  15. 7 CFR 1778.7 - Project priority.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Project priority. 1778.7 Section 1778.7 Agriculture... (CONTINUED) EMERGENCY AND IMMINENT COMMUNITY WATER ASSISTANCE GRANTS § 1778.7 Project priority. Paragraph (d... to determine the proposed project's priority for available funds. (b) State Office review. All...

  16. 47 CFR 7.7 - Product design, development, and evaluation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Product design, development, and evaluation. 7.7 Section 7.7 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do...

  17. 47 CFR 7.7 - Product design, development, and evaluation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Product design, development, and evaluation. 7.7 Section 7.7 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do...

  18. CBX7 gene expression plays a negative role in adipocyte cell growth and differentiation

    PubMed Central

    Forzati, Floriana; Federico, Antonella; Pallante, Pierlorenzo; Colamaio, Marianna; Esposito, Francesco; Sepe, Romina; Gargiulo, Sara; Luciano, Antonio; Arra, Claudio; Palma, Giuseppe; Bon, Giulia; Bucher, Stefania; Falcioni, Rita; Brunetti, Arturo; Battista, Sabrina; Fedele, Monica; Fusco, Alfredo

    2014-01-01

    ABSTRACT We have recently generated knockout mice for the Cbx7 gene, coding for a polycomb group protein that is downregulated in human malignant neoplasias. These mice develop liver and lung adenomas and carcinomas, which confirms a tumour suppressor role for CBX7. The CBX7 ability to downregulate CCNE1 expression likely accounts for the phenotype of the Cbx7-null mice. Unexpectedly, Cbx7-knockout mice had a higher fat tissue mass than wild-type, suggesting a role of CBX7 in adipogenesis. Consistently, we demonstrate that Cbx7-null mouse embryonic fibroblasts go towards adipocyte differentiation more efficiently than their wild-type counterparts, and this effect is Cbx7 dose-dependent. Similar results were obtained when Cbx7-null embryonic stem cells were induced to differentiate into adipocytes. Conversely, mouse embryonic fibroblasts and human adipose-derived stem cells overexpressing CBX7 show an opposite behaviour. These findings support a negative role of CBX7 in the control of adipocyte cell growth and differentiation. PMID:25190058

  19. The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.

    PubMed

    Wu, Xiao-Xin; Deng, Xi-Long; Yu, Dong-Shan; Yao, Wei; Ou, Hui-Lin; Weng, Tian-Hao; Hu, Chen-Yu; Hu, Feng-Yu; Wu, Nan-Ping; Yao, Hangping; Zhang, Fu-Chun; Li, Lan-Juan

    2018-01-01

    Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence. © 2018 The Author(s). Published by S. Karger AG, Basel.

  20. 40 CFR 180.422 - Tralomethrin; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .../revocation date Broccoli 0.5 7/9/13 Cotton, undelinted seed 0.02 7/9/13 Cotton, oil 0.20 7/9/13 Lettuce, head 1.00 7/9/13 Lettuce, leaf 3.00 7/9/13 Soybean, seed 0.05 7/9/13 Sunflower, seed 0.05 7/9/13 (2) A..., manufacturing, and processing establishments, such as restaurants, cafeterias, supermarkets, bakeries, breweries...

  1. 40 CFR 180.422 - Tralomethrin; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .../revocation date Broccoli 0.5 7/9/13 Cotton, undelinted seed 0.02 7/9/13 Cotton, oil 0.20 7/9/13 Lettuce, head 1.00 7/9/13 Lettuce, leaf 3.00 7/9/13 Soybean, seed 0.05 7/9/13 Sunflower, seed 0.05 7/9/13 (2) A..., manufacturing, and processing establishments, such as restaurants, cafeterias, supermarkets, bakeries, breweries...

  2. 30 CFR 15.30 - Technical requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air temperature is... natural gas, or 4.3 to 4.7 percent methane, mixed with 0.2 ounces per cubic foot of predispersed... detonators and fired in air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air...

  3. 30 CFR 15.30 - Technical requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air temperature is... natural gas, or 4.3 to 4.7 percent methane, mixed with 0.2 ounces per cubic foot of predispersed... detonators and fired in air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air...

  4. 30 CFR 15.30 - Technical requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air temperature is... natural gas, or 4.3 to 4.7 percent methane, mixed with 0.2 ounces per cubic foot of predispersed... detonators and fired in air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air...

  5. 30 CFR 15.30 - Technical requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air temperature is... natural gas, or 4.3 to 4.7 percent methane, mixed with 0.2 ounces per cubic foot of predispersed... detonators and fired in air containing 7.7 to 8.3 percent natural gas or 8.7 to 9.3 percent methane. The air...

  6. 5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

    ClinicalTrials.gov

    2018-03-28

    Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  7. 7 CFR 1.183 - Proceedings covered.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Act of 1937 (7 U.S.C. 608c(15)(A)) Animal Health Protection Act, sections 10414 and 10415 (7 U.S.C... Information Act (7 U.S.C. 2912) Capper-Volstead Act (7 U.S.C. 292) Cotton Research and Promotion Act (7 U.S.C... Research and Promotion Act (7 U.S.C. 2620) Poultry Products Inspection Act (21 U.S.C. 455, 456, 457(d), 467...

  8. Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.

    PubMed

    Zamora-Contreras, Aida Margarita; Alvarez-Salas, Luis Marat

    2018-01-01

    The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. Pre-let-7 levels were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by immunoblot. In silico tools were used to correlate let-7 and LIN28B expression and to analyze prelet- 7 sequences and structures. Lin28B protein was detected in all tested cell lines although it was more expressed in tumor cell lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs showed distinctive structural features within the preE region that may influence the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were present in pre-let-7 that may escape LIN28B regulation, but long preEstems were mostly associated with high-level pre-let-7 miRNAs. The observed differences of pre-let-7 levels in cervical cell lines may be the result of alternative preE structuring affecting interaction with LIN28B thus resulting in differential let-7 regulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Synthesis of novel quinazolin-4(3H)-one derivatives containing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety as effective agricultural bactericides against the pathogen Xanthomonas oryzae pv. oryzae.

    PubMed

    Du, Huan; Fan, Zhijiang; Yang, Lan; Bao, Xiaoping

    2018-02-01

    A series of novel quinazolin-4-one derivatives (7a-7n) bearing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety were designed, synthesized and evaluated for their inhibition activities against phytopathogenic bacteria and fungi in vitro. All of the target compounds were fully characterized through [Formula: see text] NMR, [Formula: see text] NMR, HRMS and IR spectra. Among these compounds, the structure of compound 7e was unambiguously confirmed via single-crystal X-ray diffraction analysis. The turbidimetric assays indicated that compounds 7b, 7d, 7g, 7k and 7n exhibited much more potent inhibition activities against the pathogen Xanthomonas oryzae pv. oryzae (Xoo), relative to control Bismerthiazol. Moreover, antibacterial activities of compounds 7j, 7k and 7n against the pathogen Xanthomonas axonopodis pv. citri (Xac) were comparable to that of control Bismerthiazol. As for the pathogen Ralstonia solanacearum (Rs), only compounds 7g and 7i demonstrated inhibition activities similar to control Thiadiazole-copper. Moreover, this class of compounds did not display inhibition activity against three fungi tested. The above findings indicated that quinazolin-4-one derivatives containing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety have a potential as promising candidates for the development of new and more efficient agricultural bactericides.

  10. Technical Evaluation Motor No. 7 (TEM-7)

    NASA Technical Reports Server (NTRS)

    Hughes, Phil

    1991-01-01

    The Technical Evaluation Motor No. 7 (TEM-7) test was a full-scale, full duration static test firing of a high performance motor-configuration solid rocket motor with nozzle vectoring. The final test report documents the procedures, performance, and results of the static test firing of TEM-7. All observations, discussions, conclusions, and recommendations included in the report are complete and final except for the TEM-7 fixed housing unbond investigation. A presentation and discussion of TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107, Rev A, Space Shuttle Technical Evaluation Motor No. 7 (TEM-7) Static Fire Test Plan are included.

  11. Comparing Three Approaches to Transformational Programming

    DTIC Science & Technology

    1991-04-22

    FE 3...a0+.-/%k’)-k$D:?O/7Q# U/# ’)-J3O�’):’°4J$)+.-6:abO/7Q#7’TB67N3+21 +.$&-la_’D1H([’&B67&\\ ]_O/7T:?# ’)-J1R$&#(A’):+.$&-J’>54J’)# ’ DBD +8%D...d$&:?7Y:OJ’):b:?O6+21d%)+.X&7N1b’)-l’>5.%&7QU/# ’>+23IRS$&#?(,G652’):+.$&-�$)R:?O/7A`QÚd+.X&+2B67T’)-JB¿¹H$&-J«DG/7Q# c,4J’)# ’ DBD

  12. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    ClinicalTrials.gov

    2018-06-18

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  13. A malformed child with a recombinant chromosome 7, rec(7) dup p, derived from a maternal pericentric inversion inv(7)(p15q36).

    PubMed Central

    Delicado, A; Escribano, E; Lopez Pajares, I; Diaz de Bustamante, A; Carrasco, S

    1991-01-01

    We report a child with facial dysmorphic features, hypoplasia of the external genitalia, intestinal malrotation, congenital cardiac defect, and minor limb anomalies. Chromosome studies showed a recombinant chromosome 7, rec(7) dup p, resulting from a maternal pericentric inversion inv(7)(p15 q36). Thus, this child had partial trisomy 7p in addition to a small distal monosomy 7. The clinical findings are compared with those found in previous reports of trisomy 7p. Finally, some general principles for genetic counselling are discussed. Images PMID:2002483

  14. Glembatumumab Vedotin, Nivolumab, and Ipilimumab in Treating Patients With Advanced Metastatic Solid Tumors That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2018-06-11

    Advanced Malignant Solid Neoplasm; Estrogen Receptor Negative; GPNMB Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Uveal Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

  15. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

    ClinicalTrials.gov

    2018-04-23

    Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

  16. A Study of the Cost Savings Potential of the Military - Civilian Health Services Partnership Program in the Nuclear Medicine and Radioimmunoassay Services at Ireland Army Community Hospital, Fort Knox, Kentucky

    DTIC Science & Technology

    1989-01-01

    Esophageal Studies Patient 1 Sequential Images for Transit and or Reflux 30 Computer Acq/Process 20 (b) Stomach Patient 1 Sequential Images Transit...132 141 119 113 150 159 152 124 1715 Liver-Spleen 8 12 7 9 7 5 6 14 5 13 12 12 110 Renal 10 9 19 8 7 8 15 8 7 9 7 7 114 Renal Reflux 4 2 1 0 0 0 0 2 0 0...Scan 0 0 0 0 0 0 0 0 0 1 0 0 Gastric Reflux 0 0 0 0 0 0 0 1 0 1 0 0 2 1-123 Thyroid 11 3 5 9 9 7 10 7 9 11 7 14 102 Thyroid Uptake 11 S 5 9 9 7 10 7 9

  17. 17 CFR 210.7-01 - Application of §§ 210.7-01 to 210.7-05.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., INVESTMENT ADVISERS ACT OF 1940, AND ENERGY POLICY AND CONSERVATION ACT OF 1975 Insurance Companies § 210.7-01 Application of §§ 210.7-01 to 210.7-05. This article shall be applicable to financial statements...

  18. 17 CFR 210.7-01 - Application of §§ 210.7-01 to 210.7-05.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., INVESTMENT ADVISERS ACT OF 1940, AND ENERGY POLICY AND CONSERVATION ACT OF 1975 Insurance Companies § 210.7-01 Application of §§ 210.7-01 to 210.7-05. This article shall be applicable to financial statements...

  19. 7 CFR 932.7 - Variety group 2.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Variety group 2. 932.7 Section 932.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 932.7 Variety group 2. Variety group 2 means the following varieties and...

  20. 7 CFR 932.7 - Variety group 2.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Variety group 2. 932.7 Section 932.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Regulating Handling Definitions § 932.7 Variety group 2. Variety group 2 means the following varieties and...

  1. 7 CFR 932.7 - Variety group 2.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Variety group 2. 932.7 Section 932.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Regulating Handling Definitions § 932.7 Variety group 2. Variety group 2 means the following varieties and...

  2. 7 CFR 3407.7 - Actions normally requiring an environmental assessment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Actions normally requiring an environmental assessment. 3407.7 Section 3407.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE IMPLEMENTATION OF NATIONAL ENVIRONMENTAL POLICY ACT § 3407.7...

  3. 7 CFR 3407.7 - Actions normally requiring an environmental assessment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Actions normally requiring an environmental assessment. 3407.7 Section 3407.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE IMPLEMENTATION OF NATIONAL ENVIRONMENTAL POLICY ACT § 3407.7...

  4. 7 CFR 3407.7 - Actions normally requiring an environmental assessment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Actions normally requiring an environmental assessment. 3407.7 Section 3407.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE IMPLEMENTATION OF NATIONAL ENVIRONMENTAL POLICY ACT § 3407.7...

  5. 7 CFR 3407.7 - Actions normally requiring an environmental assessment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Actions normally requiring an environmental assessment. 3407.7 Section 3407.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE IMPLEMENTATION OF NATIONAL ENVIRONMENTAL POLICY ACT § 3407.7...

  6. 7 CFR 932.7 - Variety group 2.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Variety group 2. 932.7 Section 932.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 932.7 Variety group 2. Variety group 2 means the following varieties and...

  7. 7 CFR 3203.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Title. 3203.7 Section 3203.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF PROCUREMENT AND PROPERTY MANAGEMENT... PURSUANT TO SECTION 14220 OF THE 2008 FARM BILL § 3203.7 Title. Title of ownership to excess computers or...

  8. 7 CFR 1217.7 - Department or USDA.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Department or USDA. 1217.7 Section 1217.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., and Industry Information Order Definitions § 1217.7 Department or USDA. Department or USDA means the U...

  9. 7 CFR 1217.7 - Department or USDA.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Department or USDA. 1217.7 Section 1217.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., and Industry Information Order Definitions § 1217.7 Department or USDA. Department or USDA means the U...

  10. 7 CFR 1217.7 - Department or USDA.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Department or USDA. 1217.7 Section 1217.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., and Industry Information Order Definitions § 1217.7 Department or USDA. Department or USDA means the U...

  11. 7 CFR 624.7 - Cost-sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Cost-sharing. 624.7 Section 624.7 Agriculture... AGRICULTURE WATER RESOURCES EMERGENCY WATERSHED PROTECTION § 624.7 Cost-sharing. (a) Except as provided in paragraph (b) of this section, the Federal contribution toward the implementation of emergency measures may...

  12. Bacteriophage T7 RNA polymerase-based expression in Pichia pastoris.

    PubMed

    Hobl, Birgit; Hock, Björn; Schneck, Sandra; Fischer, Reinhard; Mack, Matthias

    2013-11-01

    A novel Pichia pastoris expression vector (pEZT7) for the production of recombinant proteins employing prokaryotic bacteriophage T7 RNA polymerase (T7 RNAP) (EC 2.7.7.6) and the corresponding promoter pT7 was constructed. The gene for T7 RNAP was stably introduced into the P. pastoris chromosome 2 under control of the (endogenous) constitutive P. pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter (pGAP). The gene product T7 RNAP was engineered to contain a nuclear localization signal, which directed recombinant T7 RNAP to the P. pastoris nucleus. To promote translation of uncapped T7 RNAP derived transcripts, the internal ribosomal entry site from hepatitis C virus (HCV-IRES) was inserted directly upstream of the multiple cloning site of pEZT7. A P. pastoris autonomous replicating sequence (PARS1) was integrated into pEZT7 enabling propagation and recovery of plasmids from P. pastoris. Rapid amplification of 5' complementary DNA ends (5' RACE) experiments employing the test plasmid pEZT7-EGFP revealed that transcripts indeed initiated at pT7. HCV-IRES mediated translation of the latter mRNAs, however, was not observed. Surprisingly, HCV-IRES and the reverse complement of PARS1 (PARS1rc) were both found to display significant promoter activity as shown by 5' RACE. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.

    PubMed

    Matschke, Veronika; Piccini, Ilaria; Schubert, Janina; Wrobel, Eva; Lang, Florian; Matschke, Johann; Amedonu, Elsie; Meuth, Sven G; Strünker, Timo; Strutz-Seebohm, Nathalie; Greber, Boris; Scherkenbeck, Jürgen; Seebohm, Guiscard

    2016-01-01

    Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. We show that currents carried by Kv7.1 (EC50 = 1.48 μM), Kv7.1/KCNE1 (EC50 = 4.9 μM), and Kv7.4 (EC50 = 0.148 μM) are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1. Rottlerin or an optimized derivative holds a potential as QT interval correcting drug. © 2016 The Author(s) Published by S. Karger AG, Basel.

  14. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

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

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{supmore » +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.« less

  15. DEEP LBT/LUCI SPECTROSCOPY OF AN Ly{alpha} EMITTER CANDIDATE AT z {approx_equal} 7.7

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

    Jiang Linhua; Bian Fuyan; Fan Xiaohui

    2013-07-01

    We present deep spectroscopic observations of an Ly{alpha} emitter (LAE) candidate at z {approx_equal} 7.7 using the infrared spectrograph LUCI on the 2 Multiplication-Sign 8.4 m Large Binocular Telescope (LBT). The candidate is the brightest among the four z {approx_equal} 7.7 LAE candidates found in a narrowband imaging survey by Krug et al. Our spectroscopic data include a total of 7.5 hr of integration with LBT/LUCI and are deep enough to significantly (3.2{sigma}-4.9{sigma}) detect the Ly{alpha} emission line of this candidate based on its Ly{alpha} flux 1.2 Multiplication-Sign 10{sup -17} erg s{sup -1} cm{sup -2} estimated from the narrowband photometry.more » However, we do not find any convincing signal at the expected position of its Ly{alpha} emission line, suggesting that this source is not an LAE at z {approx_equal} 7.7. The non-detection in this work, together with the previous studies of z {approx_equal} 7.7 LAEs, puts a strong constraint on the bright-end Ly{alpha} luminosity function (LF) at z {approx_equal} 7.7. We find a rapid evolution of the Ly{alpha} LF from z {approx_equal} 6.5 to 7.7: the upper limit of the z {approx_equal} 7.7 LF is more than five times lower than the z {approx_equal} 6.5 LF at the bright end (f{>=} 1.0 Multiplication-Sign 10{sup -17} erg s{sup -1} cm{sup -2} or L{>=} 6.9 Multiplication-Sign 10{sup 42} erg s{sup -1}). This is likely caused by an increasing neutral fraction in the intergalactic medium that substantially attenuates Ly{alpha} emission at z {approx_equal} 7.7.« less

  16. Low-field spin dynamics of Cr7Ni and Cr7Ni-Cu -Cr 7Ni molecular rings as detected by μ SR

    NASA Astrophysics Data System (ADS)

    Sanna, S.; Arosio, P.; Bordonali, L.; Adelnia, F.; Mariani, M.; Garlatti, E.; Baines, C.; Amato, A.; Sabareesh, K. P. V.; Timco, G.; Winpenny, R. E. P.; Blundell, S. J.; Lascialfari, A.

    2017-11-01

    Muon spin rotation measurements were used to investigate the spin dynamics of heterometallic Cr7Ni and Cr7Ni -Cu-Cr7Ni molecular clusters. In Cr7Ni the magnetic ions are arranged in a quasiplanar ring and interact via an antiferromagnetic exchange coupling constant J , while Cr7Ni -Cu-Cr7Ni is composed of two Cr7Ni linked by a bridging moiety containing one Cu ion, that induces an inter-ring ferromagnetic interaction J'≪J . The longitudinal muon relaxation rate λ collected at low magnetic fields μ0H <0.15 Tesla, shows that the two systems present differences in spin dynamics vs temperature. While both samples exhibit a main peak in the muon relaxation rate vs temperature, at T ˜10 K for Cr7Ni and T ˜8 K for Cr7Ni -Cu-Cr7Ni , the two compounds have distinct additional features: Cr7Ni shows a shoulder in λ (T ) for T <8 K, while Cr7Ni -Cu-Cr7Ni shows a flattening of λ (T ) for T <2 K down to temperatures as low as T =20 mK. The main peak of both systems is explained by a Bloembergen-Purcell-Pound (BPP)-like heuristic fitting model that takes into account of a distribution of electronic spin characteristic times for T >5 K, while the shoulder presented by Cr7Ni can be reproduced by a BPP function that incorporates a single electronic characteristic time theoretically predicted to dominate for T <5 K. The flattening of λ (T ) in Cr7Ni -Cu-Cr7Ni occurring at very low temperature can be tentatively attributed to field-dependent quantum effects and/or to an inelastic term in the spectral density of the electronic spin fluctuations.

  17. Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels.

    PubMed

    Qin, Xin; Yue, Zhichao; Sun, Baonan; Yang, Wenzhong; Xie, Jia; Ni, Eric; Feng, Yi; Mahmood, Rafat; Zhang, Yanhui; Yue, Lixia

    2013-03-01

    Transient receptor potential melastatin 7 (TRPM7) is a unique channel kinase which is crucial for various physiological functions. However, the mechanism by which TRPM7 is gated and modulated is not fully understood. To better understand how modulation of TRPM7 may impact biological processes, we investigated if TRPM7 can be regulated by the phospholipids sphingosine (SPH) and sphingosine-1-phosphate (S1P), two potent bioactive sphingolipids that mediate a variety of physiological functions. Moreover, we also tested the effects of the structural analogues of SPH, N,N-dimethyl-D-erythro-sphingosine (DMS), ceramides and FTY720 on TRPM7. HEK293 cells stably expressing TRPM7 were used for whole-cell, single-channel and macropatch current recordings. Cardiac fibroblasts were used for native TRPM7 current recording. SPH potently inhibited TRPM7 in a concentration-dependent manner, whereas S1P and other ceramides did not produce noticeable effects. DMS also markedly inhibited TRPM7. Moreover, FTY720, an immunosuppressant and the first oral drug for treatment of multiple sclerosis, inhibited TRPM7 with a similar potency to that of SPH. In contrast, FTY720-P has no effect on TRPM7. It appears that SPH and FTY720 inhibit TRPM7 by reducing channel open probability. Furthermore, endogenous TRPM7 in cardiac fibroblasts was markedly inhibited by SPH, DMS and FTY720. This is the first study demonstrating that SPH and FTY720 are potent inhibitors of TRPM7. Our results not only provide a new modulation mechanism of TRPM7, but also suggest that TRPM7 may serve as a direct target of SPH and FTY720, thereby mediating S1P-independent physiological/pathological functions of SPH and FTY720. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  18. Bladder contractility is modulated by Kv7 channels in pig detrusor.

    PubMed

    Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja; Sheykhzade, Majid; Nordling, Jørgen; Bouchelouche, Pierre

    2013-09-05

    Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view to determining the effects of the following potassium channel activators: ML213 (Kv7.2/Kv7.4 channels) and retigabine (Kv7.2-7.5 channels). Retigabine produced a concentration-dependent relaxation of carbachol- and electric field-induced contractions. The potency was similar in magnitude to that of ML213-induced relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P<0.05), which in turn confirmed Kv7 channel selectivity. Subtype-selective effects were further investigated by incubating the detrusor with 10µM chromanol 293B (Kv7.1 channel blocker). Regardless of the experimental protocol, this did not cause a further increase in the evoked contraction. In contrast, the addition of XE991 potentiated the KCl-induced contractions, but not those induced by carbachol or electric field, indicating the presence of a phosphatidyl-inositol-4,5-biphosphate-dependent mechanism amongst the Kv7 channels in detrusor. qRT-PCR studies of the mRNA transcript level of Kv7.3-7.5 channels displayed a higher level of Kv7.4 transcript in detrusor compared to that present in brain cortex and heart tissues. Thus, we have shown that Kv7.4 channels are expressed and functionally active in pig detrusor, and that the use of selective Kv7.4 channel modulators in the treatment of detrusor overactivity seems promising. © 2013 Elsevier B.V. All rights reserved.

  19. Basic metabolic panel

    MedlinePlus

    SMAC7; Sequential multi-channel analysis with computer-7; SMA7; Metabolic panel 7; CHEM-7 ... breathing problems, diabetes or diabetes-related complications, and medicine side effects. Talk to your provider about the ...

  20. 7 CFR 30.7 - Group.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

  1. 7 CFR 30.7 - Group.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

  2. 7 CFR 30.7 - Group.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

  3. 7 CFR 30.7 - Group.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

  4. 47 CFR 7.15 - Generally.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Generally. 7.15 Section 7.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.15 Generally. (a) For purposes of §§ 7.15-7.23 of this...

  5. 7 CFR 3560.7 - Delegation of responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Delegation of responsibility. 3560.7 Section 3560.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS General Provisions and Definitions § 3560.7 Delegation of responsibility. The RHS...

  6. 7 CFR 1610.7 - Acquisition of certain exchange facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 11 2011-01-01 2011-01-01 false Acquisition of certain exchange facilities. 1610.7 Section 1610.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL TELEPHONE BANK, DEPARTMENT OF AGRICULTURE LOAN POLICIES § 1610.7 Acquisition of certain exchange facilities. In the interest...

  7. 7 CFR 356.7 - Petition for remission or mitigation of forfeiture.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Petition for remission or mitigation of forfeiture. 356.7 Section 356.7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FORFEITURE PROCEDURES § 356.7 Petition for...

  8. 7 CFR 210.7 - Reimbursement for school food authorities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Reimbursement for school food authorities. 210.7 Section 210.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION... Process for States and School Food Authorities § 210.7 Reimbursement for school food authorities. (a...

  9. 7 CFR 1779.5-1779.7 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] 1779.5-1779.7 Section 1779.5-1779.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS §§ 1779.5-1779.7 [Reserved] ...

  10. 7 CFR 2901.7 - Review of denials.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Review of denials. 2901.7 Section 2901.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE ADMINISTRATIVE PROCEDURES FOR ADJUSTMENTS OF NATURAL GAS CURTAILMENT PRIORITY § 2901.7 Review of...

  11. 7 CFR 2901.7 - Review of denials.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Review of denials. 2901.7 Section 2901.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE ADMINISTRATIVE PROCEDURES FOR ADJUSTMENTS OF NATURAL GAS CURTAILMENT PRIORITY § 2901.7 Review of...

  12. 7 CFR 2901.7 - Review of denials.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Review of denials. 2901.7 Section 2901.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE ADMINISTRATIVE PROCEDURES FOR ADJUSTMENTS OF NATURAL GAS CURTAILMENT PRIORITY § 2901.7 Review of...

  13. 7 CFR 2901.7 - Review of denials.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Review of denials. 2901.7 Section 2901.7 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ENERGY POLICY AND NEW USES, DEPARTMENT OF AGRICULTURE ADMINISTRATIVE PROCEDURES FOR ADJUSTMENTS OF NATURAL GAS CURTAILMENT PRIORITY § 2901.7 Review of...

  14. 7 CFR 30.7 - Group.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Group. 30.7 Section 30.7 Agriculture Regulations of... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.7 Group. A group of grades, or a division of a type covering several closely related grades, based on the...

  15. 7 CFR 3411.7 - Use of funds; changes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Use of funds; changes. 3411.7 Section 3411.7 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL INSTITUTE OF FOOD AND AGRICULTURE NATIONAL RESEARCH INITIATIVE COMPETITIVE GRANTS PROGRAM General § 3411.7 Use of funds; changes. (a...

  16. 7 CFR 1900.7 - Effect on other regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Effect on other regulations. 1900.7 Section 1900.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Delegations of Authority § 1900.7 Effect on other regulations. This subpart does not...

  17. 7 CFR 319.75-7 - Costs and charges.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Costs and charges. 319.75-7 Section 319.75-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Khapra Beetle § 319.75-7 Costs and charges...

  18. 7 CFR 319.75-7 - Costs and charges.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Costs and charges. 319.75-7 Section 319.75-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Khapra Beetle § 319.75-7 Costs and charges...

  19. 7 CFR 319.75-7 - Costs and charges.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Costs and charges. 319.75-7 Section 319.75-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Khapra Beetle § 319.75-7 Costs and charges...

  20. 7 CFR 319.75-7 - Costs and charges.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Costs and charges. 319.75-7 Section 319.75-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Khapra Beetle § 319.75-7 Costs and charges...

  1. 7 CFR 3405.7 - Joint project proposals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Joint project proposals. 3405.7 Section 3405.7... AGRICULTURE HIGHER EDUCATION CHALLENGE GRANTS PROGRAM Program Description § 3405.7 Joint project proposals. Applicants are encouraged to submit joint project proposals as defined in § 3405.2(m), which address regional...

  2. 7 CFR 201.56-7 - Lily family, Liliaceae.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Lily family, Liliaceae. 201.56-7 Section 201.56-7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... REGULATIONS Germination Tests in the Administration of the Act § 201.56-7 Lily family, Liliaceae. Kinds of...

  3. 7 CFR 277.7 - Cash depositories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Cash depositories. 277.7 Section 277.7 Agriculture... FOOD STAMP AND FOOD DISTRIBUTION PROGRAM PAYMENTS OF CERTAIN ADMINISTRATIVE COSTS OF STATE AGENCIES § 277.7 Cash depositories. (a) The term “cash depositories” refers to banks or other institutions which...

  4. 7 CFR 7.1 - Administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Administration. 7.1 Section 7.1 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF FARM SERVICE AGENCY STATE AND COUNTY COMMITTEES § 7.1 Administration. (a) The regulations in this part apply to the election and functions of the...

  5. 7 CFR 7.17 - Dual office.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Dual office. 7.17 Section 7.17 Agriculture Office of... STATE, COUNTY AND COMMUNITY COMMITTEES § 7.17 Dual office. (a) County committee membership. A member of... any other county office employee. (b) Community committee membership. A member of the community...

  6. 7 CFR § 3200.7 - Title.

    Code of Federal Regulations, 2010 CFR

    2018-01-01

    ... 7 Agriculture 15 2018-01-01 2018-01-01 false Title. § 3200.7 Section § 3200.7 Agriculture... PERSONAL PROPERTY § 3200.7 Title. Title to excess personal property obtained under Part 3200 will... will give preference to the Federal agency that will retain title in the Government. ...

  7. 7 CFR 247.7 - Selection of local agencies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Selection of local agencies. 247.7 Section 247.7 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.7 Selection of local agencies...

  8. 7 CFR 1776.7 - HWWS Grant application process.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false HWWS Grant application process. 1776.7 Section 1776.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Grants § 1776.7 HWWS Grant application...

  9. 7 CFR 1776.7 - HWWS Grant application process.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true HWWS Grant application process. 1776.7 Section 1776.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Grants § 1776.7 HWWS Grant application...

  10. 47 CFR 7.15 - Generally.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Generally. 7.15 Section 7.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.15 Generally. (a) For purposes of §§ 7.15-7.23 of this...

  11. 47 CFR 7.15 - Generally.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Generally. 7.15 Section 7.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.15 Generally. (a) For purposes of §§ 7.15-7.23 of this...

  12. 47 CFR 7.15 - Generally.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Generally. 7.15 Section 7.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.15 Generally. (a) For purposes of §§ 7.15-7.23 of this...

  13. 47 CFR 7.15 - Generally.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Generally. 7.15 Section 7.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.15 Generally. (a) For purposes of §§ 7.15-7.23 of this...

  14. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2018-04-03

    Advanced Adult Hepatocellular Carcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7

  15. PLOT3D: An Interactive Graphics Code for Three Dimensional Plots.

    DTIC Science & Technology

    1984-09-28

    INFORMITITLE.,IPERIM,IAXIS,IMASK COMMON/DATA4/XMIN , XMAX, ZMINZMAX , YMIN,YIAX COMMON/DATAS/NXPLNZPL,IPLPXIPLPZXSCAIO ,YSCALO ,ZSCALO GOTO ( SiAS ...YSP * CALL i.ETTR(XY~,7H SIZE =,00,7) - Y=Y-YSP SCAlL LFTTP(X,Y,7H XSc =.o 0,7) Y:Y-ISP CALL LETTR(X.,Y,7H YSC =,0.0,7) CAIL IETTR(X,Y,7H ZSC =,0.0

  16. 31 CFR 30.7 - Q-7: How does a TARP recipient comply with the certification and disclosure requirements under...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Q-7: How does a TARP recipient comply with the certification and disclosure requirements under § 30.4 (Q-4) of this part? 30.7 Section 30.7... CORPORATE GOVERNANCE § 30.7 Q-7: How does a TARP recipient comply with the certification and disclosure...

  17. 31 CFR 30.7 - Q-7: How does a TARP recipient comply with the certification and disclosure requirements under...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Q-7: How does a TARP recipient comply with the certification and disclosure requirements under § 30.4 (Q-4) of this part? 30.7 Section 30.7... CORPORATE GOVERNANCE § 30.7 Q-7: How does a TARP recipient comply with the certification and disclosure...

  18. 31 CFR 30.7 - Q-7: How does a TARP recipient comply with the certification and disclosure requirements under...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Q-7: How does a TARP recipient comply with the certification and disclosure requirements under § 30.4 (Q-4) of this part? 30.7 Section 30.7... CORPORATE GOVERNANCE § 30.7 Q-7: How does a TARP recipient comply with the certification and disclosure...

  19. Statistical Analysis of the Effect of Inspection and Maintenance ...

    EPA Pesticide Factsheets

    ... c.. -cc . $ 7$ ì 4í ïïï TI 71 I 4 . 4 . ë cc. 4 , IZ4 74 ï aí t . , s . ï I i ïcï 7ï ïcc 7* 77 7 a ccc ï ëI I 7* ì $ II 2 $ ï 7ïï ócc I 7t 74 S . 3 nïcc ï?il.4 7111 ne 84.ce. ...

  20. Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2018-04-18

    BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

  1. Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

    ClinicalTrials.gov

    2018-02-15

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

  2. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-06-11

    Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

  3. Measurements of the neutron-induced reactions on 7Be with CRIB by the Trojan Horse method

    NASA Astrophysics Data System (ADS)

    Hayakawa, S.; Abe, K.; Beliuskina, O.; Cha, S. M.; Chae, K. Y.; Cherubini, S.; Figuera, P.; Ge, Z.; Gulino, M.; Hu, J.; Inoue, A.; Iwasa, N.; Kahl, D.; Kim, A.; Kim, D. H.; Kiss, G.; Kubono, S.; La Cognata, M.; La Commara, M.; Lamia, L.; Lattuada, M.; Lee, E. J.; Moon, J. Y.; Palmerini, S.; Parascandolo, C.; Park, S. Y.; Pierroutsakou, D.; Pizzone, R. G.; Rapisarda, G. G.; Romano, S.; Shimizu, H.; Spitaleri, C.; Tang, X. D.; Trippella, O.; Tumino, A.; , P., Vi; Yamaguchi, H.; Yang, L.; Zhang, N. T.

    2018-04-01

    The cosmological 7Li problem has been one of the big issues left in the standard Big-Bang nucleosynthesis (BBN) model. In order to determine the radiogenic 7Li abundance by the BBN, it is important to know the production and the destruction rate of 7Be rather than 7Li itself. We performed indirect measurements of the relevant neutron-induced reactions 7Be(n, p)7Li and 7Be(n, α)4He simultaneously by the Trojan Horse Method (THM) via the three-body reactions 7Be(d,7Lip)1H and 7Be(d, αα)1H. A 7Be radioactive-isotope (RI) beam at 3.16 MeV/u was produced at Center-for-Nuclear-Study RI Beam (CRIB) separator. The Q-value spectra shows the evidence of the three-body channels of interest. We confirmed that the THM was applicable to the present measurements by the momentum distributions of the spectator proton. Preliminary excitation functions are roughly consistent with the previous studies, moreover providing new data in the BBN energy range, and suggesting that new information about the 7Be(n, p1)7Li* contribution may be obtained by carrying out a further data analysis.

  4. Loss of heterozygosity at 7p in Wilms' tumour development

    PubMed Central

    Powlesland, R M; Charles, A K; Malik, K T A; Reynolds, P A; Pires, S; Boavida, M; Brown, K W

    2000-01-01

    Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaign PMID:10646884

  5. Heterogeneous genetic diversity pattern in Plasmodium vivax genes encoding merozoite surface proteins (MSP) -7E, -7F and -7L.

    PubMed

    Garzón-Ospina, Diego; Forero-Rodríguez, Johanna; Patarroyo, Manuel A

    2014-12-13

    The msp-7 gene has become differentially expanded in the Plasmodium genus; Plasmodium vivax has the highest copy number of this gene, several of which encode antigenic proteins in merozoites. DNA sequences from thirty-six Colombian clinical isolates from P. vivax (pv) msp-7E, -7F and -7L genes were analysed for characterizing and studying the genetic diversity of these pvmsp-7 members which are expressed during the intra-erythrocyte stage; natural selection signals producing the variation pattern so observed were evaluated. The pvmsp-7E gene was highly polymorphic compared to pvmsp-7F and pvmsp-7L which were seen to have limited genetic diversity; pvmsp-7E polymorphism was seen to have been maintained by different types of positive selection. Even though these copies seemed to be species-specific duplications, a search in the Plasmodium cynomolgi genome (P. vivax sister taxon) showed that both species shared the whole msp-7 repertoire. This led to exploring the long-term effect of natural selection by comparing the orthologous sequences which led to finding signatures for lineage-specific positive selection. The results confirmed that the P. vivax msp-7 family has a heterogeneous genetic diversity pattern; some members are highly conserved whilst others are highly diverse. The results suggested that the 3'-end of these genes encode MSP-7 proteins' functional region whilst the central region of pvmsp-7E has evolved rapidly. The lineage-specific positive selection signals found suggested that mutations occurring in msp-7s genes during host switch may have succeeded in adapting the ancestral P. vivax parasite population to humans.

  6. Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.

    PubMed

    Peng, X; Katz, M; Gerzanich, V; Anand, R; Lindstrom, J

    1994-03-01

    The alpha-bungarotoxin-binding acetylcholine receptors from the human neuroblastoma cell line SH-SY5Y were found to cross-react with some monoclonal antibodies to alpha 7 subunits of nicotinic acetylcholine receptors from chicken brain. The human alpha 7 subunit cDNA from SH-SY5Y was cloned, revealing 94% amino acid sequence identity to rat alpha 7 subunits and 92% identity to chicken alpha 7 subunits. Native human alpha 7 receptors showed affinities for some ligands similar to those previously observed with native chicken alpha 7 receptors, but for other ligands there were large species-specific differences in binding affinity. These results paralleled properties of alpha 7 homomers expressed in Xenopus oocytes. Human alpha 7 homomers exhibited rapidly desensitizing, inwardly rectifying, agonist-induced, cation currents that triggered Ca(2+)-sensitive Cl- channels in the oocytes. A change in efficacy from partial agonist for chicken alpha 7 homomers to full agonist for human alpha 7 homomers was exhibited by 1,1-dimethyl-4-phenylpiperazinium. This result reveals a large species-specific pharmacological difference, despite small differences in alpha 7 sequences. This is important for understanding the effects of these drugs in humans and for identifying amino acids that may contribute to the acetylcholine binding site, for analysis by in vitro mutagenesis. These results also characterize properties of native alpha 7 receptors and alpha 7 homomers that will provide criteria for functional properties expected of structural subunits, when these can be identified, cloned, and coexpressed with alpha 7 subunits.

  7. Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.

    PubMed

    Nguyen, Joe Truong; Ray, Connor; Fox, Alexandra Lucienne; Mendonça, Daniela Baccelli; Kim, Jin Koo; Krebsbach, Paul H

    2018-05-01

    Nematode EAK-7 (enhancer-of- akt -1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration.

  8. [Inhibitory effect of Mig-7 silencing by retrovirus-mediated shRNA on vasculogenic mimicry, invasion and metastasis of human hepatocellular carcinoma cells in vitro].

    PubMed

    Qu, Bo; Sheng, Guan-Nan; Yu, Fei; Chen, Guan-Nan; Lv, Qi; Mao, Zhong-Peng; Guo, Long; Lv, Yi

    2016-11-20

    To explore the inhibitory effect of migration-inducing gene 7 (Mig-7) gene silencing induced by retroviral-mediated small hairpin RNA (shRNA) on vasculogenic mimicry (VM), invasion and metastasis of human hepatocellular carcinoma (HCC) cells in vitro. Two target sequences (Mig-7 shRNA-1 and Mig-7 shRNA-2) and one negative control sequence (Mig-7 shRNA-N) were synthesized. The recombinant retroviral vectors carrying Mig-7 shRNA were constructed, and HCC cell line MHCC-97H were transfected with Mig-7 shRNA-1, Mig-7 shRNA-2, Mig-7 shRNA-N, or the empty vector, or treated with 125 µg/mL recombinant human endostatin (ES). Mig-7 expression in the treated cells was detected using semi-quantitative PCR and Western blotting. The inhibitory effect of Mig-7 silencing on VM formation was investigated in a 3-dimensional cell culture system; the changes in cell adhesion, invasion and migration were assessed with intercellular adhesion assay, Transwell invasion assay and Transwell migration assay, respectively. The expression of Mig-7 at both mRNA and protein levels decreased significantly, VM formation, invasion and metastasis were suppressed, while intercellular adhesion increased significantly in MHCC-97H cells in Mig-7 shRNA-1 and Mig-7 shRNA-2 groups (P<0.05); such changes were not observed in cells transfected with Mig-7 shRNA-N or the empty vector, nor in cells treated with ES. Mig-7 silencing by retroviral-mediated shRNA significantly inhibits VM formation, invasion and metastasis and increases the intercellular adhesion of the HCC cells, while ES does not have such inhibitory effects.

  9. Anti-Cancer Efficacy of Silybin Derivatives - A Structure-Activity Relationship

    PubMed Central

    Agarwal, Chapla; Wadhwa, Ritambhara; Deep, Gagan; Biedermann, David; Gažák, Radek; Křen, Vladimír; Agarwal, Rajesh

    2013-01-01

    Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS), 7-O-methylsilybin (7OM), 7-O-galloylsilybin (7OG), 7,23-disulphatesilybin (DSS), 7-O-palmitoylsilybin (7OP), and 23-O-palmitoylsilybin (23OP); and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B) of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents. PMID:23555889

  10. Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7.

    PubMed

    Li, Xiaomin; Wang, Jianjun; Zhang, Chao; Lin, Chun; Zhang, Jianming; Zhang, Wei; Zhang, Wenjuan; Lu, Yanxia; Zheng, Lin; Li, Xuenong

    2018-06-26

    Circular RNAs (circRNAs) are significantly dysregulated in various cancer types. However, the roles and mechanisms of circRNAs in cancer remain largely unknown. In this study, we demonstrated that a novel circRNA (circITGA7) and its linear host gene ITGA7 are both significantly downregulated in colorectal cancer (CRC) tissues and cell lines. These decreased expression levels correlated with CRC progression. Functional assays demonstrated that ectopic circITGA7 expression suppressed the growth and metastasis of CRC cell in vitro and in vivo. Knockdown of circITGA7 or ITGA7 promoted the proliferation and migration of CRC cells in vitro and enhanced CRC growth in vivo. Mechanistically, we found that circITGA7 is a negative regulator of the Ras signalling pathway and ITGA7 is associated with cytokine-related signalling pathways through RNA-seq and KEGG enrichment analysis. In addition, circITGA7 binds to miR-370-3p to antagonize its suppression of NF1, which is a well-known negative regulator of the Ras pathway. Finally, circITGA7 upregulates the transcription of ITGA7 by suppressing RREB1 via the Ras pathway. In conclusion, our findings indicate a suppressor role of circITGA7 and ITGA7 in CRC and reveal that circITGA7 inhibits proliferation and metastasis of CRC cells by suppressing the Ras signalling pathway and promoting the transcription of ITGA7, suggesting that circITGA7 is a potential target for CRC treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. NF-κB activation primes cells to a pro-inflammatory polarized response to a TLR7 agonist

    PubMed Central

    Lee, Jongdae; Hayashi, Masaaki; Lo, Jeng-Fan; Fearns, Colleen; Chu, Wen-Ming; Luo, Yunping; Xiang, Rong; Chuang, Tsung-Hsien

    2009-01-01

    Toll-like receptor 7 (TLR7) mediates anti-viral immunity by recognizing ssRNA viruses. Small molecular weight TLR7 agonists have been approved, or are being evaluated, for treatment of cancers or infectious diseases. Although TLR7 is predominantly expressed in a restricted set of immune cell types including plasmacytoid dendritic cells (pDCs), it is also expressed in non-native expressing cells (e.g., hepatocytes) under certain circumstances. To elucidate the molecular basis of TLR7 induction by pro-inflammatory stimulation and the subsequent cellular responses in these non-native TLR7-expressing cell types, we firstly cloned and characterized the 5′-promoter region of TLR7. The proximal region of this promoter drives the transcription of the TLR7 gene. Pro-inflammatory stimuli activated TLR7 transcription via a NF-κB binding motif in this region, and this activation could be blocked by mutation of the NF-κB binding site or addition of NF-κB inhibitors. Further studies showed that pretreatment of the Hep3B hepatocytes with TNF-α or IL-1 rendered them responsive to TLR7 activation by a TLR7 agonist. However, distinct from TLR7 activation in pDCs, which respond to stimulation with Th1 polarized cytokine production, TLR7 induction by pro-inflammatory signals in hepatocytes reconstitutes the NF-κB-dependent cascade but not the IRF7-dependent cascade, resulting in a pro-inflammatory polarized response rather than a Th1 polarized response. These results indicate that inflammatory stimulation is capable of priming cells to respond to TLR7 agonist with an immune response that differs from that in native TLR7-expressing cells. PMID:19426145

  12. MicroRNA-7a regulates Müller glia differentiation by attenuating Notch3 expression.

    PubMed

    Baba, Yukihiro; Aihara, Yuko; Watanabe, Sumiko

    2015-09-01

    miRNA-7a plays critical roles in various biological aspects in health and disease. We aimed to reveal roles of miR-7a in mouse retinal development by loss- and gain-of-function analyses of miR-7a. Plasmids encoding miR-7a or miR-7a-decoy (anti-sense miR-7a) were introduced into mouse retina at P0, and the retina was cultured as explant. Then, proliferation of retinal progenitors and differentiation of retinal subtypes were examined by immunostaining. miR-7a had no apparent effect on the proliferation of retinal progenitor cells. However, the expression of Müller glia marker, cyclin D3, was reduced by miR-7a overexpression and up-regulated by miR-7a decoy, suggesting that miR-7a negatively regulates differentiation of Müller glia. Targets of miR-7a, which were predicted by using a public program miRNA.org, and Notch3 was suggested to be one of candidate genes of miR-7a target. Notch3 3' UTR appeared to contain complementary sequence to the seed sequence of miR-7a. A reporter assay in NIH3T3 cells using a plasmid containing multiple repeats of potential target sequence of 3' Notch UTR showed that miR-7a suppress expression of reporter EGFP through 3'UTR region. Expression of sh-Notch3 and over-expression of NICD3 in retina suggested that miR-7a regulates Müller glia differentiation through attenuation of Notch3 expression. Taken together, we revealed that the miR-7a regulates the differentiation of Müller glia through the suppression of Notch3 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.

    PubMed

    Bientinesi, Riccardo; Mancuso, Cesare; Martire, Maria; Bassi, Pier Francesco; Sacco, Emilio; Currò, Diego

    2017-02-01

    Voltage-gated type 7 K + (K V 7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of K V 7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of K V 7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective K V 7 channel blocker, concentration-dependently contracted the human detrusor; mean EC 50 and E max of XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective K V 7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported K V 7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the K V 7.4 band being the most intense among them. In conclusion, K V 7 channels contribute to set the basal tone of the human detrusor. In addition, K V 7 channel activators significantly relax the detrusor. The K V 7.4 channels are probably the most important K V 7 channels expressed in the human detrusor. These data suggest that selective K V 7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.

  14. Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

    PubMed Central

    Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen; Matras, Christina; Bouchelouche, Pierre

    2015-01-01

    The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1–7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome. PMID:25692982

  15. Decreased expression of Kv7 channels in Hirchsprung's disease.

    PubMed

    O'Donnell, Anne-Marie; Coyle, David; Puri, Prem

    2017-07-01

    Voltage-dependent K + channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon. We therefore designed this study to test the hypothesis that Kv7 channels are present in the normal human colon and are reduced in Hirschprung's disease (HSCR). HSCR tissue specimens were collected at the time of pull-through surgery (n=10), while normal control tissue specimens were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Kv7.3-Kv7.5 immunohistochemistry was performed and visualized using confocal microscopy to assess their distribution. Western blot analysis was undertaken to determine Kv7.3-Kv7.5 protein quantification. Kv7.3 and Kv7.4-immunoreactivity was co-localized with neuron and ICC markers, while Kv7.5 was found to be expressed on both ICCs and SMCs. Western blot analysis revealed similar levels of Kv7.3 and Kv7.5 expression in the normal colon and HSCR colon, while Kv7.4 proteins were found to be markedly decreased in ganglionic specimens and decreased further in aganglionic specimens. A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction.

    PubMed

    Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen; Matras, Christina; Bouchelouche, Pierre

    2015-01-01

    The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.

  17. FBW7 targets KLF10 for ubiquitin-dependent degradation.

    PubMed

    Yu, Su; Wang, Feng; Tan, Xiao; Gao, Guo-Li; Pan, Wei-Juan; Luan, Yi; Ge, Xin

    2018-01-08

    FBW7, a key component of SCF FBW7 E3 ubiquitin ligase, targets various proteins for degradation via the conserved Cdc4 phosphodegron (CPD) in substrates. In this study, we report that KLF10 is degraded by FBW7 via a conserved CPD. Through systematic analysis of the degradation of KLF transcription factors by FBW7, we identified KLF10 as a novel degradation target of FBW7. Ectopic expression of FBW7 markedly promoted the degradation of KLF10 while knockdown of endogenous FBW7 increased the protein levels of KLF10. In addition, simultaneous mutations of both threonine 82 (T82) and serine 86 (S86) significantly reduced the FBW7-mediated KLF10 degradation. Moreover, KLF10 containing a conserved putative CPD (TPPXSP) from amino acids 82 to 87, directly interacted with WD40 domain of FBW7 in a phosphorylation-dependent manner. Importantly, FBW7 could reverse the KLF10-mediated inhibition of Smad7 activity. Thus, our study uncovers a novel regulatory mechanism underlying which KLF10 stability and its biological function are mediated by FBW7. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7.

    PubMed

    Hao, Haibin; Xia, Guangfeng; Wang, Chao; Zhong, Fuping; Liu, Laipeng; Zhang, Dong

    2017-06-01

    Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.

  19. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

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

    Guo, Hongsheng; Wu, Fenping; Wang, Yan

    2014-08-08

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found thatmore » Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.« less

  20. Bioactive compounds from Peperomia pellucida.

    PubMed

    Xu, Su; Li, Na; Ning, Meng-Meng; Zhou, Cai-Hong; Yang, Qiao-Rong; Wang, Ming-Wei

    2006-02-01

    Five new compounds (1-5), including two secolignans, two tetrahydrofuran lignans, and one highly methoxylated dihydronaphthalenone, were isolated from the whole plant of Peperomia pellucida. These compounds were accompanied by the known peperomins A, B, C, and E, 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran, 7,8-trans-8,8'-trans-7',8'-cis-7-(5-methoxy-3,4-methylenedioxyphenyl)-7'-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-diacetoxymethyltetrahydrofuran, sesamin, and isoswertisin. New structures were elucidated mainly by NMR and MS techniques, and anticancer activities evaluated in HL-60, MCF-7, and HeLa cell lines. Compound 1 and peperomin E show growth inhibitory effects on the three cancer cell lines with IC(50) values ranging between 1.4 and 9.1 and between 1.8 and 11.1 microM, respectively. Compound 2 has a weak suppressive activity on HL-60 cells (IC(50) = 10.8 microM), while 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran exhibits estrogen-like properties (EC(50) = 3.1 microM) in CV-1 cells transfected with human estrogen receptor (ERalpha).

  1. Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia.

    PubMed

    Sander, Svenja E; Diwan, Mustansir; Raymond, Roger; Nobrega, José N; Richter, Angelika

    2016-01-01

    Dystonia is a hyperkinetic disabling movement disorder. In the dt(sz) hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the KV7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective KV7.2-5 blocker indicated a pathophysiological role of an abnormal expression of KV7 channels. We therefore investigated the expression of KV7 subunits in brains of dystonic hamsters. While KV7.2 and KV7.3 subunits were unaltered, lower KV7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The KV7.2/3 subunit-preferring channel opener N-(6-chloropyridin-3-yl)-3,4- difluorobenzamide (ICA 27243; 10-30 mg/kg i.p.) failed to reduce the severity of dystonia in mutant hamsters, suggesting that the previously observed antidystonic action of retigabine is mediated by the activation of KV7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches.

  2. Transient Receptor Potential Melastatin 7 Cation Channel Kinase: New Player in Angiotensin II-Induced Hypertension.

    PubMed

    Antunes, Tayze T; Callera, Glaucia E; He, Ying; Yogi, Alvaro; Ryazanov, Alexey G; Ryazanova, Lillia V; Zhai, Alexander; Stewart, Duncan J; Shrier, Alvin; Touyz, Rhian M

    2016-04-01

    Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein comprising a magnesium (Mg(2+))/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7 kinase-deficient mice (TRPM7Δkinase; heterozygous for TRPM7 kinase) and wild-type (WT) mice infused with angiotensin II (Ang II; 400 ng/kg per minute, 4 weeks). TRPM7 kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg(2+) was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (P<0.05). Acetylcholine-induced vasorelaxation was reduced in Ang II-infused TRPM7Δkinase mice, an effect associated with Akt and endothelial nitric oxide synthase downregulation. Vascular cell adhesion molecule-1 expression was increased in Ang II-infused TRPM7 kinase-deficient mice. TRPM7 kinase targets, calpain, and annexin-1, were activated by Ang II in WT but not in TRPM7Δkinase mice. Echocardiographic and histopathologic analysis demonstrated cardiac hypertrophy and left ventricular dysfunction in Ang II-treated groups. In TRPM7 kinase-deficient mice, Ang II-induced cardiac functional and structural effects were amplified compared with WT counterparts. Our data demonstrate that in TRPM7Δkinase mice, Ang II-induced hypertension is exaggerated, cardiac remodeling and left ventricular dysfunction are amplified, and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7 kinase expression/signaling, endothelial nitric oxide synthase downregulation, and proinflammatory vascular responses. Our findings identify TRPM7 kinase as a novel player in Ang II-induced hypertension and associated vascular and target organ damage. © 2016 American Heart Association, Inc.

  3. Differential patterns of inhibition of the sugar transporters GLUT2, GLUT5 and GLUT7 by flavonoids.

    PubMed

    Gauer, Julia S; Tumova, Sarka; Lippiat, Jonathan D; Kerimi, Asimina; Williamson, Gary

    2018-06-01

    Only limited data are available on the inhibition of the sugar transporter GLUT5 by flavonoids or other classes of bioactives. Intestinal GLUT7 is poorly characterised and no information exists concerning its inhibition. We aimed to study the expression of GLUT7 in Caco-2/TC7 intestinal cells, and evaluate inhibition of glucose transport by GLUT2 and GLUT7, and of fructose transport by GLUT2, GLUT5 and GLUT7, by flavonoids. Differentiated Caco-2/TC7 cell monolayers were used to investigate GLUT7 expression, as well as biotinylation and immunofluorescence to assess GLUT7 location. For mechanistic sugar transport studies, X. laevis oocytes were injected with individual mRNA, and GLUT protein expression on oocyte membranes was confirmed. Oocytes were incubated with D-[ 14 C(U)]-glucose or D-[ 14 C(U)]-fructose in the presence of flavonoids, and uptake was estimated by liquid scintilation counting. In differentiated Caco-2/TC7 cell monolayers, GLUT7 was mostly expressed apically. When applied apically, or to both compartments, sorbitol, galactose, L-glucose or sucrose did not affect GLUT7 mRNA expression. Fructose applied to both sides increased GLUT7 mRNA (13%, p ≤ 0.001) and total GLUT7 protein (2.7-fold, p ≤ 0.05), while the ratio between apical, basolateral and total GLUT7 protein was unchanged. In the X. laevis oocyte model, GLUT2-mediated glucose and fructose transport were inhibited by quercetin, (-)-epigallocatechin gallate (EGCG) and apigenin, GLUT5-mediated fructose transport was inhibited by apigenin and EGCG, but not by quercetin, and GLUT7-mediated uptake of both glucose and fructose was inhibited by apigenin, but not by quercetin nor EGCG. Expression of GLUT7 was increased by fructose, but only when applied to Caco-2/TC7 cells both apically and basolaterally. Since GLUT2, GLUT5 and GLUT7 show different patterns of inhibition by the tested flavonoids, we suggest that they have the potential to be used as investigational tools to distinguish sugar transporter activity in different biological settings. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Transferring Desirable Genes from Agropyron cristatum 7P Chromosome into Common Wheat.

    PubMed

    Lu, Mingjie; Lu, Yuqing; Li, Huanhuan; Pan, Cuili; Guo, Yong; Zhang, Jinpeng; Yang, Xinming; Li, Xiuquan; Liu, Weihua; Li, Lihui

    2016-01-01

    Wheat-Agropyron cristatum 7P disomic addition line Ⅱ-5-1, derived from the distant hybridization between A. cristatum (2n = 4x = 28, PPPP) and the common wheat cv. Fukuhokomugi (Fukuho), displays numerous desirable agronomic traits, including enhanced thousand-grain weight, smaller flag leaf, and enhanced tolerance to drought. In order to transfer these traits into common wheat, Ⅱ-5-1 was induced by 60Co-γ ray, leading to the creation of 18 translocation lines and three deletion lines. Genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) indicated that multiple wheat chromosomes were involved in the translocation events, including chromosome 2A, 3A, 5A, 7A, 3B, 5B, 7B, 3D and 7D. A. cristatum 7P chromosome was divided into 15 chromosomal bins with fifty-five sequence-tagged site (STS) markers specific to A. cristatum 7P chromosome. Seven and eight chromosomal bins were located on 7PS and 7PL, respectively. The above-mentioned translocation and deletion lines each contained different, yet overlapping 7P chromosomal fragments, covering the entire A. cristatum 7P chromosome. Three translocation lines (7PT-13, 7PT-14 and 7PT-17) and three deletion lines (del-1, del-2 and del-3), which contained the common chromosomal bins 7PS1-3, displayed higher thousand-grain weigh than Fukuho, suggesting that potential genes conferring high thousand-grain weigh might be located on these chromosomal bins. Therefore, wheat-A. cristatum 7P translocation lines with elite traits will be useful as novel germplasms for wheat genetic improvement.

  5. PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma.

    PubMed

    Liu, Kang; Song, Guiqin; Zhang, Xuqian; Li, Qiujiang; Zhao, Yunxia; Zhou, Yuchuan; Xiong, Rong; Hu, Xin; Tang, Zhirong; Feng, Gang

    2017-05-25

    Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer. We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration. Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells. PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.

  6. Clusterin and COMMD1 Independently Regulate Degradation of the Mammalian Copper ATPases ATP7A and ATP7B*

    PubMed Central

    Materia, Stephanie; Cater, Michael A.; Klomp, Leo W. J.; Mercer, Julian F. B.; La Fontaine, Sharon

    2012-01-01

    ATP7A and ATP7B are copper-transporting P1B-type ATPases (Cu-ATPases) that are critical for regulating intracellular copper homeostasis. Mutations in the genes encoding ATP7A and ATP7B lead to copper deficiency and copper toxicity disorders, Menkes and Wilson diseases, respectively. Clusterin and COMMD1 were previously identified as interacting partners of these Cu-ATPases. In this study, we confirmed that clusterin and COMMD1 interact to down-regulate both ATP7A and ATP7B. Overexpression and knockdown of clusterin/COMMD1 decreased and increased, respectively, endogenous levels of ATP7A and ATP7B, consistent with a role in facilitating Cu-ATPase degradation. We demonstrate that whereas the clusterin/ATP7B interaction was enhanced by oxidative stress or mutation of ATP7B, the COMMD1/ATP7B interaction did not change under oxidative stress conditions, and only increased with ATP7B mutations that led to its misfolding. Clusterin and COMMD1 facilitated the degradation of ATP7B containing the same Wilson disease-causing C-terminal mutations via different degradation pathways, clusterin via the lysosomal pathway and COMMD1 via the proteasomal pathway. Furthermore, endogenous ATP7B existed in a complex with clusterin and COMMD1, but these interactions were neither competitive nor cooperative and occurred independently of each other. Together these data indicate that clusterin and COMMD1 represent alternative and independent systems regulating Cu-ATPase quality control, and consequently contributing to the maintenance of copper homeostasis. PMID:22130675

  7. Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases.

    PubMed

    Adams, C E; Yonchek, J C; Schulz, K M; Graw, S L; Stitzel, J; Teschke, P U; Stevens, K E

    2012-04-05

    The α7* nicotinic acetylcholine receptor encoded by CHRNA7 (human)/Chrna7 (mice) regulates the release of both the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate in the hippocampal formation. A heterozygous (Het) deletion at 15q13.3 containing CHRNA7 is associated with increased risk for schizophrenia, autism, and epilepsy. Each of these diseases are characterized by abnormalities in excitatory and inhibitory hippocampal circuit function. Reduced Chrna7 expression results in decreased hippocampal α7* receptor density, abnormal hippocampal auditory sensory processing, and increased hippocampal CA3 pyramidal neuron activity in C3H mice Het for a null mutation in Chrna7. These abnormalities demonstrate that decreased Chrna7 expression alters hippocampal inhibitory circuit function. The current study examined the specific impact of reduced Chrna7 expression on hippocampal inhibitory circuits by measuring the levels of GABA, GABA(A) receptors, the GABA synthetic enzyme l-glutamic acid decarboxylase-65 (GAD-65), and the vesicular GABA transporter 1 (GAT-1) in wild-type (Chrna7 +/+) and Het (Chrna7 +/-) C3H α7 mice of both genders. GAD-65 levels were significantly decreased in male and female Het C3H α7 mice, whereas GABA(A) receptors were significantly reduced only in male Het C3H α7 mice. No changes in GABA and GAT-1 levels were detected. These data suggest that reduced CHRNA7 expression may contribute to the abnormalities in hippocampal inhibitory circuits observed in schizophrenia, autism, and/or epilepsy. Published by Elsevier Ltd.

  8. Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases

    PubMed Central

    Adams, Catherine E.; Yonchek, Joan C.; Schulz, Kalynn M.; Graw, Sharon L.; Stitzel, Jerry; Teschke, Patricia U.; Stevens, Karen E.

    2012-01-01

    The α7* nicotinic acetylcholine receptor encoded by CHRNA7 (human)/Chrna7 (mice) regulates the release of both the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the excitatory neurotransmitter glutamate in the hippocampal formation. A heterozygous deletion at 15q13.3 containing CHRNA7 is associated with increased risk for schizophrenia, autism and epilepsy. Each of these diseases is characterized by abnormalities in excitatory and inhibitory hippocampal circuit function. Reduced Chrna7 expression results in decreased hippocampal α7* receptor density, abnormal hippocampal auditory sensory processing and increased hippocampal CA3 pyramidal neuron activity in C3H mice heterozygous for a null mutation in Chrna7. These abnormalities demonstrate that decreased Chrna7 expression alters hippocampal inhibitory circuit function. The current study examined the specific impact of reduced Chrna7 expression on hippocampal inhibitory circuits by measuring the levels of GABA, GABAA receptors, the GABA synthetic enzyme glutamate decarboxylase-65 (GAD-65) and the vesicular GABA transporter GAT-1 in wild type (Chrna7 +/+) and heterozygous (Chrna7 +/−) C3H α7 mice of both genders. GAD-65 levels were significantly decreased in male and female heterozygous C3H α7 mice while GABAA receptors were significantly reduced only in male heterozygous C3H α7 mice. No changes in GABA and GAT-1 levels were detected. These data suggest that reduced CHRNA7 expression may contribute to the abnormalities in hippocampal inhibitory circuits observed in schizophrenia, autism and/or epilepsy. PMID:22314319

  9. Trophic Activity of Human P2X7 Receptor Isoforms A and B in Osteosarcoma

    PubMed Central

    Giuliani, Anna Lisa; Colognesi, Davide; Ricco, Tiziana; Roncato, Carlotta; Capece, Marina; Amoroso, Francesca; Wang, Qi Guang; De Marchi, Elena; Gartland, Allison; Di Virgilio, Francesco; Adinolfi, Elena

    2014-01-01

    The P2X7 receptor (P2X7R) is attracting increasing attention for its involvement in cancer. Several recent studies have shown a crucial role of P2X7R in tumour cell growth, angiogenesis and invasiveness. In this study, we investigated the role of the two known human P2X7R functional splice variants, the full length P2X7RA and the truncated P2X7RB, in osteosarcoma cell growth. Immunohistochemical analysis of a tissue array of human osteosarcomas showed that forty-four, of a total fifty-four tumours (81.4%), stained positive for both P2X7RA and B, thirty-one (57.4%) were positive using an anti-P2X7RA antibody, whereas fifteen of the total number (27.7%) expressed only P2X7RB. P2X7RB positive tumours showed increased cell density, at the expense of extracellular matrix. The human osteosarcoma cell line Te85, which lacks endogenous P2X7R expression, was stably transfected with either P2X7RA, P2X7RB, or both. Receptor expression was a powerful stimulus for cell growth, the most efficient growth-promoting isoform being P2X7RB alone. Growth stimulation was matched by increased Ca2+ mobilization and enhanced NFATc1 activity. Te85 P2X7RA+B cells presented pore formation as well as spontaneous extracellular ATP release. The ATP release was sustained in all clones by P2X7R agonist (BzATP) and reduced following P2X7R antagonist (A740003) application. BzATP also increased cell growth and activated NFATc1 levels. On the other hand cyclosporin A (CSA) affected both NFATc1 activation and cell growth, definitively linking P2X7R stimulation to NFATc1 and cell proliferation. All transfected clones also showed reduced RANK-L expression, and an overall decreased RANK-L/OPG ratio. Mineralization was increased in Te85 P2X7RA+B cells while it was significantly diminished in Te85 P2X7RB clones, in agreement with immunohistochemical results. In summary, our data show that the majority of human osteosarcomas express P2X7RA and B and suggest that expression of either isoform is differently coupled to cell growth or activity. PMID:25226385

  10. Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

    ClinicalTrials.gov

    2018-04-09

    Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

  11. 40 CFR 372.28 - Lower thresholds for chemicals of special concern.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...,7,8-Hexachlorodibenzofuran 39227-28-61,2,3,4,7,8-Hexachlorodibenzo-p-dioxin 57653-85-71,2,3,6,7,8-Hexachlorodibenzo-p-dioxin 19408-74-31,2,3,7,8,9-Hexachlorodibenzo-p-dioxin 35822-46-91,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin Lead Compounds 100 39001-02-01,2,3,4,6,7,8,9-Octachlorodibenzofuran 03268-87-91,2,3,4,6,7...

  12. 40 CFR 372.28 - Lower thresholds for chemicals of special concern.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...,7,8-Hexachlorodibenzofuran 39227-28-61,2,3,4,7,8-Hexachlorodibenzo-p-dioxin 57653-85-71,2,3,6,7,8-Hexachlorodibenzo-p-dioxin 19408-74-31,2,3,7,8,9-Hexachlorodibenzo-p-dioxin 35822-46-91,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin Lead Compounds 100 39001-02-01,2,3,4,6,7,8,9-Octachlorodibenzofuran 03268-87-91,2,3,4,6,7...

  13. 7 CFR 801.7 - Reference methods and tolerances for near-infrared spectroscopy (NIRS) analyzers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Reference methods and tolerances for near-infrared spectroscopy (NIRS) analyzers. 801.7 Section 801.7 Agriculture Regulations of the Department of Agriculture... methods and tolerances for near-infrared spectroscopy (NIRS) analyzers. (a) Reference methods. (1) The...

  14. 7 CFR 799.7 - Early involvement in private and state and local activities requiring Federal approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Early involvement in private and state and local activities requiring Federal approval. 799.7 Section 799.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE ENVIRONMENTAL PROTECTION ENVIRONMENTAL...

  15. 7 CFR 160.7 - Gum spirits of turpentine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Gum spirits of turpentine. 160.7 Section 160.7... STANDARDS FOR NAVAL STORES General § 160.7 Gum spirits of turpentine. The designation “gum spirits of turpentine” shall refer to the kind of spirits of turpentine obtained by distillation of the oleoresin (gum...

  16. 7 CFR 160.7 - Gum spirits of turpentine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Gum spirits of turpentine. 160.7 Section 160.7... STANDARDS FOR NAVAL STORES General § 160.7 Gum spirits of turpentine. The designation “gum spirits of turpentine” shall refer to the kind of spirits of turpentine obtained by distillation of the oleoresin (gum...

  17. 7 CFR 160.7 - Gum spirits of turpentine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Gum spirits of turpentine. 160.7 Section 160.7... STANDARDS FOR NAVAL STORES General § 160.7 Gum spirits of turpentine. The designation “gum spirits of turpentine” shall refer to the kind of spirits of turpentine obtained by distillation of the oleoresin (gum...

  18. 7 CFR 160.7 - Gum spirits of turpentine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Gum spirits of turpentine. 160.7 Section 160.7... STANDARDS FOR NAVAL STORES General § 160.7 Gum spirits of turpentine. The designation “gum spirits of turpentine” shall refer to the kind of spirits of turpentine obtained by distillation of the oleoresin (gum...

  19. 7 CFR 160.7 - Gum spirits of turpentine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Gum spirits of turpentine. 160.7 Section 160.7... STANDARDS FOR NAVAL STORES General § 160.7 Gum spirits of turpentine. The designation “gum spirits of turpentine” shall refer to the kind of spirits of turpentine obtained by distillation of the oleoresin (gum...

  20. 7 CFR 1714.7 - Interest rate cap.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Interest rate cap. 1714.7 Section 1714.7 Agriculture... PRE-LOAN POLICIES AND PROCEDURES FOR INSURED ELECTRIC LOANS General § 1714.7 Interest rate cap. Except... section, or both the rate disparity test for the interest rate cap and the consumer income test set forth...

  1. 7 CFR 15a.7 - Designation of responsible employee and adoption of grievance procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Designation of responsible employee and adoption of grievance procedures. 15a.7 Section 15a.7 Agriculture Office of the Secretary of Agriculture EDUCATION PROGRAMS OR ACTIVITIES RECEIVING OR BENEFITTING FROM FEDERAL FINANCIAL ASSISTANCE Introduction § 15a.7...

  2. 7 CFR 301.32-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.32-7 Section 301.32-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND....32-7 Assembly and inspection of regulated articles. (a) Any person, other than a person authorized to...

  3. 7 CFR 301.53-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.53-7 Section 301.53-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.53-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or other...

  4. 7 CFR 301.91-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.91-7 Section 301.91-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Canker Quarantine and Regulations § 301.91-7 Assembly and inspection of regulated articles. (a) Any...

  5. 7 CFR 301.55-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.55-7 Section 301.55-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Cactus Moth § 301.55-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  6. 7 CFR 301.87-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.87-7 Section 301.87-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Diseases Quarantine and Regulations § 301.87-7 Assembly and inspection of regulated articles. (a) Any...

  7. 7 CFR 301.87-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.87-7 Section 301.87-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Diseases Quarantine and Regulations § 301.87-7 Assembly and inspection of regulated articles. (a) Any...

  8. 7 CFR 301.50-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.50-7 Section 301.50-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.50-7 Assembly and inspection of regulated articles. (a) Any person (other than a person authorized...

  9. 7 CFR 301.87-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.87-7 Section 301.87-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Diseases Quarantine and Regulations § 301.87-7 Assembly and inspection of regulated articles. (a) Any...

  10. 7 CFR 301.92-7 - Availability of inspectors; assembly for inspection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Availability of inspectors; assembly for inspection. 301.92-7 Section 301.92-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Phytophthora Ramorum § 301.92-7 Availability of inspectors; assembly for inspection. (a) Any person (other than...

  11. 7 CFR 301.92-7 - Availability of inspectors; assembly for inspection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Availability of inspectors; assembly for inspection. 301.92-7 Section 301.92-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Phytophthora Ramorum § 301.92-7 Availability of inspectors; assembly for inspection. (a) Any person (other than...

  12. 7 CFR 301.32-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.32-7 Section 301.32-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND....32-7 Assembly and inspection of regulated articles. (a) Any person, other than a person authorized to...

  13. 7 CFR 301.87-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.87-7 Section 301.87-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Diseases Quarantine and Regulations § 301.87-7 Assembly and inspection of regulated articles. (a) Any...

  14. 7 CFR 301.92-7 - Availability of inspectors; assembly for inspection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Availability of inspectors; assembly for inspection. 301.92-7 Section 301.92-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Phytophthora Ramorum § 301.92-7 Availability of inspectors; assembly for inspection. (a) Any person (other than...

  15. 7 CFR 301.55-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.55-7 Section 301.55-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Cactus Moth § 301.55-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  16. 7 CFR 301.51-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.51-7 Section 301.51-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Beetle § 301.51-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or...

  17. 7 CFR 301.32-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.32-7 Section 301.32-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND....32-7 Assembly and inspection of regulated articles. (a) Any person, other than a person authorized to...

  18. 7 CFR 301.91-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.91-7 Section 301.91-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Canker Quarantine and Regulations § 301.91-7 Assembly and inspection of regulated articles. (a) Any...

  19. 7 CFR 301.55-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.55-7 Section 301.55-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Cactus Moth § 301.55-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  20. 7 CFR 301.86-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.86-7 Section 301.86-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Nematode § 301.86-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  1. 7 CFR 301.86-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.86-7 Section 301.86-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Nematode § 301.86-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  2. 7 CFR 301.55-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.55-7 Section 301.55-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Cactus Moth § 301.55-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  3. 7 CFR 301.50-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.50-7 Section 301.50-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.50-7 Assembly and inspection of regulated articles. (a) Any person (other than a person authorized...

  4. 7 CFR 301.55-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.55-7 Section 301.55-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Cactus Moth § 301.55-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  5. 7 CFR 301.50-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.50-7 Section 301.50-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.50-7 Assembly and inspection of regulated articles. (a) Any person (other than a person authorized...

  6. 7 CFR 301.51-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.51-7 Section 301.51-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Beetle § 301.51-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or...

  7. 7 CFR 301.50-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.50-7 Section 301.50-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.50-7 Assembly and inspection of regulated articles. (a) Any person (other than a person authorized...

  8. 7 CFR 301.50-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.50-7 Section 301.50-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.50-7 Assembly and inspection of regulated articles. (a) Any person (other than a person authorized...

  9. 7 CFR 301.51-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.51-7 Section 301.51-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Beetle § 301.51-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or...

  10. 7 CFR 301.91-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.91-7 Section 301.91-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Canker Quarantine and Regulations § 301.91-7 Assembly and inspection of regulated articles. (a) Any...

  11. 7 CFR 301.91-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.91-7 Section 301.91-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Canker Quarantine and Regulations § 301.91-7 Assembly and inspection of regulated articles. (a) Any...

  12. 7 CFR 301.92-7 - Availability of inspectors; assembly for inspection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Availability of inspectors; assembly for inspection. 301.92-7 Section 301.92-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Phytophthora Ramorum § 301.92-7 Availability of inspectors; assembly for inspection. (a) Any person (other than...

  13. 7 CFR 301.32-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.32-7 Section 301.32-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND....32-7 Assembly and inspection of regulated articles. (a) Any person, other than a person authorized to...

  14. 7 CFR 301.53-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.53-7 Section 301.53-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.53-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or other...

  15. 7 CFR 301.53-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.53-7 Section 301.53-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.53-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or other...

  16. 7 CFR 301.32-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.32-7 Section 301.32-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND....32-7 Assembly and inspection of regulated articles. (a) Any person, other than a person authorized to...

  17. 7 CFR 301.53-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.53-7 Section 301.53-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.53-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or other...

  18. 7 CFR 301.53-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.53-7 Section 301.53-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... § 301.53-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or other...

  19. 7 CFR 301.51-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.51-7 Section 301.51-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Beetle § 301.51-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or...

  20. 7 CFR 301.91-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles. 301.91-7 Section 301.91-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Canker Quarantine and Regulations § 301.91-7 Assembly and inspection of regulated articles. (a) Any...

  1. 7 CFR 301.86-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles. 301.86-7 Section 301.86-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Nematode § 301.86-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  2. 7 CFR 301.86-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.86-7 Section 301.86-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Nematode § 301.86-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  3. 7 CFR 301.51-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles. 301.51-7 Section 301.51-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Beetle § 301.51-7 Assembly and inspection of regulated articles. (a) Persons requiring certification or...

  4. 7 CFR 301.86-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Assembly and inspection of regulated articles. 301.86-7 Section 301.86-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Nematode § 301.86-7 Assembly and inspection of regulated articles. (a) Any person (other than a person...

  5. 7 CFR 301.87-7 - Assembly and inspection of regulated articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles. 301.87-7 Section 301.87-7 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND... Diseases Quarantine and Regulations § 301.87-7 Assembly and inspection of regulated articles. (a) Any...

  6. 7 CFR 1962.7 - Securing unpaid balances on unsecured loans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Securing unpaid balances on unsecured loans. 1962.7 Section 1962.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE... Security § 1962.7 Securing unpaid balances on unsecured loans. The County Supervisor will take a lien on a...

  7. 7 CFR 1962.7 - Securing unpaid balances on unsecured loans.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false Securing unpaid balances on unsecured loans. 1962.7 Section 1962.7 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE... Security § 1962.7 Securing unpaid balances on unsecured loans. The County Supervisor will take a lien on a...

  8. 7 CFR 1942.7 - Loan closing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Loan closing. 1942.7 Section 1942.7 Agriculture... REGULATIONS (CONTINUED) ASSOCIATIONS Community Facility Loans § 1942.7 Loan closing. Loans will be closed in accordance with the closing instructions issued by the OGC and § 1942.17(o) of this subpart and as soon as...

  9. 7 CFR 1434.7 - Approved storage.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Approved storage. 1434.7 Section 1434.7 Agriculture... FOR HONEY § 1434.7 Approved storage. (a) Loans will be made only on honey in approved storage, which shall consist of a storage structure located on or off the farm that is determined by CCC to be under...

  10. 7 CFR 1434.7 - Approved storage.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Approved storage. 1434.7 Section 1434.7 Agriculture... FOR HONEY § 1434.7 Approved storage. (a) Loans will be made only on honey in approved storage, which shall consist of a storage structure located on or off the farm that is determined by CCC to be under...

  11. 7 CFR 1434.7 - Approved storage.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Approved storage. 1434.7 Section 1434.7 Agriculture... FOR HONEY § 1434.7 Approved storage. (a) Loans will be made only on honey in approved storage, which shall consist of a storage structure located on or off the farm that is determined by CCC to be under...

  12. 7 CFR 1434.7 - Approved storage.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Approved storage. 1434.7 Section 1434.7 Agriculture... FOR HONEY § 1434.7 Approved storage. (a) Loans will be made only on honey in approved storage, which shall consist of a storage structure located on or off the farm that is determined by CCC to be under...

  13. 7 CFR 1434.7 - Approved storage.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Approved storage. 1434.7 Section 1434.7 Agriculture... FOR HONEY § 1434.7 Approved storage. (a) Loans will be made only on honey in approved storage, which shall consist of a storage structure located on or off the farm that is determined by CCC to be under...

  14. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  15. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this section...

  16. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  17. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h) of...

  18. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  19. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in...

  20. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of this...

  1. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in...

  2. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in...

  3. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  4. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of this...

  5. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  6. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  7. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in...

  8. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h) of...

  9. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  10. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  11. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of this...

  12. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  13. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of this...

  14. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of this...

  15. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of this...

  16. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this section...

  17. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in...

  18. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  19. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

  20. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant specified...

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